Normal weight, overweight and obese heart failure (HF) patients see similar cardiovascular benefits with SGLT2 inhibitors, suggesting body mass index (BMI) bears little weight on drug response, researchers say.
The findings are some of the latest from the randomised, placebo-controlled DELIVER trial, presented at ESC 2022, which demonstrated the efficacy and safety of 10 mg once-daily dapagliflozin in over 6,000 heart failure patients with mildly reduced (HFmrEF) or preserved (HFpEF) ejection fractions, with or without type 2 diabetes.
Tested by BMI, the study’s now shown its utility across varied body sizes — offering similar protection against worsening heart failure or cardiovascular death in patients measuring 18.5–24.9 kg/m2 (normal) to ≥ 40–50 kg/m2 (WHO obesity Class III).
It also reduced symptom severity and supported modest weight loss, particularly in obese patients.
The latter commonly have HFpEF, “generally have worse symptoms and [have] greater functional limitations than their non-obese counterparts”, the authors wrote in the European Heart Journal (study linked here).
“Consequently, finding treatments that are efficacious in HFpEF patients with concomitant obesity [is] important.”
In the 6,203 assessed patients, dapagliflozin decreased the risk of the primary outcome — the composite of time to first occurrence of a worsening HF event (HF hospitalisation or urgent outpatient HF visit requiring intravenous diuretic therapy) or cardiovascular death — to a similar extent across size brackets (P interaction = 0.82).
The authors reported hazard ratios of 0.89 (95% CI: 0.69–1.15), 0.87 (95% CI: 0.70–1.08), 0.74 (95% CI: 0.58–0.93), 0.78 (95% CI: 0.57–1.08) and 0.72 (0.47–1.08) in normal weight, overweight (BMI: 25.0–29.9 kg/m2) and obese (Class I BMI: 30–34.9 kg/m2; Class II BMI: 35.0–39.9 kg/m2 and Class III) patients, respectively.
They also saw placebo-corrected, eight-month self-reported symptom improvements of 0.9 (95% CI: -1.1–2.8), 2.5 (95% CI: 0.8–4.1), 1.9 (95% CI: -0.1–3.8), 2.7 (95% CI: -0.5–5.8), and 8.6 (95% CI: 4.0–13.2) points, (P-interaction = 0.03), according to the Kansas City Cardiomyopathy Questionnaire.
When accounting for placebo, patients lost 0.88 (95% CI: 0.47–1.28), 0.65 (95% CI: 0.26–1.04), 1.42 (95% CI: 0.94–1.89), 1.17 (95% CI: 0.40–1.94), and 2.50 (95% CI: 0.64–4.4) kilograms after 12 months on the drug (P-interaction = 0.002).
Further, the drug appeared safe across all BMI categories, with no significant interaction between size and adverse event occurrence.
The findings back SGLT2 inhibitors as an “attractive” treatment for heart failure patients with excess weight, the authors suggested.
Obesity “is part of a common triad which includes dysglycaemia and hypertension” and previous studies have shown SGLT2 inhibitors to create “modest reductions in weight, glycated haemoglobin, and blood pressure, in addition to their benefits on HF symptoms and outcomes”.
“While the main reason to use SGLT2 inhibitors in HFpEF is to improve symptoms and reduce worsening HF”, their modest weight-reducing effect may complement other weight-loss strategies, such as caloric restriction and aerobic exercise training, they wrote.
Disclaimer: The study was sponsored by AstraZeneca.