Women may benefit more from CRT-D therapy than men

Women benefited more from cardiac resynchronization therapy defibrillators than men in a meta-analysis of patients with left bundle-branch block performed by the FDA.

The difference was most apparent in patients with a QRS of 130 ms to 149 ms, the researchers wrote.

Researchers from the FDA’s Center for Devices and Radiological Health investigated whether women with left bundle-branch block (LBBB) benefited from CRT-D at a shorter QRS duration than men with LBBB. Current guidelines limit class I indications for CRT-D to those with QRS ≥150 ms. However, women have been underrepresented in CRT trials for HF, according to the study background.

The researchers pooled individual patient data from three trials covering 4,076 patients with LBBB comparing outcomes for those with CRT-D and those with implantable cardioverter defibrillators. The cohort included all participants from the MADIT-CRT trial, participants from the RAFT trial without a pacemaker at baseline and participants from the REVERSE trial for whom data on QRS morphology were available. Most patients had NYHA class II HF.

The primary outcome was time to HF event or death. The secondary outcome was death. Maximum follow-up was 3 years.

CRT-D made difference in women

According to the results, women were more likely than men to benefit from CRT-D, and the difference was greatest in patients with a QRS of 130 ms to 149 ms. In that cohort, women with a CRT-D had a 76% reduction in HF or death (absolute difference, 23%; HR=0.24; 95% CI, 0.11-0.53) and in death alone (absolute difference, 9%; HR=0.24; 95% CI, 0.06-0.89) compared with women with an ICD. However, among men in that cohort, there was no difference between the groups in HF or death (absolute difference, 4%; HR=0.85; 95% CI, 0.6-1.21) or death (absolute difference, 2%; HR=0.86; 95% CI, 0.49-1.52).

The researchers also found that both men and women with LBBB and QRS ≥150 ms benefited from a CRT-D, and that both men and women with LBBB and QRS <130 ms did not benefit from a CRT-D.

“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,” Robbert Zusterzeel, MD, and colleagues wrote. “This study exemplifies the potential public health and regulatory science value of combining data from multiple trials submitted to the FDA.”

Shortcomings of guidelines

C. Noel Bairey Merz

In an invited commentary, C. Noel Bairey Merz, MD, and Vera Regitz-Zagrosek, MD, said: “These results also shed light on a major contributor to the misdiagnosis and suboptimal treatment of CVD in women: guidelines are typically based on a male standard and do not address important differences in women. … Women remain the minority of research subjects but the majority of persons dying from CVD.”

Bairey Merz, of Cedars Sinai Heart Institute and a member of the Cardiology Today Editorial Board, and Regitz-Zagrosek, of Charite University Medicine, Berlin, wrote that evidence- and guideline-based medicine too often ignores subgroups and is becoming prohibitively expensive, and personalized medicine is too expensive to be used in clinical care and does not cover epigenetic modifications, but sex-specific medicine is preferable because it “considers an important genetic difference — sex — and includes effects of lifestyle and environment transmitted by epigenetic modifications.”

For more information:

Bairey Merz CN. JAMA Intern Med. 2014;doi:10.1001/jamainternmed.2014.320.

Zusterzeel R. JAMA Intern Med. 2014;doi:10.1001/jamainternmed.2014.2717.

Disclosure: The researchers, Bairey Merz and Regitz-Zagrosek report no relevant financial disclosures.