Canagliflozin reduces risk of CV death, hospitalization for HF in patients with T2D, high CV risk
The SGLT2* inhibitor canagliflozin reduced the risk of cardiovascular (CV) death or hospitalization for heart failure (HF) in patients with type 2 diabetes (T2D) and high CV risk, according to investigators of the CANVAS** programme presented at the American College of Cardiology Annual Scientific Session & Expo (ACC.18) in Orlando, Florida, US.
“Among patients with [T2D] and an elevated risk of CV disease, [canagliflozin] reduced the risk of a range of composite and cause-specific [HF] outcomes, … [with greater] benefits in those with a history of [HF],” said first author Professor Gemma Figtree from the University of Sydney in Sydney, Australia.
The programme included 10,142 participants (mean age 63.3 years, 35.8 percent female) from the CANVAS and CANVAS-Renal trials (n=4,330 and 5,812, respectively) who had T2D and high CV risk, 14.4 percent of whom had a history of HF. CANVAS participants were treated with canagliflozin 100 or 300 mg/day or placebo, while CANVAS-Renal participants were treated with canagliflozin (initial dose of 100 mg/day with optional uptitration to 300 mg/day from week 13) or placebo. Patients were followed for a mean 188 weeks. [Circulation 2018;doi:10.1161/CIRCULATIONAHA.118.034222; ACC.18, abstract 407-10]
Compared with placebo, canagliflozin significantly reduced the risk of CV death or hospitalization for HF (16.3 vs 20.8/1,000 patient-years [PY], hazard ratio [HR], 0.78; p=0.002)
Canagliflozin also reduced the secondary outcomes of fatal HF*** or hospitalization for HF (6.4 vs 9.7/1,000 PY, HR, 0.70; p=0.003) and hospitalization for HF alone (5.5 vs 8.7/1,000 PY, HR, 0.67; p=0.002) compared with placebo.
The benefits of canagliflozin on CV death and hospitalization for HF were greater among those with a history of HF vs those without (HR, 0.61 vs 0.87; pinteraction=0.021).
“The benefits for [HF] outcomes appeared early during follow-up, suggesting a mode of action driven primarily by volume and haemodynamic effects,” said the researchers, suggesting potential mechanisms such as reductions in preload and afterload stemming from natriuresis, systemic blood pressure reduction, intrarenal renin angiotensin axis modification, and arterial stiffness reduction. [Eur Heart J 2016;37:1526-1534; Am J Med 2017;130(6S):S30-S39; J Am Coll Cardiol 2012;60:1455-1469]
“Preservation of renal function and the mitigation of volume overload achieved with SGLT2 inhibition [could have] contributed to the observed reduction in [HF] risk,” they added.
Overall, given the high mortality outcomes in patients with T2D and HF, [Diab Vasc Dis Res 2013;10:330-336] the findings suggest that T2D patients at risk of HF may potentially benefit from canagliflozin treatment, said the researchers. “[The] beneficial effects of canagliflozin on [HF] outcomes are likely to be accrued on top of other therapies for [HF] management.”
In conjunction with the EMPA-REG OUTCOME# trial which generated similar results, the findings elucidate the protective effects of canagliflozin on HF and underscore the significance of SGLT2 inhibitors in HF prevention among patients with T2D, said the researchers, citing ongoing trials that may support these results and confirm the influence of SGLT2 inhibitors on HF. [BMJ Open 2017;7:e018097; Circulation 2016;134:752-772]