Background: Dual anti-platelet therapy (DAPT) with aspirin and clopidogrel has been the mainstay of treatment for patients with acute coronary syndrome (ACS). However, the recurrence of thrombotic events, potential aspirin and clopidogrel hypo-responsiveness, and other limitations of DAPT have led to the development of newer oral anti-thrombotic drugs. Apixaban, a new non-vitamin K antagonist, has been approved for use. In this meta-analysis, we aimed to compare the bleeding outcomes observed with the addition of apixaban to DAPT for the treatment of patients with ACS. Methods: Online databases including EMBASE, Cochrane Central, http://www.ClinicalTrials.gov , MEDLINE and Web of Science were searched for English based publications comparing the use of apixaban added to DAPT for the treatment of patients with ACS. Different categories of bleeding events and cardiovascular outcomes were assessed. The analysis was carried out by the RevMan software version 5.4. Odds ratios (OR) with 95% confidence intervals (CI) were used to represent the data following analysis. Results: This research analysis consisted of 4 trials with a total number of 9010 participants. Thrombolysis in myocardial infarction (TIMI) defined major bleeding (OR: 2.45, 95% CI: 1.45–4.12; P = .0008), TIMI defined minor bleeding (OR: 3.12, 95% CI: 1.71–5.70; P = .0002), International society of thrombosis and hemostasis (ISTH) major bleeding (OR: 2.49, 95% CI: 1.80–3.45; P = .00001) and Global Use of Strategies to Open Occluded Arteries (GUSTO) defined severe bleeding (OR: 3.00, 95% CI: 1.56–5.78; P = .01) were significantly increased with the addition of apixaban to DAPT versus DAPT alone in these patients with ACS. However fatal bleeding (OR: 10.96, 95% CI: 0.61–198.3; P = .11) was not significantly different. Conclusions: Addition of the novel oral anticoagulant apixaban to the DAPT regimen significantly increased bleeding and therefore did not show any beneficial effect in these patients with ACS. However, due to the extremely limited data, we apparently have to rely on future larger studies to confirm this hypothesis.
BackgroundRecently, several newer antiplatelet treatment strategies have been used in patients with coronary artery disease (CAD). Apart from the dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel, double dose clopidogrel (DDC), triple antiplatelet therapy (TAPT) consisting of aspirin, clopidogrel and cilostazol and other newer antiplatelet agents have shown to be effective in different ways. In this analysis, we aimed to systematically compare the adverse clinical outcomes and the bleeding events which were observed when DDC was compared to the other antiplatelet regimens in patients with CAD.MethodsEnglish publications comparing DDC with other antiplatelet regimens were searched from MEDLARS/MEDLINE, EMBASE, www.ClinicalTrials.gov and Google Scholar. Adverse cardiovascular outcomes and bleeding events were the study endpoints. Statistical analysis was carried out by the RevMan 5.3 software whereby odds ratios (OR) with 95% confidence intervals (CIs) were calculated.ResultsA total number of 23,065 participants were included. Results of this analysis showed major adverse cardiac events (MACEs), all-cause mortality, cardiac death, stroke, stent thrombosis, revascularization and myocardial infarction (MI) to have been similarly manifested in patients who were treated with DDC versus the control group with OR: 0.98, 95% CI: 0.78–1.22; p = 0.83, OR: 0.95, 95% CI: 0.77–1.17; p = 0.62, OR: 0.97, 95% CI: 0.79–1.20; p = 0.81, OR: 0.98, 95% CI: 0.65–1.48; p = 0.94, OR: 0.84, 95% CI: 0.40–1.75; p = 0.64, OR: 0.88, 95% CI: 0.52–1.49; p = 0.63, and OR: 0.89, 95% CI: 0.65–1.21; p = 0.45 respectively. Any minor and major bleedings were also similarly manifested.When DDC was compared to DAPT, no significant difference was observed in any bleeding event with OR: 1.58, 95% CI: 0.86–2.91; p = 0.14. Even when DDC was compared with either ticagrelor or prasugrel or TAPT, still no significant difference was observed in terms of bleeding outcomes.ConclusionsIn patients with CAD, adverse clinical outcomes were not significantly different when DDC was compared to the other antiplatelet regimens. In addition, bleeding events were also similarly manifested when DDC was compared to DAPT, TAPT or ticagrelor/prasugrel.
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