Search

Although glycoprotein (GP) IIb/IIIa inhibitors are recommended for patients with unstable angina and non-ST-segment elevation myocardial infarction who undergo percutaneous coronary intervention (PCI), the American College of Cardiology/American Heart Association guidelines do not specify optimal timing for their initiation. We compared patient characteristics and clinical outcomes in 30,830 patients with non-ST-segment elevation myocardial infarction included in the CRUSADE initiative (January 2001 to December 2004) who underwent PCI with upstream (>1 hour before PCI) or periprocedural use of GP IIb/IIIa inhibitors. GP IIb/IIIa inhibitors were administered upstream in 43% of patients versus periprocedurally in 57%. Time from arrival to PCI was longer for patients who received GP IIb/IIIa inhibitors upstream (median 25.6 hours) compared with periprocedurally (18.2 hours). Unadjusted incidence of in-hospital death or reinfarction was lower with upstream GP IIb/IIIa inhibitor use (3.8% vs 4.3%, p = 0.046), but after adjusting for patient and hospital characteristics, this difference was not statistically significant. Treatment with upstream GP IIb/IIIa inhibitors was associated with a lower incidence of unadjusted death or reinfarction in patients who underwent PCI <12 hours from hospital arrival. In conclusion, in this observational analysis, overall ischemic outcomes were similar between the 2 groups, but clinical trials are needed to solve the controversy over optional timing of GP IIb/IIIa inhibitor use. [ABSTRACT FROM AUTHOR]

Impaired coronary artery blood flow and left anterior descending (LAD) artery culprit location are angiographic variables that have been associated with poorer outcomes after fibrinolytic administration in patients with acute myocardial infarction (AMI). We hypothesized that culprit lesion location in the proximal portion of the culprit artery would also be associated with poorer clinical outcomes compared with a mid or distal location. Lesion location and clinical outcomes were evaluated in 2,488 patients from the Thrombolysis In Myocardial Infarction (TIMI) 4, 10A, 10B, and 14 trials. Proximal lesions were located before or at the first major branch of the parent artery, mid lesions were between the first and the second major branches, and all other lesions were classified as distal. Proximal lesions were associated with a higher incidence of in-hospital death or recurrent AMI compared with mid or distal lesions (10.5% [n = 478] vs 6.1% [n = 1,498] vs 3.7% [n = 511], p <0.001), and they were associated with a higher rate of in-hospital death (6.7% [n = 478] vs 3.2% [n = 1,498] vs 2.5% [n = 511], p = 0.001). In a multiple logistic regression model adjusting for TIMI flow grade, age, gender, and pulse, the planimetered distance from the ostium to the LAD culprit lesion was associated with 30-day death or recurrent AMI (odds ratio 0.79 per centimeter increase in distance down the artery, p = 0.01). Proximal culprit lesion location is associated with an increased risk of adverse outcomes after fibrinolytic administration, which is likely due to a larger area of subtended myocardium. In patients with a LAD culprit lesion, proximal lesion location is a multivariate correlate of adverse outcomes even after adjustment for coronary blood flow and other covariates. [ABSTRACT FROM AUTHOR]

