Targeting obesity may be ‘highly effective strategy’ for treating HFpEF, ASCVD
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Key takeaways:
- Two trials revealed that semaglutide 2.4 mg may reduce CV risk for adults with obesity and HFpEF or CVD.
- Bempedoic acid may lower the risk for MACE for adults who are unable to receive statin therapy.
Findings from two cardiovascular outcome trials revealed that targeting obesity could become a major focus for treating cardiovascular disease and heart failure with preserved ejection fraction in the future, according to a speaker.
At the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease, Mikhail Kosiborod, MD, FACC, FAHA, vice president of research at Saint Luke’s Health System and professor of medicine at the University of Missouri-Kansas City School of Medicine, discussed four CV outcome trials that were presented in 2023. Among the trials discussed were the STEP-HFpEF and SELECT trials, both of which showed the GLP-1 receptor agonist semaglutide (Ozempic/Wegovy, Novo Nordisk) could provide CV benefits for adults with obesity.
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“There are two landmark trials heralding a complete paradigm shift in targeting obesity as a highly effective strategy in HFpEF and atherosclerotic CVD,” Kosiborod said during a presentation. “I think we’re going to see a lot more in the coming years that’s really going to change practice.”
STEP-HFpEF and SELECT
In the STEP-HFpEF trial, 529 adults with obesity and HFpEF were randomly assigned to receive once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Dual primary endpoints in the study were change in Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score and body weight from baseline to 52 weeks.
At 52 weeks, adults receiving semaglutide had a 7.8-point greater improvement in KCCQ score (95% CI, 4.8-10.9; P < .001) and a 10.7% greater reduction in body weight (95% CI, –11.9 to –9.4; P < .001) compared with placebo. The semaglutide group also had a greater increase in 6-minute walking distance and a larger decrease in C-reactive protein level than the placebo group.
In the SELECT trial, researchers randomly assigned 17,604 adults with established CVD and overweight or obesity to receive semaglutide 2.4 mg or placebo once-weekly. The trial was event-driven, with the primary outcome being a composite of nonfatal myocardial infarction, nonfatal stroke or death from CV causes.
During nearly 40 months of follow-up, adults receiving semaglutide had a lower risk for any of the three primary outcomes compared with placebo (HR = 0.8; 95% CI, 0.72-0.9; P < .001 for superiority). Semaglutide was also associated with a lower risk for HF (HR = 0.82; 95% CI, 0.71-0.96) and all-cause mortality (HR = 0.81; 95% CI, 0.71-0.95).
“These two trials, STEP-HFpEF and SELECT, are really blazing the trail for what’s going to happen in obesity as a modifiable risk factor for management of CVD,” Kosiborod said.
CLEAR Outcomes
Another CV outcomes trial showed bempedoic acid (Nexletol, Esperion Therapeutics) may be beneficial for adults who are at high risk for CVD and are statin intolerant. In the CLEAR Outcomes trial, 13,970 adults who were unable or unwilling to take statins and had a high risk for CVD were randomly assigned to receive either 180 mg oral bempedoic acid or placebo once daily. The primary endpoint was a composite of major adverse CV events that included CV death, nonfatal MI, nonfatal stroke and coronary revascularization.
Adults receiving bempedoic acid had a lower risk for major adverse CV events (HR = 0.87; 95% CI, 0.79-0.96; P = .004), fatal or nonfatal MI (HR = 0.77; 95% CI, 0.6-0.91; P = .002) and coronary revascularization (HR = 0.81; 95% CI, 0.72-0.92; P = .001) compared with placebo. In a study published in JAMA that only looked at 4,206 primary prevention patients without a prior CV event, bempedoic acid lowered the risk for MACE (HR = 0.7; 95% CI, 0.55-0.89; P = .002) and fatal or nonfatal MI (HR = 0.61; 95% CI, 0.39-0.98) compared with placebo.
DAPA-MI
Data from the DAPA-MI trial revealed once-daily dapagliflozin 10 mg (Farxiga, AstraZeneca) plus standard of care was superior to placebo for improving cardiometabolic outcomes for adults without diabetes or HF who presented with MI and impaired left ventricular function. The trial’s primary outcome was a composite of seven components: death, HF hospitalization, nonfatal MI, atrial fibrillation, new-onset type 2 diabetes, decrease in body weight of 5% or more and change in HF symptoms as measured by NYHA classification.
In an analysis of the primary outcome, dapagliflozin outperformed placebo with a win ratio of 1.34 (95% CI, 1.2-1.5; P < .001). However, Kosiborod cautioned that the finding was driven primarily by cases of new-onset type 2 diabetes and body weight change.
“There were very few clinical events and there was no evidence of a benefit on clinical events such as deaths and hospitalizations,” Kosiborod said. “Even though the overall trial is positive, it’s inconclusive because the number of events were so small that we can’t say what the effects of dapagliflozin truly are on CV deaths and hospitalizations for HF in this patient population.”
References:
- James S, et al. NEJM Evid. 2023;doi:10.1056/EVIDoa2300286.
- Kosiborod M, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2306963.
- Lincoff AM, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2307563.
- Nissen SE, et al. JAMA. 2023;doi:10.1001/jama.2023.9696.
- Nissen SE, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2215024.
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Kosiborod M. CVOTs update. Presented at: World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease; Dec. 7-9, 2023; Los Angeles.
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