1. Patients without CKD (n=1996)
Supplemental data
Serious adverse events reported in the COPE trial
Patients with CKD (n=834)
Patients without CKD (n=1996)
P value
Beni + ARB
Beni + BB
Beni + TD
Total
Angina pectoris
2(0.7%)
5(1.8%)
3(1.1%)
0.499
10(1.2%)
4(0.6%)
6(0.9%)
7(1.0%)
0.689
17(0.9%)
0.393
Arteriosclerosis obliterans
0(0.0%)
2(0.8%)
0.354
4(0.5%)
3(0.5%)
1(0.2%)
1(0.1%)
0.440
5(0.3%)
0.328
Cardiac failure
1(0.3%)
1(0.4%)
4(1.5%)
0.180
6(0.7%)
2(0.3%)
0.858
7(0.4%)
0.189
Cataract operation
0.057
5(0.6%)
3(0.4%)
0.407
8(0.4%)
0.482
Cerebral hemorrhage
0.394
7(1.1%)
0.150
12(0.6%)
0.688
Gastric cancer
0.854
0.385
Lacunar infarction
4(1.4%)
0.154
0.690
9(0.5%)
0.375
Lung neoplasm malignant
0.731
0.379
4(0.2%)
0.205
Myocardial infarction
0.220
0.586
6(0.3%)
0.248
Pneumonia
0.770
9(1.1%)
0.823
0.004
Prostate cancer
3(1.0%)
0.618
0.113
Thrombotic stroke
0.998
0.844
0.976
Transient ischemic attack
0.466
0.569
0.358
Pneumonia：肺炎
Abbreviations: Beni=benidipine , ARB =angiotensin receptor blocker, BB = β-blocker, TD = thiazide diuretic,
Data are shown as number of patients (%).

2. Patients without CKD (n=1996)
Supplemental data
Adverse events reported in the COPE trial
Patients with CKD (n=834)
Patients without CKD (n=1996)
P value
Beni + ARB
Beni + BB
Beni + TD
Total
Alanine aminotransferase increased
7(2.4%)
8(2.8%)
8(3.0%)
0.911
23(2.8%)
20(3.0%)
7(1.1%)
25(3.7%)
0.009
52(2.6%)
0.834
Aspartate aminotransferase increased
7(2.7%)
0.959
22(2.6%)
19(2.9%)
10(1.5%)
19(2.8%)
0.212
48(2.4%)
0.731
Back pain
1(0.3%)
2(0.7%)
6(2.3%)
0.070
9(1.1%)
5(0.8%)
4(0.6%)
0.615
16(0.8%)
0.479
Blood alkaline phosphatase increased
6(2.1%)
1(0.4%)
2(0.8%)
0.111
8(1.2%)
11(1.6%)
0.235
23(1.2%)
0.857
Blood creatinine increased
5(1.8%)
13(4.9%)
0.076
25(3.0%)
1(0.2%)
5(0.7%)
0.117
7(0.4%)
<0.001
Blood urea increased
10(3.5%)
9(3.4%)
0.566
2(0.3%)
0.478
12(0.6%)
Bradycardia
0(0.0%)
9(3.2%)
3(0.5%)
32(4.9%)
1(0.1%)
36(1.8%)
0.156
Bronchitis
15(5.2%)
10(3.8%)
0.084
30(3.6%)
13(2.0%)
16(2.5%)
15(2.2%)
0.832
44(2.2%)
0.036
Diabetes mellitus
13(4.6%)
0.252
28(3.4%)
15(2.3%)
25(3.9%)
0.229
59(3.0%)
0.588
Eczema
4(1.4%)
0.646
8(1.0%)
0.930
11(0.6%)
0.230
Gamma-glutamyltransferase increased
3(1.1%)
0.641
6(0.7%)
0.319
21(1.1%)
0.400
Gastroenteritis
0.021
6(0.9%)
0.847
15(0.8%)
0.583
Glycosylated hemoglobin increased
5(1.9%)
0.237
10(1.2%)
9(1.3%)
0.574
20(1.0%)
0.650
Hypercholesterolemia
5(1.7%)
7(2.5%)
0.499
15(1.8%)
16(2.4%)
0.256
56(2.8%)
0.114
Hyperglycemia
0.725
0.417
0.863
Hyperkalemia
0.457
10(0.5%)
0.045
Hyperlipidemia
11(3.9%)
0.610
27(3.2%)
17(2.6%)
14(2.2%)
17(2.5%)
0.872
0.217
Hypertriglyceridemia
0.628
21(2.5%)
22(3.4%)
0.475
0.654
Hyperuricemia
28(10.6%)
42(5.0%)
12(1.9%)
47(6.9%)
66(3.3%)
0.031
Hypokalemia
7(0.8%)
20(2.9%)
25(1.3%)
0.337
Hypotension
0.266
5(0.6%)
0.807
0.988
Nasopharyngitis
0.491
24(2.9%)
13(1.9%)
0.614
43(2.2%)
0.257
Osteoarthritis
3(1.0%)
0.057
3(0.4%)
0.922
19(1.0%)
0.100
Pharyngitis
0.213
11(1.3%)
0.004
27(1.4%)
0.932
Proteinuria
4(1.5%)
0.935
13(1.6%)
0.221
17(0.9%)
0.097
Upper respiratory tract inflammation
9(3.1%)
0.751
0.390
37(1.9%)
0.189
Vertigo
0.033
9(1.4%)
12(1.8%)
0.157
0.897
Pneumonia：肺炎
Abbreviations: ALT=alanine aminotransferase, Beni=benidipine , ARB =angiotensin receptor blocker, BB = β-blocker, TD = thiazide diuretic,
Data are shown as number of patients (%).