In patients with atrial fibrillation who undergo percutaneous coronary intervention (PCI), both anticoagulation and dual antiplatelet therapy (aspirin plus a P2Y 12 inhibitor) are indicated. However, this "triple" antithrombotic therapy is associated with high rates of bleeding. Finding the right balance of reducing ischemic risk and protecting coronary stents from restenosis while not increasing bleeding risk is difficult. In the past 5 years, 6 randomized clinical trials have shown the benefit of dropping aspirin from the triple therapy regimen to create "dual" therapy (oral anticoagulants and P2Y 12 inhibitors alone) with reductions in bleeding without a significant increase in ischemic events. Because of small trends toward higher risk of stent thrombosis, especially in higher risk patients with acute coronary syndromes, current recommendations call for dual therapy as the "default" regimen, but that risk stratification be used to help inform the decision on potentially using a brief period of triple therapy in selected high ischemic risk patients. For long-term therapy (after one year post-PCI), recent studies have found oral anticoagulation alone without any antiplatelet therapy has a favorable benefit risk ratio. Thus, while dropping aspirin at varying times post-PCI has become an attractive strategy in many patient groups, careful patient selection and individualized assessment of the risk:benefit balance is warranted., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Christopher Cannon reports financial support was provided by Academic CME. Christopher Cannon reports a relationship with Amgen, Boehringer-Ingelheim (BI), Bristol-Myers Squibb (BMS), Daiichi Sankyo, Janssen, Merck, Novo Nordisk, Pfizer that includes: funding grants. Christopher Cannon reports a relationship with Aegerion, Alnylam, Amarin, Amgen, Applied Therapeutics, Ascendia, BI, BMS, Corvidia, Eli Lilly, HLS Therapeutics, Innovent, Janssen, Kowa, Merck, Pfizer, Rhoshan, Sanofi that includes: consulting or advisory. This author has no patents to disclose. The corresponding author reports no additional activities to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Dipeptidyl peptidase-4 inhibitors (DPP-4i) are one of the most widely used antihyperglycemic therapeutic classes in type 2 diabetes mellitus management. In April 2016 and August 2017, the US Food and Drug Administration (FDA) introduced sequential labelling requirements regarding heart failure risk related to DPP-4i. We explored longitudinal trends in prescription of DPP-4i before and after these FDA warnings in a multicenter health system. We identified all first-time prescriptions of DPP4i or their combinations across the Partners HealthCare system (Boston, MA) from October 2006 (FDA approval of first DPP-4i) to December 2018. Overall, 11,830 patients were newly prescribed DPP-4i during the study period. Primary care physicians (31.5%) were the most common prescribing specialty. Overall, 8.4%, 20.4%, and 11.6% had heart failure, atherosclerotic cardiovascular disease, and chronic kidney disease, respectively. Median number of background antihyperglycemic therapies was 2 [25th to 75th percentiles 1 to 2], commonly metformin (65.4%) and/or insulin (36.4%). The vast majority of prescriptions were sitagliptin (85.7%), followed by linagliptin (9.5%), saxagliptin (4.7%), and alogliptin (0.2%). Quarterly prescriptions rose gradually from 2006 to mid-2016, and have decreased consistently since then for each of the 4 DPP-4i. Declines in DPP-4i among high-risk groups and those initiated by endocrinologists were most pronounced. In conclusion, although DPP-4i remain a dominant oral antihyperglycemic therapy in clinical practice, new prescriptions have declined recently. These data may reflect relatively swift health system response to broad FDA safety communications regarding heart failure risk, which appeared to impact the entire DPP-4i class, including specific drugs that have not demonstrated any increased risk of heart failure., Competing Interests: Disclosures Dr. Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (NIH/NCATS Award UL 1TR002541), serves on advisory boards for Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, & Relypsa, and participates on clinical endpoint committees for studies sponsored by Novartis and the NIH. Dr. Singh reports no disclosures. Dr. Sharma has received support from Bayer-Canadian Cardiovascular Society, Alberta Innovates Health Solution, Bristol-Myers Squibb-Pfizer, Boehringer Ingelheim, Roche Diagnostics, and Takeda. Dr. Januzzi is supported in part by the Hutter Family Professorship; has received grant support from Abbott, Cleveland Heart Labs, Singulex, and Prevencio; has received consulting income from Roche Diagnostics, Critical Diagnostics, and Novartis; and has participated in clinical endpoint committees/data or safety monitoring boards for Novartis, Amgen, GE, Janssen, Pfizer, and Boehringer Ingelheim. Dr. Scirica reports research grants via Brigham and Women's Hospital from AstraZeneca, Eisai, Novartis, and Merck. Consulting fees from AstraZeneca, Biogen Idec, Boehringer Ingelheim, Covance, Dr. Reddy's Laboratory, Eisai, Elsevier Practice Update Cardiology, GlaxoSmithKline, Lexicon, Merck, NovoNordisk, Sanofi, St. Jude's Medical, and equity in Health [at] Scale. Dr. Butler has received research support from the NIH and European Union; and has been a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CVRx, Janssen, Luitpold Pharmaceuticals, Medtronic, Merck, Novartis, Relypsa, Vifor Pharma, and ZS Pharma. Dr. Zannad reports personal fees from Janssen Research & Development LLC and Bayer during the conduct of the study; personal fees from AstraZeneca, Boehringer Ingelheim, LivaNova, GE Healthcare, Amgen, Novartis, Quantum Genomics, Cardior Pharmaceuticals, CardioRenal, CVCT, Merck, CVRx, Vifor Fresenius Medical Care Renal Pharma, NovoNordisk, and MundiPharma outside the submitted work; fees for serving on a steering committee or a safety and data monitoring board from Actelion, Amgen, Bayer, Boehringer Ingelheim, Boston Scientific, CVRx, GE Healthcare, Janssen Research & Development LLC, Novartis, and ResMed; and consulting fees from AstraZeneca, Cardior Pharmaceuticals, CardioRenal, Quantum Genomics, and Vifor Fresenius Medical Care Renal Pharma. Dr. McGuire reports honoraria for trial leadership from Astra Zeneca, Sanofi Aventis, Janssen, Boehringer Ingelheim, Merck & Co, Pfizer, Novo Nordisk, Lexicon, Eisai, GlaxoSmithKline, Esperion, Lilly US; and honoraria for consulting for Astra Zeneca, Sanofi Aventis, Lilly US, Astra Zeneca, Boehringer Ingelheim, Merck & Co, Pfizer, Novo Nordisk, Metavant, Applied Therapeutics. Dr. Cannon reports research grants from (all >10K) Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb (BMS), Daiichi Sankyo, Janssen, Merck; and consulting fees from Alnylam, Amarin, Amgen, Boehringer-Ingelheim, BMS, Eisai, Janssen, Kowa, Merck, Pfizer, Regeneron, and Sanofi. Dr. Bhatt discloses the following relationships - Advisory Board: Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, PLx Pharma, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, Novo Nordisk, Takeda., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The RE-DUAL PCI trial reported that dabigatran dual therapy (110/150 mg twice daily, plus clopidogrel or ticagrelor) reduced bleeding events versus warfarin triple therapy (warfarin plus aspirin and clopidogrel or ticagrelor) in patients with atrial fibrillation who underwent percutaneous coronary intervention, with noninferiority in composite thromboembolic events. In this prespecified analysis, risks of first major or clinically relevant nonmajor bleeding event and composite end point of death, thromboembolic events, or unplanned revascularization were compared between dabigatran dual therapy and warfarin triple therapy in older (≥ 75 years) and younger (< 75 years) patients, using Cox proportional hazard regression. Of 2,725 patients randomized to treatment, 1,026 (37.7%) were categorized into older and 1,699 (62.3%) into younger age groups. Dabigatran 110 mg dual therapy lowered bleeding risk versus warfarin triple therapy in older (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.51 to 0.89) and younger patients (HR 0.40; 95% CI 0.30 to 0.54); interaction p value: 0.0125. Dabigatran 150 mg dual therapy lowered bleeding risk versus warfarin triple therapy in younger patients (HR 0.57; 95% CI 0.44 to 0.74), whereas no benefit could be observed in older patients (HR 1.21; 95% CI 0.83 to 1.77); interaction p value: 0.0013. For the thromboembolic end point, there was a trend for a higher risk with dabigatran 110 mg dual therapy in older patients, compared with warfarin triple therapy, whereas the risk was similar in younger patients. For dabigatran 150 mg dual therapy, the thromboembolic risk versus warfarin triple therapy was similar in older and younger patients. In conclusion, the benefits of dabigatran dual therapy differed in the 2 age groups, which may help dose selection when using dabigatran dual therapy., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

