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Background: Patients experiencing myocardial infarction (MI) remain at high risk of future major adverse cardiovascular events (MACE). While low-dose colchicine and spironolactone have been shown to decrease post-MI MACE, more data are required to confirm their safety and efficacy in an unselected post-MI population. Therefore, we initiated the CLEAR SYNERGY (OASIS 9) trial to address these uncertainties., Methods: The CLEAR SYNERGY trial is a 2 × 2 factorial randomized controlled trial of low-dose colchicine 0.5 mg daily versus placebo and spironolactone 25 mg daily versus placebo in 7,062 post-MI participants who were within 72 hours of the index percutaneous coronary intervention (PCI). We blinded participants, healthcare providers, research personnel, and outcome adjudicators to treatment allocation. The primary outcome for colchicine is the first occurrence of the composite of cardiovascular death, recurrent MI, stroke, or unplanned ischemia-driven revascularization. The coprimary outcomes for spironolactone are (1) the composite of the total numbers of cardiovascular death or new or worsening heart failure and (2) the first occurrence of the composite of cardiovascular death, new or worsening heart failure, recurrent MI or stroke. We finished recruitment with 7,062 participants from 104 centers in 14 countries on November 8, 2022, and plan to present the results in the fall of 2024., Conclusions: CLEAR SYNERGY is a large international randomized controlled trial that will inform the effects of low-dose colchicine and spironolactone in largely unselected post-MI patients who undergo PCI. (ClinicalTrials.gov Identifier: NCT03048825)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: In ST-segment elevation myocardial infarction (STEMI), complete revascularization with percutaneous coronary intervention (PCI) reduces major cardiovascular events compared with culprit-lesion-only PCI. Whether age influences these results remains unknown., Methods: COMPLETE was a multinational, randomized trial evaluating a strategy of staged complete revascularization, consisting of angiography-guided PCI of all suitable nonculprit lesions, versus a strategy of culprit-lesion-only PCI. In this prespecified subgroup analysis, treatment effect according to age (≥65 years vs <65 years) was determined for the first coprimary outcome of cardiovascular (CV) death or new myocardial infarction (MI) and the second coprimary outcome of CV death, new MI, or ischemia-driven revascularization (IDR). Median follow-up was 35.8 months (interquartile range [IQR]: 27.6-44.3 months)., Results: Of 4,041 patients randomized in COMPLETE, 1,613 were aged ≥ 65 years (39.9%). Higher event rates were observed for both coprimary outcomes in patients aged ≥ 65 years comparted with those aged < 65 years (11.2% vs 7.9%, HR 1.49, 95% CI 1.22-1.83; 14.4% vs 11.8%, HR 1.28, 95% CI 1.07-1.52, respectively). Complete revascularization reduced the first coprimary outcome in patients ≥ 65 years (9.7% vs 12.5%, HR 0.77; 95% CI, 0.58-1.04) and < 65 years (6.7% vs 9.1%, HR 0.72; 95% CI, 0.54-0.96)(interaction P = .74). The second coprimary outcome was reduced in those ≥ 65 years (HR 0.56, 95% CI, 0.43-0.74) and < 65 years (HR 0.48, 95% CI, 0.37-0.61 (interaction P = .37). A sensitivity analysis was performed with consistent results demonstrated using a 75-year threshold (albeit attenuated)., Conclusions: In patients with STEMI and multivessel CAD, complete revascularization compared with culprit-lesion-only PCI reduced major cardiovascular events regardless of patient age and could be considered as a revascularization strategy in older adults., Competing Interests: Disclosures The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Repeat coronary revascularization is a common adverse event after successful percutaneous coronary intervention. This analysis aimed to assess the effects of ticagrelor monotherapy on repeat clinically driven revascularization (CDR). In the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, high-risk patients were maintained on ticagrelor and randomly allocated to aspirin or placebo for 1 year. The primary end point of this analysis was CDR within 12 months after randomization. The key secondary end points were major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, stroke, or CDR, and net adverse clinical events (NACEs), including the individual components of MACCEs and clinically relevant bleeding. The analysis was performed in the per-protocol population. CDR occurred in 473 of 7,039 patients and was associated with a significantly higher risk of subsequent all-cause death, myocardial infarction, or stroke (adjusted hazard ratios [HRs] 2.92, 95% confidence interval [CI] 1.82 to 4.67). Ticagrelor monotherapy was associated with a similar 12-month risk of CDR (7.1% vs 6.6%; HR 1.09, 95% CI 0.90 to 1.30, p = 0.363) and MACCEs (8.9% vs 8.6%; HR 1.04, 95% CI 0.89 to 1.22, p = 0.619), and a lower risk of NACEs (12.2% vs 14.6%; HR 0.83 95% CI 0.73 to 0.94, p = 0.004) than ticagrelor plus aspirin. In conclusion, among high-risk patients who underwent percutaneous coronary intervention, ticagrelor monotherapy after 3 months of ticagrelor-based dual antiplatelet therapy was associated with a similar risk of CDR and MACCEs and a decrease of NACEs (TWILIGHT: NCT02270242)., Competing Interests: Declaration of Competing Interest Dr. Spirito received a research grant from the Swiss National Science Foundation (Bern, Switzerland). Dr. Mehta has received grant support from and has served on an executive committee and as site investigator for AstraZeneca (Cambridge, United Kingdom). Dr. Mehran reports institutional research payments from Abbott, Abiomed, Alleviant Medical, Amgen, AM-Pharmacia, Arena, AstraZeneca, Atricure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi-Sankyo, Element Science, Faraday, Humacyte, Idorsia Pharmaceuticals, Janssen, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, PLx Pharma, RenalPro, RM Global, Shockwave, Vivasure, Zoll; personal fees from Cine-Med Research, Novartis, WebMD; Equity <1% in Applied Therapeutics, Elixir Medical, Stel, ControlRad (spouse); Scientific Advisory Board for AMA, ACC (BOT Member), SCAI (Women in Innovations Committee Member), JAMA Associate Editor; Faculty CRF (no fee). Dr. Kastrati is an inventor in a patent application related to drug-eluting stent technology; he also serves in the Data and Safety Monitoring Board of the TARGET IV trial sponsored by the Cardiovascular Research Foundation in New York. Dr. Angiolillo declares that he has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo, Eli Lilly (Gilead), Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer (New York, New York), Sanofi and Vectura; D.J.A. also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, and the Scott R. MacKenzie Foundation. Dr. Baber has received honoraria from AstraZeneca and Boston Scientific. Dr. Cohen has received grant support, paid to his institution, and consulting fees from AstraZeneca, Medtronic, and Abbott Vascular; and has received grant support, paid to his institution, from Boston Scientific Dr. Dangas has received consulting fees and advisory board fees from AstraZeneca; has received consulting fees from Biosensors; and previously held stock in Medtronic. Dr. Escaned has received consulting and lecture fees from Abbott, Philips, Boston Scientific, and Medtronic; and has received lecture fees from Abiomed, Terumo, and Biosensors. Dr. Gibson has received grant support and consulting fees from Angel Medical, Bayer, CSL Behring, Janssen Pharmaceuticals, Johnson & Johnson, and Portola Pharmaceuticals; has received consulting fees from The Medicines Company, Eli Lilly Sciences, Novo Nordisk, WebMD, UpToDate Cardiovascular Medicine, Amarin Pharma, Amgen, Boehringer Ingelheim, Chiesi, Merck, PharmaMar, Sanofi, Somahlution, Verreseon, Boston Scientific, Impact Bio, MedImmume, Medtelligence, MicroPort, the PERT Consortium, and GE Healthcare (Little Chalfont, United Kingdom); holds equity in Inference; serves as chief executive officer of the Baim Institute; and has received grant support, paid to the Baim Institute, from Bristol-Myers Squibb and Astra Zeneca. Dr. Huber has received lecture fees from AstraZeneca and Bayer. The remining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: In the COMPLETE trial (Complete Versus Culprit-Only Revascularization to Treat Multivessel Disease After Early PCI for STEMI), a strategy of complete revascularization reduced the risk of major cardiovascular events compared with culprit-lesion-only percutaneous coronary intervention in patients presenting with ST-segment-elevation myocardial infarction (STEMI) and multivessel coronary artery disease. Patients with diabetes have a worse prognosis following STEMI. We evaluated the consistency of the effects of complete revascularization in patients with and without diabetes., Methods: The COMPLETE trial randomized a strategy of complete revascularization, consisting of angiography-guided percutaneous coronary intervention of all suitable nonculprit lesions, versus a strategy of culprit-lesion-only percutaneous coronary intervention (guideline-directed medical therapy alone). In prespecified analyses, treatment effects were determined in patients with and without diabetes on the first coprimary outcome of cardiovascular death or new myocardial infarction and the second coprimary outcome of cardiovascular death, new myocardial infarction, or ischemia-driven revascularization. Interaction P values were calculated to evaluate whether there was a differential treatment effect in patients with and without diabetes., Results: Of the 4041 patients enrolled in the COMPLETE trial, 787 patients (19.5%) had diabetes. The median HbA1c (glycated hemoglobin) was 7.7% in the diabetes group and 5.7% in the nondiabetes group. Complete revascularization consistently reduced the first coprimary outcome in patients with diabetes (hazard ratio, 0.87 [95% CI, 0.59-1.29]) and without diabetes (hazard ratio, 0.70 [95% CI, 0.55-0.90]), with no evidence of a differential treatment effect (interaction P =0.36). Similarly, for the second coprimary outcome, no differential treatment effect (interaction P =0.27) of complete revascularization was found in patients with diabetes (hazard ratio, 0.61 [95% CI, 0.43-0.87]) and without diabetes (hazard ratio, 0.48 [95% CI, 0.39-0.60])., Conclusions: Among patients presenting with STEMI and multivessel disease, the benefit of complete revascularization over a culprit-lesion-only percutaneous coronary intervention strategy was consistent regardless of the presence or absence of diabetes., Competing Interests: Disclosures Dr Mehta reports grants from Canadian Institute of Health Research, grants from AstraZeneca and Boston Scientific, during the conduct of the study. Dr Mehran reports grants and other from Abbott, grants and other from Abiomed, grants and other from Applied Therapeutics, grants and other from Arena, grants from AstraZeneca, grants and other from Bayer, grants and other from Biosensors, grants, personal fees and other from Boston Scientific, grants and other from CardiaWave, grants from CellAegis, grants from CERC, grants and other from Chiesi, grants and other from Concept Medical, grants and other from CSL Behring, grants and other from DSI, grants from Insel Gruppe AG, grants and other from Medtronic, other from Novartis, grants from OrbusNeich, grants and other from Philips, grants from Transverse Medical, grants from Zoll, personal fees from California Institute for Regenerative Medicine (CIRM), personal fees from Cine-Med Research, personal fees from Janssen, personal fees from WebMD, personal fees from SCAI, other from AM Pharma, other from Alleviant Medical, other from CeloNova BioSciences, other from Duke University, other from Humacyte, from Idorsia Pharmaceuticals, personal fees from AMA, other from Biotronik, other from Elixir Medical, other from STEL, other from ControlRad, other from CRF, other from ACC, outside the submitted work. Dr Storey reports personal fees from Bayer, personal fees from Bristol-Myers Squibb/Pfizer, grants and personal fees from AstraZeneca, grants and personal fees from Thromboserin, grants and personal fees from Glycardial Diagnostics, personal fees from Portola, personal fees from Medscape, grants and personal fees from Cytosorbents, personal fees from Intas Pharmaceuticals, personal fees from Hengrui, personal fees from Sanofi Aventis, personal fees from Idorsia, personal fees from PhaseBio, personal fees from Alnylam, personal fees from CSL-Behring, personal fees from Novartis, personal fees from Chiesi, outside the submitted work. Dr Pinilla-Echeverri reports grants from Boston Scientific, grants from AstraZeneca, grants from Canadian Institutes of Health Research, grants from Population Health Research Institute, during the conduct of the study; personal fees from Abbott, personal fees from Philips, personal fees from Conavi, personal fees from Novartis, outside the submitted work. Dr Moreno reports other from Abbott Vascular, other from Boston Scientific, other from Biosensors, other from Biotronik, other from Medtronic Inc., other from Daiichi-Sankyo, other from AMGEN, other from AstraZeneca, other from Edwards Lifesciences, other from Terumo, other from Philips, other from Cardinal Health, outside the submitted work. Dr Steg reports grants and personal fees from Amarin, personal fees from Amgen, personal fees and nonfinancial support from AstraZeneca, grants and personal fees from Bayer, personal fees from Bristol-Myers Squibb, personal fees from Boehringer Ingelheim, personal fees from Idorsia, personal fees from Novartis, personal fees from Novo Nordisk, personal fees from Pfizer, personal fees from Sanofi/Lexicon, grants and personal fees from Servier, personal fees from Myokardia, grants and personal fees from Sanofi, personal fees from Regeneron, personal fees from Phase Bio, outside the submitted work. Dr Cairns reports grants from Boston Scientific, grants from Astra Zeneca, grants from CIHR, during the conduct of the study; personal fees from Abbott, personal fees from Bayer, personal fees from BMS Pfizer, outside the submitted work. Dr Sibbald reports grants from Abbott Vascular and Phillips. The remainder of authors have nothing to disclose.

