Search

Cardiogenic shock (CS) is a devastating and fatal complication of acute myocardial infarction (AMI). CS can affect the pharmacokinetics and pharmacodynamics of medications. The unique properties of cangrelor make it the optimal P2Y12 inhibitor for CS-AMI, in terms of both efficacy and safety. The DAPT-SHOCK-AMI trial (ClinicalTrials.gov: NCT03551964; EudraCT: 2018-002161-19) will assess the benefits of cangrelor in patients with an initial CS-AMI undergoing primary angioplasty. This randomised, multicentre, placebo-controlled trial of approximately 550 patients (with an allowed 10% increase) in 5 countries using a double-blind design will compare initial P2Y12 inhibitor treatment strategies in patients with CS-AMI of (A) intravenous cangrelor and (B) ticagrelor administered as crushed tablets at a loading dose of 180 mg. The primary clinical endpoint is a composite of all-cause death, myocardial infarction (MI), or stroke within 30 days. The main secondary endpoints are (1) the net clinical endpoint, defined as death, MI, urgent revascularisation of the infarct-related artery, stroke, or major bleeding as defined by the Bleeding Academic Research Consortium criteria; (2) cardiovascular-related death, MI, urgent revascularisation, or heart failure; (3) heart failure; and (4) cardiovascular-related death, all (1-4) within 1 year after study enrolment. A platelet reactivity study that tests the laboratory antiplatelet benefits of cangrelor, when given in addition to standard antiplatelet therapy, will be conducted using vasodilator-stimulated phosphoprotein phosphorylation. The primary laboratory endpoints are the periprocedural rate of onset and the proportion of patients who achieve effective P2Y12 inhibition. The DAPT-SHOCK-AMI study is the first randomised trial to evaluate the benefits of cangrelor in patients with CS-AMI.

Background: Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI., Methods: The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290., Findings: Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80-1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 [11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12-2·11; p=0·0070)., Interpretation: Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI., Funding: ACTION Study Group and AstraZeneca., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Following the publication of the COMPASS trial, the European Medicines Agency has approved a regimen of combination of rivaroxaban 2.5mg twice daily and a daily dose of 75-100mg acetylsalicylic acid (ASA) for patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischemic events. However, the applicability of such a therapeutic strategy in France is currently unknown., Aims: To describe the proportion of patients eligible to COMPASS in France, their baseline clinical characteristics and the rate of major adverse cardiovascular events, using the REACH registry., Methods: From the the REduction of Atherothrombosis for Continued Health (REACH) registry database, a large international registry of patients with, or at risk, of atherothrombosis, we analyzed patients included in France with either established CAD and/or PAD and fulfilling the inclusion and exclusion criteria of the COMPASS trial. The ischemic outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke, and serious bleeding were defined as haemorrhagic stroke or bleeding leading to hospitalization or transfusion., Results: Among more than 65000 patients enrolled in REACH, 2.012 patients were evaluable and enrolled in France. Among them, 1194 patients (59.3%) were eligible to COMPASS. The main reasons for exclusion of the COMPASS trial, were high bleeding risk (59.1%), anticoagulant use (43.4%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI (24.7%). In the "COMPASS eligible population", the rate of MACE (CV, MI and stroke) at 4 years follow-up was 13.4% [11.3-15.8], and serious bleeding was 2.5% at 4 years [1.6-3.4]. Patients with polyvascular disease (n=219) had the highest rate of MACE, compared with patients with CAD only and PAD only (19.1% [13.9-26.1] vs. 11.6% [9.1-14.8] vs 13.2% [9.2-18.8], P<0.0001, respectively)., Conclusion: The COMPASS therapeutic strategy in France appears to be applicable to more than half of CAD or PAD patients. This population appears at high residual risk of atherothrombotic events, and patients with polyvascular disease experienced the highest rate of events., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Percutaneous left atrial appendage closure (LAAC) exposes to the risk of device thrombosis in patients with atrial fibrillation who frequently have a contraindication to full anticoagulation. Thereby, dual antiplatelet therapy (DAPT) is usually preferred. No randomized study has evaluated nonvitamin K antagonist oral anticoagulant after LAAC, and we decided to evaluate the efficacy and safety of reduced doses of rivaroxaban after LAAC., Methods: ADRIFT (Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban in Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure) is a multicenter, phase IIb study, which randomized 105 patients after successful LAAC to either rivaroxaban 10 mg (R 10 , n=37), rivaroxaban 15 mg (R 15 , n=35), or DAPT with aspirin 75 mg and clopidogrel 75 mg (n=33). The primary end point was thrombin generation (prothrombin fragments 1+2) measured 2 to 4 hours after drug intake, 10 days after treatment initiation. Thrombin-antithrombin