19 0.89,1.59 1.30 0.86,1.97 0.56 0.14,2.27 1.15 0.87,1.51 1.21 0.82,1.78 2–5 0.97 0.78,1.21 1.04 0.74,1.47 1.04 0.66,1.63 1.00 0.82,1.23 1.11 0.82,1.49 >5 1.01 0.80,1.29 1.06 0.74,1.50 0.89 0.73,1.08 1.00 0.80,1.24 1.05 0.78,1.41 Trend testb 0.46   0.49   0.94   0.49   0.54   HR in OS/HR in trialc 0.90 0.69,1.18 0.85 0.61,1.18 Overall HRd 1.03 0.90, 1.19 1.11 0.90, 1.37 0.90 0.75, 1.09           Coronary heart diseasee <2 1.10 0.85,1.43 1.02 0.69,1.49 0.49 0.12,2.00 1.07 0.83,1.38

0.97 0.67,1.38 2–5 0.96 0.79,1.18 1.06 0.78,1.45 1.00 0.66,1.63 1.00 0.83,1.20 1.10 0.84,1.44 >5 1.05 0.85,1.30 1.02 0.75,1.40 0.88 0.74,1.05 1.03 0.85,1.25 1.02 0.78,1.33 Trend testb 0.87   0.97   0.88   0.93   0.93   HR in OS/HR in trialc Idasanutlin research buy 0.86 0.67,1.10 0.86 0.64,1.16 Overall HRd 1.03 0.90, 1.17

1.03 0.85, 1.25 0.88 0.74, GSK2118436 1.04           Total heart diseasef <2 1.05 0.90,1.21 1.00 0.80,1.24 0.86 0.50,1.46 1.04 0.90,1.20 0.99 0.81,1.21 2–5 1.00 0.89,1.12 1.05 0.88,1.26 0.93 0.73,1.17 1.02 0.91,1.13 1.05 0.90,1.23 >5 1.04 0.91,1.19 0.98 0.81,1.20 0.87 0.79,0.97 1.02 0.91,1.15 0.99 0.84,1.16 Trend testb 0.96   0.91   0.83   0.88   0.91   HR in OS/HR in trialc 0.86 0.75,0.99 0.82 0.74,1.05 Overall HRd 1.02 0.95, 1.11 1.02 0.91, 1.14 0.87 0.79, 0.96           Strokeg <2 0.82 0.60,1.12 1.11 0.73,1.68

0.47 0.12,1.89 0.78 0.58,1.05 1.00 0.68,1.46 2–5 1.06 0.84,1.34 1.17 0.83,1.65 0.91 0.57,1.44 1.03 0.84,1.27 1.16 0.87,1.55 >5 0.92 0.73,1.17 1.09 0.79,1.52 0.93 0.77,1.11 RVX-208 0.98 0.80,1.20 1.17 0.90,1.54 Trend testb 0.71   0.93   0.43   0.37   0.53   HR in OS/HR in trialc 0.96 0.75,1.23 0.81 0.60,1.09 Overall HRd 0.95 0.82, 1.10 1.12 0.90, 1.39 0.92 0.77, 1.09           Total cardiovascular diseaseh <2 0.97 0.85,1.11 1.02 0.84,1.23 0.87 0.55,1.35 0.97 0.86,1.10 1.02 0.85,1.21 2–5 0.99 0.89,1.10 1.03 0.89,1.21 0.91 0.74,1.11 1.01 0.92,1.10 1.04 0.91,1.19 >5 1.05 0.93,1.18 1.02 0.86,1.21 0.86 0.79,0.94 1.02 0.93,1.13 1.01 0.88,1.16 Trend testb 0.37   0.97   0.84   0.42   0.93   HR in OS/HR in Trialc 0.85 0.75,0.96 0.85 0.73,0.99 Overall HRd 1.00 0.94, 1.07 1.03 0.93, 1.13 0.86 0.79, 0.94         aWomen using personal calcium or vitamin D supplements at baseline in the CaD trial are excluded bSignificance level (P value) for test of no HR trend across years from CaD initiation Stattic in vivo categories, coded as 0, 1, 2, respectively cOverall HR in the OS divided by that in the CaD trial.