Background: The optimal strategy to prevent no-reflow in ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI) is unknown., Aims: We aimed to examine the effect of thrombectomy on the outcome of no-reflow in key subgroups and the adverse clinical outcomes associated with no-reflow., Methods: We performed a post hoc analysis of the TOTAL Trial, a randomised trial of 10,732 patients comparing thrombectomy versus PCI alone. This analysis utilised the angiographic data of 1,800 randomly selected patients., Results: No-reflow was diagnosed in 196 of 1,800 eligible patients (10.9%). No-reflow occurred in 95/891 (10.7%) patients randomised to thrombectomy compared with 101/909 (11.1%) in the PCI-alone arm (odds ratio [OR] 0.95, 95% confidence interval [CI]: 0.71-1.28; p-value=0.76). In the subgroup of patients who underwent direct stenting, those randomised to thrombectomy compared with PCI alone experienced less no-reflow (19/371 [5.1%] vs 21/216 [9.7%], OR 0.50, 95% CI: 0.26-0.96). In patients who did not undergo direct stenting, there was no difference between the groups (64/504 [12.7%] vs 75/686 [10.9%)], OR 1.18, 95% CI: 0.82-1.69; interaction p-value=0.02). No-reflow patients had a significantly increased risk of experiencing the primary composite outcome (cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA Class IV heart failure) at 1 year (adjusted hazard ratio 1.70, 95% CI: 1.13-2.56; p-value=0.01)., Conclusions: In patients with STEMI treated by PCI, thrombectomy did not reduce no-reflow in all patients but may be synergistic with direct stenting. No-reflow is associated with increased adverse clinical outcomes.

In patients with non-ST-elevation myocardial infarction (NSTEMI), total occlusion of the culprit coronary artery (OCA) is not uncommon. We sought to determine the frequency and clinical impact of OCA at presentation in a large population of patients presenting with NSTEMI and who underwent systematic early invasive management. We performed a post hoc analysis of the TAO (Treatment of Acute Coronary Syndrome with Otamixaban) randomized trial, which included patients with NSTEMI with systematic coronary angiography within 72 hours. We compared the baseline characteristics and outcomes of patients according to whether the culprit vessel was occluded (thrombolysis in myocardial infarction flow grade [TFG] 0 to 1) or patent (TFG 2 to 3) at presentation. A total of 7,473 patients with NSTEMI with only 1 culprit lesion identified were enrolled, of whom 1,702 patients had OCA (22.8%). In the OCA group, coronary angiography was performed earlier (18 ± 15 vs 20 ± 16 hours, p <0.01), the culprit lesion was less likely to be the left anterior descending artery (26.5% vs 41.4%, p <0.001) but with more frequent angiographic thrombus (49.9% vs 22.7%, p <0.01). Culprit artery percutaneous coronary intervention during the index procedure was also more frequent (88.5% vs 78.1%, p <0.001) but with a lower rate of TFG grade 3 after the procedure and higher subsequent peak troponin I levels (8.3 ± 13.6 µg/L vs 5.6 ± 11.9 µg/L, p <0.001). At day 7, patients with OCA had higher mortality, and this persisted after adjustment on gender, Grace risk score, cardiovascular risk factors, and culprit vessel location (0.9% vs 0.4%, p = 0.02; adjusted odds ratio [OR] = 2.55, 95% confidence interval [CI] 1.23 to 5.29, p = 0.01). The absolute difference of mortality was maintained through 30 days: 1.2% versus 0.8%, p = 0.13; OR: 1.72, 95% CI 0.97 to 3.05, but mortality rates were similar by 180 days: 1.5% versus 1.6%, p = 0.8, adjusted OR = 1.11, 95% CI 0.69 to 1.80, p = 0.66. In conclusion, a significant proportion of patients with NSTEMI have a totally occluded culprit vessel at presentation. These patients are at higher risk of early mortality but not at 6 months., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: THEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry., Methods and Results: The THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients ≥50 years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of ≥50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a 'THEMIS-eligible population' of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy., Conclusions: In a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be 'THEMIS eligible.', Clinical Trial Registration: http://www., Clinicaltrials: gov identifier: NCT01991795., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Prior coronary artery bypass graft surgery (CABG) patients undergoing percutaneous coronary intervention (PCI) are often older and present with multiple comorbidities. Ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) has emerged as an effective bleeding-avoidance strategy among high-risk patients., Aims: We aimed to examine the effects of ticagrelor with or without aspirin in prior CABG patients undergoing PCI within the TWILIGHT trial., Methods: After 3 months of ticagrelor plus aspirin, patients were randomised to either aspirin or placebo, in addition to ticagrelor, for 12 months and compared by prior CABG status. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding. The key secondary endpoint was all-cause death, myocardial infarction (MI), or stroke., Results: Out of 7,119 patients, a total of 703 (10.8%) patients had prior CABG within the randomised cohort. Prior CABG patients had more comorbidities and a higher incidence of BARC type 2, 3, or 5 bleeding and death, MI or stroke at 1 year after randomisation, compared with patients without prior CABG. Ticagrelor monotherapy was associated with significantly less BARC 2, 3, or 5 bleeding among prior CABG patients compared with DAPT (4.9% vs 9.6%, hazard ratio [HR] 0.50, 95% confidence interval [CI]: 0.28 to 0.90; p interaction =0.676) and similar rates of death, MI or stroke (10.0% vs 8.7%, HR 1.14, 95% CI: 0.70 to 1.87; p interaction =0.484). When comparing target vessel type, treatment effects were consistent among graft- and native-vessel interventions., Conclusions: In high-risk patients with prior CABG, ticagrelor monotherapy reduced bleeding without compromising ischaemic outcomes compared with ticagrelor plus aspirin.

