Baseline patient characteristics according to CV and SHEs occurring during the study
| . | No SHE during trial (N = 14,286) . | SHE during trial (N = 466) . | CV event before SHE during trial (N = 50) . | SHE before CV event during trial (N = 66)* . | Did not have SHE and CV event during trial (N = 14,636) . |
|---|---|---|---|---|---|
| Age at randomization (years) | 62 (56, 68) | 63 (57, 70) | 67 (59, 71) | 65 (61, 70) | 62 (56, 68) |
| Female sex | 5,422 (38.0) | 181 (38.8) | 15 (30.0) | 16 (24.2) | 5,572 (38.1) |
| Race | |||||
| White | 10,865 (76.1) | 310 (66.5) | 33 (66.0) | 50 (75.8) | 11,092 (75.8) |
| Black | 832 (5.8) | 46 (9.9) | 6 (12.0) | 5 (7.6) | 867 (5.9) |
| Asian | 1,402 (9.8) | 50 (10.7) | 4 (8.0) | 6 (9.1) | 1,442 (9.9) |
| Other | 1,182 (8.3) | 60 (12.9) | 7 (14.0) | 5 (7.6) | 1,230 (8.4) |
| Duration of type 2 diabetes (years) | 12 (7, 17) | 14 (9, 22) | 16 (11, 22) | 17 (10, 24) | 12 (7, 18) |
| History of CV disease | |||||
| Coronary artery disease | 7,505 (52.5) | 289 (62.0) | 36 (72.0) | 55 (83.3) | 7,703 (52.6) |
| Cerebrovascular disease | 2,419 (16.9) | 90 (19.3) | 11 (22.0) | 23 (34.8) | 2,475 (16.9) |
| Peripheral artery disease | 2,712 (19.0) | 88 (18.9) | 13 (26.0) | 12 (18.2) | 2,775 (19.0) |
| CV event | |||||
| Prior CV event | 10,421 (72.9) | 361 (77.5) | 43 (86.0) | 64 (97.0) | 10,675 (72.9) |
| CV disease without prior event | 143 (1.0) | 6 (1.3) | 0 (0) | 0 (0) | 149 (1.0) |
| Neither prior CV event nor disease | 3,722 (26.1) | 99 (21.2) | 7 (14.0) | 2 (3.0) | 3,812 (26.0) |
| Heart failure | 2,291 (16.0) | 98 (21.0) | 16 (32.0) | 27 (40.9) | 2,346 (16.0) |
| Charlson Comorbidity Index | 5 (4, 7) | 6 (5, 8) | 7 (5, 9) | 8 (6, 9) | 5 (4, 7) |
| Systolic blood pressure (mmHg) | 135 (124, 145) | 135 (125, 148) | 136 (127, 145) | 131 (120, 145) | 135 (124, 145) |
| Diastolic blood pressure (mmHg) | 80 (70, 85) | 78 (70, 82) | 77 (68, 82) | 77 (65, 81) | 80 (70, 85) |
| Heart rate (bpm) | 72 (66, 80) | 72 (65, 80) | 74 (64, 80) | 73 (66, 84) | 72 (66, 80) |
| BMI (kg/m2) | 31.8 (28.3, 36.2) | 31.6 (27.9, 36.5) | 32.7 (29.7, 36.9) | 33.3 (28.6, 37.5) | 31.8 (28.2, 36.2) |
| HbA1c (%) | 8.0 (7.3, 8.9) | 8.1 (7.5, 8.9) | 8.6 (7.7, 9.4) | 8.0 (7.3, 9.1) | 8.0 (7.3, 8.9) |
| Total cholesterol (mg/dL) | 166 (138, 201) | 163 (137, 197) | 164 (138, 200) | 146 (123, 176) | 166 (138, 201) |