In a population with atherosclerotic cardiovascular disease, previous research indicated that approximately 86% can achieve low-density lipoprotein cholesterol (LDL-C) of <70 mg/dL with oral lipid-lowering therapies (LLT) only, whereas 14% would require a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. We aim to estimate these values accounting for varying levels of statin intolerance. A simulation model described previously was used to estimate the utilization of LLT needed to achieve LDL-C <70 mg/dL via an intensification algorithm which maximized statins before adding ezetimibe or a PCSK9 inhibitor. The current analysis took into account varying background rates of statin intolerance. We defined statin intolerance as either partial (inability to tolerate high-intensity statin) or full (inability to tolerate any statin). With treatment intensification and 10% of patients having partial statin intolerance, the use of ezetimibe (± statin ± PCSK9 inhibitor) increased from 32.7% to 34.9%, and the need for a PCSK9 inhibitor (+ ezetimibe ± statin) increased from 14.0% to 15.5%. If, instead, 10% were fully statin intolerant, the use of ezetimibe (± statin ± PCSK9 inhibitor) increased from 32.7% to 38.5%, and the use of a PCSK9 inhibitor (+ ezetimibe ± statin) increased from 14.0% to 19.7%. In conclusion, in our simulation-based study, partial statin intolerance increased the need for nonstatins only modestly (by an absolute 2.2%), whereas having 10% of patients with full statin intolerance increased the need for PCSK9 inhibitors from 14% overall to approximately 20%., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

A deeper understanding of the interplay between the renal axis and cardiovascular (CV) disease is needed in type 2 diabetes mellitus (T2DM). We aimed to explore the prognostic value of a comprehensive panel of renal biomarkers in patients with T2DM at high CV risk. We evaluated the prognostic performance of both serum (Cystatin C) and urine renal biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 protein, and indices of urinary protein excretion) in 5,380 patients with T2DM and recent acute coronary syndromes in the EXAMINE trial. Patients requiring dialysis within 14 days were excluded. Single- and multimarker covariate-adjusted Cox proportional hazards models were developed to predict times to events. Primary endpoint was composite nonfatal myocardial infarction, nonfatal stroke, or CV death. Median age was 61 years, 68% were men, and mean baseline estimated glomerular filtration rate (eGFR) was 74 mL/min/1.73 m 2 . During median follow-up of 18 months, 621 (11.5%) experienced the primary endpoint and 326 (6.1%) patients had died. All renal biomarkers were robustly associated with adverse CV events in step-wise fashion, independent of baseline eGFR. However, in the multimarker prediction model, only Cystatin C (per 1 SD) was associated with the primary endpoint (hazard ratio [HR] 1.28 [1.14 to 1.45]; p ≤ 0.001), death (HR 1.51 [1.30 to 1.74]; p ≤ 0.001), and heart failure hospitalization (HR 1.20 [0.96 to 1.49]; p = 0.11). Association between Cystatin C and the primary endpoint was similar in baseline eGFR above and below 60 mL/min/1.73 m 2 (P interaction > 0.05). In conclusion, serum and urine renal biomarkers, when tested alone, independently predict long-term adverse CV events in high-risk patients with T2DM. In an integrative panel of renal biomarkers, only serum Cystatin C remained independently associated with subsequent CV risk. Renal biomarkers informing various aspects of kidney function may further our understanding of the complex interplay between diabetic kidney disease and CV disease., (Copyright © 2018. Published by Elsevier Inc.)