Background: The THEMIS trial demonstrated that in high-risk patients with stable coronary artery disease and diabetes without previous myocardial infarction or stroke, ticagrelor, in addition to aspirin, reduced the incidence of ischemic events but increased major bleeding. Identification of patients who could derive the greatest net benefit from the addition of ticagrelor appears important. We used the CRUSADE bleeding risk score to risk stratify the THEMIS population., Methods: The population was divided into tertiles: score ≤22, 23 to 33, and ≥34. In each tertile, primary efficacy (composite of cardiovascular death, myocardial infarction, or stroke) and safety (TIMI major bleeding) outcomes were analyzed. NACE (net adverse clinical events) was defined as the irreversible harm composite, in which all-cause death, myocardial infarction, stroke, amputations, fatal bleeds, and intracranial hemorrhage were counted., Results: Patients in the lower risk tertile experienced fewer ischemic events with ticagrelor than placebo, whereas there was no significant benefit from ticagrelor in the other tertiles (P interaction  = .008). Bleeding rates were consistently increased with ticagrelor across all tertiles (P interaction  = .79). Ticagrelor reduced NACE in the first tertile (HR = 0.74, 95% CI = 0.61-0.90) but not in the others (HR = 1.03, 95% CI = 0.86-1.23 and HR = 1.05, 95% CI = 0.91-1.22, respectively; P interaction  = .012)., Conclusions: In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, only those at the lower end of the bleeding risk spectrum according to the CRUSADE score derived net benefit from ticagrelor., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate if patients with prior myocardial infarction (MI) could benefit from ticagrelor monotherapy in terms of bleeding reduction without any compromise in ischemic event prevention., Background: Patients with history of MI who undergo percutaneous coronary intervention (PCI) remain at risk for recurrent ischemic events. The optimal antithrombotic strategy for this cohort remains debated., Methods: In this prespecified analysis of the randomized TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, the authors evaluated the impact of history of MI on treatment effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing PCI with drug-eluting stent with at least 1 clinical and 1 angiographic high-risk feature and free from adverse events at 3 months after index PCI. The primary endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, and the key secondary endpoint was the composite of all-cause death, MI, or stroke, both at 12 months after randomization., Results: A total of 1,937 patients (29.7%) with and 4,595 patients (70.3%) without prior MI were randomized to ticagrelor and placebo or ticagrelor and aspirin. At 1 year after randomization, patients with prior MI experienced higher rates of death, MI, or stroke (5.7% vs 3.2%; P < 0.001) but similar BARC types 2 to 5 bleeding (5.0% vs 5.5%; P = 0.677) compared with patients without prior MI. Ticagrelor monotherapy consistently reduced the risk for the primary bleeding outcome in patients with (3.4% vs 6.7%; HR: 0.50; 95% CI: 0.33-0.76) and without (4.2% vs 7.0%; HR: 0.58; 95% CI: 0.45-0.76; P interaction  = 0.54) prior MI. Rates of the key secondary ischemic outcome were not significantly different between treatment groups irrespective of history of MI (prior MI, 6.0% vs 5.5% [HR: 1.09; 95% CI: 0.75-1.58]; no prior MI, 3.1% vs 3.3% [HR: 0.92; 95% CI: 0.67-1.28]; P interaction  = 0.52)., Conclusions: Ticagrelor monotherapy is associated with significantly lower risk for bleeding events compared with ticagrelor plus aspirin, without any compromise in ischemic prevention, among high-risk patients with history of MI undergoing PCI. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242)., Competing Interests: Funding Support and Author Disclosures This research was conducted with support from AstraZeneca Pharmaceuticals LP. Dr Baber has received honoraria from AstraZeneca and Boston Scientific. Dr Sharma has received Speakers Bureau fees from Abbott Vascular, Boston Scientific, and Cardiovascular Systems. Dr Dangas has received personal fees from Biosensors and Philips. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company; has received payments for participation in review activities from CeloNova and St Jude Medical, outside the present work; and has received research grants to his institution from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr Stefanini has received a research grant from Boston Scientific; and has received speaker and consulting fees from Bayer, Braun, Biosensors, Boston Scientific, Daiichi-Sankyo and GADA, outside the submitted work. Dr Gibson has received grants and personal fees from Johnson & Johnson, Janssen, and CSL Behring; has received personal fees from Bayer, AstraZeneca (during the conduct of the study), Angel Medical Corporation, The Medicines Company, the Boston Clinical Research Institute, the Cardiovascular Research Foundation, Gilead Sciences, WebMD, UpToDate in Cardiovascular Medicine, Boehringer Ingelheim, Somahlution, Vereseon, Boston Scientific, the Duke Clinical Research Institute, Medtelligence, Microport, PERT Consortium, Caladrius Biosciences, CeleCor Therapeutics, Thrombolytic Science, Eidos Therapeutics, Kiniksa Pharmaceuticals, Microdrop, MD Magazine, MJ Health, Samsung, the Society for Cardiovascular Angiography and Interventions, Revance Therapeutics, Pfizer, GenTech, CytoSorbents, AMAG Pharmaceuticals, Bristol Myers Squibb, Intercept Pharmaceuticals, Novartis, Syneos Health, and Amarin; has received other compensation from nference, Dyad Medical, and Absolutys, and PhaseBio; has received nonfinancial support from the Baim Institute; and has received grants from the SCAD Alliance, outside the submitted work. Dr Mehran has received institutional grants from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo Inc, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; has received personal fees from Boston Scientific, Janssen, Scientific Affairs, Sanofi, and Siemens Medical Solutions; has received consulting fees paid to the institution from Abbott Laboratories and Bristol Myers Squibb; and is an advisory board member (funding paid to the institution) for Spectranetics/Philips/Volcano. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Clinicians regularly observe increased high-sensitivity cardiac troponin (hs-cTn) concentrations in patients with low estimated glomerular filtration rate (eGFR). The challenge is to differentiate acute coronary syndrome (ACS) from increased hs-cTn results across a range of eGFR. The objective of this study was to determined the optimal hs-cTn concentrations for acute myocardial infarction (MI) and a composite cardiovascular outcome across different eGFR ranges and to assess the utility of a low hs-cTn cutoff to rule-out events., Methods: We undertook an observational study in the emergency department of patients (n = 1212) with symptoms suggestive of ACS who had an eGFR and at least one Roche hs-cTnT and one Abbott hs-cTnI result. The 7-day outcomes were MI or a composite of MI, unstable angina, congestive heart failure, serious ventricular cardiac arrhythmia, or death. The maximum hs-cTn concentration was assessed across different eGFR ranges (<30,30-59,60-89,≥90 ml/min/1.73m 2 ) by spearman correlation, ROC-curve analyses, and sensitivity and negative predictive value (NPV) for the proposed rule-out hs-cTn cutoffs (hs-cTnI<5 ng/l and hs-cTnT<6 ng/l) for the outcomes., Results: Both hs-cTnI and hs-cTnT concentrations were negatively correlated with eGFR. The lower the eGFR, the lower the AUC and the higher the optimal hs-cTn cutoffs for both MI and the composite outcome. The highest combined sensitivity (100%), NPV (100%) and proportion of low-risk for MI (45% of group) was observed for patients with hs-cTnT<6 ng/l with an eGFR≥90., Conclusion: The test performance for hs-cTn for diagnosing or ruling-out an acute cardiac event varies per the eGFR. Accurate risk stratification requires knowledge of the eGFR., (Copyright © 2018 Elsevier B.V. All rights reserved.)

While divorced or living alone, patients with stable cardiovascular disease are at increased risk for adverse cardiovascular events. The importance of marital status following a myocardial infarction (MI) is less clear. We hypothesized that marital status may affect cardiovascular outcomes following MI. We analyzed outcomes among patients with MI who underwent percutaneous coronary intervention from the Canadian Observational Antiplatelet Study (COAPT). Marital status was categorized into 3 groups: married/common-law patients living together; never married; and divorced, separated, or widowed patients. Patients were followed for 15 months and our primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of mortality, repeat acute MI, stroke, or urgent coronary revascularization. Multivariable logistic regression models were performed, with married/common-law patients living together considered the reference group. Among 2100 patients included in analyses, 1519 (72.3%) were married/common-law patients living together, 358 (17.1%) were separated/divorced/widowed, and 223 (10.6%) patients were never married. Dual antiplatelet therapy use after 15 months was similar across groups (75.4%, 77.8%, and 73.6%, respectively). The risk of MACE after 15 months was similar among married patients living together (12.7%; referent) compared with patients who were never married (13.9%; adjusted odds ratio: 1.09, 95% confidence interval: 0.58-2.07, P = 0.79) and patients separated/divorced/widowed (14.3%; adjusted odds ratio: 0.71, 95% confidence interval: 0.40-1.25, P = 0.23). Similarly, the risk of individual endpoints, including mortality, was similar across the 3 groups. Among patients stabilized following an MI, we found no association between marital status and 15-month outcomes., (© 2018 Wiley Periodicals, Inc.)

Aims: There is a paucity of real-world, contemporary data of practice patterns and clinical outcomes following dual-antiplatelet therapy (DAPT) in acute myocardial infarction (AMI) patients treated with percutaneous coronary intervention (PCI)., Methods and Results: The Canadian Observational Antiplatelet Study was a prospective, multicentre, cohort study examining adenosine diphosphate receptor antagonist use following PCI for AMI. We compared practice patterns, patient characteristics, and clinical outcomes in relation to DAPT duration (<6 weeks, 6 weeks to <6 months, 6 to <12, and ≥12 months). The primary outcome was the composite of non-fatal AMI, unplanned coronary revascularization, stent thrombosis, new or worsening heart failure, cardiogenic shock, or stroke. We identified 2034 patients with AMI treated with PCI. DAPT duration was <6 weeks in 5.2% of patients; 6 weeks to <6 months in 7.0%; 6 to <12 months in 12.6%; and ≥12 months in 75.3%. Patients who discontinued DAPT early had higher GRACE risk scores. Overall, mortality rate at 15 months was 2.5%. Compared with a duration of DAPT of ≥12 months, discontinuation of DAPT <6 weeks (P < 0.0001) and 6 weeks to <6 months (P = 0.02), but not 6 months to <12 months (P = 0.06), were independently associated with a higher incidence of the primary outcome among survivors., Conclusion: One-in-four patients with AMI treated with PCI discontinued DAPT prior to the guideline-recommended 12-month duration. Patients in whom DAPT was discontinued early were at higher baseline risk and had higher rates of non-fatal ischaemic events during follow up., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.)

