Safety of Clopidogrel vs. Ticagrelor in Dual Antiplatelet Therapy Regimens for High-Bleeding Risk Acute Coronary Syndrome Patients: A Comprehensive Meta-analysis of Adverse Outcomes.

Abstract

Introduction: Patients of acute coronary syndrome (ACS) at a high-bleeding risk (HBR) often require dual antiplatelet therapy (DAPT) to reduce the risk of recurrent cardiovascular events. Clopidogrel and ticagrelor are the most commonly used antiplatelet agents in DAPT regimens. However, the safety profiles of these drugs in ACS patients at HBR remain a subject of ongoing debate.

Aim: To investigate any difference between the safety of clopidogrel and ticagrelor used as a part of DAPT regimen in ACS patients at HBR.

Methods: A systematic search on PubMed, Cochrane Library, and Google Scholar was conducted to identify experimental and observational studies published up to the knowledge cutoff date in September 2023. Studies comparing the safety of clopidogrel and ticagrelor in ACS patients at HBR were included for analysis. The primary outcomes assessed were major bleeding events, stroke, and myocardial infarction (MI), while secondary outcomes included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), and net adverse clinical and cerebral events (NACCE).

Results: We included a total of 8 observational studies in our meta-analysis. The pooled analysis revealed a statistically significant increase in the risk of MI (pooled RR = 1.43; 95% CI 1.12-1.83; P = 0.005) in the patients using clopidogrel. There were no statistically significant differences in major bleeding events (pooled RR = 0.94; 95% CI 0.82-1.09; P = 0.44), stroke (pooled RR = 1.36; 95% CI 0.86-2.14; P = 0.18), all-cause mortality (pooled RR = 1.17; 95% CI 0.97-1.41; P = 0.10), MACCE (pooled RR = 1.07; 95% CI 0.76-1.50; P = 0.69) and NACCE (pooled RR = 0.95; 95% CI 0.66-1.37; P = 0.78) between the two groups. Subgroup analyses based on region were performed.

Conclusion: Both drugs are generally safe for treating ACS patients with HBR at baseline, although a higher risk of MI was observed with the use of clopidogrel. Nevertheless, drug choice should factor in regional variations, patient-specific characteristics, cost, accessibility, and potential drug interactions.