The natural history of patients hospitalized for acute coronary syndrome (ACS) with pre-existing versus (vs) de novo heart failure (HF) has not been previously reported over an extended duration of follow-up. The IMPROVE-IT trial enrolled 18,144 patients hospitalized for ACS and randomized them to combination simvastatin (40 mg)/ezetimibe (10 mg) vs simvastatin (40 mg). Subjects were divided into 3 groups: pre-existing HF (i.e., defined by past medical history), de novo HF (i.e., defined by Killip class II or greater during index admission), and no HF. The final analytical cohort included 14,792 patients (82%) with HF status recorded at baseline. In total, 790 patients (5.3%) reported a pre-existing diagnosis of HF and 1374 patients (9.3%) experienced de novo HF. Patients with pre-existing or de novo HF were older, more likely to be woman, and had a greater prevalence of atrial fibrillation and diabetes mellitus. The incidences of death/HF-hospitalizations at 5 years were 32%/20% for pre-existing HF, 18%/7% for de novo HF, and 8%/3% for no HF. After adjusting for potential confounders, a history of pre-existing or de novo HF was independently associated with increased risk of death (pre-existing HF: hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.68 to 2.22, p < 0.001; de novo HF: HR 1.51, 95% CI 1.33 to 1.72, p < 0.001) and hospitalizations for HF (pre-existing HF: HR 2.96, 95% CI 2.36 to 3.71, p < 0.001; de novo HF: HR 1.88, 95% CI 1.49 to 2.38, p < 0.001). There was no interaction among baseline HF status (i.e., pre-existing or de novo), lipid lowering therapy (i.e., simvastatin/ezetimibe vs simvastatin alone), and clinical outcomes. In conclusion, patients hospitalized for ACS with pre-existing or de novo HF were older and had a greater burden of medical co-morbidities. In conclusion, HF was independently associated with increased risk of long-term morbidity and mortality with the pre-existing HF cohort demonstrating the highest overall risk., (Copyright © 2018. Published by Elsevier Inc.)

The proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has been shown to substantially reduce low-density lipoprotein cholesterol (LDL-C). Demonstrating whether efficacy and safety are maintained over a long duration of exposure is vital for clinical decision-making. The COMBO II trial compared the efficacy and safety of alirocumab versus ezetimibe over 2 years. A prespecified first analysis was reported at 52 weeks. Here we report the final end-of-study data (on-treatment) and evaluate post hoc the safety profile with longer versus shorter duration of alirocumab exposure. Patients (n = 720) on maximally tolerated statin dose were treated with alirocumab (75/150 mg every 2 weeks) or ezetimibe (10 mg/day). Overall mean adherence for both treatment groups during the first and second year was >97%. At 2 years, LDL-C was reduced by 49% (alirocumab) versus 17% (ezetimibe; p <0.0001), and LDL-C <70 mg/dl was achieved by 73% of alirocumab-treated versus 40% of ezetimibe-treated patients. Overall safety was similar in both treatment groups at 2 years and during the first versus the second year. Local injection-site reactions were reported by 2.5% (alirocumab) versus 0.8% (ezetimibe) during the first year, and 0.2% versus 0.5% during the second year, indicating early occurrence during prolonged alirocumab exposure. Two consecutive calculated LDL-C values <25 mg/dl were observed in 28% of alirocumab-treated patients (vs 0.4% with ezetimibe). Persistent anti-drug antibody responses were observed in 1.3% (6 of 454) of alirocumab-treated versus 0.4% (1 of 231) of ezetimibe-treated patients. Neutralizing antibodies (that inhibit binding in vitro) were observed in 1.5% (7 of 454) of alirocumab-treated patients (0 with ezetimibe), mostly at isolated time points. Alirocumab sustained substantial LDL-C reductions and was well tolerated up to 2 years in the COMBO II trial., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Worries regarding short length of stay (LOS) adversely impacting quality of care prompted us to assess the relation between hospital LOS and inpatient guideline adherence in patients with acute coronary syndrome. We used the American Heart Association's Get with The Guidelines (GWTG)--Coronary Artery Disease data set. Data were collected from January 2, 2000, to March 21, 2010, for patients with acute coronary syndrome from 405 different sites. Of the 119,398 patients in the study, the mean LOS was 5.5 days with a median of 4 days. There was no difference in the LOS on the basis of hospital size, hospital type, or cardiac surgery availability. The population with an LOS <4 days were younger (63.8 ± 14.1 vs 70 ± 14.5, p <0.0001), men (63.8% vs 55.3%, p <0.0001) and had fewer clinical co-morbidities. The overall adherence was high in the GWTG participating hospitals. Those with the LOS <4 days were more likely to receive aspirin (adjusted odds ratio [OR] 1.12, 95% CI 1.06 to 1.19; p <0.001), clopidogrel (OR 1.77, 95% CI 1.60 to 1.95; p <0.001), lipid-lowering therapy if indicated (OR 1.13, 95% CI 1.05 to 1.21; p <0.001), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for left ventricular systolic dysfunction (OR 1.10, 95% CI 1.01 to 1.21; p = 0.04) and smoking cessation counseling (OR 1.17, 95% CI 1.1 to 1.24; p <0.001) compared to those with the LOS ≥ 4 days. In contrast, those with the LOS <4 days were less likely to receive beta blockers (OR 0.88, 95% CI 0.84 to 0.93; p <0.001). The odds of receiving defect-free care were greater for patients with the LOS <4 days (OR 1.15, 95% CI 1.1 to 1.21; p <0.001). In conclusion, in GWTG participating hospitals, a shorter LOS did not appear to adversely affect adherence to discharge quality of care measures., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Resistin is an adipokine secreted by macrophages and inflammatory cells linked to insulin resistance and inflammation. Leptin is an adipokine regulator of appetite and obesity. Although circulating levels of both have been associated with atherosclerosis, few data have reported their relation to coronary events in the context of statin therapy. This study measured on-statin levels of both resistin and leptin through enzyme-linked immunosorbent assay in a nested case-control cohort (n = 176 cases with coronary death, myocardial infarction, or unstable angina pectoris observed in follow-up matched 1:1 to 176 controls) derived from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 study, a randomized controlled trial of atorvastatin 80 mg/day versus pravastatin 40 mg/day in patients with a recent acute coronary syndrome. Resistin demonstrated a moderate association with high-sensitivity C-reactive protein (hsCRP; Spearman rho = 0.25, p <0.0001). On-statin resistin levels were linked to recurrent coronary events in conditional logistic regression analysis adjusted for additional risk factors including hsCRP and history of diabetes (tertile 3 vs 1 adjusted odds ratio 2.08; 95% confidence interval [CI] 1.04 to 4.19). An additive risk was noted when patients were stratified by resistin and glycated hemoglobin levels. In contrast, leptin levels were associated with obesity, diabetes, triglycerides, and hsCRP (p <0.001 for each) but demonstrated no association with recurrent coronary events (tertile 3 vs 1 adjusted odds ratio 0.72; 95% CI 0.28 to 1.83). In conclusion, on-statin resistin, but not leptin, is an independent marker of residual risk for recurrent coronary events in patients after hospitalization for an acute coronary syndrome., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The aim of this study was to assess the effects on lipids and safety during a 12-week reversal period after 18 months of treatment with anacetrapib. The cholesteryl ester transfer protein inhibitor anacetrapib was previously shown to reduce low-density lipoprotein cholesterol by 39.8% (estimated using the Friedewald equation) and increase high-density lipoprotein (HDL) cholesterol by 138.1%, with an acceptable side-effect profile, in patients with or at high risk for coronary heart disease in the Determining the Efficacy and Tolerability of CETP Inhibition With Anacetrapib (DEFINE) trial. A total of 1,398 patients entered the 12-week reversal-phase study, either after completion of the active-treatment phase or after early discontinuation of the study medication. In patients allocated to anacetrapib, placebo-adjusted mean percentage decreases from baseline were observed at 12 weeks off the study drug for Friedewald-calculated low-density lipoprotein cholesterol (18.6%), non-HDL cholesterol (17.6%), and apolipoprotein B (10.2%); placebo-adjusted mean percentage increases were observed for HDL cholesterol (73.0%) and apolipoprotein A-I (24.5%). Residual plasma anacetrapib levels (about 40% of on-treatment apparent steady-state trough levels) were also detected 12 weeks after cessation of anacetrapib. No clinically important elevations in liver enzymes, blood pressure, electrolytes, or adverse experiences were observed during the reversal phase. Preliminary data from a small cohort (n = 30) revealed the presence of low concentrations of anacetrapib in plasma 2.5 to 4 years after the last anacetrapib dose. In conclusion, after the cessation of active treatment, anacetrapib plasma lipid changes and drug levels decreased to approximately 40% of on-treatment trough levels at 12 weeks after dosing, but modest HDL cholesterol elevations and low drug concentrations were still detectable 2 to 4 years after the last dosing., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Patients with previous stroke are at high-risk for myocardial infarction (MI). Concern regarding increased risk of bleeding or recurrent stroke in this patient population might alter therapeutic decisions. Data were collected from 281 hospitals in the United States in the NCDR ACTION Registry. Patients with ST-segment elevation MI (STEMI; n = 15,997) or non-STEMI (NSTEMI; n = 25,514) entered into the registry from January 1, 2007 through December 31, 2007 were included. We assessed use of evidence-based medications and procedures in patients with and without previous stroke. Risk-adjusted odds ratio of death, major bleeding not related to coronary artery bypass grafting, and a composite outcome (major adverse cardiac events [MACEs], i.e., death/MI/stroke/cardiogenic shock/congestive heart failure) were calculated using logistic regression. Previous stroke was reported in 5.1% of patients with STEMI and 9.3% of those with NSTEMI. Of patients with STEMI eligible for reperfusion therapy, those with previous stroke were less likely to receive reperfusion therapy compared to patients without previous stroke. Patients with previous stroke had longer door-to-needle and door-to-balloon times. Of patients with STEMI and NSTEMI, those with previous stroke were less likely to receive evidence-based therapies. Death, MACEs, and major bleeding were more common with previous stroke. When adjusted for baseline risk, patients with previous stroke were at increased risk of death (only those with STEMI) and MACEs but not bleeding. In conclusion, patients with STEMI and previous stroke are at increased risk for death and patients with STEMI and NSTEMI are at increased risk of MACE. Despite this, previous stroke patients are less likely to receive guideline-based MI therapies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Evidence regarding the use of dual antiplatelet therapy and oral anticoagulation (i.e., triple therapy) in acute coronary syndromes (ACS) is limited. We evaluated the characteristics associated with the choice of triple therapy in ACS. Using the Get With The Guidelines (GWTG) Coronary Artery Disease national registry, we studied patients with ACS at 361 sites in the United States from 2004 to 2007. Both univariate analysis and multivariate logistic regression analysis were used to assess the factors associated using triple therapy on discharge. The Generalized Estimating Equation method was used to account for within-hospital clustering in modeling. A total of 86,304 patients presented with ACS during the study period. At discharge, 3,933 patients (4.6%) were prescribed triple therapy, 60,716 patients (70.4%) received dual antiplatelet therapy, 2,348 patients (2.7%) received single antiplatelet therapy plus oral anticoagulation, 19,065 patients (22.1%) received antiplatelet monotherapy, and 242 patients (0.3%) received oral anticoagulation alone. Patients with a history of atrial fibrillation (odds ratio 7.01, 95% confidence interval 6.06 to 8.12; p <0.001), documented new-onset atrial fibrillation (odds ratio 3.76, 95% confidence interval 2.87 to 4.93; p <0.001), or history of atrial flutter (odds ratio 3.38, 95% confidence interval 2.15 to 5.32; p <0.001) were more frequently discharged with triple therapy. In conclusion, for patients with ACS, atrial fibrillation and atrial flutter were most strongly associated with the use of triple therapy; however, this therapy was used less often than dual or single antiplatelet therapy.

