Updates in women's heart health from ACC.24

As part of our continued focus on equitable health, we hosted an interview with Nieca Goldberg, MD, a clinical associate professor of medicine at New York University and the medical director of Atria New York City, to discuss recent studies for cardiologists to be aware of pertaining to women’s health, particularly cardiovascular health.

Nieca Goldberg, MD
Credit: NYU Langone Health

CLEAR Outcomes

CLEAR Outcomes served as the basis for the recent historic label expansions awarded to bempedoic acid and bempedoic acid plus ezetimibe in March 2024. As Goldberg highlights, CLEAR Outcomes represents what she believes should be a standard for cardiovascular trials moving forward: a diverse patient population. With 48% of the trial comprised of female patients, a CLEAR Outcomes analysis presented at the ACC.24 meeting spotlighted the effects of the non-statin LDL-C-lowering agent in female patients.

Results of the analysis suggested use of bempedoic acid was associated with similar degrees of benefit for MACE-4 among female patients (HR, 0.89; 95% CI, 0.76 to 1.04) as their male counterparts (HR, 0.86; 95% CI, 0.77 to 0.97). For more on the importance of this work, check out Goldberg’s comments below.

Goldberg: Bempedoic acid, a cholesterol-lowering therapy introduced in 2020, garnered less attention due to the overshadowing impact of the COVID-19 pandemic. However, the focus on the Clear Outcomes trial is warranted, particularly for its recent sex-stratified risk analysis comparing outcomes between men and women participants. Notably, the trial organizers should be commended for enrolling a substantial proportion of women, accounting for 48% of the 14,000 patients.

Historically, lipid trials, especially statin trials, have had limited female representation, typically around 20-25%. The Clear Outcomes trial's gender balance in this sub-analysis provides a more representative sample. The findings revealed that both men and women experienced comparable reductions in LDL cholesterol (approximately 25%) and C-reactive protein while on bempedoic acid. Importantly, major adverse cardiovascular events decreased by 23% in both genders.

This is significant given common concerns among women regarding statin therapy, including muscle aches and resistance. Bempedoic acid offers an additional option for lipid management, though not as potent as statins. It can complement existing therapies or be used in combination with ezetimibe or statins. Moreover, unlike statins, bempedoic acid does not pose a risk of glucose elevation or weight gain.

The recent FDA relabeling acknowledges bempedoic acid's efficacy in lowering adverse cardiac events, further solidifying its place in clinical practice alongside statins and PCSK9 inhibitors. This diverse array of options is crucial, considering some patients may prefer oral medications over injectables like PCSK9 inhibitors.

Overall, the inclusive representation of women in the Clear Outcomes trial and the favorable outcomes observed underscore the clinical relevance of bempedoic acid as a valuable tool in lipid management.

Hormone Therapy

The next of the 3 updates of interesting spotlighted by Goldberg pertains to the nuanced conversations surrounding use of hormone therapy in aging women. As Goldberg outlines, historic differences in major trials examining the topic have created debate around the role of hormone therapy, but Goldberg suggests what these studies demonstrate, when examined collectively, is the need for individualized treatment decisions.

In her response, Goldberg advocates for an approach where hormone therapy is considered based on the age and ASCVD risk of each female patient. Specifically, Goldberg recommends considered for women considered to be low or low to intermediate risk, but avoiding hormone therapy, because of its potential for negative cardiovascular health consequences, in women with an ASCVD risk greater than 10%.

Goldberg: Another aspect of the ACC that I particularly enjoy as a cardiologist is its clinical focus. We had a talk on hormone therapy, discussing its current state of prescription. In 2003, there was a significant drop-off in hormone therapy usage following the Women's Health Initiative. However, it's now estimated that about 6,000 women per day enter menopause, with 75% experiencing symptoms like hot flashes, night sweats, brain fog, and depression. Understanding and prescribing hormone therapy appropriately is crucial for managing these symptoms.

It's important to note that many national societies recommend hormone therapy for menopausal symptom relief but not for cardiovascular disease prevention. I want to share a nuanced approach for guiding women through this journey by categorizing them into three risk groups: low risk (ASCVD risk < 5%), intermediate risk (ASCVD risk 7-10%), and high risk (ASCVD risk > 10%). For low-risk individuals, the decision is less stressful as they typically have normal blood pressure, cholesterol levels, are non-smokers, and exercise regularly. Hormone therapy is generally safe for managing menopausal symptoms in this group.