| LDL (mg/dL) | 88 (66, 116) | 87 (65, 119) | 80 (60, 104) | 77 (62, 104) | 88 (66, 116) |
| HDL (mg/dL) | 42 (35, 50) | 42 (35, 49) | 42 (34, 49) | 38 (32, 44) | 42 (35, 50) |
| Triglycerides (mg/dL) | 159 (114, 228) | 163 (106, 230) | 170 (106, 255) | 162 (104, 222) | 159 (114, 228) |
| eGFR (mL/min/1.73 m2) | 77 (61, 92) | 70 (55, 86) | 64 (54, 87) | 61 (45, 80) | 76 (61, 92) |
| ≥90 | 4,172 (29.3) | 96 (20.6) | 11 (22.0) | 9 (13.6) | 4,248 (29.1) |
| 60–89 | 7,027 (49.3) | 219 (47.1) | 19 (38.0) | 27 (40.9) | 7,200 (49.4) |
| 30–59 | 3,027 (21.3) | 150 (32.3) | 20 (40.0) | 30 (45.5) | 3,127 (21.4) |
| <30 | 14 (0.1) | 0 (0) | 0 (0) | 0 (0) | 14 (0.1) |
| CV medications | |||||
| Aspirin | 9,055 (63.4) | 325 (69.7) | 38 (76.0) | 58 (87.9) | 9,284 (63.4) |
| Thienopyridines | 2,426 (17.0) | 98 (21.0) | 16 (32.0) | 24 (36.4) | 2,484 (17.0) |
| Any antiplatelets | 10,472 (73.4) | 363 (77.9) | 45 (90.0) | 60 (90.9) | 10,730 (73.4) |
| ACEI or ARB | 11,024 (77.2) | 374 (80.3) | 38 (76.0) | 52 (78.8) | 11,308 (77.3) |
| β-Blockers | 7,933 (55.5) | 278 (59.7) | 36 (72.0) | 49 (74.2) | 8,126 (55.5) |
| Calcium channel blockers | 4,550 (31.8) | 160 (34.3) | 14 (28.0) | 28 (42.4) | 4,668 (31.9) |
| Any antihypertensive | 12,894 (90.3) | 429 (92.1) | 49 (98.0) | 65 (98.5) | 13,209 (90.3) |
| Statin | 10,479 (73.4) | 366 (78.5) | 41 (82.0) | 59 (89.4) | 10,745 (73.4) |
| Any lipid-lowering medication | 10,992 (76.9) | 378 (81.1) | 42 (84.0) | 59 (89.4) | 11,269 (77.0) |
| Diuretics | 6,208 (43.5) | 235 (50.4) | 34 (68.0) | 46 (69.7) | 6,363 (43.5) |
| Diabetes medications | |||||
| Biguanide | 10,982 (76.9) | 313 (67.2) | 29 (58.0) | 39 (59.1) | 11,227 (76.7) |
| Sulfonylurea | 5,253 (36.8) | 148 (31.8) | 11 (22.0) | 14 (21.2) | 5,376 (36.7) |
| Insulin | 6,509 (45.6) | 327 (70.2) | 40 (80.0) | 52 (78.8) | 6,744 (46.1) |
| Dose (units/kg body wt) | 0.62 (0.39, 0.89) | 0.73 (0.45, 1.07) | 0.72 (0.43, 1.12) | 0.87 (0.52, 1.19) | 0.62 (0.39, 0.90) |
| DPP-4i | 2,148 (15.0) | 55 (11.8) | 1 (2.0) | 6 (9.1) | 2,196 (15.0) |
| TZD | 565 (4.0) | 14 (3.0) | 0 (0) | 4 (6.1) | 575 (3.9) |
| Other | 610 (4.3) | 14 (3.0) | 0 (0) | 3 (4.5) | 621 (4.2) |
| Insulin/sulfonylurea/NSS | 11,005 (77.0) | 435 (93.3) | 48 (96.0) | 63 (95.5) | 11,329 (77.4) |
