Quantitative comparison of clopidogrel 600 mg, prasugrel and ticagrelor, against clopidogrel 300 mg on major adverse cardiovascular events and bleeding in coronary stenting: synthesis of CURRENT-OASIS-7, TRITON-TIMI-38 and PLATO.

The convention of loading with clopidogrel 300 mg before coronary intervention may be due for change, but to what? Newer antiplatelet agents may offer better outcomes, at some financial cost. Disappointingly for decision-making clinicians, head-to-head comparisons for the newer alternatives are not available. We systematically review and compare the three alternative strategies: clopidogrel 600 mg, prasugrel and ticagrelor. A total of 14 studies have compared these strategies with the long-standing convention of 300 mg. Throughout this analysis, we consistently report incremental costs and consequences using clopidogrel 300 mg as the reference strategy. Risk ratios for major adverse cardiovascular events at 30 days were 0.74 (95% confidence interval 0.66-0.82, p=0.002) for clopidogrel 600 mg, 0.78 (0.69-0.89; p<0.001) for prasugrel and 0.88 (0.77-1.00; p=0.045) for ticagrelor. All-cause mortality risk ratios were 0.87 (0.74-1.03) with clopidogrel 600 mg, 0.95 (0.78-1.16) with prasugrel and 0.78 (0.69-0.89) with ticagrelor. TIMI major bleeding has risk ratio 0.92 (0.74-1.16; p=0.85) with clopidogrel 600 mg, 1.32 (1.03-1.16; p=0.03) with prasugrel and 1.25 (1.03-1.53; p=0.03) with ticagrelor. Incremental cost for the first year was £0.32 (US$0.50, €0.40) with clopidogrel 600 mg, £608 (US$977, €709) with prasugrel and £665 (US$1068, €775) with ticagrelor. All three strategies have shown a similar reduction in MACE at 30 days by comparison to clopidogrel 300 mg. All three strategies offer progressive benefit, most marked with Ticagrelor. Whether this is worth both the risk of non-compliance with twice-a-day dosing in real-life patients lacking the same motivation as their trial-volunteer counterparts, and the 2000-fold difference in incremental cost, is the remaining matter for debate.