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Is there Sex-related Outcome Difference According to oral P2Y12 Inhibitors in Patients with Acute Coronary Syndromes? A Systematic Review and Meta-Analysis of 107,126 Patients

Author(s):

Oliver Ian Brown*, Jennifer A. Rossington, Gill Louise Buchanan, Giuseppe Patti and Angela Hoye   Pages 1 - 16 ( 16 )

Abstract:


Background and objectives The majority of patients included in trials of anti-platelet therapy are male. This systematic review and meta-analysis aimed to determine whether, in addition to aspirin, P2Y12 blockade is beneficial in both women and men with acute coronary syndromes.

Methods Electronic databases were searched and nine eligible randomised controlled studies were identified that had sex-specific clinical outcomes (n=107,126 patients). Risk ratios (RR) and 95% confidence intervals (CI) were calculated for a composite of cardiovascular death, myocardial infarction or stroke (MACE), and a safety endpoint of major bleeding for each sex. Indirect comparison analysis was performed to statistically compare ticagrelor against prasugrel.

Results Compared to aspirin alone, clopidogrel reduced MACE in men (RR, 0.79; 95% CI, 0.68 to 0.92; p=0.003), but was not statistically significant in women (RR, 0.88; 95% CI, 0.75 to 1.02, p=0.08). Clopidogrel therapy significantly increased bleeding in women but not men. Compared to clopidogrel, prasugrel was beneficial in men (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02) but not statistically significant in women (RR, 0.94; 95% CI, 0.83 to 1.06; p=0.30); ticagrelor reduced MACE in both men (RR, 0.85; 95% CI, 0.77 to 0.94; p=0.001) and women (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02). Indirect comparison demonstrated no significant difference between ticagrelor and prasugrel in either sex. Compared to clopidogrel, ticagrelor and prasugrel increased bleeding risk in both women and men.

Conclusion In summary, in comparison to monotherapy with aspirin, P2Y12 inhibitors reduce MACE in women and men. Ticagrelor was shown to be superior to clopidogrel in both sexes. Prasugrel showed a statistically significant benefit only in men; however indirect comparison did not demonstrate superiority of ticagrelor over prasugrel in women.

Keywords:

P2Y12 inhibitors – Coronary artery disease – Sex – Antiplatelet therapy – Bleeding – Ticagrelor – clopidogrel - prasugrel

Affiliation:

Department of Academic Cardiology, Daisy Building, Castle Hill Hospital, Kingston upon Hull, Department of Academic Cardiology, Daisy Building, Castle Hill Hospital, Kingston upon Hull, Department of Cardiology, Cumberland Infirmary, North Cumbria University Hospitals, Carlisle, Department of Cardiovascular Science, Campus Bio-Medico University, Rome, Department of Academic Cardiology, Daisy Building, Castle Hill Hospital, Kingston upon Hull



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