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Prasugrel for acute coronary syndrome: Executive summary of final report A09-02, Version 1.0

The aim of this investigation was to assess the benefit of combination therapy comprising prasugrel plus ASA in patients with ACS undergoing primary or delayed PCI. In patients with unstable angina /NSTEMI the assessment was to be conducted in comparison with combination therapy comprising clopidogrel plus ASA, or with monotherapy comprising ASA with or without prior dual antiplatelet therapy. The focus of the assessment was on patient-relevant outcomes. Due to the approval status of clopidogrel, in patients with STEMI the assessment was only to be performed versus ASA monotherapy. The results were to be analysed separately for patients with unstable angina /NSTEMI and those with STEMI.

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

Version: July 11, 2011

Comparing newer oral anti-platelets prasugrel and ticagrelor in reduction of ischemic events – evidence from a network meta-analysis

The two newer antiplatelet drugs, prasugrel and ticagrelor have both been incorporated in various national guidelines and are both under consideration for approval or have already been approved by various drug regulatory authorities. Mortality benefits with clopidogrel were comparable to newer anti-platelets, and prasugrel had great anti-ischemic potency than ticagrelor. We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials' databases for randomized controlled trials conducted between 1990 and 2012 that assessed clinical outcomes with prasugrel or ticagrelor. The comparator was standard dosage of clopidogrel. Outcomes assessed were the risk of all causes mortality, TIMI non-CABG major bleeding, and a composite of stent thrombosis, recurrent ischemia and serious recurrent ischemia in the intervention groups versus the comparator groups. Event rates were compared using a forest plot of relative risk using a random effects model (Mantel-Haenszel); and Odd's ratio was calculated in the absence of significant heterogeneity. Prasugrel was indirectly compared with ticagrelor using network meta-analysis. Four studies (total N = 34,126) met the inclusion/exclusion criteria. Both drugs had improved mortality and greater risk of bleeding compared to clopidogrel; but outcomes were comparable for both (p = NS). However a composite of recurrent ischemic events, including rates of stent thrombosis (p = 0.045) was reduced to a modest degree with prasugrel compared with ticagrelor. This systematic review suggests greater clinical efficacy of both prasugrel and ticagrelor compared with clopidogrel and an indirect comparison indicates prasugrel may be more effective than ticagrelor for preventing stent thrombosis and recurrent ischemic events.

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

Version: 2013

Adjusted indirect comparison meta-analysis of prasugrel versus ticagrelor for patients with acute coronary syndromes

The review found that the antithrombotic drugs prasugrel and ticagrelor seemed have similar efficacy and safety for acute coronary syndrome and that both were superior to clopidogrel. Given limitations in the review process, the limited search, failure to report trial quality, the small number of included trials, and questionable use of indirect comparisons, these conclusions should be regarded with caution.

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

Version: 2011

Network meta-analysis of prasugrel, ticagrelor, high- and standard-dose clopidogrel in patients scheduled for percutaneous coronary interventions

This review found potentially relevant differences in efficacy and bleeding risk between antiplatelet drugs prasugrel, ticagrelor and high-dose clopidogrel in patients undergoing percutaneous coronary interventions, but that these conclusions were not definitive as they were not based on direct comparisons of treatments. Despite some limitations, the authors' conclusions reflect the evidence and are likely to be reliable.

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

Version: 2012

Comparing Newer Antiplatelet Agents

How do antiplatelet agents compare in acute coronary syndromes managed medically?

PubMed Clinical Q&A [Internet] - National Center for Biotechnology Information (US).

Version: November 10, 2011

Drug Class Review: Newer Antiplatelet Agents: Final Update 2 Report [Internet]

We compared the effectiveness and harms of clopidogrel, ticlopidine, extended-release dipyridamole and aspirin and prasugrel in adults with acute coronary syndromes or coronary revascularization (stenting, bypass grafting), ischemic stroke or transient ischemic attack, or symptomatic peripheral vascular disease.

Drug Class Reviews - Oregon Health & Science University.

Version: June 2011
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Treatment Strategies for Patients With Peripheral Artery Disease [Internet]

For patients with peripheral artery disease (PAD), the optimal treatment for cardiovascular protection, symptom relief, preservation of walking and functional status, and prevention of amputation is not known. This review assessed the comparative effectiveness of antiplatelet therapy, medical therapy, exercise, and endovascular and surgical revascularization in PAD patients with intermittent claudication (IC) or critical limb ischemia (CLI).

Comparative Effectiveness Reviews - Agency for Healthcare Research and Quality (US).

Version: May 2013
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Pharmacologic and Mechanical Prophylaxis of Venous Thromboembolism Among Special Populations [Internet]

Venous thromboembolism (VTE) is a prevalent and avoidable complication of hospitalization. Patients hospitalized with trauma, traumatic brain injury, burns, or liver disease; patients on antiplatelet therapy; obese or underweight patients; those having obesity surgery; or with acute or chronic renal failure have unequal risks for bleeding and thrombosis and may benefit differently from prophylactic therapy medication.

Comparative Effectiveness Reviews - Agency for Healthcare Research and Quality (US).

Version: May 2013
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Dyspnea and reversibility profile of P2Y12 antagonists: systematic review of new antiplatelet drugs

BACKGROUND: Dyspnea has been consecutively reported in some trials evaluating new P2Y12 inhibitors.

