Thank you for your interest in CCO content. As a guest, please complete the following information fields. These data help ensure our continued delivery of impactful education.
Become a member (or login)? Member benefits include accreditation certificates, downloadable slides, and decision support tools.
Lee R. Goldberg, MD, MPH:
Several new interventions that will affect the care of patients with HF were presented at the 2021 American College of Cardiology (ACC) Annual Meeting.
Cardiovascular Protective Efficacy of the SGLT2 Inhibitor Empagliflozin in Asia
Over the past few years, the role of SGLT2 inhibitors has expanded from glucose lowering to a role in the prevention of cardiovascular disease, so it is critical that we understand how these drugs perform in different patient populations. In the EMPRISE study, Kim and colleagues evaluated the population effects of the use of empagliflozin by analyzing data from 3 large administrative databases from Japan, South Korea, and Taiwan. The study included 28,712 matched pairs of adult patients with type 2 diabetes initiating either empagliflozin or a dipeptidyl peptidase-4 inhibitor. Propensity score-matched analyses comparing the risk of cardiovascular outcomes with all-cause mortality were computed. Subgroup analyses were performed in patients with and without preexisting cardiovascular disease who received 10 mg of empagliflozin. Empagliflozin was associated with a lower risk of the composite outcome of hospitalization for HF and all-cause mortality. A lower risk of the combined outcome of myocardial infarction, stroke, and all-cause mortality also was found in the empagliflozin group. These results are important, as they validate the use of SGLT2 inhibitors and—in particular—empagliflozin in people of East Asian descent and add to the evidence of the cardiovascular protective efficacy of this class of drugs.
Oral sGC Stimulators: Safety and Efficacy
Oral soluble guanylate cyclase (sGC) stimulators are the newest class of drugs to be approved in the treatment of HF. This class of drugs works by increasing cyclic guanosine monophosphate, leading to peripheral vasodilatation and a decrease in inflammation. Augmentation of this pathway may be a therapeutic target, and several agents that act to stimulate sGC activity have been developed and studied in randomized trials in patients with HF with preserved ejection fraction (HfpEF) or HF with reduced ejection fraction (HfrEF), including vericiguat, riociguat, and praliciguat. Moghaddam and colleagues presented a meta-analysis of clinical trials evaluating sGC stimulators in patients with HF. Identified studies included 5707 patients with HFrEF and 1483 patients with HFpEF. They found that the drugs were well tolerated and reduced HF hospitalizations, but not cardiovascular deaths, only in those with HFrEF. There were no benefits in patients with HFpEF.
These results are dominated by the large VICTORIA trial in patients with HFrEF, as that trial contributed approximately 80% of the patients in this analysis. In the VICTORIA trial, the composite endpoint of cardiovascular mortality or HF hospitalizations was favorably affected, driven by a reduction on HF hospitalizations. Based on the VICTORIA trial findings, vericiguat was recently FDA approved for this patient population. The individual trials in patients with HFpEF were focused on symptom and function endpoints and were rigorously neutral. Thus, it would not be appropriate to use the results of this pooled analysis to apply the results to patients beyond those studied in VICTORIA. At this point, vericiguat can be considered for treatment of patients with HFrEF with a recent episode of worsening HF, consistent with its indication. This class of drugs is being incorporated into the guidelines, so it will be important to introduce those medications with both symptomatic and mortality benefits first and then add those with only symptomatic benefit further in the algorithm.
Icosapent Ethyl: Preventive Benefit on the Incidence of New HF and New HF Requiring Hospitalization
In the area of prevention of HF, Bhatt and colleagues presented tertiary endpoints of the REDUCE-IT trial. The impact of icosapent ethyl was evaluated in patients with controlled low-density lipoprotein cholesterol but elevated triglycerides on the incidence of new HF (N = 8179). This double-blind, placebo-controlled phase III trial found no difference between icosapent ethyl and placebo in the incidence of new HF. However, post-hoc analysis showed that patients with the middle and highest tertile of on-treatment eicosapentaenoic acid had a significant benefit in terms of new HF and new HF requiring hospitalization. The implication is that it may be important to achieve a specific eicosapentaenoic acid target level to get the preventive benefit. This study further emphasizes that HF is a preventable disease with aggressive comprehensive risk factor reduction.
Cardiac Rehabilitation for Patients With HFpEF
Finally, a small, important study on the impact of cardiac rehabilitation for patients with HFpEF was presented by Ayad and colleagues. In this study, 60 patients with HFpEF were randomized to receive 2-3 cardiac rehabilitation sessions weekly or usual care only. After 12 weeks, patients on cardiac rehabilitation showed improvements in Minnesota Living with Heart Failure Questionnaire score, echocardiographic parameters, and 6-minute walk distance. This observation is critical in changing policy and driving additional research to expand access to cardiac rehabilitation for patients with HFpEF.