With the halfway point of the year behind them, the cardiology community has found themselves as the recipient of a plethora of breakthroughs and advances during the first half of 2024, which included historic approvals such as semaglutide for reducing cardiovascular risk in obesity, bempedoic acid’s primary prevention indication, and the first new mechanism for an oral antihypertensive in nearly 40 years.

Although it did not boast the same onslaught of historic regulatory news and decisions, the trend of rapid pipeline movement continued through July, with the community seeing an onslaught of new data and pipeline movement as it prepares to welcome August and the European Society of Cardiology annual congress.

In our July 2024 cardiology month in review, we spotlight the most important news and clinically impactful stories from the seventh month of the year, including pipeline movement, data on the role of pooled cohort equations (PCEs), studies highlighting a need for greater emphasis on optimal lipid management, and more!

Cardiology Pipeline and Trial Updates

Obicetrapib Hits Target in Phase 3 BROOKLYN Trial for HeFH

The phase 3 BROOKLYN trial has demonstrated that obicetrapib, when added to maximally tolerated lipid-lowering therapies, significantly reduces LDL-C levels in patients with heterozygous familial hypercholesterolemia (HeFH).

According to topline results announced by NewAmsterdam Pharma on July 29, 2024, obicetrapib achieved a statistically significant least squares (LS) mean reduction in LDL-C of 36.3% relative to placebo at day 84, with this effect sustained over one year, showing a 41.5% reduction. The trial also reported statistically significant improvements in other lipid biomarkers, including HDL-C, non-HDL-C, lipoprotein(a), and apolipoprotein B.

Obicetrapib, a novel oral CETP inhibitor, has garnered significant interest due to its potential as an oral option for difficult-to-treat HeFH patients, many of whom struggle to reach guideline-recommended LDL-C levels despite multiple therapies. The BROOKLYN trial included 354 patients randomized in a 2:1 ratio to receive either obicetrapib or placebo.

Safety data from the trial indicated that obicetrapib was well-tolerated, with no significant increases in blood pressure and lower treatment discontinuation rates compared to placebo. The trial is part of a broader phase 3 development program that includes three other trials: BROADWAY, TANDEM, and PREVAIL, all aimed at evaluating obicetrapib's efficacy in various high-risk populations. Full results from the trial are expected to be presented at an upcoming medical conference and published in a major medical journal.

Semaglutide Can Preserve, Possibly Improve, NYHA Functional Class in Obesity-Related HFpEF

An analysis of the STEP-HFpEF program indicates semaglutide 2.4 mg (Wegovy) may prevent deterioration and potentially improve New York Heart Association (NYHA) functional class status in patients with obesity-related heart failure with preserved ejection fraction (HFpEF).

Leveraging data from the STEP-HFpEF and STEP-HFpEF DM trials, researchers found semaglutide provided consistent benefits across all NYHA classes, improving heart failure-related symptoms, physical limitations, exercise function, and reducing body weight and biomarkers of inflammation. Results showed patients on semaglutide were more likely to experience an improvement in NYHA functional class and less likely to see deterioration compared to placebo.

These benefits were observed across different severity levels of heart failure, with similar weight loss effects seen in all NYHA categories. Data from the study suggests the improvements may be due to both weight loss and weight-independent effects of semaglutide, highlighting its potential as a multifactorial therapeutic option in HFpEF management.

PCEs Remain Gold Standard

During the month of July, a pair of studies, both published in JAMA journals, called attention to pitfalls within the American Heart Association’s recently introduced PREVENT equations as well as the Life’s Essential 8. Coming less than 2 years after the new equations were introduced, the July 2024 studies in JAMA detail the comparative value of PCEs in predicting risk.

Pooled Cohort Equation Bests Life's Essential 8, Simple 7 for Predicting Long-Term CVD Risk

Research from the University of Alabama at Birmingham (UAB) highlights the comparative effectiveness of different cardiovascular risk calculation methods. The study, using data from NHANES, found that while Life’s Essential 8 and Life’s Simple 7 scores are valuable for promoting healthy lifestyles, they are less effective than pooled cohort equations in predicting all-cause mortality among older adults.