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

Version: 2014

Impact of clopidogrel and potent P2Y12-inhibitors on mortality and stroke in patients with acute coronary syndrome or undergoing percutaneous coronary intervention: a systematic review and meta-analysis

This review concluded that higher potency P2Y12-receptor inhibition (using prasugrel/tricagrelor anticoagulants) was associated with decreased risk of cardiovascular death and myocardial infarction, but not stroke, compared with clopidogrel. Given the unknown risk of bias of the included trials, the substantial clinical variability across the trials, and concerns about the analysis, the authors' conclusions should be treated with caution.

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

Version: 2013

Effect of smoking on comparative efficacy of antiplatelet agents: systematic review, meta-analysis, and indirect comparison

This review concluded that the efficacy of antiplatelets differed for smokers and nonsmokers, with the benefit occurring mostly for smokers and less so for nonsmokers. The review did not evaluate adverse events, so the risk-benefit profiles of the drugs are unknown, and the usefulness of the results for informing clinical practice is limited.

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

Version: 2013

Impact of new oral or intravenous P2Y12 inhibitors and clopidogrel on major ischemic and bleeding events in patients with coronary artery disease: a meta-analysis of randomized trials

OBJECTIVE: New P2Y12 inhibitors can be classified as oral (prasugrel and ticagrelor) and intravenous drugs (cangrelor and elinogrel). These P2Y12 inhibitors might be superior to clopidogrel for reducing ischemic events in patients with coronary artery disease (CAD). We performed a meta-analysis of randomized trials that compared new oral or intravenous P2Y12 inhibitors with clopidogrel to determine their efficacy and safety in patients.

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

Version: 2014

Long-term clinical efficacy and safety of adding cilostazol to dual antiplatelet therapy for patients undergoing PCI: a meta-analysis of randomized trials with adjusted indirect comparisons

OBJECTIVE: To assess the long-term clinical efficacy and safety of adding cilostazol to aspirin plus clopidogrel (triple antiplatelet therapy, TAT) in patients undergoing percutaneous coronary intervention (PCI) and explore its role in the era of new generation adenosine diphosphate (ADP)-receptor antagonists.

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

Version: 2014

Ischaemic and bleeding complications with new, compared to standard, ADP-antagonist regimens in acute coronary syndromes: a meta-analysis of randomized trials

The review concluded that new oral antiplatelet regimens to block platelet adenosine diphosphate (ADP)-receptors for patients with acute coronary syndromes were associated with a reduction in mortality, myocardial reinfarction and in-stent thrombosis without any increase in bleeding. The uncertain trial quality and limitations in review reporting mean that the reliability of the authors' conclusions is unclear.

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

Version: 2011

Antiplatelet and Anticoagulant Treatments for Unstable Angina/Non–ST Elevation Myocardial Infarction [Internet]

For patients with unstable angina or non–ST elevation myocardial infarction (UA/NSTEMI), antiplatelet and anticoagulant medications are prescribed to reduce and prevent ischemic events and mortality. There is uncertainty about the optimal dosing and timing of these medications to balance ischemic risk and bleeding risk across different treatment strategies (early invasive, initial conservative, and postdischarge).

Comparative Effectiveness Reviews - Agency for Healthcare Research and Quality (US).

Version: November 2013
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Optimal oral antithrombotic regimes for patients with acute coronary syndrome: a network meta-analysis

OBJECTIVE: We performed a network meta-analysis to investigate the optimal antithrombotic regime by indirectly comparing new antithrombotic regimes (new P2Y12 inhibitors plus aspirin or novel oral anticoagulants on top of traditional dual antiplatelet therapy [DAPT]) in patients with acute coronary syndrome (ACS).

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

Version: 2014

Assessment of bleeding risk of interventional techniques: a best evidence synthesis of practice patterns and perioperative management of anticoagulant and antithrombotic therapy

BACKGROUND: Interventional pain management is a specialty that utilizes invasive procedures to diagnose and treat chronic pain. Patients undergoing these treatments may be receiving exogenous anticoagulants and antithrombotics. Even though the risk of major bleeding is very small, the consequences can be catastrophic. However, the role of antithrombotic therapy for primary and secondary prevention of cardiovascular disease to decrease the incidence of acute cerebral and cardiovascular events is also crucial. Overall, there is a paucity of literature on the subject of bleeding risk in interventional pain management along with practice patterns and perioperative management of anticoagulant and anti-thrombotic therapy.

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

Version: 2013

Efficacy and safety of intensified antiplatelet therapy on the basis of platelet reactivity testing in patients after percutaneous coronary intervention: systematic review and meta-analysis

BACKGROUND: ADP-specific platelet function assays were shown to predict thrombotic events, and might be helpful to select candidates for more potent antiplatelet therapy. We aimed to determine the efficacy and safety of giving intensified antiplatelet therapy on the basis of platelet reactivity testing for patients undergoing percutaneous coronary intervention (PCI).

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

Version: 2013

Systematic guideline search and appraisal, as well as extraction of new and relevant recommendations, for the DMP “Coronary heart disease”: Executive summary of final report V09-05, Version 1.0

The aim of this study was to specify a potential need for updating and supplementation of the existing DMP-CHD by means of a systematic search for new, topic-relevant evidence-based CPGs and by means of a synthesis of the CPG recommendations.

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

Version: December 13, 2010

Antiplatelet treatment for prevention of cerebrovascular events in patients with vascular diseases: a systematic review and meta-analysis

BACKGROUND AND PURPOSE: The efficacy and safety of different antiplatelet regimes for prevention of stroke in patients at high risk were investigated in a systematic review and meta-analysis.

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

Version: 2014

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