Canagliflozin May Have Most Benefit in Diabetes With HF: CANVAS

Marlene Busko

March 15, 2018

ORLANDO — The antidiabetic sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin (InvokanaInvokamet, Janssen) lowered the risk for hospitalization for heart failure (HF) or dying of cardiovascular disease in patients with type 2 diabetes, regardless of whether they already had HF, researchers report.

In fact, in this exploratory analysis from the Canagliflozin Cardiovascular Assessment Study (CANVAS), the 14% of patients with type 2 diabetes who already had HF appeared to benefit most.    

Gemma Figtree, MBBS, DPhil, The George Institute for Global Health, University of New South Wales, Sydney, Australia, presented this deeper dive into CANVAS here at the American College of Cardiology (ACC) 2018 Annual Scientific Session. The study was simultaneously published online March 11 in Circulation.

"We're really excited," Figtree told theheart.org | Medscape Cardiology , that this study supports earlier hints of this benefit for HF with this class of drugs.

According to Figtree, an SGLT2 inhibitor "appears to be beneficial but potentially even more so — obviously taken into context with the increased absolute event rate — in patients who have had heart failure at baseline."

"Importantly, that needs to be tested in a heart failure–dedicated study," she cautioned, stressing that only 14% of the study population had HF at baseline and the diagnosis was based on clinical history and not adjudicated.

Nevertheless, these are encouraging early findings. "Heart failure with reduced ejection fraction (HFrEF) has lots of pharmacological treatments that improve outcomes," she observed, but for HF with preserved ejection fraction (HFpEF), which accounts for at least 50% of hospitalized patients with HF, there is "symptomatic treatment but we don't have treatment that alters outcome."

"Whether or not this beneficial effect we're seeing with the SGTL2 inhibitors is actually having an effect in patients with heart failure and preserved ejection fraction is really, really exciting and important," she said.

The heart failure signal in CANVAS was "impressive," session panelist , Elliott M Antman, MD, Brigham and Women's Hospital, Boston, Massachusetts, agreed in an interview with theheart.org | Medscape Cardiology

"We need to see more physiologic evaluation of what's behind this very positive benefit that we're repeatedly seeing now with this class of drugs," he added, "and I think that's the next big breakthrough that we're liable to encounter."

"What I heard was endorsement of the fact that for a patient with diabetes and heart failure, now we have an option that we can prescribe which has some pretty impressive results."  

EMPA-REG and CANVAS

Patients with type 2 diabetes are at increased risk for HF, with impaired quality of life and possibly the need for hospitalization, Figtree noted.

The Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes trial (EMPA-REG OUTCOME) trial of the SGLT2 inhibitor empagliflozin (Jardiance, Lilly/Boehringer Ingelheim), in a broad range of patients, and the CANVAS trial of canagliflozin showed that these SGLT2 inhibitors decreased the risk for being hospitalized for HF.

The current study examined the CANVAS dataset to specifically look at patients with HF at baseline.

CANVAS randomly assigned 10,142 participants with type 2 diabetes and high cardiovascular risk to canagliflozin or placebo, and the patients were followed for a mean of 3.6 years.

At baseline, 1461 patients (14%) had a prior diagnosis of HF.

The patients had a mean age of 64. Those with HF were more often women and were more likely to use diuretics, renin-angiotensin-aldosterone system (RAAS) blockers, and β-blockers and less likely to use statins and metformin (P < .001 for all).

The primary outcome, a composite of cardiovascular death or hospitalization for HF, was less likely in patients who were receiving canagliflozin than in those receiving placebo (hazard ratio [HR], 0.78; 95% CI, 0.67 - 0.91).

Other cardiovascular outcomes and death generally occurred more frequently in patients with a history of HF than in those without, but both groups had similar reductions in the risks for these outcomes with the use of canagliflozin vs placebo.

Canagliflozin was associated with a lower risk for hospitalization for HF compared with placebo (HR, 0.67; 95% CI, 0.52 - 0.87), with no significant interaction associated with age; sex; history of myocardial infarction; or baseline use of diuretics, β-blockers, or RAAS blockade.

The number needed to treat to prevent 1 HF event in 5 years was substantially lower in patients with prior HF (1 in 14) than in those without a history of HF (1 in 144).

Safety outcomes, including the increased risk for amputation with canagliflozin vs placebo, were similar in patients with or without HF at baseline.

"The CANVAS Program data provide clear evidence of the protective effects of canagliflozin on heart failure and, in conjunction with EMPA-REG OUTCOME, suggest an important role for SGLT2 inhibitors in the prevention of heart failure among patients with type 2 diabetes," the researchers conclude.

"Additional data from ongoing trials in diabetes will further clarify the impact of SGLT2 inhibitors on this major cause of mortality and morbidity."

The trial was funded by Janssen. Figtree has received research support from the cofunded National Health and Medical Research Council and Heart Foundation (Australia) Fellowship and from Heart Research Australia, and compensation from Janssen for serving on the adjudication panel of the CANVAS Program. Antman has received research grants from Daiichi Sankyo and Eli Lilly.

American College of Cardiology (ACC) 2018 Annual Scientific Session. Abstract 407-10. Presented March 11, 2018.

Circulation. Published online March 11, 2018. Abstract  

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