PREVENTion of non-surgical bleeding by management of HeartMate II patients without anti-platelet therapy (PREVENT II) trial

TY - JOUR

T1 - PREVENTion of non-surgical bleeding by management of HeartMate II patients without anti-platelet therapy (PREVENT II) trial

AU - PREVENT II study investigators

AU - Jorde, Ulrich P.

AU - Katz, Jason N.

AU - Colombo, Paolo C.

AU - Stulak, John

AU - Saeed, Omar

AU - Egnaczyk, Gregory

AU - Haeusslein, Ernest

AU - McCann, Patrick

AU - Crandall, Daniel

AU - Franke, Abi

AU - Adamson, Robert

N1 - Funding Information: Results from the Study of Reduced Anti-Coagulation/Anti-platelEt Therapy in Patients with the HeartMate II LVAS (Tirapazamine-Radiation and Cisplatin Evaluation [TRACE], NCT01477528), United States experience for example, revealed a stroke rate of 0.07 events per patient-year and device thrombosis rate of 0.08 events per patient-year among patients in whom anti-thrombotic therapies had been reduced in response to bleeding. 4 Similarly, the TRACE study investigators in Europe demonstrated a comparable thrombosis risk using an a priori aspirin (ASA)-free, vitamin K antagonist‒only regimen. 5 PREVENTion of non-surgical bleeding by management of HMII patients without anti-platelet therapy (PREVENT II) (refer to Supplementary Table S1 available online at www.jhltonline.org ) was a prospective, multicenter, randomized, double-blinded, placebo-controlled trial of ASA 81 mg vs placebo daily in subjects ≥50 years of age receiving warfarin after initial implantation of an HMII. PREVENT II (NCT02836652) was sponsored and funded by Abbott. See Supplementary Table S2 online for full inclusion–exclusion criteria. Investigators were asked to implant and manage subjects in accordance with the original PREVENT-recommended practices ( Supplementary Tables S3 and S4 online) aimed at reducing pump thrombosis, with the exception of the use of anti-platelet therapy. 6 The PREVENT-recommended practices have 3 objectives: maximizing flow through the pump, reducing the risk of cannula malpositioning, and ensuring adequate anti-coagulation while on LVAD support, with the overall goal of reducing pump thrombosis events. Participants were placed on the study drug once bleeding had subsided and hemodynamic stability achieved, no later than post-operative Day 15 ( Supplementary Figure S1 online). PREVENT II aimed to enroll up to 350 subjects to demonstrate, with 80% power, the non-inferiority of the primary safety and the superiority of the primary efficacy end-point; one-sided α of 0.025. The primary efficacy end-point was the composite incidence of non-surgical bleeding and primary hemorrhagic stroke at 6 months. The primary safety end-point was the composite incidence of pump thrombosis and thromboembolic stroke at 6 months after initial implantation. Descriptive end-points included hemocompatibility-related adverse events during the 12 months of follow-up. Details of the study end-points and statistical analysis are available in the Supplementary Appendix online. The study was terminated on April 9, 2018, owing to futility of enrollment, given the concurrent Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HM3 trial. Of the 72 subjects enrolled within 48 hours of HMII implant, 65 (31 placebo, 34 ASA) met the criteria for initiation of the study drug. Ischemic heart failure and bleeding history were more prevalent in patients on ASA (detailed demographics can be found in Supplementary Table S5 online). At 6 and 12 months, 47 and 35 subjects, respectively, remained on study drug. Funding Information: Dr Jorde reports other fees from Abbott, outside of the submitted work. Dr Katz reports grants from and consultancy (no Honoraria) at Abbott, outside of the submitted work. Dr Colombo reports research grants from Abbott and consultant (non-financial support) for Abbott, outside of the submitted work. Drs Egnaczyk, McCann, and Adamson report personal fees from Abbott, outside of the submitted work. Dr Saeed is supported by the National Institute of Health (K23HL145140, UL1TR001073). Drs Crandall and Franke are employees of Abbott during the conduct of the study.

PY - 2020/8

Y1 - 2020/8

UR - http://www.scopus.com/inward/record.url?scp=85088640831&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85088640831&partnerID=8YFLogxK

U2 - 10.1016/j.healun.2020.05.003

DO - 10.1016/j.healun.2020.05.003

M3 - Letter

C2 - 32571737

AN - SCOPUS:85088640831

SN - 1053-2498

VL - 39

SP - 838

EP - 840

JO - Journal of Heart and Lung Transplantation

JF - Journal of Heart and Lung Transplantation

IS - 8

ER -