The year 2024 has been transformative for cardiology, marked by significant FDA approvals and pivotal clinical trial results poised to reshape cardiovascular care. Key advancements include novel therapies and trial outcomes that could redefine clinical practice.
Tirzepatide's Impact on Heart Failure
The SUMMIT trial, presented at AHA Scientific Sessions 2024, revealed that tirzepatide significantly benefits patients with obesity and heart failure with preserved ejection fraction (HFpEF). Tirzepatide reduced the risk of heart failure hospitalization or cardiovascular death by 38% and contributed to a 12-21% reduction in body weight. The trial, involving 731 patients, showed a 46% relative reduction in worsening heart failure events (HR, 0.54; P = 0.026). Eli Lilly has submitted tirzepatide for approval to treat HFpEF and obesity to both the US FDA and the European Medicines Agency.
Finerenone's Role in Heart Failure
Bayer's FINEARTS-HF trial, a phase 3 study, met its primary endpoint, demonstrating finerenone's efficacy in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). The results, presented at the ESC Congress 2024, suggest finerenone could become a second pillar in guideline-directed medical therapy for HFmrEF/HFpEF, alongside SGLT2 inhibitors. The trial, which included 6016 patients, showed that finerenone significantly reduced the rate of primary outcome events, including cardiovascular death and heart failure hospitalizations, by 16% compared to placebo (RR, 0.84; P = 0.007).
Semaglutide's Benefits in Kidney Disease
The FLOW trial highlighted the growing recognition of cardiovascular-kidney-metabolic disease. Semaglutide 1.0 mg (Ozempic) demonstrated a 24% reduction in major kidney disease events and a 21% reduction in kidney-specific outcomes among patients with type 2 diabetes and chronic kidney disease. This landmark trial also showed that semaglutide slowed the decline in eGFR and reduced cardiovascular death by 29% compared to placebo. The trial, which included 3,553 patients, was halted early due to overwhelming efficacy.
Muvalaplin for Elevated Lipoprotein(a)
New phase 2 research presented at the AHA Annual Scientific Sessions 2024 demonstrates the potential of muvalaplin, a once-daily oral treatment, to significantly reduce lipoprotein (a) [Lp(a)] levels in adults with elevated Lp(a) and high cardiovascular risk. In the 12-week KRAKEN trial, muvalaplin reduced Lp(a) by up to 85% at the highest dose (240 mg/day). The study enrolled 233 patients with elevated Lp(a) and atherosclerotic cardiovascular disease, diabetes, or familial hypercholesterolemia.
Plozasiran for Familial Chylomicronemia Syndrome
New phase 3 data from the PALISADE trial presented at the ESC Congress 2024 highlights the potential of plozasiran, a small interfering RNA therapy, in treating familial chylomicronemia syndrome (FCS). The trial demonstrated significant reductions in triglyceride levels and a lower incidence of acute pancreatitis in patients receiving plozasiran compared to placebo. At 10 months, the 25 mg and 50 mg doses of plozasiran reduced triglycerides by 80% and 78%, respectively, compared to a 17% reduction with placebo (P <.001). Arrowhead Pharmaceuticals plans to file a New Drug Application with the FDA by the end of 2024.
Semaglutide's Expanded FDA Approval
On March 8, 2024, the FDA approved an expanded label indication for semaglutide 2.4 mg (Wegovy) to reduce the risk of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease and obesity or overweight. This approval marks the first time a weight loss medication has been approved for cardiovascular risk reduction in this patient population. The approval is based on data from the SELECT trial, a 17,604-patient study that demonstrated a 20% relative reduction in the risk of the primary cardiovascular events (HR, 0.80; P <.001) in patients receiving semaglutide compared to placebo.
Aprocitentan for Hypertension
On March 20, 2024, Idorsia Ltd. announced the FDA approved aprocitentan (Tryvio) for treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs. The approval marked the first for an oral antihypertensive agent with a new mechanism of action in more than 30 years and was based on data from the phase 3 PRECISION trial.
Bempedoic Acid Label Expansion
On March 22, 2024, Esperion announced the FDA approved label expansions for bempedoic acid (Nexletol) and bempedoic acid with ezetimibe (Nexlizet) to include primary and secondary prevention of cardiovascular risk. According to Esperion, the FDA’s decision makes bempedoic acid the first LDL-lowering non-statin agent to receive a primary prevention indication.
Olezarsen for Familial Chylomicronemia Syndrome
On December 19, 2024, the FDA approved olezarsen (TRYNGOLZA), an RNA-targeted treatment from Ionis Pharmaceuticals, for use as an adjunct to diet in reducing triglycerides in adults with familial chylomicronemia syndrome (FCS). This approval marks the first FDA-approved therapy for FCS, addressing a significant unmet need in managing this rare genetic disorder. The approval was supported by data from the Phase 3 BALANCE trial, which demonstrated significant reductions in fasting triglyceride levels.
Acoramidis for Transthyretin Amyloid Cardiomyopathy
On November 22, 2024, the FDA approved acoramidis (Attruby), an orally administered stabilizer of transthyretin (TTR), for the treatment of adults with transthyretin amyloid cardiomyopathy (ATTR-CM). This approval marks acoramidis as the first and only treatment with a label specifying near-complete TTR stabilization. The approval follows data from the phase 3 ATTRibute-CM trial, which showed significant reductions in all-cause mortality and cardiovascular-related hospitalizations.
