Table 2.
Association between second-line therapies and primary clinical outcomes according to the main analysis and selected sensitivity analyses
| Second-line agent | ||||
| SU | DPP-4i | SGLT2i | GLP-1-RA | |
| Main analysis | ||||
| Patients, n | 1208 | 1208 | 1208 | 1208 |
| MACE* | ||||
| Events, n (%) | 234 (20.2) | 176 (15.3) | 157 (13.4) | 153 (13.1) |
| HR (95% CI) | Reference | 0.78 (0.63 to 0.97) | 0.71 (0.56 to 0.88) | 0.59 (0.47 to 0.74) |
| All-cause death | ||||
| Events, n (%) | 144 (11.9) | 101 (8.4) | 74 (6.1) | 66 (5.5) |
| HR (95% CI) | Reference | 0.73 (0.55 to 0.98) | 0.66 (0.49 to 0.89) | 0.47 (0.34 to 0.66) |
| High-dimensional propensity score approach | ||||
| Patients, n | 1095 | 1095 | 1095 | 1095 |
| MACE* | ||||
| Events, n (%) | 226 (20.6) | 197 (18.0) | 143 (13.1) | 150 (13.7) |
| HR (95% CI) | Reference | 0.86 (0.70 to 1.05) | 0.69 (0.55 to 0.86) | 0.64 (0.51 to 0.79) |
| All-cause death | ||||
| Events, n (%) | 122 (11.1) | 95 (8.7) | 74 (6.8) | 57 (5.2) |
| HR (95% CI) | Reference | 0.77 (0.58 to 1.02) | 0.67 (0.49 to 0.91) | 0.40 (0.28 to 0.57) |
| Probability-of-censoring weights approach | ||||
| Patients, n | 10 577 | 8125 | 2893 | 1272 |
| MACE* | ||||
| Events, n (%) | 713 (6.8) | 418 (5.2) | 109 (3.8) | 47 (3.7) |
| HR (95% CI) | Reference | 0.72 (0.59 to 0.89) | 0.59 (0.41 to 0.85) | 0.64 (0.39 to 1.04) |
| All-cause death | ||||
| Events, n (%) | 1811 (17.1) | 829 (10.2) | 97 (3.4) | 40 (3.2) |
| HR (95% CI) | Reference | 0.75 (0.67 to 0.85) | 0.62 (0.47 to 0.82) | 0.61 (0.41 to 0.90) |
| Different definition of MACE† | ||||
| Patients, n | 1208 | 1208 | 1208 | 1208 |
| MACE† | ||||
| Events, n (%) | 103 (8.9) | 88 (7.7) | 80 (6.8) | 68 (5.8) |
| HR (95% CI) | Reference | 0.80 (0.60 to 1.06) | 0.79 (0.59 to 1.06) | 0.62 (0.45 to 0.84) |
| Changing the target population | ||||
| Patients, n | 541 | 541 | 541 | 541 |
| MACE* | ||||
| Events, n (%) | 60 (11.1) | 44 (8.1) | 29 (5.4) | 45 (8.3) |
| HR (95% CI) | Reference | 0.76 (0.51 to 1.12) | 0.52 (0.34 to 0.81) | 0.75 (0.51 to 1.11) |
| All-cause death | ||||
| Events, n (%) | 32 (5.9) | 22 (4.1) | 24 (4.4) | 21 (3.9) |
| HR (95% CI) | Reference | 0.70 (0.40 to 1.21) | 0.28 (0.13 to 0.61) | 0.54 (0.30 to 0.98) |
*Composite outcome including myocardial infarction, stroke, heart failure or all-cause deaths.
†Composite outcome including myocardial infarction, stoke or cardiovascular (CV) deaths.
DPP-4i, dipeptidyl peptidase-4 inhibitor; GLP-1-RA, glucagon-like peptide-1 receptor agonist; MACE, major adverse cardiovascular event; SGLT2i, sodium-glucose cotransporter 2 inhibitor; SU, sulfonylurea and glinides.