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Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease

Low‐dose aspirin as antiplatelet therapy is still the drug of choice for preventing cardiovascular events, but the protection aspirin gives to people at high risk of cardiovascular events is only relatively modest. This review of 28,165 people in two trials where clopidogrel was given in addition to antiplatelet treatment found that in patients with acute coronary syndromes the benefit ‐ a reduction in cardiovascular events ‐ outweighs the harm of major bleeding. However, clopidogrel plus aspirin has no clear positive risk‐benefit profile in people at high risk of cardiovascular events (multiple atherothrombotic risk factors) or in people with established cardiovascular disease (known coronary disease, ischemic cerebrovascular disease or peripheral arterial disease) but not presenting with an acute coronary syndrome, and the combination should not be prescribed routinely to prevent cardiovascular disease.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2011

Clopidogrel versus acetylsalicylic acid for the secondary prevention of vascular diseases: Executive Summary A04-01A

The aims of this evaluation were: - the comparative evaluation of the benefits and harms of clopidogrel and ASA as antiplatelet monotherapy for secondary prevention in patients with manifest ischaemic heart disease (IHD), ischaemic cerebrovascular disease (ICVD), or symptomatic peripheral arterial disease (PAD). and - the specific comparative evaluation of benefits and harms of a switch in therapy to clopidogrel versus continuation of existing ASA therapy for secondary prevention (as described above) in patients who had previously suffered an adverse event during ASA therapy (in particular a thromboembolic event or severe bleeding).

Institute for Quality and Efficiency in Health Care: Executive Summaries [Internet] - Institute for Quality and Efficiency in Health Care (IQWiG).

Version: October 4, 2006

Clopidogrel plus acetylsalicylic acid in acute coronary syndrome: Executive summary of final report A04-01B, Version 1.0

The aim of this research was to assess the benefit of clopidogrel plus ASA combination therapy versus ASA monotherapy in patients with acute coronary syndrome (acute coronary syndrome without ST-segment elevation [NSTE-ACS] or ST-segment elevation myocardial infarction [STEMI]). The focus of the assessment was on patient-relevant therapy goals.

Institute for Quality and Efficiency in Health Care: Executive Summaries [Internet] - Institute for Quality and Efficiency in Health Care (IQWiG).

Version: January 28, 2009

Systematic review in clopidogrel therapy coronary heart disease with chronic nephropathy

Bibliographic details: Zhang L, Zhai SD.  Systematic review in clopidogrel therapy coronary heart disease with chronic nephropathy. Chinese Pharmaceutical Journal 2010; 45(24): 1933-1939

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2010

Clopidogrel and Modified-Release Dipyridamole for the Prevention of Occlusive Vascular Events (Review of Technology Appraisal No. 90): A Systematic Review and Economic Analysis

Occlusive vascular events such as myocardial infarction (MI), ischaemic stroke and transient ischaemic attack (TIA) are the result of a reduction in blood flow associated with an artery becoming narrow or blocked through atherosclerosis and atherothrombosis. Peripheral arterial disease is the result of narrowing of the arteries that supply blood to the muscles and other tissues, usually in the lower extremities. The primary objective in the treatment of all patients with a history of occlusive vascular events and peripheral arterial disease is to prevent the occurrence of new occlusive vascular events.

Health Technology Assessment - NIHR Journals Library.

Version: September 2011
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Acute Upper Gastrointestinal Bleeding: Management

The incidence of acute upper gastrointestinal haemorrhage in the United Kingdom ranges between 84–172 /100,000/year, equating to 50–70,000 hospital admissions per year. This is therefore a relatively common medical emergency; it is also one that more often affects socially deprived communities.

NICE Clinical Guidelines - National Clinical Guideline Centre (UK).

Version: June 2012
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Impact of perioperative use of clopidogrel on coronary bypass grafting patients: a meta-analysis

Bibliographic details: Ma J, Xu WJ, Xu GP.  Impact of perioperative use of clopidogrel on coronary bypass grafting patients: a meta-analysis. Chinese Journal of Evidence-Based Medicine 2013; 13(7): 827-835

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Clopidogrel used in combination with aspirin compared with aspirin alone in the treatment of non-ST-segment-elevation acute coronary syndromes: a systematic review and economic evaluation

Most of the mortality and morbidity associated with non-ST-segment elevation acute coronary syndromes (ACS) arises from disruption of atheromatous plaques, followed by platelet aggregation and thrombus formation. Aspirin is the most commonly prescribed antiplatelet agent, which is known to reduce the risk of fatal and non-fatal myocardial infarction in patients with unstable angina. Clopidogrel, a different antiplatelet agent, inhibits platelet aggregation induced by adenosine diphosphate, thereby reducing ischaemic events. Combining clopidogrel with aspirin may therefore have an additive effect as each acts via a different inhibitory pathway.