complex, D-dimers, rivaroxaban concentrations were also measured at 10 days and 3 months. Clinical end points were evaluated at 3-month follow-up., Results: The primary end point was reduced with R 10 (179 pmol/L [interquartile range (IQR), 129-273], P <0.0001) and R 15 (163 pmol/L [IQR, 112-231], P <0.0001) as compared with DAPT (322 pmol/L [IQR, 218-528]). We observed no significant reduction of the primary end point between R 10 and R 15 while rivaroxaban concentrations increased significantly from 184 ng/mL (IQR, 127-290) with R 10 to 274 ng/mL (IQR, 192-377) with R 15 , P <0.0001. Thrombin-antithrombin complex and D-dimers were numerically lower with both rivaroxaban doses than with DAPT. These findings were all confirmed at 3 months. The clinical end points were not different between groups. A device thrombosis was noted in 2 patients assigned to DAPT., Conclusions: Thrombin generation measured after LAAC was lower in patients treated by reduced rivaroxaban doses than DAPT, supporting an alternative to the antithrombotic regimens currently used after LAAC and deserves further evaluation in larger studies. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03273322.

Background: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y 12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting., Methods: Assessment of Loading with the P2Y 12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier)., Conclusion: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: To describe the characteristics and outcomes of patients receiving bailout glycoprotein IIb/IIIa inhibitors (GPI) for thrombotic complications of percutaneous coronary intervention (PCI) in a large, contemporary trial., Methods and Results: In the CHAMPION PHOENIX trial, the use of GPI was restricted to bailout for thrombotic complications. We describe the characteristics and outcomes of patients requiring bailout GPI compared to patients not receiving GPIs, with adjustment through propensity-score. A multivariable model was constructed to identify independent correlates associated with bailout GPI use. A total of 380 out of 10,942 patients received GPI (3.5%); GPI patients were younger, more frequently male, more likely to present with ST segment elevation myocardial infarction and less frequently treated with cangrelor. At 48 h, GPI patients experienced higher rates of the primary composite outcome of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis (ST) (19.2% vs 4.8%; adjusted OR: 5.65(4.08, 7.82), p < 0.0001) and a higher rate of GUSTO severe or moderate bleeding (2.6% vs 0.4% adjusted OR: 4.90 (1.98, 12.18), p = 0.0006) compared with non GPI patients. Independent correlates of GPI use were STEMI, use of unfractionated heparin, drug-eluting stents and longer procedure duration., Conclusions: In a large contemporary trial, patients receiving bailout GPI for thrombotic complications of PCI experienced very high risks of both ischemic and bleeding complications, suggesting that prevention of periprocedural complications rather than bailout GPI may be preferable., Clinical Trial Registration: http://www.clinicaltrials.gov identifier: NCT01156571., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: In patients undergoing percutaneous coronary intervention (PCI), who did not receive P2Y 12 inhibitor pretreatment, the optimal timing of P2Y 12 inhibitor loading dose remains debated. We sought to examine whether the choice of administration of the clopidogrel loading dose before or after the start of PCI had an impact on periprocedural complications, including bleeding., Methods and Results: The CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention) double-blind randomized trial compared cangrelor with clopidogrel loading dose at the time of PCI. Pretreatment with clopidogrel before randomization was not permitted per protocol. In the clopidogrel-only group (n=5438), a loading dose was given before (early load [EL]) or after the start of PCI (late load [LL]) according to physician choice. Overall, 3442 (63.3%) patients had EL and 1997 LL (36.7%). Median times were 5 minutes before and 20 minutes after the start of PCI, respectively. EL was more frequently used among patients with ST-segment-elevation myocardial infarction (84.4%) and non-ST-segment-elevation acute coronary syndromes (71.5%) than in stable patients (53.7%). At 48 hours, rates of the primary outcome of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis were similar (6.0% versus 5.4%) for EL versus LL, respectively (odds ratio [OR], 1.11 [95% CI, 0.87-1.41]; P=0.41), and remained so after adjustment for potential confounders, including clinical presentation (OR [95% CI], 1.39 [0.90-2.15]; P=0.14). Compared with clopidogrel, cangrelor consistently reduced the primary outcome in both EL (4.8% versus 6.0%; OR [95% CI], 0.80 [0.64-0.98]) and LL (4.3% versus 5.4%; OR [95% CI], 0.79 [0.59-1.06]; interaction P=0.99). Global Use of Strategies to Open Occluded Coronary Arteries severe/moderate bleeding rates were similar between treatment arms for both EL (OR [95% CI], 1.24 [0.58-2.66]) and LL (OR [95% CI], 2.53 [0.98-6.54]; interaction P=0.25)., Conclusions: In a nonrandomized comparison of patients with clopidogrel loading before or after the start of PCI, the rates of periprocedural PCI complications, including bleeding, were similar, as were the benefits of cangrelor, regardless of the timing., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01156571.

