Metformin, but not sulfonylurea, may reduce poor outcome risk post HHF
medwireNews: Initiating metformin following hospitalization for heart failure (HHF) may reduce the risk for death or further HHF in older people with comorbid diabetes, but only if they have a preserved ejection fraction (EF), study findings indicate.
Conversely, sulfonylurea initiation may be associated with an increased risk for death or HHF, irrespective of EF, report Stephen Greene (Duke University School of Medicine, Durham, North Carolina, USA) and co-authors in JACC: Heart Failure.
Greene and team evaluated Medicare data for 5852 individuals aged 65 years and older (median 75 years) who were hospitalized for HF with comorbid diabetes and recorded in the Get With The Guidelines–Heart Failure Registry between 2006 and 2014.
Of these, 7.8% initiated metformin treatment and 8.6% began a sulfonylurea within 90 days of discharge from hospital, including 2.3% who started both therapies.
During 12 months of follow-up, which began 90 days postdischarge, 30.7% of patients who initiated metformin died or were hospitalized for HF, compared with 39.7% of those who did not initiate metformin.
After adjusting for 29 potential confounders, the researchers found that metformin use was associated with a significant 19% reduced risk for the composite outcome of all-cause mortality or HHF during follow-up, relative to no metformin use.
Conversely, there was no significant risk reduction with versus without metformin when all-cause mortality (18.5 vs 20.5%) and HHF (19.5 vs 25.8%) rates were analyzed separately.
There was, however, a significant interaction between EF and metformin-associated risk reduction.
Specifically, individuals with HF and a preserved EF (HFpEF; >40%) had a significant 32% lower risk for the composite of death or HHF and a significant 42% lower risk for HHF alone with metformin use relative to no use, whereas there was no benefit to metformin initiation among the subgroup with HF and a reduced EF (HFrEF; ≤40%).
Initiation of a sulfonylurea was associated with a significant 17% increased risk for the composite outcome, as well as a significant 24% increased risk for mortality versus no sulfonylurea use. Sulfonylurea use was also associated with a 22% increased risk for HHF, which was of borderline statistical significance.
The crude rates with versus without a sulfonylurea were a respective 42.1% and 38.7% for the composite outcome, 23.8% and 20.1% for all-cause mortality, and 27.1% versus 25.1% for HHF.
In this case, the findings were consistent in both EF subgroups and no significant interaction was detected.
Greene et al say that in the context of increasing sodium-glucose cotransporter (SGLT)2 inhibitor use to reduce cardiovascular risk, “understanding the effects of metformin and sulfonylurea therapies on clinical outcomes among patients with HF and [diabetes] is increasingly relevant given their continued dominant use in routine practice.”
They believe that the lack of benefit with metformin in the HFrEF group supports “prioritizing SGLT2 inhibitors before metformin as first-line therapy for type 2 [diabetes]” in this setting.
They add that sulfonylureas “may best be avoided” in people with HF and diabetes, while further randomized clinical trials are needed to confirm the benefit of metformin in individuals with HFpEF.
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