PRAETORIAN
PubMed • Full text • PDF • ClinicalTrials.gov
Clinical Question
In patients with an indication for implantable defibrillator (ICD), are subcutaneous ICDs non-inferior to traditional transvenous ICDs with respect to device-related complications and inappropriate shocks?
Bottom Line
In patients with an indication for ICD, the 49-month incidence of device-related complications and inappropriate shocks was similar in individuals randomized to subcutaneous ICD (15.1%) versus those randomized to transvenous ICD (15.7%). With subcutaneous ICD, device-related complications were non-significantly lower (hazard ratio [HR] 0.69, 95% CI 0.44-1.09), while inappropriate shocks were non-significantly higher (HR 1.43, 95% CI 0.89-2.30).
Major Points
Implantable defibrillators (ICDs) are effective in the prevention of sudden cardiac death (SCD) due to ventricular arrhythmias. ICDs are generally indicated for individuals with a history of malignant ventricular arrhythmias (see AVID), as well as selected individuals without a history of arrhythmias but at elevated risk due to underlying heart disease, most commonly significant systolic heart failure (see SCD-HEFT and MADIT-II).
ICDs traditionally consist of an indwelling generator placed in a pocket under the skin, with electrodes wired from the pocket into the ventricle via systemic veins (transvenous ICDs). More recently, ICDs operating completely within the subcutaneous pocket without the need for intravascular wires/electrodes have been developed (subcutaneous ICDs). Since a major complication of transvenous devices are lead-related complications such as infection, subcutaneous devices may provide a favorable adverse event profile. At the same time, since subcutaneous ICDs rely fully on surface monitoring to detect malignant arrhythmias, they may have a higher rate of inappropriate therapies (e.g., shocks delivered in the absence of life-threatening arrhythmias). Although prospective registry studies suggested that subcutaneous ICDs are relatively safe and effective,[1] a randomized trial comparing transvenous and subcutaneous ICDs for SCD prevention was needed.
The 2020 Prospective Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy (PRAETORIAN) trial randomized 849 patients with an established ICD indication to subcutaneous ICD versus transvenous ICD and assessed for non-inferiority of subcutaneous ICDs with regard to device-related complications and inappropriate shocks. At median 49 months, the incidence of device-related complications and inappropriate shocks was similar in individuals randomized to subcutaneous ICD (15.1%) versus those randomized to transvenous ICD (15.7%). The criteria for non-inferiority of subcutaneous ICD was met (hazard ratio [HR] 0.99, 95% CI 0.71-1.39, non-inferiority p = 0.01). Device-related complications were numerically lower with subcutaneous ICD (hazard ratio [HR] 0.69, 95% CI 0.44-1.09), while inappropriate shocks were numerically higher (HR 1.43, 95% CI 0.89-2.30). There was no observed difference in all-cause deaths (HR 1.23, 95% CI 0.89-1.70), and there were 18 sudden cardiac deaths in both groups.
PRAETORIAN provides important evidence that subcutaneous ICDs appear to provide similar short- to intermediate-term efficacy and composite complication rates when compared to transvenous ICDs among individuals who are candidates for either device type. Specifically, subcutaneous ICDs appear to offer a favorable device-related complication rate, but potentially at the cost of a higher inappropriate shock rate. Further evidence is needed to determine whether slightly different adverse event profiles may have implications for long-term hard outcomes. Importantly, unlike transvenous ICDs, subcutaneous ICDs currently do not provide ventricular pacing, and are not uncommonly contraindicated at extremes of body size. As a result, the findings of PRAETORIAN should be generalized only to individuals who require an ICD but do not require pacing, and have no technical contraindication to a subcutaneous device.
Guidelines
As of January 2021, no guidelines have been published that reflect the results of this trial.
Design
- Multicenter, open-label, randomized, controlled trial
- N=849
- Subcutaneous ICD (N=426)
- Transvenous ICD (N=423)
- Setting: 39 sites in Europe and the United States
- Enrollment: March 2011 - January 2017
- Median follow-up: 49.1 months
- Analysis: Modified intention-to-treat (excluded patients who did not receive any device after randomization)
- Primary Outcome: Device-related complication or inappropriate shock
Population
Inclusion Criteria
- Age ≥ 18 years
- Class I or IIa indication for ICD therapy
Exclusion Criteria
- Documented therapy refractory monomorphic ventricular tachycardia
- Patients with ventricular tachycardia less than 170 bpm
- Indication for pacing therapy
- Patients that fail appropriate QRS/T-wave sensing with the S-ICD ECG patient screening tool
provided by Cameron Health/Boston Scientific
- Patients with incessant ventricular tachycardia
- Patients who have had a previous ICD implant
- Patient who receive cardiac contractility modulation therapy or are likely to receive cardiac
contractility modulation therapy
- Patients with a serious known concomitant disease with a life expectancy of less than one
year
- Patients with circumstances that prevent follow-up (no permanent home or address,
transient, etc.)