In the era of early reperfusion therapy for ST-segment elevation myocardial infarction, preserved left ventricular (LV) function is common. Despite preservation of LV ejection fraction (LVEF), there remains a spectrum of risk for adverse cardiovascular events, including ventricular tachycardia (VT) and ventricular fibrillation (VF). Larger infarct size has been independently associated with death, VT/VF, and heart failure in the post-myocardial infarction population. It was hypothesized that infarct size, as estimated by peak serum creatine kinase (CK)-MB concentration, would be associated with the incidence of VT/VF in patients with preserved LV function after ST-segment elevation myocardial infarctions. The Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28 (CLARITY-TIMI 28) study enrolled 3,491 patients with ST-segment elevation myocardial infarctions who underwent fibrinolytic therapy. The association between estimated infarct size (ratio of peak CK-MB to the upper limit of normal), the LVEF (measured using left ventriculography or echocardiography), and the incidence of VT/VF through 30 days was assessed. A total of 1,436 patients underwent assessments of LV function, of whom 1,133 had adequate CK-MB for analysis. The median LVEF in this group was 55% (interquartile range 45% to 65%), and most patients (n = 814 [87.1%]) had LVEF > or =40%. Among patients with LVEF > or =40%, the ratio of peak CK-MB to the upper limit of normal was significantly associated with the incidence of VT/VF through 30 days (2.2%, 3.7%, and 5.5% across tertiles, respectively, p = 0.041 for trend) and the incidence of the composite of cardiovascular death, heart failure, shock, and VT/VF through 30 days (3.7%, 6.0%, 8.5%, respectively, p = 0.018 for trend). In conclusion, in patients with ST-segment elevation myocardial infarction with preserved LV function after reperfusion therapy, larger infarct size, as estimated by peak serum CK-MB concentration, is significantly associated with VT/VF as well as other adverse clinical outcomes.

To improve hospital performance in door-to-balloon (DTB) times nationally, the American College of Cardiology D2B Alliance recently enrolled approximately 1,000 hospitals that perform percutaneous coronary intervention (PCI) across the United States in a large national quality improvement effort. We evaluated recent changes in DTB times in hospitals within the Get-With-The-Guidelines (GWTG) Coronary Artery Disease (CAD) program, a partner in the D2B Alliance. Within GWTG-CAD participating hospitals, we studied DTB in nontransferred patients with ST-elevation myocardial infarction treated with primary PCI from July 2006 to March 2008. We evaluated the percentage of patients treated within 90 minutes and used multivariable models with generalized estimating equations to examine trends over time after accounting for changes in patients' characteristics. A total of 5,801 patients at 167 hospitals were included in our analysis, with 3,567 patients at 98 hospitals that joined the D2B Alliance. From July to September 2006, 54.1% of patients received primary PCI within 90 minutes. This number increased significantly during the study period: 335 (74.1%) of 452 patients at GWTG-CAD participating hospitals were treated within 90 minutes from January to March 2008, including 229 of 304 patients (75.3%) treated at hospitals that joined the D2B Alliance and 106 of 148 patients (71.6%) treated at other GWTG-CAD participating hospitals (p <0.001 for all comparisons over time). No statistically significant differences were noted in the rate of change between hospitals that joined the D2B Alliance and other GWTG-CAD participating hospitals. In conclusion, the percentage of patients treated with 90 minutes has dramatically increased at hospitals participating within the GWTG-CAD program, coinciding with the launch of the D2B Alliance. These improvements were broad and not limited to hospitals that joined the D2B Alliance.

Electrocardiographic measures can facilitate the identification of patients at risk of death after acute coronary syndromes. This study evaluates a new risk metric, morphologic variability (MV), which measures beat-to-beat variability in the shape of the entire heart beat signal. This metric is analogous to heart rate variability (HRV) approaches, which focus on beat-to-beat changes in the heart rate. MV was calculated using a dynamic time-warping technique in 764 patients from the DISPERSE2 (TIMI 33) trial for whom 24-hour continuous electrocardiograph was recorded within 48 hours of non-ST-elevation acute coronary syndrome. The patients were evaluated during a 90-day follow-up for the end point of death. Patients with high MV showed an increased risk of death during follow-up (hazard ratio 8.46; p <0.001). The relationship between high MV and death could be observed even after adjusting for baseline clinical characteristics and HRV measures (adjusted hazard ratio 6.91; p = 0.001). Moreover, the correlation between MV and HRV was low (R < or =0.25). These findings were consistent among several subgroups, including patients under the age of 65 and those with no history of diabetes or hyperlipidemia. In conclusion, our results suggest that increased variation in the entire heart beat morphology is associated with a considerably elevated risk of death and may provide information complementary to the analysis of heart rate.