Background: Monitoring anticoagulation with activated clotting time (ACT) has been proposed to reduce ischemic or bleeding events. However, the value of using ACT to improve outcomes is uncertain. This study sought to determine the relationship between ACT and outcomes during percutaneous coronary intervention in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) treated by unfractionated heparin with GPIs (glycoprotein IIb/IIIa inhibitors)., Methods and Results: From the randomized TAO trial (Treatment of Acute Coronary Syndromes With Otamixaban), we analyzed the value of ACT to predict ischemic and bleeding outcomes in the 3275 patients receiving unfractionated heparin plus eptifibatide. Ischemic and safety outcomes were analyzed according to ACT to determine the best threshold. Median peak ACT was 225 s. There was no correlation ( r =-0.02; P =0.24) between the unfractionated heparin dose received and the ACT value before percutaneous coronary intervention. There was no evidence of a nonlinear association between ACT and either ischemic or bleeding events ( P =0.66; P =0.07). No threshold was found to predict ischemic complications. Conversely, increased bleeding was observed with ACT >230 s with an optimal threshold of ACTs ≥250 s (4.53% versus 6.17%; odds ratio, 1.46; 95% confidence interval, 1.04-2.06; P =0.028). This optimal threshold varied according to access site: ≥250 s (6.86% versus 10.18%; odds ratio, 1.57; 95% confidence interval, 1.00-2.45; P =0.047) by femoral approach and ≥290 s (2.86% versus 5.43%; odds ratio, 2.24; 95% confidence interval, 1.05-4.44; P =0.027) by radial approach., Conclusions: In the TAO trial, peak procedural ACT ≥250 s was associated with increased bleeding risk in non-ST-segment-elevation acute coronary syndrome patients treated with unfractionated heparin plus GPIs. This threshold was increased to 290 s when performing radial approach., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01076764., (© 2018 American Heart Association, Inc.)

Background: It remains uncertain whether patients with atrial fibrillation (AF) requiring long-term oral anticoagulation (OAC) and with stable coronary artery disease (CAD) should receive antiplatelet therapy (APT) in addition to OAC., Hypothesis: APT in addition to OAC would be more effective than OAC alone in preventing ischaemic events in such patients., Methods: In the international REduction of Atherothrombosis for Continued Health (REACH) Registry including 68 236 outpatients with or at risk for atherothrombosis, we identified 2347 patients with stable CAD and AF receiving vitamin K antagonists (VKA). Using propensity score matching, patients treated with VKA (n = 1481) were compared with those receiving VKA + APT at inclusion (n = 866). The primary outcome was major adverse cardiovascular events (MACE) at 4 years (cardiovascular death, myocardial infarction, or stroke). Secondary outcomes were all-cause death and bleeding leading to hospitalization and transfusion., Results: Patients receiving VKA only were older (74 vs 72 years, P < 0.01), had less diabetes (37% vs 42%, P = 0.02), and less frequent history of percutaneous coronary intervention (28.7% vs 43.9%, P < 0.01). The mean CHA 2 DS 2 -VaSc score was 4.9 in the VKA group vs 4.7 in the VKA + APT group (P < 0.01). After propensity score matching, the rate of MACE was similar between groups: hazard ratio = 1.01 (0.77-1.33) (P = 0.94), whereas bleeding tended to be more frequent in the VKA + APT group: odds ratio = 1.87 (0.99-3.50) (P = 0.051)., Conclusions: In this observational analysis, the use of APT in addition to OAC in patients with stable CAD and AF was not associated with lower risk of ischemic events but possibly with higher bleeding rates. Randomized trials are necessary to determine the optimal long-term antithrombotic strategy., (© 2017 Wiley Periodicals, Inc.)

Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality., Methods: In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events., Results: A total of 822 patients (4.4%) had ≥1 spontaneous ischemic event; 485 patients (2.6%), ≥1 spontaneous PLATO major bleed, 282 (1.5%), ≥1 spontaneous TIMI major bleed; and 207 (1.1%), ≥1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% CIs) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P>0.05) CONCLUSIONS: In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem "prognostically equivalent" to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Early infarct-related artery (IRA) patency is associated with better clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). Using the French Registry of ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2010 registry, we investigated factors related to IRA patency (thrombolysis in myocardial infarction [TIMI] 2/3 flow) at the start of procedure in patients admitted for primary percutaneous coronary intervention. FAST-MI 2010 is a nationwide French registry including 4,169 patients with acute MI. Of 1,452 patients with STEMI with primary percutaneous coronary intervention, 466 (32%) had TIMI 2/3 flow of IRA before the procedure. Mean age (62 ± 14 years in both groups), Global Registry of Acute Coronary Event score (141 ± 31 vs 142 ± 34), and time from onset to angiography (472 ± 499 vs 451 ± 479 minutes) did not differ according to IRA patency (TIMI 2/3 vs TIMI 0/1). Using multivariate logistic regression analysis, IRA patency was more frequently found in patients having called earlier (time from onset to electrocardiogram [ECG] <120 minutes; odds ratio [OR] 1.49; 95% confidence interval [CI] 1.17 to 1.89), or receiving rapid-onset of action (prasugrel or glycoprotein IIb-IIIa) antiplatelet therapy in the prehospital setting (OR 1.59, 95% CI 1.14 to 2.21). Increasing time from diagnostic ECG to angiography was also associated with IRA patency (>90 minutes; OR 1.37, 95% CI 1.08 to 1.75). In conclusion, preprocedural IRA patency is observed in one third of patients with STEMI, it is more frequently found in patients having received fast-acting antiplatelet therapy before angiography, and in patients having called early. Higher IRA patency with increasing time delays from qualifying ECG to angiography suggests an additional role of spontaneous or medication-mediated fibrinolysis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Although trials comparing antiplatelet strategies after percutaneous coronary intervention report average risks of bleeding and ischemia in a population, there is limited information to guide choices based on individual patient risks, particularly beyond 1 year after treatment. Patient-level data from Patient Related Outcomes With Endeavor vs Cypher Stenting Trial (PROTECT), a broadly inclusive trial enrolling 8,709 subjects treated with drug-eluting stents (sirolimus vs zotarolimus-eluting stent), and PROTECT US, a single-arm study including 1,018 subjects treated with a zotarolimus-eluting stent, were combined. The risk of ischemic events, cardiovascular death/non-periprocedural myocardial infarction (MI)/definite or probable stent thrombosis, and bleeding events, Global Use of Strategies to Open Occluded Arteries moderate or severe bleed, were predicted using logistic regression. At median follow-up of 4.1 years, major bleeding occurred in 260 subjects (2.8%) and ischemic events in 595 (6.3%). Multivariate predictors of bleeding were older age, smoking, diabetes mellitus, congestive heart failure, and chronic kidney disease (all p <0.05). Ischemic events shared all the same predictors with bleeding events and gender, body mass index, previous MI, previous coronary artery bypass graft surgery, ST-segment elevation MI on presentation, stent length, and sirolimus-eluting stent use (all p <0.05). Within individual subjects, bleeding and ischemic risks were strongly correlated; 97% of subjects had a greater risk of ischemic events than bleeding. In conclusion, individual patient risks of ischemia and bleeding are related to many common risk factors, yet the predicted risks of ischemic events are greater than those of major bleeding in the large majority of patients in long-term follow-up., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Patients on antiplatelet therapy have a gastrointestinal bleeding risk. It is increased by risk factors. The frequency of those risk factors, the prevalence of upper digestive symptoms and their management in patients on antiplatelet agents is unknown., Patients and Methods: We performed an observational multi-centred prospective survey among 560 French cardiologists with private practice. Each cardiologist completed a questionnaire for the first four patients treated with antiplatelet agents in primary or secondary prevention., Results: Among the 2182 patients included, (age = 67 ± 11 years; 74% male), 83% had at least one gastrointestinal bleeding risk factor and 38.9% had a history of upper digestive tract symptom. A history of gastrointestinal bleeding was reported in 3.4% and a history of documented gastro-duodenal ulcer in 5.5%. A proton pump inhibitor was already prescribed in 39% of the patients. At the time of the consultation, upper digestive