The intermediate risk group requires more consideration. These individuals may have diabetes, high cholesterol, high blood pressure, or metabolic syndrome. Within this group, it's essential to assess individual risk factors and inform patients about specific risks associated with hormone therapy. For example, studies indicate that hormone therapy does not reduce cardiovascular disease risk and can elevate blood pressure and triglyceride levels, particularly estrogen therapy. High-risk individuals, such as those with a history of heart attacks or strokes, should avoid hormone therapy altogether. However, for those in the intermediate group, a thorough evaluation of risk factors is necessary. Discussing the risks of hormone therapy, including its potential to increase the risk of stroke and venous thromboembolism, is crucial. Additionally, considering the form of hormone therapy (oral vs. transdermal) can impact lipid and blood pressure levels, with transdermal therapy being less likely to affect them.

I advise all physicians not to overlook patients' symptoms and to collaborate with them to provide the best information regarding the risks and benefits of hormone therapy. Engaging in this discussion empowers patients to make informed decisions about their health.

TAVR in Women

The third and final update in women’s cardiovascular health highlighted by Goldberg was the PERFORM-TAVR trial. A randomized, parallel-group, multicenter trial conducted in 11 Canadian hospitals, the PERFORM-TAVR trial was launched to assess the effects of protein supplementation and exercise in older patients undergoing TAVR. A total of 210 patients were enrolled in the trial. Of note, more than 70% of participants were 80 years of age or older and 45% were women.

Results of the study pointed to a multivariable-adjusted difference of 0.9 points (95% CI, 0.3–1.6; P = .006) for change in mean short physical performance battery scale from baseline to week 12 with the intervention relative to control. However, Goldberg suggests it is important to consider the limitations of the intervention imposed as a result of the COVID-19 pandemic when attempting to assess the absolute benefit of such an approach, which she explains in the response below.

Goldberg: In my clinical practice as a cardiologist, I frequently encounter individuals with calcified aortic valves who are being considered for transcatheter aortic valve replacement. Many of these patients, particularly older individuals, are women, as women tend to live longer than men. A recent Canadian study presented at the American College of Cardiology focused on patients undergoing TAVR, revealing an average age of 83 years old among participants. The study, initiated around the onset of the pandemic, aimed to implement prehabilitation strategies, including pre-surgery physical therapy and protein supplementation due to potential dietary deficiencies in older individuals. Additionally, post-surgery physical therapy sessions were conducted twice a week, with participants in the treatment group encouraged to walk and provided with accelerometers and protein drinks as supplements.

The study found that while prehabilitation efforts were not as successful as anticipated due to shorter timeframes between referral and TAVR, post-operative physical therapy significantly improved outcomes. Participants in the treatment group experienced lower rates of rehospitalization, increased strength, and engagement in more activities.

This underscores the importance for clinicians to consider the comprehensive clinical status of patients undergoing TAVR, including ensuring adequate nutrition and protein intake, particularly in older individuals who may be deficient. Encouraging post-surgery physical activity, such as walking, is crucial. Furthermore, cardiac rehabilitation is an option to enhance the strength and well-being of patients following valve surgery, potentially reducing hospital readmissions.

Nieca Goldberg, MD, has no relevant financial relationships to report.

Editor's note: this transcript was edited for grammar and clarity using artificial intelligence.

References:

1. Cho L, Plutzky J, Brennan D, et al. CHARACTERISTICS AND OUTCOMES FOR STATIN-INTOLERANT WOMEN RECEIVING BEMPEDOIC ACID IN THE CLEAR OUTCOMES TRIAL. Presented at: American College of Cardiology (ACC.24) Annual Scientific Session. April 6 – 8, 2024. Atlanta, GA.
2. Afilalo J, et al. Protein and Exercise to Reverse Frailty in Older Men and Women Undergoing Transcatheter Aortic Valve Replacement: The PERFORM-TAVR Trial. Presented at: American College of Cardiology (ACC.24) Annual Scientific Session. April 6 – 8, 2024. Atlanta, GA.