Purpose of Review: Multivessel disease (MVD) is common in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) and is associated with significant risk of future cardiovascular (CV) events including short and longer-term mortality. In this review, we examine the pathophysiologic construct contributing to adverse prognosis of MVD in STEMI, relevant available evidence that currently guides the management of the noninfarct-related artery (IRA) stenosis and define the remaining knowledge gaps for future studies., Recent Findings: Results of recent small sized randomized trials, when pooled, suggest improvement in CV outcomes including CV mortality and repeat revascularization with revascularization of the non-IRA stenosis compared with medical management alone. In addition, there does not appear to be an increase in bleeding, contrast-induced nephropathy or stroke, as suggested by earlier observational data., Summary: These recent data have led to a Class IIb recommendation in the American College of Cardiology/American Heart Association guidelines stating that non-IRA revascularization may be considered in selected patients with STEMI and MVD who are hemodynamically stable, either at the time of primary PCI or as a planned staged procedure. The ongoing COMPLETE and CULPRIT-SHOCK studies will provide additional data to further inform the role of non-IRA revascularization and its timing in the management of these patients.

Aims: Bioabsorbable polymer drug-eluting stents (DES) may reduce the inflammation and delayed healing associated with some permanent polymer-coated DES. Whether late clinical outcomes are improved, particularly among patients with medically treated diabetes, is unknown. Therefore, we analysed outcomes from a pre-specified substudy of the EVOLVE II trial to evaluate the safety and effectiveness of the SYNERGY stent in patients with diabetes mellitus., Methods and Results: SYNERGY is a thin-strut, platinum-chromium everolimus-eluting stent with an ultra-thin bioabsorbable poly(DL-lactide-co-glycolide) abluminal polymer. The EVOLVE II randomised, controlled trial proved the non-inferiority of the SYNERGY versus the PROMUS Element Plus stent for one-year target lesion failure (TLF: ischaemia-driven target lesion revascularisation [ID-TLR], target vessel myocardial infarction [TVMI], or cardiac death). The pre-specified EVOLVE II diabetes substudy prospectively pooled randomised patients with diabetes (N=263) with a sequential single-arm diabetic cohort (n=203). The substudy primary endpoint was one-year TLF compared with a pre-specified performance goal (14.5%). The primary endpoint occurred in 7.5% of SYNERGY-treated patients with diabetes, significantly less than the performance goal (p<0.0001). The two-year rate of TLF was 11.2% (cardiac death 1.5%, TVMI 6.4%, ID-TLR 6.8%) and definite/probable stent thrombosis occurred in 1.1% of patients., Conclusions: The EVOLVE II diabetes substudy demonstrates the efficacy and safety of the SYNERGY stent in patients with medically treated diabetes.

Background: We have previously demonstrated the utility of a rule-in/rule-out strategy for myocardial infarction (MI) using glycemic biomarkers in combination with cardiac troponin in the emergency department (ED). Given that the cost of assessing patients with possible MI in the ED is increasing, we sought to compare the health services cost of our previously identified early rule-in/rule-out approaches for MI among patients who present to the ED with symptoms suggestive of acute coronary syndrome (ACS)., Methods: We compared the cost differences between different rule-in/rule-out strategies for MI using presentation cardiac troponin I (cTnI), high-sensitivity cTnI (hs-cTnI), high-sensitivity cardiac troponin T (hs-cTnT), glucose, and/or hemoglobin A 1c (Hb A 1c ) in 1137 ED patients (7-day MI n = 133) as per our previously defined algorithms and compared them with the European Society of Cardiology (ESC) 0-h algorithm-cutoffs. Costs associated with each decision model were obtained from site-specific sources (length of stay) and provincial sources (Ontario Case Costing Initiative)., Results: Algorithms incorporating cardiac troponin and glucose for early rule-in/rule-out were the most cost effective and clinically safest methods (i.e., ≤1 MI missed) for early decision making, with hs-cTnI and glucose yielding lower costs compared to cTnI and glucose, despite the higher price for the hs-cTnI test. The addition of Hb A 1c to the algorithms increased the cost of these algorithms but did not miss any additional patients with MI. Applying the ESC 0-h algorithm-cutoffs for hs-cTnI and hs-cTnT were the most costly., Conclusions: Rule-in/rule-out algorithms incorporating presentation glucose with high-sensitivity cardiac troponin are the safest and most cost-effective options as compared to the ESC 0-h algorithm-cutoffs., (© 2016 American Association for Clinical Chemistry.)

Background: After myocardial infarction (MI) treated with percutaneous coronary intervention (PCI), guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and an ADP receptor inhibitor (ADPri) for at least 1year. However, whether real-world Canadian practice patterns reflect this recommendation is unknown., Methods: We studied 2175 MI patients treated with PCI and discharged from 26 Canadian hospitals between 12/2011 and 05/2013 in the Canadian Observational Antiplatelet sTudy (COAPT). Hierarchical Cox proportional hazard regression modeling was used to determine baseline demographic and clinical factors associated with duration of ADPri therapy post-discharge., Results: At index-hospitalization discharge, 1597 (73%) patients were treated with clopidogrel, 220 (10%) with prasugrel, and 358 (17%) with ticagrelor. ADPri was discontinued prior to 1year in 474 (21.8%) patients; discontinuation rates were lowest for patients discharged on prasugrel (17.7%), compared with clopidogrel (22.5%) or ticagrelor (21.0%), (log rank test, p=0.03). In addition to regional variability, factors associated with shorter ADPri duration included older age, low body weight, Killip III/IV heart failure, atrial fibrillation, ticagrelor on discharge, and bare metal stent use, while longer ADPri duration was associated with history of prior MI., Conclusions: One in five PCI-treated MI patients did not complete Canadian guideline-recommended 1-year course of ADPri treatment. Premature ADPri discontinuation was most strongly associated with factors that increase the risk of bleeding. Further study is required to assess the clinical implications of premature ADPri discontinuation on patient outcomes., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Early rule-in/rule-out of myocardial infarction (MI) in patients presenting to the emergency department (ED) is important for patient care and resource allocation. Given that dysglycemia is a strong risk factor for MI, we sought to explore and compare different combinations of cardiac troponin (cTn) cutoffs with glycemic markers for the early rule-in/rule-out of MI., Methods: We included ED patients (n = 1137) with symptoms suggestive of acute coronary syndrome (ACS) who had cTnI, high-sensitivity cTnI (hs-cTnI), hs-cTnT, glucose, and hemoglobin A 1c (Hb A 1c ) measurements. We derived rule-in/rule-out algorithms using different combinations of ROC-derived and literature cutoffs for rule-in and rule-out of MI within 7 days after presentation. These algorithms were then tested for MI/cardiovascular death and ACS/cardiovascular death at 7 days. ROC curves, sensitivity, specificity, likelihood ratios, positive and negative predictive values (PPV and NPV), and CIs were determined for various biomarker combinations., Results: MI was diagnosed in 133 patients (11.7%; 95% CI, 9.8-13.8). The algorithms that included cTn and glucose produced the greatest number of patients ruled out/ruled in for MI and yielded sensitivity ≥99%, NPV ≥99.5%, specificity ≥99%, and PPV ≥80%. This diagnostic performance was maintained for MI/cardiovascular death but not for ACS/cardiovascular death. The addition of hemoglobin A 1c (Hb A 1c ) (≥6.5%) to these algorithms did not change these estimates; however, 50 patients with previously unknown diabetes may have been identified if Hb A 1c was measured., Conclusions: Algorithms incorporating glucose with cTn may lead to an earlier MI diagnosis and rule-out for MI/cardiovascular death. Addition of Hb A 1c into these algorithms allows for identification of diabetes. Future studies extending these findings are needed for ACS/cardiovascular death. ClinicalTrials.gov identifier: NCT01994577., (© 2016 American Association for Clinical Chemistry.)

