DECLARE analyses show dapagliflozin benefits for reduced ejection fraction, prior MI subgroups
medwireNews: Further analysis of the DECLARE-TIMI 58 trial shows dapagliflozin to be of particular benefit for patients who have previous myocardial infarction (MI) or heart failure (HF) with reduced ejection fraction.
The two papers were presented at the American College of Cardiology 68th Annual Scientific Session in New Orleans, Louisiana, with simultaneous publication in Circulation.
Similar to the CANVAS analysis reported the previous day, Stephen Wiviott (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and co-investigators found numerical reductions associated with dapagliflozin versus placebo in the risk for cardiovascular mortality or HF hospitalization among study participants with a history of HF irrespective of their ejection fraction.
However, the reduction was significant only among those known to have a reduced ejection faction (<45%), at 38% (or a 9.2% absolute reduction), and the reduction in this subgroup was significantly greater than the 12% reduction in the subgroup without reduced ejection fraction.
This resulted mainly from a 45% relative reduction in cardiovascular mortality risk for patients with reduced ejection fraction, which emerged within the first 3 months of treatment, whereas patients with preserved ejection fraction began to benefit only after a year of treatment.
Writing in an editorial accompanying the journal publications, Subodh Verma (University of Toronto, Ontario, Canada) and John McMurray (University of Glasgow, UK) describe this pattern of benefit as “intriguing but based on small numbers.”
They also note that the prevalence of reduced ejection fraction, recorded in 3.9% of the 17,160 people with type 2 diabetes recruited to the trial, “was perhaps higher than might be expected.”
They say: “Often the focus in diabetes has been on heart failure with preserved [ejection fraction], which although more common, is not the sole heart failure phenotype and carries considerably less risk of adverse outcomes than heart failure with reduced [ejection fraction].”
The prevalence of HF without reduced ejection fraction was 7.7%, although less than two-thirds of these people actually had a recording of preserved ejection fraction. But among placebo-treated patients, the 4-year rate of cardiovascular mortality or HF hospitalization was 14.8%, compared with 27.1% for those with a reduced ejection fraction.
However, the editorialists advise waiting for the results of dedicated ongoing trials of sodium-glucose cotransporter (SGLT)2 inhibitors in people with type 2 diabetes and HF before changing prescribing practice.
The second analysis found a significant benefit for study participants with previous MI, with these 3584 (20.9%) patients having major adverse cardiovascular event (MACE) rates of 15.2% with dapagliflozin versus 17.8% with placebo, giving a relative risk reduction of 16% and a number needed to treat of 39 patients over 4 years.
By contrast, dapagliflozin did not influence MACE rates in the 13,576 participants without prior MI (7.1 vs 7.1% with placebo) or even in those with established atherosclerotic disease but no MI (12.6 vs 12.8%).
The researchers found evidence that the benefits of dapagliflozin could be strongest in people whose MI had occurred within 2 years before enrolment, but the editorialists caution that this “should be considered hypothesis-generating” because of the small number of events within this timeframe.
Nevertheless, Verma and McMurray believe that “[i]n patients with diabetes who have had a prior MI, the use of an SGLT2 inhibitor should be strongly considered as part of routine secondary prevention.”
They point out that the absolute risk reductions “are similar and additive to what are observed with antiplatelet therapies and intensive [low-density lipoprotein cholesterol] lowering in recent trials.”
However, they caution that the safety and efficacy of treating people with recent acute coronary syndromes need to be tested before definitive recommendations are possible.
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