ACC.22 Update: Exercise Capacity, Hyperkalemia, and Cholesterol

Volume 14, Issue 1

It’s that time of year again! The American College of Cardiology annual meeting was this past weekend in Washington, DC, and yours truly was in attendance. When I wasn’t taking in the sights of the city and the smells of the lovely blooming cherry blossoms, I was attending some exciting sessions on late-breaking clinical trials.

In the DIAMOND study, the potassium binder patiromer proved efficacious in preventing hyperkalemia events and facilitating uptitration of renin-angiotensin-aldosterone system (RAAS) inhibitors in patients with heart failure with reduced ejection fraction (HFrEF). These data are important, as hyperkalemia is often a dose-limiting toxicity for RAAS inhibitors, and higher doses of RAAS inhibitors are generally preferred to reduce adverse heart failure-related outcomes in patients with HFrEF.

My one critique of this paper is the choice of agent, as sodium zirconium cyclosilicate (Lokelma) is my preferred potassium binder due to faster onset of action and less potential for interaction with other medications.

Omecamtiv, a cardiac-specific myosin activator, already has one published clinical trial (GALACTIC-HF), which showed a reduction in heart failure hospitalizations in patients with more severe heart failure. At ACC.22, the METEROIC-HF trial found that omecamtiv did not improve exercise capacity in a cohort of relatively stable patients with class II HFrEF. These patients were also on an extremely effective background of guideline-directed medical therapy.

I am not surprised at all by the findings of this trial, given these patients were relatively less sick than those in GALACTIC-HF and most patients were already maxed on standard guideline-directed medical therapy. I think the designers of this trial did this drug a disservice, and they should have studied the effects of the drug in patients with more severe heart failure or those who cannot tolerate standard guideline-directed medical therapy.

The TRANSLATE-TIMI 70 study showed treatment with vupanorsen, a novel antisense oligonucleotide targeting hepatic angiopoietin-like 3, achieved modest reductions in non-high-density lipoprotein cholesterol at 24 weeks at all doses studied. The decrease was largely attributed to a 41.3%-56.8% decrease in triglycerides, with mild (~16%) reductions in low-density lipoprotein cholesterol. This was a phase 2 study, so no data are available as to whether these reductions in triglycerides are associated with clinically meaningful endpoints, like reductions in rates of major adverse cardiac events.