NIHR Health Technology Assessment programme: Executive Summaries - NIHR Journals Library.

Version: 2004

Clinical effectiveness and cost-effectiveness of clopidogrel and modified-release dipyridamole in the secondary prevention of occlusive vascular events: a systematic review and economic evaluation

Eleven databases were searched for randomised clinical trials (RCTs) and reviews for the assessment of the clinical effectiveness and cost-effectiveness of clopidogrel and MR-dipyridamole. Additional searches were conducted in five databases for systematic reviews of side effects associated with aspirin treatment. A further MEDLINE search was carried out to identify economic costs related to heart disease in the UK.

NIHR Health Technology Assessment programme: Executive Summaries - NIHR Journals Library.

Version: 2004

The effect of different treatment durations of clopidogrel in patients with non-ST-segment elevation acute coronary syndromes: a systematic review and value of information analysis

Acute coronary syndrome (ACS) is a fissuring or rupturing of atheromatous plaques leading to occlusive thrombi in the arteries. Non-ST-elevation-ACS (NSTE-ACS) can be classified as unstable angina with undetectable markers but with electrocardiogram changes, or non-ST-elevation myocardial infarction (NSTEMI) where there is evidence of myocardial necrosis. Sixteen-year survival rates for men aged 50–59 years are 34% with a history of myocardial infarction (MI) and 53% with a history of angina, compared with 72% of those with no history of coronary disease. For patients with confirmed NSTE-ACS, UK guidelines recommend early treatment with antiplatelets, which are effective in preventing ischaemic vascular events in patients at increased risk. Guidance by the National Institute for Health and Clinical Excellence (NICE) in 2004 was based in part on a Technology Assessment Report undertaken by the Centre for Reviews and Dissemination (CRD) and the Centre for Health Economics (CHE), and published as a Health Technology Assessment (HTA) report (Main et al., 2004). The report presented the results of a systematic review assessing the clinical effectiveness and cost-effectiveness of clopidogrel in combination with aspirin for people with NSTE-ACS. Only one relevant trial was identified for inclusion in the systematic review [the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial]. For patients with NSTE-ACS at moderate to high risk of ischaemic events treated with clopidogrel, the NICE guidance recommended that it be given in combination with aspirin.

NIHR Health Technology Assessment programme: Executive Summaries - NIHR Journals Library.

Version: 2009

Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events (review of Technology Appraisal No. 90): a systematic review and economic analysis

Occlusive vascular events such as myocardial infarction (MI), ischaemic stroke and transient ischaemic attack (TIA) are the result of a reduction in blood flow associated with an artery becoming narrow or blocked through atherosclerosis and atherothrombosis. Peripheral arterial disease is the result of narrowing of the arteries that supply blood to the muscles and other tissues, usually in the lower extremities. Patients with symptomatic peripheral arterial disease (typically intermittent claudication) are at increased risk of experiencing an initial occlusive vascular event. Given the nature of the health problem, some people have multivascular disease, disease in more than one vascular bed, and appear to be at even greater risk of death, MI or stroke than those with disease in a single vascular bed. The primary objective in the treatment of all patients with a history of occlusive vascular events and peripheral arterial disease is to prevent the occurrence of new occlusive vascular events.

NIHR Health Technology Assessment programme: Executive Summaries - NIHR Journals Library.

Version: 2011

Safety of clopidogrel-proton pump inhibitors combination therapy on cardiovascular events: a systematic review

Bibliographic details: Kuang JY, Tan J, Zou JJ, Chen SL.  Safety of clopidogrel-proton pump inhibitors combination therapy on cardiovascular events: a systematic review. Chinese Journal of Evidence-Based Medicine 2011; 11(3): 283-291 Available from: http://www.cjebm.org.cn/oa/DArticle.aspx?type=view&id=201103009

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Correlation between the genetic polymorphism of CYP2C19*2, *3 and the clinical efficacy of clopidogrel: a systematic review

Bibliographic details: Yang LP, Xie J, Liu Y, Hu X.  Correlation between the genetic polymorphism of CYP2C19*2, *3 and the clinical efficacy of clopidogrel: a systematic review. Chinese Journal of Evidence-Based Medicine 2012; 12(9): 1063-1070 Available from: http://www.cjebm.org.cn/en/oa/DArticle.aspx?type=view&id=201209006

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

Branded versus generic clopidogrel in cardiovascular diseases: a systematic review

