Aernoud Fiolet

182 Chapter 7 (Supplementary material, Figure SA3A). No significant interaction between treatment and sex for the primary (P=0.402) or the secondary (P=0.083) endpoint was observed (Supplementary material, Figure SA3B). The number needed to treat for the composite of myocardial infarction, stroke, coronary revascularization, or cardiovascular death varied greatly between trials from 30 to 98 patients for 1year with a weighted-average estimate of 84 and from 9 to 60 for 3years with a weighted-average estimate of 40 (Supplementary material, Table SA3). Treatment effect was directionally consistent for components of the composite endpoint (Figure 2). Overall, colchicine significantly reduced the risk for myocardial infarction by 22% (RR 0.78; 95% CI 0.64–0.94; P=0.010), for stroke by 46% (RR 0.54; 95% CI 0.34–0.86 P=0.009), and for coronary revascularization by 23% (RR 0.77; 95% CI 0.66–0.90; P<0.001). The risk reduction for stroke was mostly driven by ischaemic stroke (RR 0.49; 95% CI 0.30–0.81; P=0.005), as the incidence of haemorrhagic strokes was very low with 10 events (Supplementary material, Figure S2). Fatalities are summarized in Figure 3.We observed no difference in all-cause death (RR 1.08; 95% CI 0.71–1.62; P=0.726), with a lower incidence of cardiovascular death (RR 0.82; 95% CI 0.55–1.23; P=0.339) counterbalanced by a higher incidence of non-cardiovascular death (RR 1.38; 95% CI 0.99–1.92; P=0.060). Safety information is summarized in Figure 4 and was available from three trials: COLCOT, COPS, and LoDoCo2.13,14,25 Overall, colchicine was not associated with an increased risk for hospitalization for infection in general (RR 1.08; 95% CI 0.78–1.51; P=0.636) or hospitalization for pneumonia (RR 1.67; 95% CI 0.58– 4.77, P=0.339, with high level of heterogeneity, I 2 = 75.0%). Hospitalizations for gastro-intestinal disorders did not differ between treatment groups (RR 1.13; 95% CI 0.81–1.56; P=0.470). Overall, no differences in the risk for new cancer was seen in those allocated colchicine vs. no colchicine or placebo (RR 0.987, 95% CI 0.80– 1.21; P=0.861). Results for the primary and secondary composite endpoints, for the individual endpoints, and for fatalities were essentially unchanged in a sensitivity analysis that removed the non-placebo-controlled LoDoCo trial. Sensitivity analyses using a fixed-effects model and analyses using the original endpoint definitions of the trials showed consistent results, albeit with slightly smaller estimated effect sizes (Supplementary material, Figures S4–S6).