April 2020

CARDIOVASCULAR

SEX MAY INFLUENCE EFFECTIVENESS OF COMMON HEART FAILURE DRUG

Featuring: Sanjiv Shah, ’00 MD
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​​Women saw a greater benefit than men from a novel combination heart failure drug called sacubitril-valsartan, with a bigger reduction in risk of hospitalizations for heart failure and death from cardiovascular causes, according to a study published in Circulation.
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The study, co-authored by Sanjiv Shah, ’00 MD, the Neil J. Stone, MD, Professor in the Division of Cardiology, may suggest that the effectiveness of pharmacologic treatments for heart failure with preserved ejection fraction (HFpEF) may depend on the patient’s sex.

Unlike heart failure with reduced ejection fraction, there is currently no approved treatment for HFpEF, in which the heart muscle contracts relatively normally but the ventricles do not relax normally during ventricular filling. The condition is also more prevalent in women than in men, according to Shah.

The reason for this disparity, according to Shah, is that women are actually less likely to develop the form of heart failure with reduced ejection fraction, making them more likely to develop HFpEF. Women with HFpEF also have lower levels of B-type natriuretic peptide levels, a beneficial protein the helps blood vessels relax and tells the kidney to get rid of fluid.

“Sacubitril-valsartan augments the action of B-type natriuretic peptide,” Shah said.
Additionally, women also have a higher “set-point” for their ejection fraction, or the contracting function of the heart. Therefore, women who develop HFpEF may actually have greater heart muscle problems than men in the same category.

For the current study, the investigators compared hospitalizations due to heart failure and death from cardiovascular causes in participants involved in the PARAGON-HF trial, which involved more than 4,700 men and women with HFpEF to take either sacubitril-valsartan or valsartan.

The investigators found that sacubitril-valsartan reduced the risk of heart failure hospitalization more among women compared to men. However, symptoms didn’t improve in women taking the drug.

“Even though there is plenty of scientific rationale for women benefiting more than men, the findings from the study suggest that the benefit in women may have been a chance finding,” Shah said, and noted that future studies may tease out more of the differences in treatment between men and women.

Currently, Shah and colleagues are studying the intersection of sex hormones, heart muscle structure and function during exercise, body composition and hormone signaling in men and women with HFpEF which, according to Shah, may aide in the development of new treatments.

This work was supported by an American Heart Association Go Red for Women Strategically Focused Research Network grant.

This article was originally published in the Feinberg School of Medicine News Center on April 6, 2020 . 
Sanjiv Shah, ’00 MD, the Neil J. Stone, MD, Professor in the Division of Cardiology, was a co-author of the study published in Circulation.

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