symptoms were described in 21% of the patients. In those patients with symptoms, 85% had no modification in antiplatelet therapy and 62.7% were prescribed gastro-protective drugs (proton pump inhibitors: 51.8%, H(2)-blockers 3.6% other anti-acid medication: 7.3%)., Conclusion: Among patients on antiplatelet agents, the prevalence of upper digestive symptoms and risk factors for gastrointestinal bleeding is high. Preventative management needs to be clarified in this population., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The von Willebrand factor (vWF) aptamer, ARC1779 that blocks the binding of vWF A1-domain to platelet glycoprotein 1b (GPIb) at high shear, may deliver a site-specific antithrombotic effect. We investigated the efficiency of ARC1779 on platelet function in patients with coronary artery disease (CAD) on double antiplatelet therapy. Blood from patients taking aspirin and clopidogrel and from normal volunteers was treated ex vivo with ARC1779 or abciximab, either prior to perfusion (pretherapy) or 10 minutes following the initiation of perfusion (posttherapy) on damaged arteries. Under pre- but not posttherapy, platelet adhesion was significantly reduced by ARC1779 at 83 and 250 nmol/L and by abciximab (100 nmol/L) versus placebo (4.8, 3.8, and 2.9 vs 7.3 platelets × 10(6)/cm(2), P < .05). In contrast to abciximab, ARC1779 did not significantly affect platelet aggregation, P-selectin expression, and platelet-leukocyte binding. These proof-of-concept data may constitute the framework for randomized clinical investigations of this novel antiplatelet therapy among patients with CAD.

Objectives: The purpose of this study was to determine whether the speed of response to clopidogrel loading predicts the final degree of response., Background: Fast inhibition of platelet aggregation is important in the setting of acute coronary syndromes and percutaneous coronary intervention, but its association with the final degree of inhibition is not well established., Methods: We performed a post hoc analysis of the ALBION study; early kinetic profiles of adenosine diphosphate 20 micromol/l maximal platelet aggregation (MPA) and DeltaMPA (with baseline sample as reference) were studied at 8 time points within the 24 h after clopidogrel loading (300, 600, or 900 mg) in non-ST-segment elevation acute coronary syndrome patients. Low response was defined as DeltaMPA <10% over the first 24 h, fast response as DeltaMPA > or =10% at 1 h or before loading (the others being slow responders), and high post-treatment platelet reactivity as MPA > or =56.56% (fourth quartile). Inflammatory markers (PAC-1 and P-selectin) and vasodilator-stimulated phosphoprotein (VASP) were also evaluated according to onset of action., Results: Fifty-five percent of patients were slow responders. Noncurrent smoking and body mass index > or =25 kg/m(2) were associated with slower and lower responses. High post-treatment platelet reactivity was more frequent in slow responders (28% vs. 14%, p < 0.0001). There was a clopidogrel dose-effect relationship on DeltaMPA, with a trend toward faster onset of platelet inhibition in the 900-mg loading dose group. Slow responders had a slower and lower decrease in PAC-1 and P-selectin and higher VASP index at 6 h (76.5% vs. 66.4%, p = 0.019) and 24 h (70.3% vs. 61.5%, p = 0.049)., Conclusions: Slow response to clopidogrel, within the first hour of administration, is a reliable marker of low response at 24 h and high post-treatment platelet reactivity., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The objective of this study was to compare the level of platelet inhibition achieved by 3 different clopidogrel loading regimens in patients undergoing elective angiography and percutaneous coronary intervention when appropriate., Background: Optimal platelet inhibition is a key therapeutic goal for patients undergoing percutaneous coronary intervention. Although 600 mg has been described as the maximum absorbed dose when given as a single bolus, the effects of 2 boluses given 24 h apart have not been described., Methods: Patients (n = 148) were randomly assigned to one of 3 regimens: Group A, clopidogrel 300 mg the day before (>or=15 h) + 75 mg the morning of the procedure; Group B, clopidogrel 600 mg the morning of the procedure (>or=2 h); and Group C, clopidogrel 600 mg the day before (>or=15 h) and 600 mg the morning of the procedure (>or=2 h). Blood samples were obtained at baseline and immediately before angiography. Peak and late platelet aggregation were measured in platelet rich plasma, with researchers blinded to treatment allocation., Results: There was a consistent difference favoring Group C in all aggregation parameters. Percent inhibition in Groups A, B, and C was 31.4%, 29.0%, and 49.5%, respectively, for peak aggregation (5 micromol/l adenosine diphosphate; p < 0.0001) and 54.1%, 57.7%, and 81.1%, respectively, for late aggregation (p < 0.0001). Similar striking reductions were observed when 20 micromol/l adenosine diphosphate was used. All comparisons between Group C and the other 2 groups were statistically significant, and those between Groups A and B were not., Conclusions: Clopidogrel 600-mg double bolus achieves greater platelet inhibition than conventional single loading doses.

