Dose Comparisons of Clopidogrel and Aspirin in Acute Coronary Syndromes

Mehta, Rajendra H.; Bassand, Jean‐Pierre; Dı́az, Rafael; Latinoamérica, Estudios Clinicos; Eikelboom, John W.; Granger, Christopher B.; Jolly, Sanjit S.; Univer, McMaster; Joyner, Campbell; Afzal, Rizwan; Yusuf, Salim

doi:10.1056/nejmoa0909475

Cited by 658 publications

(101 citation statements)

References 34 publications

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“…The AG agrees with the manufacturer's conclusion that the results from the overall population of the CURRENT-OASIS 7 45 trial do not appear to support the use of a 600-mg loading dose of clopidogrel over a 300-mg dose. However, the AG considers that the results of the subgroup analysis 45 of the 69% (17,263) of patients treated with PCI suggest that the trial protocol clopidogrel regimen of a 600-mg loading dose followed by 7 days at 150 mg and then 75 mg daily statistically significantly reduces CV events (including stent thrombosis) when compared with a loading dose of 300 mg followed by 75 mg daily.…”

Section: Assessment Group Commentssupporting

confidence: 76%

“…The Scottish Intercollegiate Guidelines Network (SIGN) 43 guidelines recommend the use of a 300-mg loading dose, whereas the European Society for Cardiology (ESC) advocates both 300-mg and 600-mg loading doses. 10,11,44 The manufacturer states that the case for the additional benefit of 600 mg rather than 300 mg is not proven and cites the results of the CURRENT-OASIS (Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events-Seventh Organization to Assess Strategies in Ischemic Syndromes 7) 45 trial, published in 2010. In this trial, patients with ACS (n = 25,806) who were scheduled for early angiography and PCI were randomised to receive a loading dose of 300 mg or 600 mg of clopidogrel and either high-or low-dose aspirin.…”

Section: Manufacturer Commentsmentioning

confidence: 99%

“…The manufacturer concludes that the results of the overall CURRENT-OASIS 45 trial do not demonstrate any clear benefit associated with the use of a 600-mg loading dose of clopidogrel compared with a 300-mg dose and thus it is unlikely that the use of 600 mg of clopidogrel in the TRITON-TIMI 38 36 trial would have changed the efficacy results, although it may have resulted in an increase in the number of bleeding events in the clopidogrel arm.…”

Section: Manufacturer Commentsmentioning

confidence: 99%

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Prasugrel (Efient®) with percutaneous coronary intervention for treating acute coronary syndromes (review of TA182): systematic review and economic analysis