- Patients who are unable to give informed consent
Baseline Characteristics
From subcutaneous ICD group.
- Demographics: Age 63 years, male 21%
- Comorbidities: BMI 27, HTN 54%, HLD 38%, smoker 29%, DM 26%, CABG 20%, AF 27%, sustained VT 11%, syncope 6%
- ICD indication: Ischemic CM 68%, non-ischemic CM 23%, genetic syndrome 5%, hypertrophic CM 4%, idiopathic VT 3%, congenital heart disease 1%, other 1%
- Cardiac: LVEF 30%, QRS duration 105ms, NYHA I 34%, NYHA II 49%, NYHA III-IV 18%
- Other: Secondary prevention 19%
- CHF: NYHA I 11%, NYHA II 58%, NYHA III 29%, NYHA IV 2%, ischemic 40%, nonischemic 60%, LVEF 32.5%
- AF: paroxysmal 30%, persistent 70%, long-standing persistent 28%, LA diameter 48mm
- Devices: CRT-D 27%, ICD 73%,
- Medications: History of amiodarone use 57%
Interventions
- Patients randomized 1:1
- Subcutaneous ICD
- Transvenous ICD
- Randomization stratified by center
- All subcutaneous ICDs manufactured by Cameron Health - Boston Scientific
- Choice of transvenous ICD manufacturer/model at discretion of operator
- All patients were seen for follow-up at 4 months. Thereafter, devices were interrogated at least twice per year, and patients had at least one annual follow-up visit.
- Programming of the parameters for the detection of ventricular tachycardia or ventricular fibrillation and for therapeutic variables was standardized and based on the best available evidence at the time of protocol development. However, deviations were allowed at the discretion of the treating physician. Default values:
- The cutoff for the fast ventricular tachycardia zone was set as close to 182 beats per minute as possible
- The cutoff for the ventricular fibrillation zone was 250 beats per minute
- There was one burst of antitachycardia pacing for the transvenous ICD
- A clinical-events committee consisting of three electrophysiologists who were not otherwise involved in the trial adjudicated all clinical and arrhythmic events.
Outcomes
Comparisons are subcutaneous vs. transvenous ICD
Primary Outcome
- Device-related complication or inappropriate shock
- 68 (15.1%) vs. 68 (15.7%); HR 0.99 (95% CI 0.71-1.39); non-inferiority p=0.01; superiority p=0.95
Secondary Outcomes
- Device-related complication
- 31 (5.9%) vs. 44 (9.8%); HR 0.69 (95% CI 0.44-1.09)
- Inappropriate shock
- 41 (9.7%) vs. 29 (7.3%); HR 1.43 (95% CI 0.89-2.30)
- Death
- 83 vs. 68; HR 1.23 (95% CI 0.89-1.70)
- Appropriate shock
- 19.2% vs. 11.5%; HR 1.52 (95% CI 1.08-2.12)
Subgroup Analysis
- There were no between-group differences in the occurrence of the primary end point across prespecified subgroups of age, sex, and body mass index
Criticisms
- Duration of follow-up is intermediate (median follow-up 49 months). Certain complications (e.g., chronic lead infections) tend to occur many years after device placement, while battery longevity may be shorter for the subcutaneous ICD.
- Although composite outcomes were similar, the implications of varying component adverse event profiles (more inappropriate shocks for subcutaneous ICD, versus more device-related complications for transvenous ICD) for hard outcomes is less clear
- Findings only generalizable to individuals who are candidates for either transvenous or subcutaneous ICD (e.g., no need for pacing support, body size amenable to subcutaneous device)
- Unblinded trial which introduces potential bias in outcomes ascertainment
Funding
- Study funded by Cameron Health - Boston Scientific who provided all subcutaneous devices but otherwise had no role in the design of the trial, analysis of the data, or the drafting and submission of the manuscript.
- Authors with multiple ties to industry