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Antithrombotic agents for secondary prevention after acute coronary syndromes: A systematic review and network meta-analysis.

ABSTRACT:

Background

Nine oral antithrombotic medications currently available in the United States and Europe have been studied in clinical trials for secondary prevention of cardiac events following acute coronary syndrome (ACS). Few combinations of these medications have been directly compared, and studies have used multiple different comparator regimens.

Methods

We performed a systematic review and network meta-analysis of randomized controlled trials evaluating one or more available oral antithrombotic therapies in patients with ACS or prior myocardial infarction (MI). Co-primary outcomes were all-cause and cardiovascular mortality compared with imputed placebo and aspirin monotherapy.

Results

Forty-seven studies (196,057 subjects) met inclusion criteria and were included in the systematic review. Almost all studies tested either aspirin monotherapy compared with placebo or a combination of antithrombotic agents that included aspirin. Nearly all regimens reduced all-cause and cardiovascular mortality compared with imputed placebo. However, compared with imputed aspirin monotherapy, only combination therapy with aspirin plus ticagrelor was associated with lower cardiovascular mortality (OR 0.80, 95% CI 0.68-0.93), and triple therapy with aspirin, clopidogrel, and very low dose rivaroxaban was associated with lower all-cause mortality (OR 0.67, 95% CI 0.49-0.90). Major bleeding was increased 45-95% with dual antithrombotic therapy, and 2-6-fold with triple therapy.

Conclusion

Few combinations of antithrombotic therapy were associated with a reduction in mortality compared with aspirin monotherapy, highlighting the difficulty in clinical interpretation of composite ischemic endpoints. Future studies may need to focus on limiting the number of antithrombotic therapies tested in combination to best balance ischemic event reduction and bleeding.

SUBMITTER: Fanaroff AC

PROVIDER: S-EPMC5469706 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Antithrombotic agents for secondary prevention after acute coronary syndromes: A systematic review and network meta-analysis.

Fanaroff Alexander C AC Hasselblad Vic V Roe Matthew T MT Bhatt Deepak L DL James Stefan K SK Steg Ph Gabriel PG Gibson C Michael CM Ohman E Magnus EM

International journal of cardiology 20170314

<h4>Background</h4>Nine oral antithrombotic medications currently available in the United States and Europe have been studied in clinical trials for secondary prevention of cardiac events following acute coronary syndrome (ACS). Few combinations of these medications have been directly compared, and studies have used multiple different comparator regimens.<h4>Methods</h4>We performed a systematic review and network meta-analysis of randomized controlled trials evaluating one or more available ora ...[more]

PMID: 28320608

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Project description:ImportancePatients with acute coronary syndrome (ACS) remain at high risk for experiencing recurrent ischemic events. Direct oral anticoagulants (DOAC) have been proposed for secondary prevention after ACS.ObjectiveTo evaluate the safety and efficacy of DOAC in addition to antiplatelet therapy (APT) after ACS, focusing on treatment effects stratified by baseline clinical presentation (non-ST-segment elevation ACS [NSTE-ACS] vs ST-segment elevation myocardial infarction [STEMI]).Data sourcesPubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched from inception to March 1, 2017.Study selectionRandomized clinical trials on DOAC after ACS were evaluated for inclusion. Overall, 473 studies were screened, 19 clinical trials were assessed as potentially eligible, and 6 were included in the meta-analysis.Data extraction and synthesisPreferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to abstract data and assess quality and validity. The risk of bias tool, version 2.0 (Cochrane) was used for risk of bias assessment. Data were pooled using random-effects models.Main outcomes and measuresThe prespecified primary efficacy end point was the composite of cardiovascular death, myocardial infarction, and stroke. The prespecified primary safety end point was major bleeding.ResultsSix trials that included 29 667 patients were identified (14 580 patients [49.1%] with STEMI and 15 036 [50.7%] with NSTE-ACS). The primary efficacy end point risk was significantly lower in patients who were treated with DOAC as compared with APT alone (odds ratio [OR], 0.85; 95% CI, 0.77-0.93; P < .001). This benefit was pronounced in patients with STEMI (OR, 0.76; 95% CI, 0.66-0.88; P < .001), while no significant treatment effect was observed in patients with NSTE-ACS (OR, 0.92; 95% CI, 0.78-1.09; P = .36; P for interaction = .09). With respect to safety, DOACs were associated with a higher risk of major bleeding as compared with APT alone (OR, 3.17; 95% CI, 2.27-4.42; P < .001), with consistent results in patients with STEMI (OR, 3.45; 95% CI, 1.95-6.09; P < .001) and NSTE-ACS (OR, 2.19; 95% CI, 1.38-3.48; P < .001; P for interaction = .23).Conclusions and relevanceTo our knowledge, these findings are the first evidence to support differential treatment effects of DOAC in addition to APT according to ACS baseline clinical presentation. In patients with NSTE-ACS, the risk-benefit profile of DOAC appears unfavorable. Conversely, DOAC in addition to APT might represent an attractive option for patients with STEMI.

