Prasugrel versus clopidogrel for patients with unstable angina or non-ST-segment elevation myocardial infarction with or without angiography: a secondary, prespecified analysis of the TRILOGY ACS trial

Wiviott, Stephen D.; White, Harvey D.; Ohman, E. Magnus; Fox, Keith A.A.; Armstrong, Paul W.; Prabhakaran, Dorairaj; Hafley, Gail E.; Lokhnygina, Yuliya; Boden, William E.; Hamm, Christian W.; Clemmensen, Peter; Nicolau, José Carlos; Menozzi, Alberto; Rużyłło, Witold; Widimský, Petr; Oto, Ali̇; Leiva-Pons, José L.; Pavlides, Gregory; Winters, Kenneth J.; Roe, Matthew T.; Bhatt, Deepak L.

doi:10.1016/s0140-6736(13)61451-8

Cited by 103 publications

(60 citation statements)

References 26 publications

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“…34 In addition, prasugrel reduced ischemic events in patients with angiographically confirmed-CAD (10.7% vs. 14.9%, HR 0.77, 95% CI 0.61-0.98; P=0.032) but not in patients who did not undergo coronary angiography (16.3% vs. 16.7%, HR 1.01, 95% CI, 0.84-1.20; P=0.94; P for interaction=0.08). 35 Rates of severe and intracranial bleeding were similar between groups. DM patients showed a higher event rate irrespective of treatment group (17.8% in prasugrel group vs. 20.4% in clopidogrel group) than non-DM patients (11.5% in prasugrel group vs. 13.2% in clopidogrel group).…”

Section: Park Y Et Almentioning

confidence: 83%

Antithrombotic Therapy for Secondary Prevention in Patients With Diabetes Mellitus and Coronary Artery Disease

Park

Franchi

Rollini

et al. 2016

Circ J

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Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp itor clopidogrel, which has represented the mainstay of treatment for many years, has significantly reduced the incidence of recurrent atherothrombotic events. 3 However, recurrence rates in DM patients still remain high despite this treatment regimen, which may be partly related to inadequate platelet inhibition induced by standard DAPT with aspirin and clopidogrel. 4-6 This underpins the need for more potent antithrombotic regimens for secondary prevention of atherothrombotic events in DM patients following an ACS or PCI. 2 This review article encompasses the most recent updates and pitfalls of oral antithrombotic therapies for secondary prevention of DM patients following ACS/PCI. Prothrombotic Milieu in DMMultiple factors contribute to the prothrombotic status of DM patients, which plays a pivotal role in the initiation and progression of atherothrombosis. 1,2 Among them, hyperreactive platelets undermine the integrity of vascular homeostasis and iabetes mellitus (DM) is a pandemic public health burden with a prevalence of 346 million patients worldwide. 1 Importantly, DM patients have a 3-fold higher risk of coronary artery disease (CAD), 5-fold higher cardiovascular (CV) mortality and 3-fold higher all-cause mortality than non-DM patients. 1 Moreover, DM is a key determinant of recurrent CV events in patients with acute coronary syndrome (ACS) or those undergoing percutaneous coronary intervention (PCI). 1 These observations suggest the need for DM-specific therapeutic regimens. Multiple factors, such as hyperglycemia, oxidative stress, endothelial dysfunction, platelet dysfunction and abnormal coagulation factors, contribute to the prothrombotic milieu that characterizes DM patients and thus to the high prevalence of cardiovascular disease (CVD) manifestations in this patient population. 2 These observations underscore the need for effective oral antithrombotic treatment regimens for secondary prevention of atherothrombotic events, particularly after ACS and/or PCI. Indeed, dual antiplatelet therapy (DAPT) with aspirin and the P2Y12 inhib- Diabetes mellitus (DM) is a key risk factor for recurrent atherothrombotic events in patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention (PCI). The prothrombotic milieu that characterizes patients with DM underscores the importance of oral antithrombotic therapy for secondary prevention of recurrent events in these patients. Indeed, dual antiplatelet therapy (DAPT) with aspirin and the P2Y12 inhibitor clopidogrel, which has represented the mainstay of treatment for many years, has significantly reduced the incidence of recurrent atherothrombotic events. However, recurrence rates in DM patients still remain high despite this treatment regimen, which may be partly related to inadequate platelet inhibition induced by standard DAPT with aspirin and clopidogrel. This underpins the need for more potent antithrombotic treatment re...

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Section: Park Y Et Almentioning

confidence: 83%

Antithrombotic Therapy for Secondary Prevention in Patients With Diabetes Mellitus and Coronary Artery Disease

Park

Franchi

Rollini

et al. 2016

Circ J

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“…In the TaRgeted Platelet Inhibition to CLarify the Optimal StrateGy to MedicallY Manage ACS (TRILOGY ACS) study, medically-managed patients with non-ST-segmentelevation ACS were treated with prasugrel or clopidogrel on a background of aspirin for up to 30 months. 25 In a prespecified analysis, the subgroup of patients in TRILOGY ACS who underwent coronary angiography before randomization 26 had a greater reduction in ischemic events, including both cardiovascular death and MI, through 30 months without an increase in major bleeding with long-term prasugrel compared with clopidogrel, even though few patients underwent coronary revascularization. Thus, outcomes in both TRITON TIMI 38 and the angiographic subgroup of TRILOGY ACS suggest that more potent inhibition of platelet activation during maintenance dosing with prasugrel compared with clopidogrel confers benefit in patients with angiographically confirmed coronary artery disease.…”

