Clinical effectiveness of primary prevention implantable cardioverter-defibrillators: results of the EU-CERT-ICD controlled multicentre cohort study
Authors: Zabel Markus , Willems Rik , Lubinski Andrzej , Bauer Axel , Brugada Josep , Conen David , Flevari Panagiota , Hasenfuß Gerd , Svetlosak Martin , Huikuri Heikki V , Malik Marek , Pavlović Nikola , Schmidt Georg , Sritharan Rajevaa , Schlögl Simon , Szavits-Nossan Janko , Traykov Vassil , Tuinenburg Anton E , Willich Stefan N , Harden Markus , Friede Tim , Svendsen Jesper Hastrup , Sticherling Christian , Merkely Béla ,   EU-CERT-ICD Study Investigators, Merkely Béla , Perge Peter , Sallo Zoltan , Szeplaki Gabor , Szegedi Nandor , Nagy Klaudia Vivien , Zabel Markus , Lüthje Lars , Schlögl Simon , Sritharan R , Haarmann Helge , Bergau Leonard , Seegers Joachim , Hasenfuß Gerd , Munoz-Exposito Pascal , Tichelbäcker Tobias , Kirova Aleksandra , Hasenfuß Gerd , Friede Tim , Zabel Markus , Schlögl Simon , Friede Tim , Harden Markus , Malik Marek , Hnatkova Katerina , Vos Marc A , Willich Stefan N , Reinhold Thomas , Willems Rik , Vandenberk Bert , Klinika Magdalena , Szavits-Nossan Janko , Rotkvić L , Flevari Panayota , Katsimardos Andreas , Katsaras Dimitrios , Hatala Robert , Svetlosak Martin , Lubinski Andrzej , Kuczejko Tomasz , Hansen Jim , Sticherling Christian , Conen David , Pavlović Nikola , Manola Šime , Vinter Ozren , Benko Ivica , Tuinenburg Anton , Sprenkeler David , Smoczynska A , Vos M A , Bauer Axel , Meyer-Zürn Christine , Eick Christian , Svendsen Jesper Hastrup , Brugada Josep , Arbelo Elena , Kaliska Gabriela , Martinek Jozef , Schmidt Georg , Dommasch Michael , Steger Alexander , Kääb Stefan , Bauer Axel , Sinner Moritz F , Rizas Konstantinos D , Hamm Wolfgang , Traykov V , Cygankiewicz Iwona , Ptaszyński Pawel , Kaczmarek K , Poddebska I , Iovev Svetoslav , Novotný Tomáš , Kozak Milan , Huikuri Heikki , Kenttä Tuomas , Pelli Ari , Kasprzak Jaroslaw D , Qavoq Dariusz , Brusich Sandro , Avdovic Ervin , Klasan Marina , Galuszka Jan , Taborsky Milos , Velchev Vasil , Dissmann Rüdiger , Shalganov T , Guzik P , Krauze T , Bimmel Dieter , Lieberz Christiane , Ludwigsburg Klinikum , Stefanow Stefan , Rüb Norman , Wolpert Christian , Seegers Joachim , Meier Lars S , Behrens Steffen , Jurisic Zrinka , Braunschweig Frieder , Blaschke Florian , Pieske Burkert , Bakotic Zoran , Anic Ante , Weiden Klinikum , Schwinger Robert H G , Platonov Pyotr , Grönefeld Gerian , Klingenheben Thomas 
Published: March 2020

Abstract

Aims
The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter-Defibrillators (EU-CERT-ICD), a prospective investigator-initiated, controlled cohort study, was conducted in 44 centres and 15 European countries. It aimed to assess current clinical effectiveness of primary prevention ICD therapy.

Methods and results
We recruited 2327 patients with ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and guideline indications for prophylactic ICD implantation. Primary endpoint was all-cause mortality. Clinical characteristics, medications, resting, and 12-lead Holter electrocardiograms (ECGs) were documented at enrolment baseline. Baseline and follow-up (FU) data from 2247 patients were analysable, 1516 patients before first ICD implantation (ICD group) and 731 patients without ICD serving as controls. Multivariable models and propensity scoring for adjustment were used to compare the two groups for mortality. During mean FU of 2.4 ± 1.1 years, 342 deaths occurred (6.3%/years annualized mortality, 5.6%/years in the ICD group vs. 9.2%/years in controls), favouring ICD treatment [unadjusted hazard ratio (HR) 0.682, 95% confidence interval (CI) 0.537–0.865, P = 0.0016]. Multivariable mortality predictors included age, left ventricular ejection fraction (LVEF), New York Heart Association class &lt;III, and chronic obstructive pulmonary disease. Adjusted mortality associated with ICD vs. control was 27% lower (HR 0.731, 95% CI 0.569–0.938, P = 0.0140). Subgroup analyses indicated no ICD benefit in diabetics (adjusted HR = 0.945, P = 0.7797, P for interaction = 0.0887) or those aged ≥75 years (adjusted HR 1.063, P = 0.8206, P for interaction = 0.0902).

Conclusion
In contemporary ICM/DCM patients (LVEF ≤35%, narrow QRS), primary prophylactic ICD treatment was associated with a 27% lower mortality after adjustment. There appear to be patients with less survival advantage, such as older patients or diabetics.