Project description:BackgroundExtended antithrombotic treatment is recommended for secondary prevention of unprovoked venous thromboembolism (VTE), however, there is no consensus on which antithrombotic strategy is preferable.AimTo compare the efficacy and safety of different antithrombotic strategies for secondary prevention unprovoked VTE.MethodsCochrane Central Register of Controlled Trials, Embase, and MEDLINE were systematically searched from inception to 22 July 2020 for randomized controlled trials (RCTs) that compared the efficacy and/or safety of extended antithrombotic strategies including aspirin, warfarin and direct oral anticoagulants (DOACs) for secondary prevention of unprovoked VTE. The primary outcome was risk of major bleeding and the secondary outcomes were risks of recurrent VTE and all-cause death. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using pairwise and network meta-analysis with random effect. Possible ranking of extended antithrombotic strategies was plotted using the surface under the cumulative ranking curve and mean ranks.ResultsSeventeen RCTs met the inclusion criteria, and meta-analysis results showed that warfarin was associated with significantly higher risk of major bleeding than placebo/observation (OR 2.71, 95% CI 1.32-5.55) or apixaban (OR 10.65, 95% CI 1.06-107.13). Apixaban and low-apixaban were the top two strategies according to the ranking of major bleeding. Warfarin (OR 0.25, 95%CI 0.13-0.49), rivaroxaban (OR 0.18, 95%CI 0.03-0.90), apixaban (OR 0.18, 95%CI 0.04-0.85) and low-apixaban (OR 0.18, 95%CI 0.04-0.82) were related to significantly lower risk than placebo/observation; edoxaban was non-inferior to warfarin on the risk of recurrent VTE. Furthermore, apixaban was linked with significantly lower risk of all-cause death than placebo/observation (OR 0.29, 95% CI 0.09-0.88).ConclusionApixaban showed superiority to other antithrombotic strategies on major bleeding and all-cause death for secondary prevention of unprovoked VTE. Further studies are warranted owing to the limited number of studies and positive cases.Key messagesAll antithrombotic strategies including warfarin, DOACs and aspirin were superior to placebo/observation on recurrent VTE for secondary prevention of unprovoked VTE.Apixaban demonstrated lower risk of major bleeding than warfarin, and lower risk of all-cause death than placebo/observation.Further research about the efficacy and safety of antithrombotic treatments for secondary prevention of unprovoked VTE is warranted.

Project description:BackgroundWorldwide, coronary heart disease accounts for 7 million deaths each year. In Sweden, acute coronary syndrome (ACS) is a leading cause of hospitalization and is responsible for 1 in 4 deaths.ObjectiveThe aim of this analysis was to assess the cost-effectiveness of rivaroxaban 2.5 mg twice daily (BID) in combination with standard antiplatelet therapy (ST-APT) versus ST-APT alone, for the secondary prevention of ACS in adult patients with elevated cardiac biomarkers without a prior history of stroke/transient ischemic attack (TIA), from a Swedish societal perspective, based on clinical data from the global ATLAS ACS 2-TIMI 51 trial, literature-based quality of life data and costs sourced from Swedish national databases.MethodsA Markov model was developed to capture rates of single and multiple myocardial infarction (MI), ischemic and hemorrhagic stroke, thrombolysis in myocardial infarction (TIMI) major, minor, and "requiring medical attention" bleeds, revascularization events, and associated costs and utilities in patients who were stabilized after an initial ACS event. Efficacy and safety data for the first 2 years came from the ATLAS ACS 2-TIMI 51 trial. Long-term probabilities were extrapolated using safety and effectiveness of acetylsalicylic acid data, which was estimated from published literature, assuming constant rates in time. Future cost and effects were discounted at 3.0%. Univariate and probabilistic sensitivity analyses were conducted.ResultsIn the base case, the use of rivaroxaban 2.5 mg BID was associated with improvements in survival and quality-adjusted life years (QALYs), yielding an incremental cost per QALY of 71,246 Swedish Krona (SEK) (€8045). The outcomes were robust to changes in inputs. The probabilistic sensitivity analysis demonstrated rivaroxaban 2.5 mg BID to be cost-effective in >99.9% of cases, assuming a willingness-to-pay threshold of SEK 500,000 (€56,458).ConclusionCompared with ST-APT alone, the use of rivaroxaban 2.5 mg BID in combination with ST-APT can be considered a cost-effective treatment option for ACS patients with elevated cardiac biomarkers without a prior history of stroke/TIA in Sweden.FundingBayer Pharma AG.

