Tu N Nguyen, Jie Yu, Vlado Perkovic, Meg Jardine, Kenneth W Mahaffey, Clara K Chow, Clare Arnott, Richard I Lindley
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引用次数: 0
Abstract
Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to improve renal and cardiovascular outcomes in patients with type 2 diabetes. Limited evidence exists about the efficacy and safety of SGLT2 inhibitors in patients with frailty.
Methods: This was a post hoc pooled, participant-level data analysis of the CANVAS Program (CANVAS and CANVAS-R) and the CREDENCE trial. We examined the effect of canagliflozin on: (1) Major adverse cardiovascular events (MACE), (2) Cardiovascular mortality, (3) all-cause mortality, and (4) key safety outcomes. Frailty was defined by a Frailty Index (FI) based on a deficit accumulation approach (FI > 0.25: frail). Cox proportional-hazard models were used to estimate the efficacy and safety of canagliflozin overall and according to frailty status.
Results: There were 14,543 participants (10,142 from the CANVAS Program, 4401 from the CREDENCE trial). Their mean age was 63.2 years; 35.3% were female. Frailty was present in 56% of the study participants. The benefits of canagliflozin were observed in both the frail and non-frail subgroups: HRs for MACE 0.80 (95% CI 0.70-0.90) in the frail versus 0.91 (95% CI 0.75-1.09) in the non-frail (p for interaction = 0.27); HRs for cardiovascular mortality 0.79 (95% CI 0.67-0.95) in the frail versus 0.94 (95% CI 0.70-1.27) in the non-frail (p for interaction = 0.38); HRs for all-cause mortality 0.81 (95% CI 0.70-0.94) in the frail versus 0.93 (95% CI 0.74-1.16) in the non-frail (p for interaction = 0.39). Adverse events were similar among frail and non-frail participants, except for osmotic diuresis (HRs 1.67, 95% CI 1.22-2.28 in the frail vs. 3.05, 95% CI 2.13-4.35 in the non-frail, p for interaction = 0.01).
Conclusions: Canagliflozin improved cardiovascular and mortality endpoints in participants with type 2 diabetes irrespective of frailty status, with a similar safety profile. Our findings, in addition to those from other recent studies, provide evidence to support the introduction of SGLT2 inhibitor therapy in patients perceived to be frail.
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