Table 2.
Comparison of time to first event analysis and win odds in the seven selected trials
| DAPA-CKD | CREDENCE | FIDELIO-DKD | SONAR | RENAAL | IDNT | ALTITUDE | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Comparisons | Dapagliflozin versus Placebo | Canagliflozin versus Placebo | Finerenone versus Placebo | Atrasentan versus Placebo | Losartan versus Placebo | Irbesartan versus Placebo | Aliskiren versus Placebo | |||||||
| n | HR (95% CI) | n | HR (95% CI) | n | HR (95% CI) | n | HR (95% CI) | n | HR (95% CI) | n | HR (95% CI) | n | HR (95% CI) | |
| Event | ||||||||||||||
| All-cause mortality | 247 | 0.69 (0.53 to 0.88) | 369 | 0.83 (0.68 to 1.02) | 463 | 0.90 (0.75 to 1.07) | 162 | 0.80 (0.67 to 0.96) | 313 | 1.02 (0.81 to 1.27) | 180 | 0.92 (0.69 to 1.23) | 734 | 1.07 (0.92 to 1.23) |
| Kidney replacement | 174 | 0.66 (0.49 to 0.90) | 176 | 0.74 (0.55 to 1.00) | 258 | 0.86 (0.67 to 1.10) | 287 | 0.70 (0.55 to 0.88) | 341 | 0.71 (0.58 to 0.88) | 183 | 0.77 (0.57 to 1.03) | 229 | 1.09 (0.84 to 1.41) |
| GFR <15 ml/min per 1.73 m2 | 204 | 0.67 (0.51 to 0.88) | 203 | 0.60 (0.45 to 0.80) | 366 | 0.82 (0.67 to 1.01) | 114 | 0.76 (0.52 to 1.10) | 409 | 0.76 (0.62 to 0.91) | 196 | 0.61 (0.46 to 0.81) | 175 | 1.12 (0.83 to 1.51) |
| 57% GFR decline | 201 | 0.61 (0.46 to 0.82) | 156 | 0.41 (0.29 to 0.57) | 412 | 0.68 (0.55 to 0.82) | 103 | 0.62 (0.42 to 0.92) | 359 | 0.74 (0.60 to 0.92) | 166 | 0.65 (0.48 to 0.89) | 304 | 1.10 (0.88 to 1.37) |
| 50% GFR decline | 313 | 0.53 (0.42 to 0.67) | 262 | 0.53 (0.41 to 0.69) | 638 | 0.73 (0.62 to 0.85) | 193 | 0.58 (0.44 to 0.78) | 443 | 0.80 (0.67 to 0.97) | 248 | 0.61 (0.47 to 0.79) | 468 | 1.08 (0.90 to 1.30) |
| 40% GFR decline | 538 | 0.63 (0.53 to 0.74) | 454 | 0.59 (0.48 to 0.71) | 1056 | 0.81 (0.72 to 0.92) | 329 | 0.81 (0.65 to 1.01) | 598 | 0.88 (0.75 to 1.04) | 400 | 0.83 (0.68 to 1.01) | 832 | 1.12 (0.98 to 1.28) |
| GFR slopea | 1.12 (0.80,1.43) | 1.66 (1.30,2.00) | 0.64 (0.40 to 0.89) | 0.60 (0.23 to 0.97) | 1.08 (0.40 to 1.76) | 1.10 (0.47 to 1.74) | -0.30 (-0.6 to 0.01) | |||||||
| Treatment effect composite end point | ||||||||||||||
| HR (Cox) | 0.61 (0.51 to 0.73) | 0.70 (0.59 to 0.82) | 0.82 (0.73 to 0.93) | 0.71 (0.58 to 0.88) | 0.79 (0.66 to 0.94) | 0.74 (0.59 to 0.94) | 1.08 (0.95 to 1.23) | |||||||
| WOsb | 1.41 (1.32 to 1.52) | 1.48 (1.38 to 1.58) | 1.26 (1.19 to 1.34) | 1.16 (1.07 to 1.25) | 1.13 (1.00 to 1.27) | 1.17 (1.02 to 1.34) | 0.84 (0.80 to 0.88) | |||||||
Hazard ratios for the composite end point and components were calculated using Cox proportional hazards regression models. The win odds for the kidney hierarchical composite end point are shown in the bottom row. Values are n (%). Hazard ratios were calculated using Cox proportional hazards regression models and were adjusted for covariates as described in the primary publication of each trial. DAPA-CKD, Dapagliflozin and Prevention of Adverse Outcomes in CKD; CREDENCE, Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation; FIDELIO-DKD, FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease; SONAR, Study Of diabetic Nephropathy with AtRasentan; RENAL, Reduction of Endpoints in Non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist Losartan; IDNT, Irbesartan Diabetic Nephropathy Trial; ALTITUDE, Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints; HR, hazard ratio; CI, confidence interval; WO, win odd.
In each trial, the total GFR slope is defined as the annual decline in GFR from randomization until 36 months of follow-up time. Inclusion criteria differ between trials and do not allow direct comparison of results.
Win odds were computed in a hierarchy: all-cause mortality, kidney replacement, GFR <15 ml/min per 1.73 m2, 57%, 50%, 40% GFR decline, and GFR slope.