Beta blockers have a proven benefit in the management of patients with acute coronary syndromes (ACS) and for secondary prevention of coronary events. Current guidelines list such reactive airway diseases (RADs) such as asthma and chronic obstructive pulmonary disease as relative contraindications to beta-blocker use. However, the co-morbid burden of RAD and coronary heart disease is substantial, and data suggest that the treatment benefit of beta blockers is shared by patients with RAD. The Get with the Guidelines (GWTG) database was used to evaluate use of beta blockers within 24 hours of admission and at discharge in patients with ACS with (n = 12,967) and without (n = 81,140) a history of RAD. Data were collected in 435 hospitals between January 2000 and September 2006. A multivariable logistic regression model was used to determine predictors of beta-blocker treatment. In patients with no RAD history, beta-blocker prescription rates were 78.3% at admission and 88.7% at discharge; in patients with a RAD history, rates were 65.6% at admission and 77.2% at discharge. Compared with patients with no history of RAD, patients with a history of RAD were 42% less likely (odds ratio 0.58, confidence interval 0.54 to 0.62, p <0.0001) to receive a beta blocker upon admission and 55% less likely (odds ratio 0.45, confidence interval 0.41 to 0.48, p <0.0001) to receive a beta blocker at discharge in multivariable analysis. Among all other clinical factors, RAD history was the most significant predictor of likelihood of not receiving a beta blocker at admission or discharge. Receipt of beta blockers within 24 hours after admission was associated with a lower in-hospital mortality rate for patients with RAD (odds ratio = 0.52, p <0.001) and for patients without RAD (odds ratio = 0.38, p <0.001). Careful assessment of beta-blocker safety and RAD severity by physicians is needed to improve beta-blocker prescription rates in this large group of patients with ACS.

Anticoagulation therapy significantly reduces the incidence of thromboembolic events in patients with atrial fibrillation (AF), and warfarin therapy at discharge is a class I-indicated drug in patients with ischemic stroke with persistent or paroxysmal AF without contraindications. The aim was to determine whether participation in the Get With The Guidelines-Stroke (GWTG-S) quality improvement program would be associated with improved adherence to anticoagulation guidelines for patients with all types of AF. Adherence to warfarin treatment at hospital discharge was assessed in eligible patients with AF who presented with stroke or transient ischemic attack, based on type of AF. Of patients with stroke, 10.5% presented with some form of AF. When AF was documented using electrocardiography or telemetry (ECG) during the present admission, eligible patients were more likely to receive warfarin compared with patients for whom AF was reported using medical history only (78.8% vs 49.4%; p<0.0001). Improvement after GWTG-S participation in warfarin use was observed in patients with ECG-documented AF (73.8% at baseline vs 88.5% after the intervention; p<0.0001), but not patients using history only. Women and elderly patients were less likely to receive warfarin, and these gaps in treatment did not narrow during the quality improvement program for patients with ECG-documented AF and those with history only. In conclusion, anticoagulation for stroke prevention was underused in general for patients with AF, even in such high-risk groups as patients with stroke. GWTG-S was associated with improved adherence for patients with ECG-documented AF, but patients with a history of AF alone were largely untreated.

Metabolic syndrome and type 2 diabetes mellitus are individually associated with increased cardiovascular risk; furthermore, the combination of metabolic syndrome with diabetes accentuates this risk. An atherogenic dyslipidemia characterized by elevated triglycerides, low high-density lipoprotein cholesterol, or both conditions is a key modifiable risk factor associated with both conditions. As the development of this atherogenic mixed dyslipidemia precedes the onset of overt glycemia and the clinical diagnosis of diabetes, early effective intervention is recommended to reduce the risk of premature cardiovascular disease morbidity and mortality.

Among the 5 million patients presenting to emergency departments with chest pain each year in the United States, approximately 1 million are diagnosed with myocardial infarction (MI). Physicians have the difficult task of making decisions regarding admission and treatment and identifying patients at high risk for adverse outcomes, such as early mortality, left ventricular dysfunction (LVD), and heart failure. Several measures can be implemented in the process of risk assessment, including clinical judgment, electrocardiographic and echocardiographic findings, and the presence of biomarkers. Biomarkers--which can be classified as antecedent, screening, diagnostic, staging, or prognostic--may help identify the subset of patients who need early intervention and/or intensive therapy. Using a multimarker strategy that combines a marker of hemodynamic stress (brain natriuretic peptide) or of inflammation (C-reactive protein) with a marker of necrosis (cardiac troponin) may help to risk-stratify patients, guide treatment, and optimize admission and discharge decisions. This article discusses the potential benefits of risk assessment tools in the management of post-MI patients with LVD.

