ClinicalDeviceGender differences in clinical outcome and primary prevention defibrillator benefit in patients with severe left ventricular dysfunction: A systematic review and meta-analysis
Introduction
Multiple randomized clinical trials have shown primary prevention of sudden cardiac death (SCD) with an implantable cardioverter-defibrillator (ICD) in patients with left ventricular dysfunction to be effective.1 However, the real benefit of prophylactic ICD therapy in underrepresented subgroup of patients, such as women, has not been consistently demonstrated.2, 3, 4, 5 In fact, studies assessing gender differences in arrhythmic risk showed conflicting results,2, 3, 4, 5, 6, 7 and no clear-cut evidence supports the same benefit of prophylactic ICD therapy in the two genders.8
To better evaluate the presence and possible causes of gender differences in effectiveness of prophylactic ICD therapy in patients with left ventricular dysfunction, we performed a meta-analysis of primary prevention ICD studies on the end-points of total mortality, appropriate ICD intervention, and net ICD survival benefit in women compared to men.
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Searching strategy and selection process
Two trained investigators (PS, GP) independently searched major web databases for all published studies that (1) had a prospective randomized design, (2) tested ICD therapy versus placebo in patients with dilated cardiomyopathy (DCM) who did not previously experience major arrhythmic events, and (3) reported an estimate of the risk for specified end-points for women compared to men, adjusted for all possible baseline confounders or covariates. Citations initially selected by systematic search
Search results and study selection
The search permitted retrieval of 3,467 citations. We identified nine eligible citations, which were assessed according to compliance to the inclusion criteria. Among the retrieved but excluded studies, DINAMIT (Defibrillator in Acute Myocardial Infarction Trial)12 and IRIS (Immediate Risk Stratification Improves Survival)13 did not provide adjusted estimates of the risk of total mortality and appropriate ICD therapy in women compared to men and thus did not meet inclusion criteria.
Ultimately,
Discussion
This systematic review was designed to assess gender differences in outcome after prophylactic ICD placement and is based on the statistical pooling of five randomized studies, which enrolled more than 7,200 patients, and specifically compared women with men with regard to clinical outcome.
With more than 1,600 women, this meta-analysis includes the largest women cohort to date and shows that women enrolled in primary prevention ICD trials have the same overall mortality as compared to men,
Conclusion
This review presents a meta-analysis of data from five primary prevention randomized ICD studies that assessed gender differences in outcome and shows a smaller impact of SCD on overall mortality in women, which may explain their smaller and nonsignificant survival benefit from prophylactic ICD therapy.
Our findings challenge current LVEF-based prophylactic ICD recommendations, raising concerns about the appropriateness of generalizing such recommendations to subgroups of patients
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2022, JACC: Clinical ElectrophysiologyCitation Excerpt :Also, anatomical differences between women and men are well known at the cardiac level. The left ventricular size is significantly smaller in women, with a reduced number of re-entrant propagating electrical waves and a less susceptible substrate.19 Finally, other less-quantifiable factors, including adherence to a low-risk lifestyle, psychological factors, and patient care decisions may also play roles.
Dr. Natale has received compensation for belonging to the speakers' bureau for St. Jude Medical, Boston Scientific, Medtronic, and Biosense Webster and has received a research grant from St. Jude Medical.