Supplementary Table 1. Number and rates of treatment discontinuation among patients according to background aspirin and/or statin therapy
Aspirin Statin Both None Overall
P for heterogeneit
y Both Trials
combined Active Placeb
o Active Placeb
o Active Placeb
o Active Placeb
o Active Placebo Discontinue for
any reason (%)
473 (18.3)
417 (16.6)
145 (22.4)
131 (20.4)
225 (22.2)
252 (23.5)
507 (16.4)
524 (16.8)
1350 (18.4)
1324
(18.0) 0.340
Hypotension(%
)
33 (1.27)
14 (0.56)
11 (1.70)
2 (0.31)
15 (1.48)
9 (0.84)
39 (1.26)
15 (0.48)
98 (1.34)
40
(0.54) 0.615
Cough (%) 48
(1.85)
13 (0.52)
26 (4.02)
11 (1.72)
45 (4.44)
22 (2.05)
83 (2.69)
29 (0.93)
202 (2.75)
75
(1.02) 0.612
Patient
preference (%)
238 (9.2)
250 (10.0)
71 (11.0)
73
(11.4) 99 (9.8) 140 (13.0)
259 (8.4)
345
(11.1) 667 (9.1) 808
(11.0) 0.2215 Adverse drug
reaction (%) 40 (1.5) 48 (1.9) 19 (2.9) 17 (2.7) 32 (3.2) 31 (2.9) 38 (1.2) 51 (1.6) 129 (1.8) 147 (2.0)
0.5805
Other (%) 114
(4.4) 92 (3.7) 18 (2.8) 28 (4.4) 34 (3.4) 50 (4.7) 88 (2.8) 84 (2.7) 254 (3.5) 254 (3.5)
0.0907 ADVANCE Active Placeb
o Active Placeb
o Active Placeb
o Active Placeb
o Active Placebo Discontinue for
any reason (%)
262 (20.9)
230 (19.0)
134 (28.3)
122 (25.5)
214 (29.8)
235 (30.4)
403 (19.1)
403 (19.0)
1013 (22.2)
990
(21.6) 0.822
Hypotension(%
)
16 (1.28)
4 (0.33)
9 (1.90)
0 (0)
13 (1.81)
8 (1.04)
31 (1.47)
10 (0.47)
69 (1.51)
22
(0.48) 0.349
Cough (%) 38
(3.04)
12 (0.99)
24 (5.07)
11 (2.30)
44 (6.14)
21 (2.72)
78 (3.69)
28 (1.32)
184 (4.04)
72
(1.57) 0.848
Patient
preference (%)
141 (11.3)
154 (12.7)
69 (14.6)
71 (14.9)
96 (13.4)
132 (17.1)
215 (10.2)
278 (13.1)
521 (11.4)
635
(13.9) 0.628
Adverse drug 26 (2.1) 26 (2.1) 18 (3.8) 15 (3.1) 31 (4.3) 31 (4.0) 31 (1.5) 43 (2.0) 106 (2.3) 115 (2.5) 0.564
reaction (%)
Other (%) 41 (3.3) 34 (2.8) 14 (3.0) 25 (5.2) 30 (4.2) 43 (5.6) 48 (2.3) 44 (2.1) 133 (2.9) 146 (3.2) 0.203 PROGRESS Active Placeb
o Active Placeb
o Active Placeb
o Active Placeb
o Active Placebo Discontinue for
any reason (%)
211 (24.4)
187 (21.3)
11 (37.9)
9 (29.0)
11 (15.5)
17 (34.0)
104 (22.3)
121 (25.3)
337 (23.5)
334
(23.2) 0.121
Hypotension(%
)
17 (1.97)
10 (1.14)
2 (6.90)
2 (6.45)
2 (2.82)
1 (2.00)
8 (1.71)
5 (1.05)
29 (2.03)
18
(1.25) 0.968
Cough (%) 10
(1.16)
1 (0.11)
2 (6.90)
0 (0)
1 (1.41)
1 (2.00)
5 (1.07)
1 (0.21)
18 (1.26)
3
(0.21) 0.550 Patient
preference (%)
97 (11.2)
96
(10.9) 2 (6.9) 2 (6.5) 3 (4.2) 8 (16.0) 44 (9.4)
67 (14.0)
146 (10.2)
173
(12.0) 0.160
Adverse drug
reaction (%) 14 (1.6) 22 (2.5) 1 (3.4) 2 (6.5) 1 (1.4) 0 7 (1.5) 8 (1.7) 23 (1.6) 32 (2.2) 0.793 Other (%) 73 (8.5) 58 (6.6) 4 (13.8) 3 (9.7) 4 (5.6) 2 (4.0) 40 (8.6) 40 (8.4) 121 (8.4) 108 (7.5) 0.901
Supplemental Figure 1. Proportion of patients prescribed aspirin and/or statin therapy in A) ADVANCE and B) PROGRESS
A) ADVANCE
B) PROGRESS
Supplemental Figure 2. Change in mean systolic blood pressure over time between active and placebo arms according to background aspirin and statin use in the combined analysis of ADVANCE and PROGRESS. Blood pressure measurements were combined for
ADVANCE and PROGRESS at each time point, the final PROGRESS measure was collected at 54 months and combined and plotted together with the final ADVANCE
measurement at 60 months.Black solid line = aspirin, red dashed line = statin, green dotted line = both aspirin and statin, blue dotted-dashed line = neither aspirin nor statin.
Supplemental Figure 3. Adjusted hazard ratios for a) cardiovascular death, b) non-fatal myocardial infarction and c) non-fatal stroke associated with combination indapamide and perindopril in patients with baseline background aspirin and/or statin therapy according to ADVANCE and PROGRESS trials. Model adjusted for baseline age, sex, systolic blood pressure, body mass index, diabetes, current smoking status, hypertension treatment, previous stroke and previous coronary heart disease. HR less than 1 favours active / HR greater than 1 favours placebo
A) Cardiovascular death
b) Non-fatal myocardial infarction
c) Non-fatal stroke
Supplemental Figure 4. Adjusted hazard ratios for major vascular events and all-cause mortality associated with combination indapamide and perindopril in patients with baseline background aspirin and/or statin therapy according to ADVANCE and PROGRESS trials.
Model adjusted for baseline age, sex, systolic blood pressure, body mass index, diabetes, current smoking status, hypertension treatment, previous stroke and previous coronary heart disease. HR less than 1 favours active / HR greater than 1 favours placebo
Major cardiovascular events - ADVANCE (p for heterogeneity = 0.668)
Major cardiovascular events - PROGRESS (p for heterogeneity = 0.635)
All-cause mortality - ADVANCE (p for heterogeneity = 0.677)
All-cause mortality - PROGRESS (p for heterogeneity = 0.761)
Supplemental Figure 5. Adjusted hazard ratios for major vascular events and all-cause mortality associated with combination indapamide and perindopril in patients with the time varying effect of background aspirin and/or statin therapy across the trial period according to ADVANCE and PROGRESS trials. Model adjusted for baseline age, sex, systolic blood pressure, body mass index, diabetes, current smoking status, hypertension treatment, previous stroke and previous coronary heart disease. HR less than 1 favours active / HR greater than 1 favours placebo
Major cardiovascular events - ADVANCE (p for heterogeneity = 0.553)
Major cardiovascular events - PROGRESS (p for heterogeneity = 0.170)
All-cause mortality - ADVANCE (p for heterogeneity =0.501)
All-cause mortality - PROGRESS (p for heterogeneity = 0.802)