Section: Discussionmentioning

confidence: 99%

Prasugrel Plus Aspirin Beyond 12 Months Is Associated With Improved Outcomes After Taxus Liberté Paclitaxel-Eluting Coronary Stent Placement

et al. 2015

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T he TAXUS Liberté Post Approval Study (TL-PAS) is a prospective, multicenter, open-label study developed to review clinical performance of the TAXUS Liberté paclitaxel-eluting coronary stent (PES) in routine clinical practice in the United States. The TAXUS Liberté PES is a secondgeneration PES produced by Boston Scientific Corporation (Marlborough, MA), designed to ease stent placement and enhance drug delivery through use of a lower mass 316 L stainless steel stent (97 μm thickness) with a novel strut configuration; the polymer compound and paclitaxel formulation were unchanged from those used in the first generation TAXUS Express 2 PES. 1,2 The principal objective of TL-PAS was to fulfill United States (US) Food and Drug Administration (FDA) requirements for surveillance of drug-eluting stent (DES) performance after commercial release. As TL-PAS was being developed, the Dual Anti-Platelet Therapy (DAPT) Study was organized.3 The DAPT Study is a multi-center, randomized, double-blind, placebo-controlled trial comparing dual antiplatelet therapy for 12 versus 30 months after DES placement. FDA had requested that US stent manufacturers provide

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“…11,12 In the prespecified angiographic substudy of the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY-ACS) substudy, treatment effect diverged significantly after 12 months in favor of prasugrel without a significant excess of major bleeding in this medically managed non--ST-segment--elevation acute coronary syndrome population. Reaching the optimal net clinical benefit by fine-tuning the potency and duration of DAPT is a key step to further improve outcomes after DES.…”

Section: Article See P 62mentioning

confidence: 99%

“…Avoidance of spontaneous myocardial infarction is a clear advantage of prolonged DAPT as demonstrated with clopidogrel versus placebo 11 and more recently with prasugrel versus clopidogrel when coronary artery disease is characterized angiographically. 11,12 In the prespecified angiographic substudy of the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY-ACS) substudy, treatment effect diverged significantly after 12 months in favor of prasugrel without a significant excess of major bleeding in this medically managed non--ST-segment--elevation acute coronary syndrome population.…”

Section: Article See P 62mentioning

confidence: 99%

Long-Term Secondary Prevention After High-Risk Stenting

Collet¹,

Silvain²,

Montalescot³

2015

Circulation

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Editorial 13D ual antiplatelet therapy (DAPT), the combination of aspirin and an inhibitor of the platelet P2Y 12 receptor, is the foundation to prevent acute stent thrombosis (ST), the sudden thrombotic coronary occlusion that can lead to myocardial infarction or death in one third of patients. 1 The appropriate duration of DAPT in patients who have received coronary stents is an important dilemma for interventional cardiologists and a daily concern. We have entered the third decade of coronary stent implantation, the dominant strategy for myocardial revascularization, without clear guidance on the duration of DAPT.2 Professional guidelines are not entirely consistent, recommending extension of DAPT up to 6 months after implantation of a second-generation drug-eluting stent (DES) 3 or at least 12 months after implantation of a DES unless patients are at high risk for bleeding. 4 None of these guidelines recommend long-term or lifelong DAPT. The current discrepancies may reflect either a different interpretation of the data by experts of the guideline committees or, more likely, an active area of clinical investigation in which early certainties about DAPT duration after coronary stenting are being challenged. Article see p 62So far, 12 randomized, interruption studies investigating various durations of DAPT, whether short, intermediate, or prolonged (≥2 years), have been conducted (Figure). All published randomized trials to date (n>19 000) indicate no benefit of extended DAPT with clopidogrel beyond 6 or 12 months after DES but harm, 5 suggesting that the pendulum has swung back toward short DAPT duration (Table). The lack of power for important safety end points such as death, major bleeding, or ST is a common limitation of these trials. In addition, 1 randomized trial 6 and 2 registries 7,8 suggest that DAPT duration should be device specific, further adding complexity to this unresolved issue. Finally, most of the evidence has been obtained with clopidogrel, whereas more potent P2Y 12 inhibitors such as ticagrelor and prasugrel have demonstrated superiority over clopidogrel in reducing spontaneous myocardial infarction and ST after stenting.Long-term DAPT of 6 to 12 months has been recommended 9 to overcome the susceptibility of first-generation DES to ST, accounted for mainly by delayed endothelialization and polymer hypersensitivity.10 There was no randomized evidence to support this endorsement for the approved devices. The 2014 European myocardial revascularization guidelines recommend 6 months of DAPT after implantation of a new-generation DES on the basis of randomized trials demonstrating enhanced safety and effectiveness with these devices compared with their earlier counterparts.2 An even shorter duration may be used when there is a high risk of bleeding. These guidelines refer only to new-generation DES. The same guidelines also specify that DAPT may be used beyond 6 months in patients at high ischemic risk and low bleeding risk, further recognizing that prolonged DAPT may be useful and that opt...

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Prasugrel versus clopidogrel for patients with unstable angina or non-ST-segment elevation myocardial infarction with or without angiography: a secondary, prespecified analysis of the TRILOGY ACS trial

Cited by 103 publications

References 26 publications

Antithrombotic Therapy for Secondary Prevention in Patients With Diabetes Mellitus and Coronary Artery Disease

Antithrombotic Therapy for Secondary Prevention in Patients With Diabetes Mellitus and Coronary Artery Disease

Prasugrel Plus Aspirin Beyond 12 Months Is Associated With Improved Outcomes After Taxus Liberté Paclitaxel-Eluting Coronary Stent Placement

Long-Term Secondary Prevention After High-Risk Stenting

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