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

Abstract

AimsThe clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU‐CERT‐ICD) aims to assess its current clinical value.Methods and resultsThe EU‐CERT‐ICD is a prospective investigator‐initiated non‐randomized, controlled, multicentre observational cohort study performed in 44 centres across 15 European Union countries. We will recruit 2250 patients with ischaemic or dilated cardiomyopathy and a guideline indication for primary prophylactic ICD implantation. This sample will include 1500 patients at their first ICD implantation and 750 patients who did not receive a primary prevention ICD despite having an indication for it (non‐randomized control group). The primary endpoint is all‐cause mortality; the co‐primary endpoint in ICD patients is time to first appropriate shock. Secondary endpoints include sudden cardiac death, first inappropriate shock, any ICD shock, arrhythmogenic syncope, revision procedures, quality of life, and cost‐effectiveness. At baseline (and prior to ICD implantation if applicable), all patients undergo 12‐lead electrocardiogram (ECG) and Holter ECG analysis using multiple advanced methods for risk stratification as well as detailed documentation of clinical characteristics and laboratory values. Genetic biobanking is also organized. As of August 2018, baseline data of 2265 patients are complete. All subjects will be followed for up to 4.5 years.ConclusionsThe EU‐CERT‐ICD study will provide a necessary update about clinical effectiveness of primary prophylactic ICD implantation. This study also aims for improved risk stratification and patient selection using clinical and ECG risk markers.

Decision‐making regarding primary prevention implantable cardioverter‐defibrillators among older adults

“…To address our gap in knowledge regarding ICD efficacy in older patients, a multisite, randomized clinical trial comparing ICD implantation and optimal medical therapy to optimal medical therapy alone among patients 70 years of age and older is underway in the Department of Veterans Affairs health care system . To address our knowledge gap regarding ICD effectiveness in the modern therapeutic era, a multisite, observational cohort study is underway in 44 centers across 15 European Union countries . While the latter study does not specifically target older patients, it may nonetheless yield updated information on the effectiveness of primary prevention ICDs among patients of advanced age given an anticipated enrollment exceeding 2300 patients.…”

“…41 To address our knowledge gap regarding ICD effectiveness in the modern therapeutic era, a multisite, observational cohort study is underway in 44 centers across 15 European Union countries. 42 While the latter study does not specifically target older patients, it may nonetheless yield updated information on the effectiveness of primary prevention ICDs among patients of advanced age given an anticipated enrollment exceeding 2300 patients.…”

Present criteria for prophylactic ICD implantation: Insights from the EU-CERT-ICD (Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in EUrope) project

“…Estimated from previous studies, an annualized mortality of 4.5% and a first appropriate ICD shock rate of 4.5% were expected. For a power of 80% at a two-sided significance level of 5%, in a 4-year study a sample of 1500 ICD patients and 750 controls was calculated to generate at least 279 death events (20). For independent binary or dichotomized risk stratifiers to provide hazard ratios of about 2 between a high and a low risk group we calculated that 122 deaths yielded J o u r n a l P r e -p r o o f 95% power for a two-sided significance level of 5%.…”

“…The number of patients with atrial fibrillation was limited to 15%. A large number of clinical baseline parameters were documented at enrollment of each patient (20). ICD patients were followed every 3 to 6 months or remotely.…”

Potential drug-drug interactions in patients with indication for prophylactic implantation of a cardioverter defibrillator: a cross-sectional analysis

“…Since there are only few studies in Germany that assessed the frequency of PDDI so far [16], the present analysis investigates the topic of these PDDI. The study is focused on PDDI in patients with indication for prophylactic implantation of a cardioverter defibrillator (ICD), which were included in the EU-CERT-ICD study [17]. The objective was to examine the frequency of PDDI in this specific group of patients descriptively and to compare those patients with or without PDDI to identify potential underlying factors.…”