Background: Several biomarkers have been shown to improve risk stratification in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS); however, they have not been integrated into risk prediction tools., Methods: C-reactive-protein, N-terminal-pro-brain natriuretic peptide (NT-proBNP), and haemoglobin A1C were measured in 6447 patients with NSTEACS who were enrolled in the Clopidogrel in Unstable Angina to Prevent Recurrent Events trial. A risk score to predict cardiovascular (CV) death, myocardial infarction (MI), or stroke at 1 year was developed by incorporating biomarkers that were independently predictive of events with traditional variables, electrocardiogram, and troponin-T. Model discrimination was evaluated using c-statistic, integrated discrimination improvement, and net reclassification index, and validated using bootstrap methods., Results: During 1 year of follow-up, 686 patients experienced a CV event. Each biomarker predicted CV death, MI, or stroke; however, only NT-proBNP and haemoglobin A1C improved model discrimination, increasing the c-statistic (0.66-0.71), integrated discrimination improvement to 3.4%, and net reclassification index to 17.5% (P < 0.0001 for all measures). A risk score ranging from 0 to 20 points including variables for age, prior MI/stroke, sex, ST-segment deviation, troponin-T, NT-proBNP, and haemoglobin A1C classified individuals into low-, intermediate-, and high-risk groups with rates of CV death, MI, stroke of 3.7%, 9.1%, 17.8%, respectively. The absolute benefit of dual antiplatelet therapy vs aspirin alone was 1.0%, 4.7%, and 3.0% in low-, intermediate-, and high-risk groups, respectively., Conclusions: The addition of NT-proBNP and haemoglobin A1C to 5 standard variables creates a 7-variable risk score that improves prediction of CV events at 1 year and aids in risk-based selection of patients with NSTEACS for dual antiplatelet therapy., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Since the introduction of newer, more potent P2Y12 receptor inhibitors (P2Y12ris), practice patterns and associated clinical outcomes in patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) and also requiring oral anticoagulation (OAC) have not been fully characterized., Methods: The Canadian Observational Antiplatelet Study was a prospective, multicenter, longitudinal, observational study (26 hospitals, December 2011 to May 2013) describing P2Y12ri treatment patterns and outcomes in patients with ST-elevation and non-ST-elevation MI undergoing PCI. We describe the clinical characteristics, treatment patterns, bleeding, and ischemic outcomes over the 15-month follow-up within and between the subgroups of patients discharged on either dual-antiplatelet therapy (DAPT) (acetyl salicylic acid [ASA]+P2Y12ri) or triple therapy (ASA+P2Y12ri+OAC)., Results: Of the 2,034 patients at discharge, 86% (n = 1,757) were on DAPT, whereas 14% (n = 277) were on triple therapy (50% warfarin, 50% non-vitamin K OAC [NOAC]). The frequency of newer P2Y12ri use (prasugrel or ticagrelor) was similar in the DAPT and triple therapy groups (28% vs 26%, respectively). In the triple therapy group, NOAC use was higher in those receiving a new P2Y12ri compared to those receiving clopidogrel (75% vs 41%, respectively, P < .0001). The unadjusted and adjusted events of major cardiovascular event (MACE) and bleeding were higher in the triple therapy group. For patients on triple therapy, the bleeding or MACE events were not significantly different between those on clopidogrel versus those on ticagrelor or prasugrel., Conclusion: In this observational study of MI patients requiring PCI, 1 in 8 were discharged on triple antithrombotic therapy, of whom 26% were on newer P2Y12ris. Patients on triple therapy had higher risk at baseline, with higher unadjusted and adjusted MACE and bleeding events compared to those on DAPT alone. Among triple therapy-treated patients, there was no difference in the MACE and bleeding events regardless of the P2Y12ri used., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Two large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice., Methods: The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10,732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear. In this longer-term follow-up of the TOTAL study, we report the results on the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure) and secondary outcomes at 1 year. Analyses of the primary outcome were by modified intention to treat and only included patients who underwent index PCI. This trial is registered with ClinicalTrials.gov, number NCT01149044., Findings: Between Aug 5, 2010, and July 25, 2014, 10,732 eligible patients were enrolled and randomly assigned to thrombectomy followed by PCI (n=5372) or to PCI alone (n=5360). After exclusions of patients who did not undergo PCI in each group (337 in the PCI and thrombectomy group and 331 in the PCI alone group), the final study population comprised 10,064 patients (5035 thrombectomy and 5029 PCI alone). The primary outcome at 1 year occurred in 395 (8%) of 5035 patients in the thrombectomy group compared with 394 (8%) of 5029 in the PCI alone group (hazard ratio [HR] 1·00 [95% CI 0·87-1·15], p=0·99). Cardiovascular death within 1 year occurred in 179 (4%) of the thrombectomy group and in 192 (4%) of 5029 in the PCI alone group (HR 0·93 [95% CI 0·76-1·14], p=0·48). The key safety outcome, stroke within 1 year, occurred in 60 patients (1·2%) in the thrombectomy group compared with 36 (0·7%) in the PCI alone group (HR 1·66 [95% CI 1·10-2·51], p=0·015)., Interpretation: Routine thrombus aspiration during PCI for STEMI did not reduce longer-term clinical outcomes and might be associated with an increase in stroke. As a result, thrombus aspiration can no longer be recommended as a routine strategy in STEMI., Funding: Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic Inc., Competing Interests: Declaration of interests SSJ has received grants from Medtronic during the conduct of the study. JAC has received grants from the Canadian Institutes of Health Research and Medtronic during the conduct of the study, and grants from Medtronic outside the submitted work. RM has received personal fees from Medtronic during the conduct of the study. AG has received personal fees and advisory board fees from AstraZeneca, and grants, meeting support, and research grants from Medronic, outside the submitted work. PGS has received personal fees from Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck-Sharpe-Dohme, Novartis, Otsuka, Pfizer, Roche, Medtronic, Vivus, Janssen, Orexigen, and Regado; grants and personal fees from Sanofi and Servier; and personal fees and non-financial support from The Medicines Company, outside the submitted work. RCW has received personal fees from Medtronic; grants from Abbott Vascular and Edwards Lifesciences, grants and personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Jansen and BMS/Pfizer, outside the submitted work. SVR has received personal fees from Medtronic, outside the submitted work. SP has received personal fees from Medtronic, outside the submitted work. VD has received an institutional grant to conduct the trial from the TOTAL Coordinating Centre during the conduct of the study. All other coauthors declare no competing interests., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The aim of this study was to assess the efficacy and safety of an early invasive strategy post-fibrinolysis in relation to time from symptom onset to fibrinolysis in patients with ST-elevation myocardial infarction (STEMI). The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized 1,059 patients receiving fibrinolysis for STEMI to an early invasive strategy versus standard therapy. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days. In this post hoc subgroup analysis, we examined the effect of an early invasive strategy on efficacy and safety outcomes after stratification by time from symptom onset to fibrinolysis (<2 or ≥2 hours). Of 1,059 patients in TRANSFER-AMI, 557 (53%) received fibrinolysis <2 hours and 502 (47%) ≥2 hours after symptom onset. Compared to patients who received fibrinolysis within 2 hours of symptoms, patients who received fibrinolysis ≥2 hours after symptom onset had higher Global Registry of Acute Coronary Events risk scores (median 127 vs 122, p = 0.004). The effect of an early invasive strategy did not differ between symptom-to-fibrinolysis time strata for the primary efficacy end point (p-heterogeneity = 0.67), 30-day mortality, the composite of death or reinfarction at 30 days, 6 months, or 1 year, or bleeding (all p-heterogeneity >0.40). In conclusion, the efficacy and safety of an early invasive strategy in patients undergoing fibrinolysis for STEMI do not vary in relation to time (<2 or ≥2 hours) from symptom onset to fibrinolysis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Activated clotting time (ACT) is widely used to guide unfractionated heparin dosing during percutaneous coronary intervention. However, its value in predicting complications is controversial in the modern era. We sought to examine the relationship between ACT and outcomes in non-ST-segment-elevation acute coronary syndrome patients., Methods and Results: In the Fondaparinux With Unfractionated Heparin During Revascularization in Acute Coronary Syndromes (FUTURA/OASIS-8) trial, 2026 patients with non-ST-segment-elevation acute coronary syndrome treated with fondaparinux 2.5 mg/d and undergoing percutaneous coronary intervention were randomized to low-dose unfractionated heparin (50 U/kg) or standard-dose unfractionated heparin (85 U/kg or 60 U/kg with glycoprotein IIb/IIIa inhibitors, with ACT guidance). No difference was shown for major bleeding and there was a trend toward a reduction in ischemic events with standard-dose unfractionated heparin. To clarify the additional value of ACT guidance, we analyzed with logistic modeling peri-percutaneous coronary intervention outcomes according to peak ACT as a linear function. A threshold effect was then investigated. No linear correlation was found between ACT and thrombotic or bleeding events. In patients not receiving planned glycoprotein IIb/IIIa inhibitors, a significant increase in rates of death, myocardial infarction, and target vessel revascularization was identified in patients with an ACT≤300 s (4.86% versus 2.78%; adjusted odds ratio, 1.84; 95% confidence interval, 1.06-3.21; P=0.03). No threshold was found for hemorrhagic complications in patients with or without glycoprotein IIb/IIIa inhibitors., Conclusions: Non-ST-segment-elevation acute coronary syndrome patients undergoing percutaneous coronary intervention with an ACT≤300 s are at increased risk of thrombotic complications. ACT, however, does not predict hemorrhagic complications., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790907., (© 2015 American Heart Association, Inc.)

