Halfway through 2024, the field of cardiology and its practitioners have been the beneficiaries of what many fields would consider decades worth of clinically significant advancements, including new guidelines in hypertrophic cardiomyopathy, a first-of-its-kind indication for semaglutide in reducing cardiovascular risk specifically among patients with obesity, the first FDA approval for an oral antihypertensive agent with a new mechanism of action in more than 30 years, and bempedoic acid becoming the first LDL-lowering non-statin agent to receive a primary prevention indication.

Closing out the first half of the year, June 2024 may not have boasted the same level of historically significant news or readouts as previous months, but it still evidenced the continued pursuit of advancement within the cardiology community. In June, much of that news and advancement centered around pipeline movement, lipid management, and heart failure. With this in mind, our Cardiology Month in Review for June 2024 spotlights the pharmacotherapies making waves within the pipeline, the latest news in dyslipidemia, and updates in heart failure.

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Pipeline News

FDA Grants Priority Review for Olezarsen in Familial Chylomicronemia Syndrome

The US Food and Drug Administration has accepted the New Drug Application for olezarsen, an investigational RNA-targeted medicine from Ionis Pharmaceuticals, in familial chylomicronemia syndrome (FCS) for priority review, according to a company announcement.

Announced on June 25, 2024, the company notes the FDA has set a PDUFA date of December 19, 2024 and is not expected to require an advisory committee meeting for the agent. In the announcement, the company also pointed out the completion of enrollment for their phase 3 CORE, CORE2, and ESSENCE trials evaluating olezarsen in the treatment of severe hypertriglyceridemia, which are expected to return results in the second half of 2025.

Vutrisiran Reduces Mortality, CV Events in ATTR-CM in Phase 3 Trial

Topline results from the Phase 3 HELIOS-B study demonstrate statistical significance on all primary and secondary endpoints for vutrisiran (AMVUTTRA) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).

Announced by Alnylam Pharmaceuticals, Inc. on June 24, 2024, vutrisiran led to significant 28% and 33% reductions in the composite of all-cause mortality and recurrent cardiovascular events in both the overall and monotherapy populations, respectively, as well as benefits on key measures of disease progression.

Zerlasiran Provides Significant Lp(a) Reductions at 48 Weeks, Phase 2 Data Shows

Use of zerlasiran was associated with a meaningful effect on lipoprotein(a) [Lp(a)] levels in patients at high risk of cardiovascular events, according to new phase 2 topline data announced by Silence Therapeutics.

Announced on June 20, 2024, results of the study indicate use of the short interfering RNA agent was associated with statistically significant reductions in baseline Lp(a) relative to placebo therapy, with a median maximum Lp(a) reduction of approximately 90% or greater observed for both doses during the treatment period

PALISADE: Plozasiran Lowers Triglycerides in Familial Chylomicronemia Syndrome

Topline results from the pivotal Phase 3 PALISADE study revealed investigational plozasiran successfully met the primary endpoint of triglyceride-lowering in patients with genetically confirmed or clinically diagnosed FCS.

Announced by Arrowhead Pharmaceuticals on June 3, 2024, plozasiran achieved statistically significant reductions in triglyceride levels up to 80%, with an average lowering in Apolipoprotein C-III up to 94%, at the primary endpoint of 10 months.

Heart Failure

Sotagliflozin Demonstrates Cost-Effectiveness in T2D and Heart Failure

New research leveraging data from the landmark SOLOST-WHF trial suggests sotagliflozin (Inpefa) represents a cost-effective option for patients with diabetes and recent worsening of heart failure.

Using a Markov model to estimate the lifetime impact of sotagliflozin on data from the National Inpatient Sample, investigators found use of the agent had up to an 89.7% probability of cost-effectiveness in patients with type 2 diabetes and worsening heart failure at the high end of common willingness-to-pay thresholds.

Lp(a), Oxidized Phospholipids Can Predict Progression of Heart Failure, Study Finds

An analysis of data from the CASABLANCA study shed new light on the prognostic value of elevated Lp(a) and oxidized phospholipids (OxPLs) among patients in the early stages of heart failure.

Results indicated those with elevated Lp(a) had a 90% greater risk of new-onset symptomatic heart failure and a 71% greater risk of those composite of heart failure hospitalization and cardiovascular death. When adding supramedian results for each OxPL to the fully adjusted model, the following results were observed for predicting risk of progression to heart failure:

• When elevated OxPL apoB‐100 added: HR, 3.97; 95% CI, 1.63 to 9.64; P = .002
• When elevated OxPL apolipoprotein(a) added: HR, 2.90; 95% CI, 1.28 to 6.54; P = .01

Dyslipidemia

PREVENT Equation Could Disrupt Prescription of Statins in Primary Prevention

At the American Heart Association 2023 Scientific Sessions, the AHA debuted their new and improved risk calculator: PREVENT. Billed as an improvement over previous calculators for its inclusion of cardiovascular-kidney-metabolic syndrome in risk prediction as well as provide a 30-year risk score, the advent of the new equation was lauded by the cardiology community.

Now, less than a year later, a new study suggests use of the PREVENT equation could result in a reduction in use of statin therapy on a population level. An analysis of NHANES data form more than 3700 people, results indicate use of the equation could reduce the number of US adults meeting criteria for primary prevention statin therapy by more than 15 million.

Jennifer Goldman, RPh, PharmD: How Advances in Lipid Management Fit Into Diabetes Care

Few people with diabetes, management of cardiovascular risk sits at the forefront of discussions regarding care. With this in mind, keeping up to date on updates within the field of lipid management stands to play a significant role in optimal management of this risk for people with diabetes.

At ADA 2024, we spoke with Jennifer Goldman, RPh, PharmD, clinical pharmacist and director of the Cardiometabolic Program at Well Life as well as a professor of Pharmacy Practice at the Massachusetts College of Pharmacy and Health Sciences, on the role of the endocrinology in cardiovascular risk management, how the role of statins and other traditional therapies has evolved in recent years, and the role of educating clinicians beyond cardiology on emerging risk factors.