High-risk percutaneous coronary intervention with or without mechanical circulatory support: Will Impella show superiority in the PROTECT IV randomized trial?

Background: PROTECT IV is a current enrolling randomized controlled trial evaluating high-risk percutaneous coronary intervention (HR-PCI) with prophylactic Impella versus no Impella to reduce the composite primary endpoint of all-cause death, stroke, myocardial infarction (MI), or cardiovascular hospitalization. In a PROTECT IV-like cohort of patients who underwent HR-PCI without Impella, we aimed to report the rate of major adverse events to determine whether the trial is adequately powered.
Methods and Results: A total of 700 patients meeting similar inclusion/exclusion criteria of PROTECT IV who underwent HR-PCI without Impella at a single tertiary center from 2008 to 2022 were included in the analysis. The composite rates of all-cause death, MI, target lesion revascularization, and target vessel revascularization at 1, 2, and 3 years were estimated using the Kaplan-Meier method, and the results were used to calculate the sample size under the constant hazard ratio assumption and expected number of events to be observed used in planning PROTECT IV. The primary endpoint occurred in 30.8 % of patients at 2 years. PROTECT IV assumes a hazard ratio of 0.75 using a multivariate Cox regression, which, under a 5 % level and 90 % power, yields 516 events. This implies a 2-year primary outcome rate of 50 % for the non-Impella arm.
Conclusion: Therefore, PROTECT IV estimates that a sample size of 1252 patients is required for Impella to be declared superior to the non-Impella group. Using our observed 2-year outcome of 30.8 %, we estimate that PROTECT IV requires 1966 patients, demonstrating that PROTECT IV is probably underpowered.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kalyan R. Chitturi – Consultant: Glass Health. Brian C. Case – Speaker: Asahi Intecc USA, Zoll Medical. Toby Rogers – Consultant: Edwards Lifesciences, Medtronic, Boston Scientific, Abbott, Anteris, and Transmural Systems; Advisory board: Medtronic, Boston Scientific; Equity: Transmural Systems; Intellectual property: co-inventor on patents, assigned to NIH, for transcatheter electrosurgery devices. Hayder D. Hashim – Advisory Board, Speaker: Abbott Vascular, Boston Scientific, Philips IGT. Ron Waksman – Advisory Board: Abbott Vascular, Boston Scientific, Medtronic, Philips IGT, Pi-Cardia Ltd.; Consultant: Abbott Vascular, Append Medical, Biotronik, Boston Scientific, JC Medical, MedAlliance/Cordis, Medtronic, Philips IGT, Pi-Cardia Ltd., Swiss Interventional/SIS Medical AG, Transmural Systems Inc.; Institutional Grant Support: Biotronik, Medtronic, Philips IGT; Investor: Append Medical, Pi-Cardia Ltd., Transmural Systems Inc. All other authors – None.
(Copyright © 2024 Elsevier Inc. All rights reserved.)