Table 2.
Meta-analysis for major cardiovascular outcomes in empagliflozin and DPP-4i initiators stratified by pre-existing cardiovascular disease
| Outcomesa,b | With history of cardiovascular disease (CVD) | Without history of cardiovascular disease (CVD) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Empagliflozin | DPP-4i | Meta-analysis | Empagliflozin | DPP-4i | Meta-analysis | |||||
| Events | PY | Events | PY | HR (95% CI)c | Events | PY | Events | PY | HR (95% CI)c | |
| Hospitalization for heart failure (broad definition)d | 430 | 6847.38 | 532 | 6594.72 | 0.81 (0.71–0.92) | 80 | 16,140.31 | 126 | 15,243.11 | 0.61 (0.45–0.82) |
| Hospitalization for heart failure (specific definition)e | 391 | 17,599.16 | 572 | 21,466.81 | 0.72 (0.58–0.89)f | 47 | 15,244.29 | 91 | 18,579.66 | 0.61 (0.42–0.88) |
| Hospitalization for heart failure (broad + specific)g | 663 | 21,025.10 | 920 | 24,749.03 | 0.74 (0.64–0.86) | 97 | 30,723.15 | 167 | 33,288.62 | 0.62 (0.48–0.80) |
| Cardiovascular mortalityh | 79 | 12,174.75 | 206 | 16,212.16 | 0.55 (0.38–0.80) | 23 | 15,705.27 | 41 | 19,634.39 | 0.72 (0.39–1.31) |
| Composite outcome of hospitalization for heart failure or cardiovascular mortalityi | 183 | 10,281.26 | 425 | 14,201.76 | 0.57 (0.48–0.67) | 16 | 10,608.68 | 66 | 14,606.81 | 0.35 (0.20–0.60) |
| Myocardial infarction (MI)j | 250 | 21,258.76 | 295 | 25,146.95 | 1.00 (0.84–1.19) | 102 | 33,298.33 | 107 | 36,643.56 | 1.09 (0.77–1.54) |
| Strokek | 242 | 21,189.34 | 312 | 25,060.14 | 0.79 (0.67–0.94) | 134 | 33,801.77 | 168 | 37,039.94 | 0.90 (0.71–1.14) |
| 3-point MACE (MI, stroke, and cardiovascular mortality)l | 258 | 12,042.29 | 327 | 16,026.79 | 1.04 (0.83–1.31) | 130 | 16,159.66 | 153 | 19,981.63 | 1.03 (0.81–1.30) |
| Coronary revascularization proceduresm | 529 | 19,544.07 | 581 | 23,478.00 | 1.03 (0.83–1.27)f | 153 | 28,937.27 | 173 | 32,497.05 | 0.94 (0.75–1.17) |
CI confidence interval, CPRD Clinical Practice Research Datalink, DPP-4i dipeptidyl peptidase-4 inhibitors, HR hazard ratio, PY person-years, THIN The Health Improvement Network, UK United Kingdom
aAn as-treated approach was used and 100% grace period with no risk window was applied
bCountries with insufficient number of outcome events were omitted from the individual outcome meta-analysis. The number of countries included in each analysis therefore may vary
cBased on random-effects model
dDefined as any diagnosis of heart failure associated with hospitalizations, specialist outpatient and primary care encounters, and/or a dispensation/record of high-ceiling or loop diuretics. Includes Israel, Japan, South Korea, Spain, Taiwan and UK CPRD (in with CVD)
eDefined as a diagnosis of heart failure during hospitalization. Includes Denmark, Finland, Germany, Israel, Japan, Norway (in with CVD), Sweden and Taiwan (in with CVD)
fThese analyses showed high level of heterogeneity I2 ≥ 50% or p < 0.1
gIncludes broad definition in Japan, South Korea, Spain, Taiwan and UK CPRD (in with CVD), and specific definition in Denmark, Finland, Germany, Israel, Norway (in with CVD), Sweden
hIncludes Finland, Norway, Sweden, Taiwan and UK CPRD (in with CVD)
iIncludes Finland, Norway, Sweden and UK CPRD (in with CVD)
jIncludes Denmark, Finland, Germany (in with CVD), Israel, Japan, Norway, South Korea, Spain, Sweden, Taiwan, UK CPRD (in with CVD) and UK THIN
kIncludes Denmark, Finland, Germany (in with CVD), Israel, Japan, Norway, South Korea, Spain, Sweden, Taiwan, UK CPRD and UK THIN (in without CVD)
lIncludes Finland, Norway, Sweden, Taiwan and UK CPRD
mIncludes Denmark, Finland, Israel, Japan, South Korea, Norway, Sweden, Taiwan, UK CPRD and UK THIN (in with CVD)