| . | No SHE during trial (N = 14,286) . | SHE during trial (N = 466) . | CV event before SHE during trial (N = 50) . | SHE before CV event during trial (N = 66)* . | Did not have SHE and CV event during trial (N = 14,636) . |
|---|---|---|---|---|---|
| Age at randomization (years) | 62 (56, 68) | 63 (57, 70) | 67 (59, 71) | 65 (61, 70) | 62 (56, 68) |
| Female sex | 5,422 (38.0) | 181 (38.8) | 15 (30.0) | 16 (24.2) | 5,572 (38.1) |
| Race | |||||
| White | 10,865 (76.1) | 310 (66.5) | 33 (66.0) | 50 (75.8) | 11,092 (75.8) |
| Black | 832 (5.8) | 46 (9.9) | 6 (12.0) | 5 (7.6) | 867 (5.9) |
| Asian | 1,402 (9.8) | 50 (10.7) | 4 (8.0) | 6 (9.1) | 1,442 (9.9) |
| Other | 1,182 (8.3) | 60 (12.9) | 7 (14.0) | 5 (7.6) | 1,230 (8.4) |
| Duration of type 2 diabetes (years) | 12 (7, 17) | 14 (9, 22) | 16 (11, 22) | 17 (10, 24) | 12 (7, 18) |
| History of CV disease | |||||
| Coronary artery disease | 7,505 (52.5) | 289 (62.0) | 36 (72.0) | 55 (83.3) | 7,703 (52.6) |
| Cerebrovascular disease | 2,419 (16.9) | 90 (19.3) | 11 (22.0) | 23 (34.8) | 2,475 (16.9) |
| Peripheral artery disease | 2,712 (19.0) | 88 (18.9) | 13 (26.0) | 12 (18.2) | 2,775 (19.0) |
| CV event | |||||
| Prior CV event | 10,421 (72.9) | 361 (77.5) | 43 (86.0) | 64 (97.0) | 10,675 (72.9) |
| CV disease without prior event | 143 (1.0) | 6 (1.3) | 0 (0) | 0 (0) | 149 (1.0) |
| Neither prior CV event nor disease | 3,722 (26.1) | 99 (21.2) | 7 (14.0) | 2 (3.0) | 3,812 (26.0) |
| Heart failure | 2,291 (16.0) | 98 (21.0) | 16 (32.0) | 27 (40.9) | 2,346 (16.0) |
| Charlson Comorbidity Index | 5 (4, 7) | 6 (5, 8) | 7 (5, 9) | 8 (6, 9) | 5 (4, 7) |
| Systolic blood pressure (mmHg) | 135 (124, 145) | 135 (125, 148) | 136 (127, 145) | 131 (120, 145) | 135 (124, 145) |
| Diastolic blood pressure (mmHg) | 80 (70, 85) | 78 (70, 82) | 77 (68, 82) | 77 (65, 81) | 80 (70, 85) |
| Heart rate (bpm) | 72 (66, 80) | 72 (65, 80) | 74 (64, 80) | 73 (66, 84) | 72 (66, 80) |
| BMI (kg/m2) | 31.8 (28.3, 36.2) | 31.6 (27.9, 36.5) | 32.7 (29.7, 36.9) | 33.3 (28.6, 37.5) | 31.8 (28.2, 36.2) |
| HbA1c (%) | 8.0 (7.3, 8.9) | 8.1 (7.5, 8.9) | 8.6 (7.7, 9.4) | 8.0 (7.3, 9.1) | 8.0 (7.3, 8.9) |
| Total cholesterol (mg/dL) | 166 (138, 201) | 163 (137, 197) | 164 (138, 200) | 146 (123, 176) | 166 (138, 201) |
| LDL (mg/dL) | 88 (66, 116) | 87 (65, 119) | 80 (60, 104) | 77 (62, 104) | 88 (66, 116) |
| HDL (mg/dL) | 42 (35, 50) | 42 (35, 49) | 42 (34, 49) | 38 (32, 44) | 42 (35, 50) |