Compared with non-smokers, cigarette smokers with ST-segment elevation myocardial infarctions derive greater benefit from fibrinolytic therapy. However, it is not known whether the optimal treatment strategy after fibrinolysis differs on the basis of smoking status. The Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized patients with ST-segment elevation myocardial infarctions to a routine early invasive (pharmacoinvasive) versus a standard (early transfer only for rescue percutaneous coronary intervention or delayed angiography) strategy after fibrinolysis. The efficacy of these strategies was compared in 1,051 patients on the basis of their smoking status. Treatment heterogeneity was assessed between smokers and non-smokers, and multivariable analysis was performed to evaluate for an interaction between smoking status and treatment strategy after adjusting for baseline Global Registry of Acute Coronary Events (GRACE) risk score. Smokers (n=448) were younger, had fewer cardiovascular risk factors, and had lower GRACE risk scores. They had a lower rate of the primary composite end point of 30-day mortality, reinfarction, recurrent ischemia, heart failure, or cardiogenic shock and fewer deaths or reinfarctions at 6 months and 1 year. Smoking status was not a significant predictor of either primary or secondary end points in multivariable analysis. Pharmacoinvasive management reduced the primary end point compared with standard therapy in smokers (7.7% vs 13.6%, p=0.04) and non-smokers (13.1% vs 19.7%, p=0.03). Smoking status did not modify treatment effect on any measured outcomes (p>0.10 for all). In conclusion, compared with non-smokers, current smokers receiving either standard or early invasive management of ST-segment elevation myocardial infarction after fibrinolysis have more favorable outcomes, which is likely attributable to their better baseline risk profile. The beneficial treatment effect of a pharmacoinvasive strategy is consistent in smokers and non-smokers., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims: Delcasertib is a selective inhibitor of delta-protein kinase C (delta-PKC), which reduced infarct size during ischaemia/reperfusion in animal models and diminished myocardial necrosis and improved reperfusion in a pilot study during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI)., Methods and Results: A multicentre, double-blind trial was performed in patients presenting within 6 h and undergoing primary PCI for anterior (the primary analysis cohort, n = 1010 patients) or inferior (an exploratory cohort, capped at 166 patients) STEMI. Patients with anterior STEMI were randomized to placebo or one of three doses of delcasertib (50, 150, or 450 mg/h) by intravenous infusion initiated before PCI and continued for ∼2.5 h. There were no differences between treatment groups in the primary efficacy endpoint of infarct size measured by creatine kinase MB fraction area under the curve (AUC) (median 5156, 5043, 4419, and 5253 ng h/mL in the placebo, delcasertib 50, 150, and 450 mg/mL groups, respectively) in the anterior STEMI cohort. No treatment-related differences were seen in secondary endpoints of infarct size, electrocardiographic ST-segment recovery AUC or time to stable ST recovery, or left ventricular ejection fraction at 3 months. No differences in rates of adjudicated clinical endpoints (death, heart failure, or serious ventricular arrhythmias) were observed., Conclusions: Selective inhibition of delta-PKC with intravenous infusion of delcasertib during PCI for acute STEMI in a population of patients treated according to contemporary standard of care did not reduce biomarkers of myocardial injury., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aim: A genetic variant (rs20417) of the PTGS2 gene, encoding for COX-2, has been associated with decreased COX-2 activity and a decreased risk of cardiovascular disease (CVD). However, this genetic association and the role of COX-2 in CVD remain controversial., Methods and Results: The association of rs20417 with CVD was prospectively explored in 49 232 subjects (ACTIVE-A, CURE, epiDREAM/DREAM, ONTARGET, RE-LY, and WGHS) and the effect of potentially modifiable risk factors on the genetic association was further explored in 9363 INTERHEART participants. The effect of rs20417 on urinary thromboxane and prostacyclin metabolite concentrations was measured in 117 healthy individuals. Carriage of the rs20417 minor allele was associated with a decreased risk of major CVD outcomes (OR = 0.78, 95% CI: 0.70-0.87; P = 1.2 × 10(-5)). The genetic effect was significantly stronger in aspirin users (OR: 0.74, 95% CI: 0.64-0.84; P = 1.20 × 10(-5)) than non-users (OR: 0.87, 95% CI: 0.72-1.06; P = 0.16) (interaction P-value: 0.0041). Among patients with previous coronary artery disease (CAD), rs20417 carriers had a stronger protective effect on risk of major adverse events when compared with individuals without previous CAD (interaction P-value: 0.015). Carriers had significantly lower urinary levels of thromboxane (P = 0.01) and prostacyclin (P = 0.01) metabolites when compared with non-carriers., Conclusion: The rs20417 polymorphism is associated with a reduced risk of major cardiovascular events and lower levels of thromboxane and prostacyclin. Our results suggest that a genetic decrease in COX-2 activity may be beneficial with respect to CVD risk, especially, in higher risk patients on aspirin., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Objective: We evaluated the efficacy and safety of an early invasive strategy post-fibrinolysis in relation to glycoprotein (GP) IIb/IIIa inhibitor use., Methods: The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomised 1059 ST elevation myocardial infarction patients to an early invasive strategy or standard therapy post-fibrinolysis. The primary end point was the composite of death, reinfarction, recurrent ischaemia, new or worsening heart failure, or cardiogenic shock at 30 days. In this pre-specified analysis, we examined efficacy and safety outcomes of an early invasive strategy after stratification by GPIIb/IIIa inhibitor use, which was permitted during percutaneous coronary intervention (PCI) at the discretion of the treating physician., Results: A total of 695 patients (65.6%) received GPIIb/IIIa inhibitors. There was significant heterogeneity (p<0.001) in the efficacy of an early invasive strategy compared to standard therapy, between the strata with GPIIb/IIIa inhibitor use (primary end point 9.6% vs 22.3% respectively, p<0.001) and without GPIIb/IIIa inhibitor use (primary end point 14.8% vs 10.4% respectively, p=0.21). Patients who received GPIIb/IIIa inhibitors had lower Global Registry of Acute Coronary Events (GRACE) risk scores compared to those without GPIIb/IIIa inhibitor use (median 121 vs 130, p<0.001). After adjusting for the interaction between GRACE risk score and treatment assignment, the heterogeneity in the efficacy of an early invasive strategy with respect to GPIIb/IIIa inhibitor use was no longer significant (p interaction=0.08)., Conclusions: The apparent difference in the efficacy of an early invasive strategy between GPIIb/IIIa inhibitor strata likely reflects an association between GPIIb/IIIa inhibitor use and baseline risk. GPIIb/IIIa inhibitor use during PCI at the discretion of the treating physician does not appear to modulate the efficacy of an early invasive strategy post-fibrinolysis., Clinical Trial Registration: http://www.clinicaltrials.gov/ct2/show/NCT00164190, NCT00164190.

Background: The echocardiographic substudy of the OASIS-6 trial evaluated the prognostic implications of left ventricle (LV) systolic and diastolic dysfunction early postacute ST-segment elevation myocardial infarction (STEMI) in patients treated with fondaparinux versus usual care., Methods: Comprehensive echocardiograms were performed a median of 6 days after the index STEMI in 528 patients, 258 randomized to fondaparinux and 270 to usual care (unfractionated heparin or placebo), to assess LV systolic and diastolic function, LV mass, and LV end-systolic and end-diastolic volumes. A total of 245 (46.4%) patients were followed up for 3 months and 283 (53.6%) for 6 months. Major cardiac events (MACE) were defined as the composite of death, reinfarction, heart failure, or cardiogenic shock and resuscitated cardiac arrest., Results: Patients with LV ejection fraction (LVEF) ≤ 45% and restrictive diastolic function (RDF) were at greatly increased risk of MACE (hazard ratio [HR] = 8.85, 95% CI, 4.21–18.60) compared to patients with LVEF ≥ 45% and without RDF. RDF remained a strong predictor for MACE in patients with LVEF ≥ 45% (HR = 4.38, 95% CI, 1.52–12.60) and in multivariate models adjusted for LVEF, LV end-systolic volume, and clinical variables., Conclusion: In this large international trial, LV systolic and diastolic function, as determined by echocardiography early following STEMI, are incremental predictors of MACE. In addition, RDF is a strong independent predictor of MACE after STEMI across a broad range of LVEF.

