HRS: Women respond better to CRT, but we still don't know why
Previous trials have found that women benefit from CRT more than men. Arshad said a large number of these studies have shown that these benefits may be due to remodeling; however, better evidence is needed to help explain these differences. “The etiology of death post-CRT may be different between the genders as well,” Arshad said. Additionally, these trials have found cardiovascular events to be decreased in women who received CRT.
As far as advanced heart failure (HF) goes, CRT is an effective treatment for patients with drug-refractory chronic heart failure.
“Subgroup analyses of most CRT trials suggest that women may have a better response to CRT as measured by clinical and fatal outcomes and reverse remodeling,” Arshad said. However, she noted that there are some important caveats, including the fact that these subanalyses may be prone to bias.
She also outlined a change in FDA and European Society of Cardiology indications in 2010 that were expanded to include indications for CRT. These indications now include left bundle branch block (LBBB) patients, NYHA Class I and ischemic Class I HF patients with an left ventricular ejection fraction (LVEF) of less than 30 percent and a QRS duration of more than130 ms.
Arshad touched on MADIT-CRT substudy results that showed dramatic differences in HF-free survival between the sexes. “Groups that benefited from CRT therapy most were females and those with a wider QRS,” she noted. “Women derived almost twice the benefit from CRT-D.”
While male patients who received CRT-D did not see significant reductions in death, women did.
“Females in MADIT-CRT received a striking benefit from CRT-D therapy with significant reduction in all cause mortality as well as HF death,” Arshad offered. Additionally, she said that results of the RAFT trial, which looked at early stage heart failure, had similar results as MADIT-CRT, showing that in female patients, those with a wider QRS and those with LBBB fared better.
“Why do women respond better after CRT?” Arshad asked. She said that these results may be due to the fact that the risk of HF is greater for women compared with men, which could result in a greater benefit from preventive CRT-D therapy in women.
Additionally, Arshad noted that there is a CRT utilization disparity. She noted that while 51 percent of the U.S. population is women, enrollments seen within clinical trials only include nearly one-quarter or one-third of women.
And while results of the IMPROVE-HF trials showed improved utilization of CRT, women were still less likely to receive anticoagulation, less CRT-D and HF education when compared with men.
“Aggressive efforts should be undertaken to increase the enrollment of women and other underrepresented groups in clinical trials,” Arshad concluded.
Additionally, she added that women should receive device therapy “at a rate appropriate to the prevalence of disease.”
There should be additional education efforts to evaluate why women may respond better to these types of therapies with specific reference to CRT. This could help physicians better understand patient response to CRT.