Subcutaneous implantable cardioverter defibrillators (S-ICDs) are as protective as transvenous implantable cardioverter-defibrillators (ICDs) in the prevention of sudden cardiac death, but have a better safety profile, the results of a prospective, randomised trial online in a late-breaking trial session at Heart Rhythm Society (HRS) 2020 Science, have found. The findings of the PRAETORIAN trial, which is an investigator-initiated, international, multicentre, randomised, non-inferiority study, will also be published in The New England Journal of Medicine.
PRAETORIAN—A prospective, randomised comparison of subcutaneous and transvenous implantable cardioverter defibrillator therapy—was conducted by Reinoud Knops, Academisch Medisch Centrum, Universiteit van Amsterdam, (Amsterdam, The Netherlands) and colleagues, is the first to compare the safety and efficacy of S-ICDs to transvenous ICDs. The trial was supported by the device manufacturer, Boston Scientific. According to the study team, the results highlight that S-ICDS are an important treatment option for patients in need of an ICD without pacing indication.
“Transvenous ICDs are effective, but come with major limitations,” Knops said during his presentation of the findings highlighting in particular a 10–20% lead failure rate after six years follow-up for the devices. “For that reason, subcutaneous ICDs were developed to overcome these lead-related complications,” he explained.
Knops noted in his presentation that currently there is only registry data to demonstrate the outcomes of the use of S-ICDs, which he said mostly come from young patients with relatively preserved left ventricular ejection fraction (LVEF), showing a high shock efficacy and fewer ICD-related complications, but more inappropriate shocks than transvenous ICDs. There are no randomised, controlled trials comparing the two therapies to date, and so the PRAETORIAN trial was designed to demonstrate the non-inferiority of the S-ICD compared to the transvenous ICD, with respect to acute and long-term device-related complications and inappropriate shocks over a follow-up period of 48 months.
Inclusion criteria for the study were patients of 18 years or above with a class I or IIa indication for ICD therapy for primary or secondary prevention. Exclusion criteria were indication for pacing therapy: brady, cardiac resynchronisation therapy (CRT) and antitachycardia pacing ), and failed S-ICD vector screening. A total of 849 patients with a class I or IIa indication for ICD therapy and without the need for pacing from 39 centres in the USA and Europe, were randomised and followed until a median of four years. Of the patients, 426 patients were assigned to receive an S-ICD and 423 were assigned to a transvenous ICD, with similar baseline characteristics in the two groups. The baseline characteristics are comparable to those of other major ICD trials, thereby showing that the trial reflects a general ICD population, Knops said. The trial population was 20% female, with a median age of 63 years (55‒70 years), and 69% had ischaemic cardiomyopathy with a median left ventricular ejection fraction of 30% (25‒35%).
Results of the trial outlined by Knops show that in a general ICD-population, the subcutaneous ICD is non-inferior to the transvenous ICD with regards to major ICD-related adverse events with significantly less lead-related complications in patients treated with the S-ICD. “At four years, the primary composite endpoint of inappropriate shocks and complications occurred in the transvenous ICD arm in 15.7% of the patients,” Knops said. “I think that the big news of this study, [is that] in the S-ICD arm, there was no difference at four years of the occurrence of the primary endpoint at 15.1% in the S-ICD [arm]. This means that the S-ICD is non-inferior to the transvenous ICD, with regard to this primary endpoint.” Breaking this down further, Knops said that there was a difference between transvenous ICDs and S-ICDs in terms of the rate of inappropriate shocks. In the S-ICD arm, inappropriate shocks occurred in 9.7% of patients, compared to 7.3% in the transvenous ICD arm (p=0.14). “I think it is important to mention that the main driver of inappropriate shocks in the transvenous-ICD arm was AF and supraventricular tachycardia, and the main driver in the S-ICD arm was cardiac over-sensing,” Knops said. The results showed a lower rate of device-related complications recorded in S-ICD patients (5.9%) compared to transvenous ICDs (9.8%) [p=0.11]. “There were more infections in the transvenous ICD arm,” Knops said, adding “but this was counterbalanced by more bleedings in the S-ICD arm. The major difference in numbers in the complications was caused by lead-related complications [1.4% S-ICD vs. 6.6% TV-ICD].” There was no significant difference in mortality measured in the trial, Knops reported.
In his concluding remarks, Knops said: “In a conventional primary and secondary prevention ICD population, S-ICD is non-inferior to the transvenous ICD with respect to major ICD-related adverse events.” He added that S-ICDs should be considered in all patients in need of an ICD without a pacing indication. Since the rate of most lead-related complications of transvenous ICDs occur after more than four years, patient cohort of the PRAETORIAN study will be followed for another four years. The authors of the study suggest that future results could reflect S-ICD updates that help prevent inappropriate shocks that may have occurred in earlier stages of the trial.
Commenting, following Knops’ presentation on the study’s findings, Sana M Al-Khatib, professor of medicine, Duke University Medical Center, Durham, USA said it is “great to finally have a randomised controlled trial that compares the S-ICD with the transvenous ICD,” but noted that numerically there were fewer complications with the S-ICD, but that these were counterbalanced by a higher number of inappropriate shocks. In terms of the clinical implications of the trial, Al-Khatib said that the option of an S-ICD versus transvenous ICD should be presented to patients with ICD indications, no pacing need and who pass the screening test. However, she commented that she would not extrapolate the results of the trial to every patient seen in clinical practice.