Technological developments in percutaneous coronary interventions (PCI) allow the possibility for less invasive revascularization in an increasing number of patients with atherosclerotic coronary artery disease. Bare-metal stents (BMS) have considerably improved the efficacy of PCI in addition to greatly reducing restenosis. However, even with standard stents, restenosis has remained a significant limitation of this revascularization technique. The advent of drug-eluting stents (DES) has dramatically reduced in-stent restenosis and, as a result, the need for repeat revascularization. However, their potential thrombogenicity has raised concerns about their clinical utility and long-term safety. Indeed, there is a possible higher rate of late stent thrombosis (LST) with DES compared with BMS. Antiplatelet therapy has been shown to be efficient in preventing DES thrombosis. Nevertheless, in the future, significant improvement will occur to improve the safety and efficacy of this therapy. This article will summarize the pathophysiology and the epidemiology of stent thrombosis (ST). Definitions of definite, probable and possible ST will be described. Furthermore, clinical risk factors for ST will be clearly enumerated. Then, the various antiplatelet therapeutic strategies used to prevent ST will be taken in consideration. Finally, a summary of the major recommendations about antiplatelet therapy made by some of the most prestigious learned societies will be presented.

The use of drug-eluting stents (DESs) dramatically reduced in-stent restenosis. However, the increasing use of these stents has raised concern about their potential thrombogenicity. Indeed, the particularity of DES thrombosis compared with bare metal stent thrombosis is a high rate of late thrombosis. Antiplatelet therapy is efficient in preventing DES thrombosis. However, this therapy could be optimized and may be improved in the future. This article will review the mechanisms and the epidemiology of stent thrombosis. Then, we will summarize the antiplatelet therapeutic strategies used to prevent stent thrombosis and especially DES-associated thrombosis. Finally, we will present some data with regard to potential advantages and pitfalls in DES thrombosis prevention using novel antiplatelet agents currently under development, as well as future stent designs with improved healing properties.

Abstract: Objectives: Patients on antiplatelet therapy have a gastrointestinal bleeding risk. It is increased by risk factors. The frequency of those risk factors, the prevalence of upper digestive symptoms and their management in patients on antiplatelet agents is unknown. Patients and methods: We performed an observational multi-centred prospective survey among 560 French cardiologists with private practice. Each cardiologist completed a questionnaire for the first four patients treated with antiplatelet agents in primary or secondary prevention. Results: Among the 2182 patients included, (age=67±11 years; 74% male), 83% had at least one gastrointestinal bleeding risk factor and 38.9% had a history of upper digestive tract symptom. A history of gastrointestinal bleeding was reported in 3.4% and a history of documented gastro-duodenal ulcer in 5.5%. A proton pump inhibitor was already prescribed in 39% of the patients. At the time of the consultation, upper digestive symptoms were described in 21% of the patients. In those patients with symptoms, 85% had no modification in antiplatelet therapy and 62.7% were prescribed gastro-protective drugs (proton pump inhibitors: 51.8%, H2-blockers 3.6% other anti-acid medication: 7.3%). Conclusion: Among patients on antiplatelet agents, the prevalence of upper digestive symptoms and risk factors for gastrointestinal bleeding is high. Preventative management needs to be clarified in this population. [Copyright &y& Elsevier]