Background: In patients with ST-elevation myocardial infarction treated with fibrinolysis, routine early percutaneous coronary intervention (r-PCI) improves clinical outcomes at 30 days compared with a more standard approach of performing early PCI only for failed fibrinolysis (s-PCI)., Methods: We report prespecified secondary clinical outcomes and cost implications of r-PCI compared with s-PCI from the Canadian TRANSFER-AMI trial. Average cost per patient in each arm was calculated based on a microcosting approach. Bootstrap method (5,000 samples) was used to calculate standard errors and 95% CI., Results: At 1 year, rates of death or reinfarction (10.3% vs 11.6%, P = .50), hospital readmission (15.4% vs 16.5%, P = .64) and subsequent revascularization after index hospitalization (6.9% vs 8.7%, P = .30) were similar between the r-PCI and s-PCI arms. The difference in cost per patient between r-PCI and s-PCI was CAD $1,003 (95% CI, -$247 to $2,211). Since a greater proportion of patients were transported by air (vs land) in the r-PCI arm (9.4% vs 3%), and the ratio of abciximab to eptifibatide use was higher in the r-PCI arm compared with s-PCI (2:1 vs 4:5), we undertook additional post hoc cost scenario analyses. In a scenario where patients are transported by land only and eptifibatide is used as the sole GPIIb/IIIa inhibitor, the difference in cost per patient between r-PCI and s-PCI was estimated to be CAD $108 (95% CI, -$1,114 to $1,344)., Conclusions: At 1 year, there is no difference in the clinical composite outcome of death or reinfarction between r-PCI and s-PCI strategies. Greater cost with r-PCI, although statistically insignificant, is economically important., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objectives: The authors sought to compare the radiation dose between radial and femoral access., Background: Small trials have shown an increase in the radiation dose with radial compared with femoral access, but many were performed during the operators' learning curve of radial access., Methods: Patients were randomized to radial or femoral access, as a part of the RIVAL (RadIal Vs. femorAL) trial (N = 7,021). Fluoroscopy time was prospectively collected in 5740 patients and radiation dose quantified as air kerma in 1,445 patients and dose-area product (DAP) in 2,255 patients., Results: Median fluoroscopy time was higher with radial versus femoral access (9.3 vs. 8.0 min, p < 0.001). Median air kerma was nominally higher with radial versus femoral access (1,046 vs. 930 mGy, respectively, p = 0.051). Median DAP was not different between radial and femoral access (52.8 Gy-cm(2) vs. 51.2 Gy·cm(2), p = 0.83). When results are stratified according to procedural volume, air kerma was increased only in the lowest tertile of radial volume centers (low 1,425 vs. 1,045 mGy, p = 0.002; middle 987 vs. 958 mGy, p = 0.597; high 652 vs. 621 mGy, p = 0.403, interaction p = 0.026). Multivariable regression showed procedural volume was the greatest independent predictor of lower air kerma dose (ratio of geometric means 0.55; 95% confidence interval 0.49 to 0.61 for highest-volume radial centers)., Conclusions: Radiation dose as measured by air kerma was nominally higher with radial versus femoral access, but differences were present only in lower-volume centers and operators. High-volume centers have the lowest radiation dose irrespective of which access site approach that they use. (A Trial of Trans-radial Versus Trans-femoral Percutaneous Coronary Intervention (PCI) Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy [RIVAL]; NCT01014273)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to determine the consistency of the effects of radial artery access in patients with ST-segment elevation myocardial infarction (STEMI) and in those with non-ST-segment elevation acute coronary syndrome (NSTEACS)., Background: The safety associated with radial access may translate into mortality benefit in higher-risk patients, such as those with STEMI., Methods: We compared efficacy and bleeding outcomes in patients randomized to radial versus femoral access in RIVAL (RadIal Vs femorAL access for coronary intervention trial) (N = 7,021) separately in those with STEMI (n = 1,958) and NSTEACS (n = 5,063). Interaction tests between access site and acute coronary syndrome type were performed., Results: Baseline characteristics were well matched between radial and femoral groups. There were significant interactions for the primary outcome of death/myocardial infarction/stroke/non-coronary artery bypass graft-related major bleeding (p = 0.025), the secondary outcome of death/myocardial infarction/stroke (p = 0.011) and mortality (p = 0.001). In STEMI patients, radial access reduced the primary outcome compared with femoral access (3.1% vs. 5.2%; hazard ratio [HR]: 0.60; p = 0.026). For NSTEACS, the rates were 3.8% and 3.5%, respectively (p = 0.49). In STEMI patients, death/myocardial infarction/stroke were also reduced with radial access (2.7% vs. 4.6%; HR 0.59; p = 0.031), as was all-cause mortality (1.3% vs. 3.2%; HR: 0.39; p = 0.006), with no difference in NSTEACS patients. Operator radial experience was greater in STEMI versus NSTEACS patients (400 vs. 326 cases/year, p < 0.0001). In primary PCI, mortality was reduced with radial access (1.4% vs. 3.1%; HR: 0.46; p = 0.041)., Conclusions: In patients with STEMI, radial artery access reduced the primary outcome and mortality. No such benefit was observed in patients with NSTEACS. The radial approach may be preferred in STEMI patients when the operator has considerable radial experience. (A Trial of Trans-radial Versus Trans-femoral Percutaneous Coronary Intervention (PCI) Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy [RIVAL]; NCT01014273)., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The TRANSFER-AMI study demonstrated that early routine percutaneous coronary intervention post-fibrinolysis (pharmacoinvasive strategy) is superior to conservative management for ST-elevation myocardial infarction. However, it is not clear whether treatment efficacy differs between men and women., Methods: In this pre-specified subgroup analysis, we compared the efficacy of a pharmacoinvasive strategy in men versus women with acute ST-elevation myocardial infarction who were randomized to a pharmacoinvasive versus standard management following fibrinolysis. The primary end point was a composite of death, recurrent myocardial infarction, recurrent ischemia, heart failure and shock at 30 days. We tested for treatment heterogeneity between men and women using the Breslow-Day test. We also performed multivariable analysis adjusting for GRACE risk score and its interaction with treatment assignment, and evaluated for death/recurrent myocardial reinfarction as a secondary outcome., Results: Of the 1059 patients, 843 were men and 216 were women. Compared to men, women were older, had worse Killip class, higher GRACE risk score, and higher rates of death and death/myocardial reinfarction at 30 days. The primary end point did not differ significantly between men and women (13.4% vs 16.7%, P = .22). Compared to standard treatment, a pharmacoinvasive strategy was associated with a lower rate of the primary end point in men (17.5% vs 9.4%, respectively, P < .001), but not in women (16.2% vs 17.1%, P = .86). There was a trend toward an interaction between treatment assignment and sex for the composite primary end point (P = .06). After adjustment for the significant interaction between GRACE risk score and treatment (P < .001), there was no significant interaction between sex and treatment for all the end points (all P > .40)., Conclusion: The borderline heterogeneity in treatment efficacy of a pharmacoinvasive strategy in men versus women was no longer evident after adjustment for the difference in baseline risk. This suggests that sex per se was not an important determinant of the efficacy of a pharmacoinvasive strategy. Owing to the small number of women in this trial, further study in this area is needed., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: Elevated glucose levels are common after an acute myocardial infarction (AMI) and increase the risk of death. Prior trials of glucose control after AMI have been inconsistent in their ability to lower glucose levels and have reported mixed effects on mortality. We developed a paper-based glucose-lowering algorithm and assessed its feasibility and safety in the setting of AMI., Research Design and Methods: A total of 287 participants with an acute ST segment elevation myocardial infarction (STEMI) and a capillary glucose level ≥8.0 mmol/L were randomly allocated to glucose management with intravenous glulisine insulin using this algorithm in the coronary care unit (CCU), followed by once-daily subcutaneous insulin glargine for 30 days versus standard glycemic approaches. The primary outcome was a difference in mean glucose levels at 24 h. Participants were followed for clinical outcomes through 90 days., Results: At 24 h, the mean glucose level was 1.41 mmol/L (95% CI 0.69-2.13) lower in the insulin (6.53 vs. 7.94 mmol/L). Differences in glucose levels were maintained at 72 h and 30 days. A total of 22.7% of the insulin group versus 4.4% of the standard group had biochemical hypoglycemia (with neither signs nor symptoms) in the CCU because of lower glycemic goals. However, there were no differences in symptomatic hypoglycemia or clinical outcomes between the groups., Conclusions: A paper-based insulin algorithm targeting glucose levels of 5.0-6.5 mmol/L (90-117 mg/dL) can be feasibly implemented in the CCU. A cardiovascular outcomes trial using this approach can determine whether targeted glucose lowering improves patient outcomes.

Acute ST-segment elevation myocardial infarction (STEMI) accounts for approximately 30% of all acute coronary syndromes (ACS). The high early mortality for patients with STEMI is largely due to the extent of the ischemic injury. However, immediate reperfusion either pharmacologically with fibrinolysis or mechanically by primary percutaneous coronary intervention (PCI) limits the size of the infarction and reduces mortality. Reperfusion therapy by primary PCI reduces mortality and the risk of reinfarction, beyond the benefits achieved by fibrinolysis, especially when the primary PCI is initiated within 90 minutes of first medical contact. The use of adjuvant therapy with antiplatelet and anticoagulant agents is essential to enhance the results of reperfusion, and/or maintain vessel patency following either mode of reperfusion. This review discusses the assessment and management of the patient with an acute STEMI, using recommendations from the most recent American College of Cardiology/American Heart Association, European Society of Cardiology, and existing Canadian guidelines. It provides an updated perspective and critical appraisal with practical application of the recommendations within the Canadian Healthcare system., (Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Aims: The OASIS-6 trial demonstrated the benefit of fondaparinux in patients with ST-segment elevation myocardial infarction (STEMI) not undergoing primary percutaneous coronary intervention. Elderly compared to younger patients are at higher risk of bleeding and could have a different balance of benefits and risks when treated with antithrombotic therapy., Methods and Results: We explored the efficacy and safety of fondaparinux compared to control according to age tertiles in 12,092 patients with STEMI in the OASIS-6 trial. Death or myocardial infarction rates were reduced by fondaparinux in tertile I (age<56 years, 4.5% vs 4.8%, hazard ratio [HR] 0.94, 95% CI 0.71-1.25), in tertile II (age 56-68 years, 7.9% vs 9.7%, HR 0.80, 0.65-0.98), and in tertile III (age≥69 years, 17.2% vs 19.8%, HR 0.87, 95% CI 0.75-1.01, P for heterogeneity=0.87). Severe hemorrhage rates were reduced in tertile I (0.5% vs 0.6%, HR 0.94, 95% CI 0.41-2.12), in tertile II (0.9% vs 1.5%, HR 0.63, 95% CI 0.35-1.11), and in tertile III (2.1% vs 2.4%, HR 0.86, 95% CI 0.56-1.33, P for heterogeneity=0.86). Death, myocardial infarction, or severe hemorrhage rates were reduced in tertile I (4.8% vs 5.0%, HR 0.95, 95% CI 0.72-1.25), in tertile II (8.1% vs 10.1%, HR 0.79, 95% CI 0.65-0.97), and in tertile III (17.6% vs 20.4%, HR 0.86, 95% CI 0.74-1.00, P for heterogeneity=0.77)., Conclusion: The balance of benefits and risks of fondaparinux is consistent across age tertiles, supporting its use across the age spectrum of patients with STEMI who do not undergo primary percutaneous coronary intervention., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Background: In patients with acute myocardial infarction (AMI), hyperglycemia predicts death, but the prognostic significance of hypoglycemia is controversial., Methods and Results: We evaluated the prognostic significance of hypoglycemia and hyperglycemia in 30 536 AMI patients in a post hoc analysis of 2 large trials of glucose-insulin-potassium therapy in AMI. Glucose levels on admission and at 6 and 24 hours after admission, as well as 30-day mortality, were documented. In separate multivariable Cox models for admission and postadmission glucose, we compared the prognostic value of hypoglycemia (< or =70 mg/dL) and hyperglycemia (> or =140 mg/dL) with normoglycemia (>70 and <140 mg/dL). Analyses were repeated with hypoglycemia defined as glucose < or =60 mg/dL and in key subgroups based on diabetes or insulin (glucose-insulin-potassium) allocation status. Both high and low percentiles of admission glucose predicted increased 30-day mortality. However, for postadmission glucose, this U-shaped relationship was attenuated so that only high and not low glucose levels remained prognostic. Hyperglycemia (> or =140 mg/dL), both on admission (adjusted hazard ratio 1.43, 95% confidence interval 1.32 to 1.56, P<0.0001) and after admission (adjusted hazard ratio 1.47, 95% confidence interval 1.31 to 1.66, P<0.0001), predicted death compared with normoglycemia. In contrast, hypoglycemia (glucose < or =70 mg/dL) on admission was not prognostic (adjusted hazard ratio 1.16, 95% confidence interval 0.84 to 1.62, P=0.37), nor was postadmission hypoglycemia (adjusted hazard ratio 0.96, 95% confidence interval 0.72 to 1.26, P=0.75). Exploratory analyses that redefined hypoglycemia as glucose < or =60 mg/dL showed consistent results, as did analyses restricted to diabetic patients (18% of the study population). Postadmission hypoglycemia was more common in insulin (glucose-insulin-potassium)-treated patients (6.9%) than in untreated patients (3.4%) but did not predict mortality in either subgroup., Conclusions: Both admission and postadmission hyperglycemia predict 30-day death in AMI patients. In contrast, only hypoglycemia on admission predicted death, and this relationship dissipated after admission. These data suggest hypoglycemia may not be a direct mediator of adverse outcomes in AMI patients.

