DECLARE-TIMI 58 outcomes consistent in people with peripheral artery disease
medwireNews: Patients with type 2 diabetes and peripheral artery disease (PAD) may derive greater absolute benefit from dapagliflozin than those without the comorbidity due to their increased risk for cardiovascular and renal events, DECLARE-TIMI 58 data show.
The findings, presented at the American College of Cardiology 68th Annual Scientific Session in New Orleans, Louisiana, also revealed that patients receiving the sodium-glucose cotransporter (SGLT)2 inhibitor had no significantly increased risk for lower limb amputation, regardless of whether or not they had PAD.
In DECLARE-TIMI 58, 17,160 patients with type 2 diabetes were randomly assigned to receive either dapagliflozin 10 mg daily or placebo. Of these, 1025 (6%) had PAD. The initial analysis showed that patients receiving dapagliflozin had a significant 17% lower risk for cardiovascular death or hospitalization for heart failure (HHF) than those receiving placebo.
In the current analysis, Marc Bonaca and colleagues from the Brigham and Women’s Hospital in Boston, Massachusetts, USA, found that patients with PAD had approximately double the risk for major cardiovascular events, cardiovascular death or HHF, and renal events compared with those without PAD regardless of whether they received dapagliflozin or placebo.
Nonetheless, patients both with and without PAD benefitted from treatment with dapagliflozin versus placebo, with relative reductions of 14% and 18%, respectively, for CV death or HHF and 22% and 24%, respectively, for renal events. The risk reductions were only significant, however, for the patients without PAD.
By contrast, absolute risk reductions with dapagliflozin versus placebo were greater among the patients with PAD than among those without, at 1.4% versus 0.9% for CV death or HHF and 2.1% versus 1.3% for renal events.
Given the current uncertainty surrounding a potential increased risk for limb amputation among patients receiving SGLT2 inhibitors, Bonaca and team also analyzed the DECLARE-TIMI 58 data for limb complications.
They found that during a median follow-up period of 4.2 years, there were 560 limb ischemic adverse events and 236 amputations overall. The rates of these events did not differ significantly between the patients who received dapagliflozin and those who received placebo, at 3.37% versus 3.16% for limb ischemia and 1.43% versus 1.32% for amputation, respectively.
And although the patients with PAD had higher rates of limb complications overall, there was also no excess risk associated with dapagliflozin use in this group. Specifically, the rates of any limb ischemic adverse event were 19.4% and 20.3% for dapagliflozin and placebo, respectively, while those for amputation were 8.4% and 5.6%, respectively, with no significant between group differences observed.
Finally, the investigators analyzed amputation risk in subgroups according to age, diabetes duration, renal function, and glycated hemoglobin level but found “no consistent pattern of risk or benefit related to limb events” associated with dapagliflozin use.
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group