Sex differences in outcomes of primary prevention implantable cardioverter-defibrillator therapy: combined registry data from eleven European countries

Abstract

AimsTherapy with an implantable cardioverter defibrillator (ICD) is established for the prevention of sudden cardiac death (SCD) in high risk patients. We aimed to determine the effectiveness of primary prevention ICD therapy by analysing registry data from 14 centres in 11 European countries compiled between 2002 and 2014, with emphasis on outcomes in women who have been underrepresented in all trials.Methods and resultsRetrospective data of 14 local registries of primary prevention ICD implantations between 2002 and 2014 were compiled in a central database. Predefined primary outcome measures were overall mortality and first appropriate and first inappropriate shocks. A multivariable model enforcing a common hazard ratio for sex category across the centres, but allowing for centre-specific baseline hazards and centre specific effects of other covariates, was adjusted for age, the presence of ischaemic cardiomyopathy or a CRT-D, and left ventricular ejection fraction ≤25%. Of the 5033 patients, 957 (19%) were women. During a median follow-up of 33 months (IQR 16–55 months) 129 women (13%) and 807 men (20%) died (HR 0.65; 95% CI: [0.53, 0.79], P-value < 0.0001). An appropriate ICD shock occurred in 66 women (8%) and 514 men (14%; HR 0.61; 95% CI: 0.47–0.79; P = 0.0002).ConclusionOur retrospective analysis of 14 local registries in 11 European countries demonstrates that fewer women than men undergo ICD implantation for primary prevention. After multivariate adjustment, women have a significantly lower mortality and receive fewer appropriate ICD shocks.

Rationale and design of the EU‐CERT‐ICD prospective study: comparative effectiveness of prophylactic ICD implantation

“…In addition to the described prospective study, a retrospective registry 17 and meta-analyses in primary prophylactic ICD patients were set up 18,19 (Figure 1). In addition to the described prospective study, a retrospective registry 17 and meta-analyses in primary prophylactic ICD patients were set up 18,19 (Figure 1).…”

“…58 From the original DANISH data, it was shown that increasing age is associated with loss of ICD survival benefit. 8,23,58,17 It is therefore uncertain whether the survival benefit of prophylactic ICDs is still the same. 8,23,58,17 It is therefore uncertain whether the survival benefit of prophylactic ICDs is still the same.…”

“…The 'EUropean Comparative Effectiveness Research to assess the use of primary prophylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD)' was funded by the European Community's Seventh Framework Programme as a modular research project to study the effectiveness of prophylactic ICDs. In addition to the described prospective study, a retrospective registry 17 and meta-analyses in primary prophylactic ICD patients were set up 18,19 (Figure 1). Over the course of the project, several original papers [20][21][22][23][24][25][26][27] and editorials [28][29][30][31][32][33] have been published from the various work packages.…”

“…61 Important outcomes in primary prevention ICD patients-that is, overall mortality and shocks-have improved considerably. 8,23,58,17 It is therefore uncertain whether the survival benefit of prophylactic ICDs is still the same. It had been hypothesized from original SCD-HeFT 56 and MADIT-II 62 data that patients with very high mortality do not benefit from prophylactic ICDs due to a high rate of non-arrhythmic or non-cardiac deaths.…”

Trends in the use of implantable cardioverter‐defibrillators for prevention of sudden cardiac arrest: A South Korean nationwide population‐based study

“…The predominance of men in the implanted population was found in other observational and registry studies. 27,28 The cause for this finding is most likely a higher cardiac disease prevalence in men, but this result raises the possibility that ICD therapy might be underutilized in women. Underutilization could be addressed by comparing gender…”