Background: Thrombus removal using aspiration-thrombectomy (AT) may improve outcomes in Acute Myocardial Infarction (AMI). We performed a meta-analysis of randomized trials evaluating AT during primary Percutaneous Coronary Intervention (PCI) to determine its impact on mortality and morbidity., Methods: Studies were included if they were randomized trials evaluating AT versus control in patients with AMI undergoing primary-PCI. Databases were searched for eligible studies (1990-February 2008). Efficacy outcomes including death as a primary and composite of death, re-MI, stroke and repeat revascularization as a secondary outcome were evaluated at follow-up. Trials were combined using a fixed effects model and heterogeneity was evaluated., Results: 18 trials involving 3871 patients were included. At average follow up of 8.9 months, mortality was significantly reduced in favour of AT (2.9% vs. 4.2%, OR 0.70, CI 0.49-0.99, P=0.04). The secondary outcome of composite of death, MI or stroke at average follow up of 8.9 months was not significantly reduced (5.6% vs. 7.1%, P=0.08) while the secondary outcome of death, MI, stroke, TVR & bleeding was significantly reduced (11% vs. 13.6% OR 0.77, CI 0.63-0.99, P 0.01) in the AT group. Thrombectomy devices were associated with a higher rate of thrombolysis in myocardial infarction 3 flow (OR 1.42; CI 1.17-1.72), Myocardial Blush Grade 3 flow (2.01; 1.74-2.31) and ST resolution (2.40; 2.08-2.78). There was no significant heterogeneity in any of the outcomes., Conclusions: In primary PCI, the addition of AT reduces both mortality and recurrent ischemic events at follow up. These benefits are associated with improved early infarct-related artery patency.

Background: Patients with a myocardial infarction with ST-segment elevation who present to hospitals that do not have the capability of performing percutaneous coronary intervention (PCI) often cannot undergo timely primary PCI and therefore receive fibrinolysis. The role and optimal timing of routine PCI after fibrinolysis have not been established., Methods: We randomly assigned 1059 high-risk patients who had a myocardial infarction with ST-segment elevation and who were receiving fibrinolytic therapy at centers that did not have the capability of performing PCI to either standard treatment (including rescue PCI, if required, or delayed angiography) or a strategy of immediate transfer to another hospital and PCI within 6 hours after fibrinolysis. All patients received aspirin, tenecteplase, and heparin or enoxaparin; concomitant clopidogrel was recommended. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening congestive heart failure, or cardiogenic shock within 30 days., Results: Cardiac catheterization was performed in 88.7% of the patients assigned to standard treatment a median of 32.5 hours after randomization and in 98.5% of the patients assigned to routine early PCI a median of 2.8 hours after randomization. At 30 days, the primary end point occurred in 11.0% of the patients who were assigned to routine early PCI and in 17.2% of the patients assigned to standard treatment (relative risk with early PCI, 0.64; 95% confidence interval, 0.47 to 0.87; P=0.004). There were no significant differences between the groups in the incidence of major bleeding., Conclusions: Among high-risk patients who had a myocardial infarction with ST-segment elevation and who were treated with fibrinolysis, transfer for PCI within 6 hours after fibrinolysis was associated with significantly fewer ischemic complications than was standard treatment. (ClinicalTrials.gov number, NCT00164190.), (2009 Massachusetts Medical Society)

Background: Both a history of diabetes mellitus and elevated inhospital glucose levels predict death after acute myocardial infarction (AMI). However, only diabetes history (and not glucose levels) is routinely considered in AMI risk assessment., Methods: We conducted a post hoc analysis of 2 randomized controlled trials of AMI with ST-segment elevation to compare the prognostic value of inhospital glucose levels with diabetes history in 30,536 subjects. Average inhospital glucose (mean of glucose levels at admission, 6 hours, and 24 hours), diabetes history, and death at 30 days (occurring in 2,808 subjects) were documented., Results: Average glucose predicted 30-day death (OR 1.10 per 1-mmol/L [18-mg/dL] increase, 95% CI 1.09-1.11, P < .0001); this was unchanged after adjusting for diabetes history. In contrast, diabetes history alone predicted 30-day death (OR 1.63, 95% CI 1.48-1.78, P < .0001), but not after adjusting for average glucose (OR 0.98, 95% CI 0.88-1.09, P = .72). The C-indices (areas under the receiver operating characteristic curves) for 30-day death were 0.54 for diabetes history alone, 0.64 for average glucose alone, and 0.64 for glucose plus diabetes. Higher glucose levels predicted death in patients with and without diabetes history, but this relationship was more steep in nondiabetic subjects such that their rate of 30-day death (13.2%) matched that of diabetic patients (13.7%) when average glucose was > or =144 mg/dL (8 mmol/L) (P = .55 after multivariable adjustment)., Conclusions: Although diabetes history is routinely considered in the risk stratification of AMI patients, inhospital glucose levels are a much stronger predictor of death and should be incorporated in their risk assessment. Patients with AMI with inhospital glucose > or =144 mg/dL have a very high risk of death regardless of diabetes history.

Aims: In the setting of percutaneous coronary intervention (PCI), due to a paucity of data, the optimal dose of aspirin is uncertain. We evaluated the safety of different doses of aspirin after PCI., Methods and Results: In the PCI-CURE study, 2658 patients with acute coronary syndromes undergoing PCI were stratified into three aspirin dose groups >/=200 mg (high, n = 1064), 101-199 mg (moderate, n = 538), and

Aims: Bleeding in patients with coronary artery disease has been linked with adverse outcomes. We examined the incidence and outcomes after bleeding in 20 078 patients with acute coronary syndromes (ACS) enrolled in the OASIS-5 trial who were treated with fondaparinux or the low-molecular weight heparin, enoxaparin., Methods and Results: Nine hundred and ninety (4.9%) patients developed major bleeding and 423 (2.1%) developed minor bleeding. Fondaparinux compared with enoxaparin reduced fatal bleeding [0.07 vs. 0.22%, relative risk (RR) 0.30, 95% CI: 0.13-0.71], non-fatal major bleeding (2.2 vs. 4.2%, RR 0.52, 95% CI: 0.44-0.61), minor bleeding (1.1 vs. 3.2%, RR 0.34, 95% CI: 0.27-0.42), and need for transfusion (1.8 vs. 3.1%, RR 0.56, 95% CI: 0.47-0.61) during the first 9 days. One of every six deaths during the first 30 days occurred in patients who experienced bleeding. Cox proportional hazards model revealed that major bleeding was associated with about a four-fold increased hazard of death, myocardial infarction, or stroke during the first 30 days and about a three-fold increased hazard during 180 days of follow up., Conclusion: Bleeding in patients with ACS is a powerful determinant of fatal and non-fatal outcomes. Reducing the risk of bleeding using a safer anticoagulant strategy during the first 9 days is associated with substantial reductions in morbidity and mortality.

Aims: No antithrombotic therapy has been shown to reduce mortality when used with thrombolytics in acute myocardial infarction (AMI). In the OASIS-6 trial, fondaparinux significantly reduced mortality and reinfarction without increasing bleeding in 12 092 patients with acute ST elevation MI., Methods and Results: We report the results of a subgroup analysis in the 5436 patients (45%) receiving thrombolytics. According to local practice, 4415 patients did not have an indication for unfractionated heparin (stratum 1) and 1021 did (stratum 2). Fondaparinux reduced the primary study outcome of death or MI at 30 days [Hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.68-0.92] with consistent reductions in both mortality (HR and CI) and reinfarction (HR and CI). There was a non-significantly lower rate of stroke (HR 0.77, CI 0.48-1.25). The risk of severe bleeding was significantly reduced (HR 0.62, CI 0.40-0.94), and thus the balance of benefit and risk (death, MI and severe haemorrhage) was clearly reduced by fondaparinux (HR 0.77, 95% CI 0.67-0.90). Results were consistent in the two strata, by the different types of thrombolytics and across various time intervals from symptom onset to treatment., Conclusion: In STEMI patients treated with thrombolytic agents (predominantly streptokinase), fondaparinux significantly reduced the risk of death, re-MI and severe bleeds.