Greenhalgh

Bagust

Boland

et al. 2015

Health Technology Assessment

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BackgroundAcute coronary syndromes (ACSs) are life-threatening conditions associated with acute myocardial ischaemia. There are three main types of ACS: ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI) and unstable angina (UA). One treatment for ACS is percutaneous coronary intervention (PCI) plus adjunctive treatment with antiplatelet drugs. Dual therapy antiplatelet treatment [aspirin plus either prasugrel (Efient®, Daiichi Sankyo Company Ltd UK/Eli Lilly and Company Ltd), clopidogrel or ticagrelor (Brilique®, AstraZeneca)] is standard in UK clinical practice. Prasugrel is the focus of this review.ObjectivesThe remit is to appraise the clinical effectiveness and cost-effectiveness of prasugrel within its licensed indication for the treatment of ACS with PCI and is a review of National Institute for Health and Care Excellence technology appraisal TA182.Data sourcesFour electronic databases (MEDLINE, EMBASE, The Cochrane Library, PubMed) were searched from database inception to June 2013 for randomised controlled trials (RCTs) and to August 2013 for economic evaluations comparing prasugrel with clopidogrel or ticagrelor in ACS patients undergoing PCI.MethodsClinical outcomes included non-fatal and fatal cardiovascular (CV) events, adverse effects of treatment and health-related quality of life (HRQoL). Cost-effectiveness outcomes included incremental cost per life-year gained and incremental cost per quality-adjusted life-year (QALY) gained. An independent economic model assessed four mutually exclusive subgroups: ACS patients treated with PCI for STEMI and with and without diabetes mellitus and ACS patients treated with PCI for UA or NSTEMI and with and without diabetes mellitus.ResultsNo new RCTs were identified beyond that reported in TA182. TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel Thrombolysis in Myocardial Infarction 38) compared prasugrel with clopidogrel in ACS patients scheduled for PCI. No relevant economic evaluations were identified. Our analyses focused on a key subgroup of patients: those aged < 75 years who weighed > 60 kg (no previous stroke or transient ischaemic attack). For the primary composite end point (death from CV causes, non-fatal myocardial infarction or non-fatal stroke) statistically significantly fewer events occurred in the prasugrel arm (8.3%) than in the clopidogrel arm (11%). No statistically significant difference in major bleeding events was noted. However, there was a significant difference in favour of clopidogrel when major and minor bleeding events were combined (3.0 vs. 3.9%). No conclusions could be drawn regarding HRQoL. The results of sensitivity analyses confirmed that it is likely that, for all four ACS subgroups, within 5–10 years prasugrel is a cost-effective treatment option compared with clopidogrel at a willingness-to-pay threshold of £20,000 to £30,000 per QALY gained. At the full 40-year time horizon, all estimates are < £10,000 per QALY gained.LimitationsLack of data precluded a clinical comparison of prasugrel with ticagrelor; the comparative effectiveness of prasugrel compared with ticagrelor therefore remains unknown. The long-term modelling exercise is vulnerable to major assumptions about the continuation of early health outcome gains.ConclusionA key strength of the review is that it demonstrates the cost-effectiveness of prasugrel compared with clopidogrel using the generic price of clopidogrel. Although the report demonstrates the cost-effectiveness of prasugrel compared with clopidogrel at a threshold of £20,000 to £30,000 per QALY gained, the long-term modelling is vulnerable to major assumptions regarding long-term gains. Lack of data precluded a clinical comparison of prasugrel with ticagrelor; the comparative effectiveness of prasugrel compared with ticagrelor therefore remains unknown. Well-audited data are needed from a long-term UK clinical registry on defined ACS patient groups treated with PCI who receive prasugrel, ticagrelor and clopidogrel.Study registrationThis study is registered as PROSPERO CRD42013005047.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Section: Assessment Group Commentssupporting

confidence: 76%

Section: Manufacturer Commentsmentioning

confidence: 99%

Section: Manufacturer Commentsmentioning

confidence: 99%

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Prasugrel (Efient®) with percutaneous coronary intervention for treating acute coronary syndromes (review of TA182): systematic review and economic analysis

Greenhalgh

Bagust

Boland

et al. 2015

Health Technology Assessment

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“…The recorded side effects included severe bleeding (intracranial haemorrhage or gastrointestinal bleeding, haemoptysis-associated unstable circulation, haemoglobin decreased by ≥ 5 g/dL, or haematocrit decreased by ≥ 15%), moderate bleeding (amount of haemoptysis or haematemesis ≥ 100 mL/d, melena, and/or gross haematuria), and mild bleeding (amount of haemoptysis or haematemesis < 100 mL/d, haematoma at the puncture site, skin ecchymosis, mucosal and gingival bleeding, or microscopic haematuria). The post-PCI infarction-related arterial Thrombolysis in Myocardial Infarction (TIMI) flow grade and TIMI myocardial perfusion grade (TMPG) were also recorded [11][12][13]. The judgment criteria for the TIMI flow grade and TMPG were the same as those used by Chesebro et al [11] and Liu et al [12], respectively.…”

Section: Outcome Indexesmentioning

confidence: 99%

Short-term efficacy and safety of three different antiplatelet regimens in diabetic patients treated with primary percutaneous coronary intervention: a randomised study