| Triglycerides (mg/dL) | 159 (114, 228) | 163 (106, 230) | 170 (106, 255) | 162 (104, 222) | 159 (114, 228) |
| eGFR (mL/min/1.73 m2) | 77 (61, 92) | 70 (55, 86) | 64 (54, 87) | 61 (45, 80) | 76 (61, 92) |
| ≥90 | 4,172 (29.3) | 96 (20.6) | 11 (22.0) | 9 (13.6) | 4,248 (29.1) |
| 60–89 | 7,027 (49.3) | 219 (47.1) | 19 (38.0) | 27 (40.9) | 7,200 (49.4) |
| 30–59 | 3,027 (21.3) | 150 (32.3) | 20 (40.0) | 30 (45.5) | 3,127 (21.4) |
| <30 | 14 (0.1) | 0 (0) | 0 (0) | 0 (0) | 14 (0.1) |
| CV medications | |||||
| Aspirin | 9,055 (63.4) | 325 (69.7) | 38 (76.0) | 58 (87.9) | 9,284 (63.4) |
| Thienopyridines | 2,426 (17.0) | 98 (21.0) | 16 (32.0) | 24 (36.4) | 2,484 (17.0) |
| Any antiplatelets | 10,472 (73.4) | 363 (77.9) | 45 (90.0) | 60 (90.9) | 10,730 (73.4) |
| ACEI or ARB | 11,024 (77.2) | 374 (80.3) | 38 (76.0) | 52 (78.8) | 11,308 (77.3) |
| β-Blockers | 7,933 (55.5) | 278 (59.7) | 36 (72.0) | 49 (74.2) | 8,126 (55.5) |
| Calcium channel blockers | 4,550 (31.8) | 160 (34.3) | 14 (28.0) | 28 (42.4) | 4,668 (31.9) |
| Any antihypertensive | 12,894 (90.3) | 429 (92.1) | 49 (98.0) | 65 (98.5) | 13,209 (90.3) |
| Statin | 10,479 (73.4) | 366 (78.5) | 41 (82.0) | 59 (89.4) | 10,745 (73.4) |
| Any lipid-lowering medication | 10,992 (76.9) | 378 (81.1) | 42 (84.0) | 59 (89.4) | 11,269 (77.0) |
| Diuretics | 6,208 (43.5) | 235 (50.4) | 34 (68.0) | 46 (69.7) | 6,363 (43.5) |
| Diabetes medications | |||||
| Biguanide | 10,982 (76.9) | 313 (67.2) | 29 (58.0) | 39 (59.1) | 11,227 (76.7) |
| Sulfonylurea | 5,253 (36.8) | 148 (31.8) | 11 (22.0) | 14 (21.2) | 5,376 (36.7) |
| Insulin | 6,509 (45.6) | 327 (70.2) | 40 (80.0) | 52 (78.8) | 6,744 (46.1) |
| Dose (units/kg body wt) | 0.62 (0.39, 0.89) | 0.73 (0.45, 1.07) | 0.72 (0.43, 1.12) | 0.87 (0.52, 1.19) | 0.62 (0.39, 0.90) |
| DPP-4i | 2,148 (15.0) | 55 (11.8) | 1 (2.0) | 6 (9.1) | 2,196 (15.0) |
| TZD | 565 (4.0) | 14 (3.0) | 0 (0) | 4 (6.1) | 575 (3.9) |
| Other | 610 (4.3) | 14 (3.0) | 0 (0) | 3 (4.5) | 621 (4.2) |
| Insulin/sulfonylurea/NSS | 11,005 (77.0) | 435 (93.3) | 48 (96.0) | 63 (95.5) | 11,329 (77.4) |
Data are n (%) or median (25th, 75th percentile). ACEI, ACE inhibitor; ARB, angiotensin receptor blocker; DPP-4i, dipeptidyl peptidase 4 inhibitor; NSS, nonsulfonylurea secretagogues; TZD, thiazolidinedione.
Four patients with CV event and SHE on the same day are included with the SHE before CV event group.