Project description:BackgroudAntithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and efficacy remains undefined. Our objective was to evaluate the effectiveness and safety of antithrombotic options and identify the optimal treatment option for patients with CCS.MethodsWe used the MEDLINE, CENTRAL and Embase databases to search for randomized controlled trials with follow-up periods longer than 12 months that compared aspirin (ASA) monotherapy with other antithrombotic therapies in patients with CCS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Extracted data [hazard ratios (HR)] were pooled using Bayesian fixed-effect models, allowing the estimation of credible intervals (CrI) and posterior probabilities of benefit, harm, and practical equivalence. Confidence in the results was assessed with the Confidence In Network Meta-Analysis (CINeMA) tool. The primary efficacy and safety outcomes were major adverse cardiovascular events (MACE) and primary bleeding, respectively. Secondary outcomes were acute myocardial infarction, ischemic stroke, all-cause, and cardiovascular-specific mortality.ResultsFive trials with a total of 80,605 patients were included. Mean patient age ranged from 61 to 69 years, while 20.3% to 31.4% were women. The reference treatment was ASA monotherapy. ASA + prasugrel 10 mg and clopidogrel 75 mg monotherapy presented the greatest benefit for MACE [HR 0.52 (95% CrI, 0.39-0.71); and 0.68 (95% CrI, 0.54-0.88)]. There was a probability of 98.8% that ASA + ticagrelor was practically equivalent to ASA monotherapy. Regarding the primary bleeding outcome, clopidogrel 75 mg monotherapy performed best [HR 0.64 (0.42, 0.99)]. There was a probability of 97.4% that ASA + Prasugrel 10 mg increases bleeding (HR > 1.0). Secondary outcome results followed a similar treatment ranking pattern as in primary outcomes. Overall, CINeMA confidence ratings were judged as either low or very low.ConclusionsThese results revealed that clopidogrel monotherapy might provide the best risk-benefit balance in treating CCS. However, low CINeMA confidence ratings may preclude more forceful conclusions. Our analysis suggests that current guidelines recommending ASA as first-line therapy for CCS management need to be revised to include additional pharmacological options.

Project description:ObjectiveTo examine the comparative efficacy and safety of antithrombotic treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists (VKA) at a standard adjusted dose (target international normalised ratio 2.0-3.0), acetylsalicylic acid (ASA), ASA and clopidogrel) for non-valvular atrial fibrillation and among subpopulations.DesignSystematic review and network meta-analysis.Data sourcesA systematic literature search strategy was designed and carried out using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and the grey literature including the websites of regulatory agencies and health technology assessment organisations for trials published in English from 1988 to January 2014.Eligibility criteria for selecting studiesRandomised controlled trials were selected for inclusion if they were published in English, included at least one antithrombotic treatment and involved patients with non-valvular atrial fibrillation eligible to receive anticoagulant therapy.ResultsFor stroke or systemic embolism, dabigatran 150 mg and apixaban twice daily were associated with reductions relative to standard adjusted dose VKA, whereas low-dose ASA and the combination of clopidogrel plus low-dose ASA were associated with increases. Absolute risk reductions ranged from 6 fewer events per 1000 patients treated for dabigatran 150 mg twice daily to 15 more events for clopidogrel plus ASA. For major bleeding, edoxaban 30 mg daily, apixaban, edoxaban 60 mg daily and dabigatran 110 mg twice daily were associated with reductions compared to standard adjusted dose VKA. Absolute risk reductions with these agents ranged from 18 fewer per 1000 patients treated each year for edoxaban 30 mg daily to 24 more for medium dose ASA.ConclusionsCompared with standard adjusted dose VKA, new oral anticoagulants were associated with modest reductions in the absolute risk of stroke and major bleeding. People on antiplatelet drugs experienced more strokes compared with anticoagulant drugs without any reduction in bleeding risk. To fully elucidate the comparative benefits and harms of antithrombotic agents across the various subpopulations, rigorously conducted comparative studies or network meta-regression analyses of patient-level data are required.Systematic review registration numberPROSPERO registry-CRD42012002721.

