In nonischemic cardiomyopathy, women with CRT-D appear to have best outcomes: BIO-LIBRA
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Key takeaways:
- Among patients with nonischemic cardiomyopathy, women were less likely to die or have a ventricular event than men.
- The trend was strongest in women with a cardiac resynchronization therapy defibrillator.
In patients with nonischemic cardiomyopathy, women had lower rates of ventricular arrhythmias and death than men, especially if they had a cardiac resynchronization therapy defibrillator, according to the results of the BIO-LIBRA study.
Results from the second interim analysis of BIO-LIBRA, which was designed to include at least 40% women, who are traditionally underrepresented in implantable cardiac device trials, were presented by Valentina Kutyifa, MD, PhD, FHRS, FACC, FESC, professor of medicine at the University of Rochester Medical Center School of Medicine and Dentistry, at Heart Rhythm 2023.
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“We had a particular emphasis on the role of sex in this patient population,” Kutyifa said at a press conference. “We wanted to address two knowledge gaps in this study. The first one being that women are underrepresented in device clinical studies, with only 15% to 30% of the participation. These percentages did not change over recent years. We also know that recent data on nonischemic cardiomyopathy, the kind of cardiomyopathy that leads to a weakened heart muscle, heart failure hospitalizations and life-threatening ventricular arrhythmia events, are not currently available in the United States.”
Among the patient population of 1,000 people with nonischemic cardiomyopathy requiring device therapy (mean age, 62 years), 47.5% were women, exceeding the enrollment goal of 40%, Kutyifa said at a press conference, noting that 51% of women were implanted with an implantable cardioverter defibrillator and 49% were implanted with a CRT defibrillator (CRT-D), whereas in the male population, 58% had an ICD and 42% had a CRT-D. All devices used in the study were made by Biotronik.
The model for recruitment “included a very simple set of tools, including championing female recruitment at sites, closely tracking female enrollment and providing tips for consent ... and providing specially developed materials for patients, [including] the BIO-LIBRA Patient Guide, which particularly focused on diverse representation of patients of different sexes and races,” Kutyifa said. “We also included educational materials and a very detailed FAQ so patients can understand what it means to participate in a clinical trial and what it means to have heart disease, which is the leading cause of death in women. What was surprising is that by increasing the enrollment of women, we also increased enrollment of a racially diverse population; 30% of our patients were ‘non-white’ and 10% of our patients self-reported as Hispanic or Latino.”
Compared with men, women were more likely to have NYHA class III HF (55% vs. 46%; P = .007) and were less likely to have paroxysmal atrial fibrillation (10% vs. 15%; P < .001), according to the researchers.
Medication use was similar by sex except for diuretics, which were more often used by women (P = .009), the researchers found.
“The use of newer therapeutic agents such as SGLT2 inhibitors and [angiotensin receptor/neprilysin inhibitors] was high and increasing over time,” Kutyifa said at the press conference. “Patients had improvements in their medical therapy even after they were implanted with an ICD or a CRT-D.”
At a mean follow-up of 2.27 years, 9.6% of patients died and 8.2% had a ventricular tachycardia (VT) or ventricular fibrillation (VF) event, the researchers found.
Compared with men, women had lower risk for death, VT or VF (adjusted HR = 0.65; 95% CI, 0.46-0.91; P = .013; log-rank P < .001), and the rate of death/VF/VT was numerically lower in those with a CRT-D compared with those with an ICD (aHR = 0.79; 95% CI, 0.56-1.1; P = .163; log-rank P = .166), according to the researchers.
VT/VF event risk favored women over men (HR = 0.56; 95% CI, 0.35-0.91; P = .019; log-rank P = .004) and numerically favored CRT-D over ICD (HR = 0.81; 95% CI, 0.5-1.3; P = .377; log-rank P = .203), the researchers found.
Women with CRT-D had the lowest cumulative probability of death/VT/VF at 8%, followed by women with ICD at 17%, men with ICD at 19% and men with CRT-D at 20% (P for interaction = .007; log-rank P < .001), Kutyifa said at the press conference.
“There was an interesting, intricate relationship between sex and device type, which we had a large enough population of women to assess and report on,” Kutyifa said at the press conference. “We are really hopeful that this study will pave the path for future clinical studies to further transform the way we enroll men and women in trials, and provide us with a more balanced view of all sexes and races.”
Perspective
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BIO-LIBRA addresses an important limitation in current device-based therapy with implantation of ICD and CRT-D, that is, we are using 20-year-old data to guide current clinical practice.
Women have historically been underrepresented in ICD trials, accounting for less than 30% of the study population in all major trials. BIO-LIBRA is the first large-scale study (1,000 patients enrolled in multiple centers) to assess sex-device (ICD and CRT-D) interactions and outcomes in the setting of modern-day medical therapies for HF, including ARNI and SGLT2 inhibitors.
BIO-LIBRA highlights an important issue when counseling patients about the benefits and risks of ICD and CRT-D implantation. About the benefit of ICD and CRT-D, men and women are different and should be counseled differently. The benefit of an ICD, for example, in a woman with nonischemic cardiomyopathy (not MI-related weakening) may be marginal as compared to a man. Also, there is an increasing role of CRT therapy to prevent death and arrhythmias and to improve heart function beyond ICD therapy in women.
Perspective
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An intentional strategy that encourages treatment in underrepresented groups is beneficial and perhaps could be applied more broadly into everyday clinical practice. New research and science are now more quickly integrated into everyday clinical practice, perhaps due to faster and wider communication among health care providers. Finally, even with modern treatment strategies including implant of an ICD, mortality and ventricular arrhythmias remain significant (10% to 15% at 2 years).
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Kutyifa V, et al. Late Breaking Clinical Trials and Science – Ventricular Arrhythmias. Presented at: Heart Rhythm 2023; May 19-21, 2023; New Orleans (hybrid meeting).
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