Late breaking clinical trials at ACC 22

During the scientific sessions of the American College of Cardiology 2022 annual conference, important novel trial evidence informing treatments of cardiovascular disease was presented. Among the many excellent studies and presentations, we would like to highlight a few.

SODIUM-HF

The Study of Dietary Intervention under 100 mmol in Heart Failure (SODIUM-HF) randomized 806 ambulatory patients with a diagnosis of heart failure in a 1:1 fashion to standard dietary recommendation as per local guidelines vs. low-sodium intake diet, with a target daily sodium intake <1500 mg. Median sodium intake was 1658 mg/day (1301–2189) in the active treatment group, and 2073 mg/day (1541–2900) in the control group. At 12 months of follow-up, no difference was observed between the two groups in the composite of cardiovascular-related hospitalization, emergency department visit, and all-cause death [hazard ratio (HR) 0.89 (95% confidence interval, CI, 0.63–1.26); P = 0.53].¹ The trial was substantially negative, and showed that further reduction of sodium beyond what is currently recommended of 2000 mg/day may not provide any short-term advantages in terms of clinical events for heart failure patients. A signal for improved quality of life was seen favouring lower sodium intake.

VALOR-HCM

A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy (VALOR-HCM) randomized 112 patients with hypertrophic obstructive cardiomyopathy (HOCM) and indication to septal reduction treatment (surgical or percutaneous) to either mavacamtem, a selective modulator of myosin β-chain inhibiting sarcomere force output to reduce contractility, or placebo in a 1:1 fashion.² After 16 weeks of treatment, the active treatment arm had significantly lower resting and post-exercise gradients (14 vs. 46 mmHg, P < 0.05, and 28 vs. 78 mmHg, P < 0.05, respectively), which led to a significantly lower number of patients requiring septal reduction treatment (17.9% in the mavacamtem arm vs. 76.8% in the placebo arm). Significant improvement in quality-of-life measures was also observed with the mavacamtem arm. No serious adverse events were reported. While further studies and long-term follow-up data are warranted, mavacamtem may become a viable non-invasive alternative to septal reduction therapies in HOCM patients.

TRANSLATE-TIMI 70

Angiopoietin-like protein 3 (ANGPTL3) inhibits lipases, therefore impairing the metabolism of triglyceride-rich lipoproteins. In loss-of-function mutations in the ANGPTL3 gene, lower levels of triglycerides and low-density lipoprotein cholesterol (LDL-C) have been described. The Targeting ANGPTL3 with an Antisense Oligonucleotide in Adults with Dyslipidemia—Thrombolysis in Myocardial Infarction 70 (TRANSLATE-TIMI 70) trial was a phase 2b trial randomizing 286 subjects with elevated non-high density lipoprotein cholesterol (non-HDL-C) on statin to either placebo or increasing doses of vupanorsen, an antisense oligonucleotide targeting ANGPTL3 mRNA in the liver, for either 12 or 24 weeks.³ Vupanorsen was associated with a placebo-adjusted decrease in non-HDL-C ranging between 22.0% and 27.7% and in triglycerides between 41.3% and 56.8%, with larger effects with higher doses. The effects on LDL-C and apoliprotein-B were modest and with no dose response. Liver enzyme elevation was common, reaching 44.4% in the high-dose group. One-third of the patients developed antidrug antibodies. This study emphasizes the importance of rigorous evaluation of new lipid-lowering therapies, assessing for tolerability, efficacy, and sustainability, and it may provide mechanistic insight as additional metabolic targets are studied going forward.

Conflict of interest: None declared.

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