Project description:ObjectiveTo assess the effects of different oral antithrombotic drugs that prevent saphenous vein graft failure in patients undergoing coronary artery bypass graft surgery.DesignSystematic review and network meta-analysis.Data sourcesMedline, Embase, Web of Science, CINAHL, and the Cochrane Library from inception to 25 January 2019. ELIGIBILITY CRITERIA: for selecting studies Randomised controlled trials of participants (aged ≥18) who received oral antithrombotic drugs (antiplatelets or anticoagulants) to prevent saphenous vein graft failure after coronary artery bypass graft surgery.Main outcome measuresThe primary efficacy endpoint was saphenous vein graft failure and the primary safety endpoint was major bleeding. Secondary endpoints were myocardial infarction and death.ResultsThis review identified 3266 citations, and 21 articles that related to 20 randomised controlled trials were included in the network meta-analysis. These 20 trials comprised 4803 participants and investigated nine different interventions (eight active and one placebo). Moderate certainty evidence supports the use of dual antiplatelet therapy with either aspirin plus ticagrelor (odds ratio 0.50, 95% confidence interval 0.31 to 0.79, number needed to treat 10) or aspirin plus clopidogrel (0.60, 0.42 to 0.86, 19) to reduce saphenous vein graft failure when compared with aspirin monotherapy. The study found no strong evidence of differences in major bleeding, myocardial infarction, and death among different antithrombotic therapies. The possibility of intransitivity could not be ruled out; however, between-trial heterogeneity and incoherence were low in all included analyses. Sensitivity analysis using per graft data did not change the effect estimates.ConclusionsThe results of this network meta-analysis suggest an important absolute benefit of adding ticagrelor or clopidogrel to aspirin to prevent saphenous vein graft failure after coronary artery bypass graft surgery. Dual antiplatelet therapy after surgery should be tailored to the patient by balancing the safety and efficacy profile of the drug intervention against important patient outcomes.Study registrationPROSPERO registration number CRD42017065678.

Project description:OBJECTIVES:In Barbados, high case fatality rates have been reported after myocardial infarction (MI) with higher rates in women than men. To explore this inequality, we examined documented pharmacological interventions for ST-segment elevated myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable and chronic angina in women and men. DESIGN:Prospective cohort registry data for STEMI and NSTEMI and retrospective chart review for unstable and chronic angina. SETTING:Tertiary care (acute coronary syndromes) and primary care (chronic angina) centres in Barbados. PARTICIPANTS:For the years 2009-2016, a total of 1018 patients with STEMI or NSTEMI were identified via the prospective study. For unstable and chronic angina, 136 and 272 notes were reviewed respectively for the years 2010-2014. OUTCOME MEASURES:The proportions of patients prescribed recommended medication during the first 24 hours after an acute event, at discharge and for chronic care were calculated. Prescribed proportions were analysed by gender after adjustment for age. RESULTS:Between 2009 and 2016, for the acute management of patients with NSTEMI and STEMI, only two (aspirin and clopidogrel) of six drugs had documented prescription rates of 80% or more. Patients with STEMI (n=552) had higher prescription rates than NSTEMI (n=466), with gender differences being more pronounced in the former. Among patients with STEMI, after adjustment for age, diabetes, hypertension and smoking, men were more likely to receive fibrinolytics acutely, OR 2.28 (95% CI 1.24 to 4.21). Compared with men, a higher proportion of women were discharged on all recommended treatments; this was only statistically significant for beta-blockers: age-adjusted OR 1.87 (95% CI 1.16 to 3.00). There were no statistically significant differences in documented prescription of drugs for chronic angina. CONCLUSION:Following acute MI in Barbados, the proportion of patients with documented recommended treatment is relatively low. Although women were less likely to receive appropriate acute care than men, by discharge gender differences were reversed.

Dataset Information

Antithrombotic agents for secondary prevention after acute coronary syndromes: A systematic review and network meta-analysis.

Background

Methods

Results

Conclusion

Publications

Antithrombotic agents for secondary prevention after acute coronary syndromes: A systematic review and network meta-analysis.

Similar Datasets

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