Determining the safety and effectiveness of medical devices between genders is not always easy. There are numerous cardiovascular differences amongst men and women, but often times studies aren’t gender specific or one gender is underrepresented, making sex-specific conclusions difficult to obtain. Women are largely the minority in cardiac resynchronization therapy (CRT) trials for heart failure (20 percent of enrollees are female) leaving guidelines and conclusions to be based on a male standard.

In a study supported by the U.S. Food and Drug Administration (FDA) Office of Women’s Health, published June 23 in JAMA: Internal Medicine, Robbert Zusterzeel, MD, along with a team of colleagues, sought to evaluate whether women with left bundle branch block (LBBB) benefit from CRT-defibrillators (CRT-Ds) at a shorter QRS duration than men. The authors found that "women with LBBB benefited from CRT-D at a shorter QRS duration than men with LBBB," and consequently women are less likely to receive a CRT-D than men.

The CRT benefit in women was assessed using meta-analysis that combined individual patient data from three clinical trials. The criteria included randomized clinical trials comparing CRT-D vs. implantable cardioverter defibrillators in a population of patients with primarily mild heart failure, trials reporting heart failure and mortality outcomes, and trials that had individual-patient data submitted to the FDA as a part of a premarket approval application.

The researchers looked at a total of 4,076 patients, and found that women benefitted from CRT more than men with a difference in QRS of 130 to 149 milliseconds. Results showed women had a reduced heart failure or death rate of 76 percent (absolute difference 23 percent) and a 76 percent reduction in death alone (absolute difference 9 percent), but there was no significant benefit in men.

Importantly, there were differences in QRS times in women. "This is important because recent guidelines limit the class I indication for CRT-D to patients with LBBB and QRS of 150 milliseconds or longer," the authors note. "While guidelines do give a class IIa indication to patients with LBBB and a QRS of 120 to 149 milliseconds, the present findings are important to communicate because women are less likely to receive CRT-D than men are."

They add that moving forward, "this study exemplifies the potential public health and regulatory science value of combining data from multiple clinical trials submitted to the FDA."

In a corresponding editorial comment, C. Noel Bairey Merz, MD, FACC, states, "These results shed light on a major contributor to the misdiagnosis and suboptimal treatment of cardiovascular disease in women: guidelines are typically based on a male standard and do not address important differences in women."

"To better understand and respond to sex and gender differences, we need initiatives to increase awareness of these differences, develop a common knowledge basis and exchange between researchers of different disciplines, develop career opportunities for young scientists, provide common training tools to introduce students early into the disciplines, and establish systematic sex- and gender- specific medicine research as an independent discipline," she adds.