In the United States, patent for branded Plavix has recently expired. Some studies have compared branded and generic clopidogrel in terms of pharmacokinetic parameters in healthy volunteers, but data on patients and clinical outcomes are scarce. We aimed to review efficacy and safety data from studies comparing Plavix with generic clopidogrel in patients with cardiovascular disease. Electronic databases were searched (from inception to May 2012) for prospective studies evaluating branded versus generic clopidogrel in patients with cardiovascular diseases. Studies' characteristics and data estimates were retrieved. Pooled risk ratio (RR) and 95% confidence intervals (95% CIs) were estimated through a random-effects model. Three studies evaluating 760 patients were included: 2 randomized controlled trials and 1 cohort study. The RR for major cardiovascular events was 1.01 (95% CI, 0.67-1.52). Incidence of adverse events was similar between Plavix and generic (RR 0.85; 95% CI, 0.49-1.48). The risks of mortality, bleeding, and drug discontinuation were also not different between groups. There are a limited number of studies comparing Plavix and generic clopidogrel in patients with cardiovascular diseases and reporting hard clinical end points. The available evidence is therefore limited and does not support the existence of differences in efficacy or safety between branded and generic clopidogrel.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Dual antiplatelet therapy with aspirin and clopidogrel: what is the risk in noncardiac surgery? A narrative review

Clopidogrel is one of the most commonly prescribed medications and is currently recommended along with aspirin as treatment to be used for 1 year in all patients without contraindications following an acute coronary syndrome. Patients who are committed to clopidogrel therapy due to recent coronary artery stent implantation may require noncardiac surgery during this recommended period of dual antiplatelet therapy (DAPT). Due to differing rates of endothelialization, patients who undergo bare-metal stent implantation generally require ≥ 1 month of uninterrupted DAPT, and those who undergo drug-eluting stent implantation require ≥ 12 months. Many surgeons ask their patients to stop taking clopidogrel in advance of their procedure to decrease perioperative bleeding. This practice is based largely on anecdotal experience and extrapolated from limited data in cardiac surgery. Premature cessation of aspirin and/or clopidogrel following coronary artery stenting, however, has been associated with acute stent thrombosis, myocardial infarction, and death. We searched PubMed for English language articles published from 1960 to 2012, using the keywords aspirin, clopidogrel, surgery, general, vascular, genitourinary, thoracic, orthopedic, ophthalmologic, dermatologic, endoscopy, colonoscopy, cardiac device implantation, pacemaker, defibrillator, bronchoscopy, bridging, bleeding complications, and transfusion, including various combinations. s were reviewed to confirm relevance, and then the full articles were extracted. References from extracted articles were also reviewed for relevant articles. Literature regarding perioperative clopidogrel continuation is predominantly composed of small, nonrandomized data, but suggests that most noncardiac surgeries or procedures can be performed safely while patients are taking clopidogrel. In this article, we review the current best evidence on the risk for bleeding with clopidogrel therapy in noncardiac surgery, summarize recent guidelines on appropriate duration of DAPT, and make recommendations on the management of perioperative DAPT.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

The efficacy and adverse reaction of bleeding of clopidogrel plus aspirin as compared to aspirin alone after stroke or TIA: a systematic review

BACKGROUND AND PURPOSE: Given the high risk of stroke after TIA (transient ischemia attack) or stroke and the adverse reaction of bleeding of antiplatelets, we undertook a meta-analysis, reviewed randomized controlled trials (RCTs) comparing aspirin plus clopidogrel with aspirin alone to determine the efficacy and adverse reaction of bleeding of the two protocols in the prevention of stroke.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

CYP2C19 genotype has a greater effect on adverse cardiovascular outcomes following PCI and in Asian populations treated with clopidogrel: a meta-analysis

BACKGROUND: The degree to which cytochrome P450 (CYP) 2C19 genotype influences the effectiveness of clopidogrel remains uncertain because of considerable heterogeneity in results between studies and potential publication bias. Clopidogrel indication and ethnic population have been proposed to influence the effect of CYP2C19 genotype.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

No consistent evidence of differential cardiovascular risk amongst proton-pump inhibitors when used with clopidogrel: meta-analysis

BACKGROUND: Data from pharmacokinetic and pharmacodynamic studies indicate that the adverse clopidogrel-proton pump inhibitor (PPI) interaction may vary between PPIs, with pantoprazole considered relatively less problematic. We aimed to evaluate systematically whether individual PPIs differ in their risk for cardiovascular events when concomitantly administered with clopidogrel.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Effects of proton pump inhibitors on platelet function in patients receiving clopidogrel: A systematic review.

BACKGROUND: There is considerable debate regarding the negative impact of concomitant proton pump inhibitor (PPI) therapy on the antiplatelet efficacy of clopidogrel.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

Meta-analysis: colonoscopic post-polypectomy bleeding in patients on continued clopidogrel therapy

BACKGROUND: Current guidelines recommend the cessation of clopidogrel therapy 5 days and 7-10 days prior to colonoscopic polypectomy. Recent studies have advocated for continued clopidogrel as post-polypectomy bleeding (PPB) rates have been similar to those in the general population not on antithrombotic therapy.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

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