Outcomes are typically graded on the basis of diagnoses coded according to the International Classification of Diseases, Ninth Revision (ICD-9). To facilitate performance measurement, the ICD-9 codes for acute myocardial infarction changed in October 2005 to completely separate non-ST elevation myocardial infarction (NSTEMI; code 410.71) and ST elevation myocardial infarction (STEMI; all other codes 410.x), yet it is unclear whether these changes have been implemented by coders. Patients in the National Registry of Myocardial Infarction (NRMI), version 5, were categorized in 2 ways: by electrocardiographic (ECG) findings and ICD-9 codes. Agreement between ECG findings and ICD-9 codes for type of myocardial infarction (STEMI or NSTEMI) was assessed before and after ICD-9 revision. Mortality rates were measured in a subgroup of patients discharged without transfer after the coding change. There were 102,679 hospitalizations before October 2005 and 63,012 hospitalizations after the coding change, among which the mean age was 66.7 years. Previously, 81% of NSTEMIs (by ECG diagnosis) were coded ICD-9 410.71; after the reclassification of code 410.71 to reflect NSTEMI, 82% of NSTEMIs were coded 410.71 (p <0.001). Overall, the correlation of ECG diagnosis with ICD-9 code improved only slightly after the coding change. In conclusion, despite more distinctly separated definitions of STEMI and NSTEMI in the new ICD-9 coding system as of October 2005, there appears to be little change in coding, which may reflect a lack of awareness of this substantial change in classification.

In patients with ST-segment elevation myocardial infarction (STEMI), the restoration of normal epicardial flow following fibrinolytic administration is associated with improved clinical outcomes. The goal of this analysis was to examine the relation between hyperemic flow and outcomes following fibrinolytic administration for STEMI. In Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28 (CLARITY-TIMI 28), patients with STEMI (n=3,491) treated with fibrinolytic therapy were scheduled to undergo angiography 48 to 192 hours after randomization. Corrected TIMI frame count (CTFC) and TIMI myocardial perfusion grade (TMPG) were assessed, and their associations with outcomes at 30 days were evaluated. When evaluating initial angiography of the infarct-related artery, there was a nearly linear relation between CTFC and 30-day mortality, with faster flow (lower CTFC) associated with improved outcomes. Conversely, in patients who underwent percutaneous coronary intervention (PCI), very fast flow (CTFC<14) after intervention was associated with worse outcomes. Post-PCI hyperemic flow (CTFC<14) was associated with a higher incidence of mortality (p=0.056), recurrent myocardial infarction (p=0.011), and a composite of death or myocardial infarction (p<0.001) compared with normal flow (CTFC 14 to 28). When post-PCI CTFC was further stratified by TMPG, there was a U-shaped relation between mortality and CTFC in patients with poor myocardial perfusion (TMPG 0 or 1). This relation appeared to be linear in patients with TMPG 2 or 3. In conclusion, in patients who undergo PCI after fibrinolytic therapy for STEMI, hyperemic flow on coronary angiography is associated with an increased incidence of adverse outcomes. Hyperemic flow with associated impaired myocardial perfusion may be a marker of more extensive downstream microembolization.

Rimonabant is the first selective blocker of the cannabinoid-1 receptor in development for the treatment of obesity, diabetes mellitus, and cardiometabolic risk factors. (Recently, an FDA Advisory Committee recommended a delay in the approval of rimonabant because of safety issues that need to be addressed in further studies.) Although it is associated with favorable effects on weight, waist circumference, serum lipids, C-reactive protein, and an improvement in glycemic control in type 2 diabetes, there are concerns about side effects. Generally, rimonabant has been well tolerated, with a primary side effect of nausea. Other side effects seen in trials have been anxiety and depressive symptoms, as well as neurologic events, albeit at low rates. When rimonabant becomes clinically available, physicians should be vigilant regarding the expected side effects and use alternative therapies if needed.

Previous studies of hospitalized patients have suggested an "obesity paradox" with lower short-term mortality as weight increases. We hypothesized that some of this difference might be related to more aggressive management. To evaluate the effect of body mass index (BMI) on treatments and outcomes in patients with coronary artery disease (CAD), the Get With The Guidelines database was investigated. From 409 United States hospitals, 130,139 hospitalizations for CAD were identified with documented height and weight. Patients were stratified by BMI, with 3,305 (2.5%) underweight (BMI <18.5 kg/m(2)), 34,697 (27%) of healthy weight (BMI 18.5 to 24.9 kg/m(2)), 47,883 (37%) overweight (BMI 25 to 29.9 kg/m(2)), 37,686 (29%) obese (BMI 30 to 39.9 kg/m(2)), and 6,568 (5%) extremely obese (BMI > or =40 kg/m(2)). As BMI increased, patients were significantly younger but more likely to be men and have hypertension, diabetes, and hyperlipidemia. Unadjusted in-hospital mortality was highest in the underweight group (10.4%) and significantly lower in the healthy-weight (5.4%), overweight (3.1%), obese (2.4%), and extremely obese (2.9%) patients. Higher BMI was associated with increased use of standard medical therapies such as aspirin, beta blockers, inhibitors of the renin-angiotensin system, and lipid-lowering therapy in the hospital and at discharge. In adjusted analyses, compared with the healthy-weight group, overweight and obese patients were more likely to undergo invasive procedures and had lower mortality (p <0.01 for all odds ratios). In conclusion, increasing BMI appears to be associated with better use of guideline-recommended medical treatment and invasive management of CAD, which may explain the observed lower rates of in-hospital mortality.