According to the research, led by Pankaj Arora, MD, the PCEs are superior for individual risk assessment due to their comprehensive approach. The American Heart Association developed Life’s Simple 7 in 2010 and expanded it to Life’s Essential 8 in 2022, adding factors like sleep and more detailed metrics on diet and nicotine exposure. The study emphasizes the need to focus on the intended use of these scores for tracking cardiovascular health rather than for individual risk prediction.

PREVENT Equations Could Result in 100,000 CVD Events by Reducing Statin, Antihypertensive Prescribing

A new study raises concerns about the American Heart Association’s (AHA) recently introduced Predicting Risk of Cardiovascular Disease Events (PREVENT) equations, suggesting they may lead to significant underprescription of statins and antihypertensive agents.

The study projects that using PREVENT instead of the current pooled cohort equations (PCE) could result in 107,000 additional ASCVD events over 10 years due to reduced treatment eligibility for an estimated 15.8 million US adults.

Despite the goal of more accurate cardiovascular risk prediction, the potential decrease in preventive therapies warrants a reevaluation of treatment thresholds. While the inclusion of factors like kidney function and HbA1c in PREVENT is lauded as an advancement, the study highlights the importance of refining risk thresholds to prevent adverse outcomes. An accompanying editorial suggests that PREVENT could improve risk prediction but stresses the need for continued research and adherence to current cardiovascular prevention guidelines.

Growing Need for Optimal CV Care

To round out the July 2024 cardiology month in review, we are spotlighting a series of studies shining new light on the need for optimal cardiovascular care in the US. These studies spotlight a lack of access, lack of screening, need for equitable care between men and women, and more!

Despite Similar Treatment Effects, Women with FH Less Likely to Receive Treatment or Meet Goals

A recent large-scale study on familial hypercholesterolemia (FH) reveals that females with FH receive less intensive care and are less likely to reach LDL-C target goals compared to males, despite similar benefits from lipid-lowering therapies.

This systematic review, which included data from over 120,000 patients, found that women were 26% less likely to be on lipid-lowering therapy and had a lower likelihood of achieving optimal LDL-C levels. However, male patients experienced a higher rate of cardiovascular events. According to investigators, the study underscores the need to address sex-related disparities in FH treatment and suggests that sex-specific strategies could enhance cardiovascular disease prevention.

Few Youth Receive Lipid Screening, Highlighting Missed Opportunity to Reduce CVD Risk

New research reveals that less than 15% of children and adolescents undergo lipid screening, despite recommendations for universal screening to identify and manage dyslipidemias in these patients. An analysis of data from over 3.2 million youths from the IQVIA Ambulatory Electronic Medical Record database found that only 11.3% had lipid screening results available, with significant variations based on age, race, ethnicity, and BMI.

Results indicated 59.3% of those screened had elevated lipid levels and 30.2% had abnormal results. An accompanying commentary underscores the importance of lipid screening to identify genetic conditions like familial hypercholesterolemia and dyslipidemias linked to lifestyle, advocating for increased awareness and adherence to screening guidelines.

Nearly Half of US Counties Lack Practicing Cardiologists

Nearly half of US counties lack a practicing cardiologist, particularly in rural and socioeconomically disadvantaged areas with a higher burden of cardiovascular disease, according to a study in The Journal of the American College of Cardiology.

These counties have a 31% higher cardiovascular risk index, increased mortality rates, and a one-year shorter life expectancy compared to counties with cardiologists. Rural counties are especially affected, with 86.2% having no cardiologist. Residents in these areas often face longer travel distances to access care, poorer access to primary care and healthy food, and higher rates of being uninsured. Native Americans are the group most likely to live in counties without cardiologists. The study calls for policy interventions, such as expanding telemedicine and providing financial incentives for clinicians to practice in underserved areas.