Liu¹,

Liu

Hao

et al. 2017

Kardiol Pol

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A b s t r a c t Background and aim:This study aimed to investigate the efficacy and safety of dual and triple antiplatelet therapy (DAPT and TAPT) in patients with diabetes and acute ST segment elevation myocardial infarction (D-STEMI), who had undergone primary percutaneous coronary intervention (PCI). Methods:We designed a phase IV, single-centre, randomised, double-blind, placebo-controlled study. The D-STEMI patients (n = 258) were randomly divided into three groups. Control group A (85 patients), was treated with aspirin and clopidogrel; group B (87 patients) received aspirin, clopidogrel, and tirofiban; and group C (86 patients) were treated with aspirin, ticagrelor, and tirofiban. Patients in all three groups received oral DAPT, and patients in groups B and C received intravenous tirofiban when primary PCI was performed.Results: Compared to the findings in group A, the post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow in groups B and C increased significantly (TIMI grade 3 in groups A, B, C: 74%, 91%, and 98%, respectively; TIMI myocardial perfusion grade [TMPG] grade 3 in groups A, B, C: 59%, 86%, and 97%, respectively), and the incidence of major adverse cardiac events (MACE) decreased significantly (p < 0.05). Compared to the findings in group B, the rate of TMPG 3 in group C was significantly higher (p < 0.05) and the incidence of MACE was significantly lower (p < 0.05). Patients in group B exhibited minor bleeding; however, the incidence of mild to moderate bleeding in group C increased significantly (p < 0.05).Conclusions: TAPT effectively improved the TIMI blood flow and TMPG and reduced the occurrence of MACE. Ticagrelor was more effective than clopidogrel in TAPT; however, when using the combination of aspirin, ticagrelor, and tirofiban, close monitoring is required for possible bleeding complications.

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“…Optimal medical therapy with antiplatelet drugs, statins, and other guideline‐recommended therapies3, 4, 5, 6, 7, 8, 9, 10 are of paramount importance in preventing recurrent cardiovascular events in patients after an ACS 11. In addition, other strategies for risk‐factor modification and lifestyle changes such as diet, cardiac rehabilitation, exercise, and smoking cessation reduce the rate of recurrent cardiovascular events 12, 13, 14.…”

Section: Introductionmentioning

confidence: 99%

Guideline‐Recommended Therapies and Clinical Outcomes According to the Risk for Recurrent Cardiovascular Events After an Acute Coronary Syndrome

Hammer

Iakobishvili

Hasdai

et al. 2018

JAHA

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BackgroundPatients who have had an acute coronary syndrome (ACS) are at increased risk of recurrent cardiovascular events; however, paradoxically, high‐risk patients who may derive the greatest benefit from guideline‐recommended therapies are often undertreated. The aim of our study was to examine the management, clinical outcomes, and temporal trends of patients after ACS stratified by the Thrombolysis in Myocardial Infarction (TIMI) risk score for secondary prevention, a recently validated clinical tool that incorporates 9 clinical risk factors.Methods and ResultsIncluded were patients with ACS enrolled in the biennial Acute Coronary Syndrome Israeli Surveys (ACSIS) between 2008 and 2016. Patients were stratified by the TIMI risk score for secondary prevention to low (score 0–1), intermediate (2), or high (≥3) risk. Clinical outcomes included 30‐day major adverse cardiac events (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularization) and 1‐year mortality. Of 6827 ACS patients enrolled, 35% were low risk, 27% were intermediate risk, and 38% were high risk. Compared with the other risk groups, high‐risk patients were older, were more commonly female, and had more renal dysfunction and heart failure (P<0.001 for each). High‐risk patients were treated less commonly with guideline‐recommended therapies during hospitalization (percutaneous coronary intervention) and at discharge (statins, dual‐antiplatelet therapy, cardiac rehabilitation). Overall, high‐risk patients had higher rates of 30‐day major adverse cardiac events (7.2% low, 8.2% intermediate, and 15.1% high risk; P<0.001) and 1‐year mortality (1.9%, 4.6%, and 15.8%, respectively; P<0.001). Over the past decade, utilization of guideline‐recommended therapies has increased among all risk groups; however, the rate of 30‐day major adverse cardiac events has significantly decreased among patients at high risk but not among patients at low and intermediate risk. Similarly, the 1‐year mortality rate has decreased numerically only among high‐risk patients.ConclusionsDespite an improvement in the management of high‐risk ACS patients, they are still undertreated with guideline‐recommended therapies. Nevertheless, the outcome of high‐risk patients after ACS has significantly improved in the past decade, thus they should not be denied these therapies.

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Dose Comparisons of Clopidogrel and Aspirin in Acute Coronary Syndromes

Cited by 658 publications

References 34 publications

Prasugrel (Efient®) with percutaneous coronary intervention for treating acute coronary syndromes (review of TA182): systematic review and economic analysis

Prasugrel (Efient®) with percutaneous coronary intervention for treating acute coronary syndromes (review of TA182): systematic review and economic analysis

Short-term efficacy and safety of three different antiplatelet regimens in diabetic patients treated with primary percutaneous coronary intervention: a randomised study

Guideline‐Recommended Therapies and Clinical Outcomes According to the Risk for Recurrent Cardiovascular Events After an Acute Coronary Syndrome

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