Eight studies were identified (n=48,469, range 70 to 18,624 from the table; the authors stated the total as n=48,599.) All were randomised double-blind controlled trials, three of which were phase 2 studies. There were four subgroup analyses of larger studies (n=25,366).
Global analysis (eight RCTs): New P2Y12 inhibitors versus clopidogrel significantly reduced death (OR 0.83, 95% CI 0.75 to 0.92), cardiovascular death (OR 0.82, 95% CI 0.72 to 0.92), MACE (OR 0.86, 95% CI 0.80 to 0.93), myocardial infarction, stent thrombosis and target vessel revascularisation. There was no significant difference for stroke. There was a significant increase for P2Y12 inhibitors versus clopidogrel for TIMI major bleeding (OR 1.21, 95% CI 1.05 to 1.40) and TIMI major or minor bleeding (OR 1.15, 95% CI 1.01 to 1.31). There was no significant heterogeneity for these analyses. Results were confirmed in a fixed-effect model.
PCI-treated patients (any PCI) (six studies): New P2Y12 inhibitors versus clopidogrel significantly reduced death (OR 0.85, 95% CI 0.75 to 0.96), cardiovascular death (OR 0.84, 95% CI 0.72 to 0.96), MACE (OR 0.87, 95% CI 0.79 to 0.95) and stent thrombosis (OR 0.60, 95% CI 0.44 to 0.81). There was no significant difference for stroke. A relative decrease in myocardial infarction (OR 0.86, 95% CI 0.74 to 1.01) was of marginal significance. There was a significant increase for P2Y12 inhibitors versus clopidogrel for TIMI major bleeding (OR 01.23, 95% CI 1.04 to 1.46) and TIMI major or minor bleeding (OR 1.25, 95% CI 1.11 to 1.40). Results were confirmed in a fixed-effect model. Sensitivity analysis after removal of the largest study produced similar results. Results for myocardial infarction and TIMI major bleeding were not significant. The result was still significant for TIMI major or minor bleeding.
STEMI patients treated by PCI (four studies): New P2Y12 inhibitors versus clopidogrel significantly reduced death (OR 0.78, 95% CI 0.66 to 0.92), cardiovascular death (OR 0.81, 95% CI 0.67 to 0.97), MACE (OR 0.82, 95% CI 0.73 to 0.92), stent thrombosis (OR 0.66, 95% CI 0.53 to 0.83; three studies) and myocardial infarction (OR 0.81, 95% CI 0.69 to 0.95). There was a significant increase in stroke for P2Y12 inhibitors versus clopidogrel (OR 1.48, 95% CI 1.07 to 2.07), but no significant difference between groups for TIMI major bleeding or TIMI major or minor bleeding (three studies). Results of sensitivity analysis after removal of the largest study were similar for most outcomes and still significant for death, MACE and stent thrombosis. Results were no longer significant for cardiovascular death, myocardial infarction and stroke. Sensitivity analysis restricted to primary PCI patients confirmed all results.
For all analyses similar results were obtained when cangrelor studies were removed from the analysis. Additional data were available in the online version of the article.
There was no evidence of publication bias (funnel plots not presented).