Switching to Clopidogrel in Patients With Acute Coronary Syndrome Managed With Percutaneous Coronary Intervention Initially Treated With Prasugrel or Ticagrelor: Systematic Review and Meta-analysis

Objective: To evaluate the effects of switching from ticagrelor or prasugrel to clopidogrel in acute coronary syndrome (ACS) patients managed with percutaneous coronary intervention on major adverse cardiovascular events (MACEs) and bleeding. Data Sources: We searched MEDLINE, EMBASE, CENTRAL, bibliographies of relevant articles, and clinicaltrials.gov for eligible articles published from inception to January 27, 2019. Study Selection and Data Extraction: We included randomized controlled trials (RCTs) and cohort and case-control studies that reported on >= 1 outcome of interest. Primary outcomes were MACE and major bleeding, and the secondary outcome was any bleeding. Data Synthesis: From 483 articles, we included 7 relevant studies (2 RCTs, 5 cohort studies) at high/unclear risk of bias. Random-effects meta-analysis revealed inconclusive effects on MACE (hazard ratio [HR] = 1.00, 95% CI = 0.59-1.68; I-2 = 82%), major bleeding (HR = 0.51; 0.19-1.35; I-2 = 91%), and any bleeding (HR = 0.64; 0.38-1.07; I-2 = 85%). Similar nonsignificant results were obtained in secondary analyses evaluating risk ratios. Relevance to Patient Care and Clinical Practice: Ticagrelor and prasugrel, are now considered preferred therapy over clopidogrel in patients with ACS. Switching from these potent P2Y(12) inhibitors to clopidogrel is commonly performed to reduce bleeding risk, other adverse effects, or costs. Current best-available evidence is inconclusive regarding the effects of switching to clopidogrel on the risk of MACE and bleeding. Overall, studies were underpowered to detect clinically important differences. Conclusions: Until adequately powered trials demonstrate an advantage to switching to clopidogrel from prasugrel or ticagrelor, clinicians may consider this approach as clinically indicated on an individual, case-by-case basis.