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Randomized Controlled Trial
. 2024 Oct 1;9(10):901-908.
doi: 10.1001/jamacardio.2024.2454.

Routine Protamine Administration for Bleeding in Transcatheter Aortic Valve Implantation: The ACE-PROTAVI Randomized Clinical Trial

Pieter A Vriesendorp  1   2   3 , Shane Nanayakkara  1   4   5 , Samuel Heuts  3   6 , Jocasta Ball  5 , Jaya Chandrasekar  7   8   9 , Ronald Dick  7 , Kawa Haji  1   7 , Nay Min Htun  1 , David McGaw  10 , Samer Noaman  1   7 , Sonny Palmer  1   11 , Sesto Cairo  11   12 , Mark Shulman  1   12 , Enjarn Lin  1   12 , Stuart Hastings  1   12 , Benedict Waldron  1   12 , George Proimos  7 , Kean H Soon  7   11 , Matias B Yudi  7   13 , Adam Zimmet  1 , Dion Stub  1   5   10 , Antony S Walton  1   5   7
Affiliations
Randomized Controlled Trial

Routine Protamine Administration for Bleeding in Transcatheter Aortic Valve Implantation: The ACE-PROTAVI Randomized Clinical Trial

Pieter A Vriesendorp et al. JAMA Cardiol. .

Abstract

Importance: Vascular complications after transfemoral transcatheter aortic valve implantation (TAVI) remain an important cause of procedure-related morbidity. Routine reversal of anticoagulation with protamine at the conclusion of transfemoral TAVI could reduce complications, but data remain scarce.

Objective: To evaluate the efficacy and safety of routine protamine administration after transfemoral TAVI.

Design, setting, and participants: The ACE-PROTAVI trial was an investigator-initiated, double-blind, placebo-controlled randomized clinical trial performed at 3 Australian hospitals between December 2021 and June 2023 with a 1-year follow-up period. All patients accepted for transfemoral TAVI by a multidisciplinary heart team were eligible for enrollment.

Interventions: Eligible patients were randomized 1:1 between routine protamine administration and placebo.

Main outcomes and measures: The coprimary outcomes were the rate of hemostasis success and time to hemostasis (TTH), presented as categorical variables and compared with a χ2 test or as continuous variables as mean (SD) or median (IQR), depending on distribution. The major secondary outcome was a composite of all-cause death, major and minor bleeding complications, and major and minor vascular complications after 30 days, reported in odds ratios (ORs) with 95% CIs and P values.

Results: The study population consisted of 410 patients: 199 patients in the protamine group and 211 in the placebo group. The median (IQR) patient age in the protamine group was 82 (77-85) years, and 68 of 199 patients receiving protamine (34.2%) were female. The median (IQR) patient age in the placebo group was 80 (75-85) years, and 89 of 211 patients receiving the placebo (42.2%) were female. Patients receiving up-front protamine administration had a higher rate of hemostasis success (188 of 192 patients [97.9%]) than patients in the placebo group (186 of 203 patients [91.6%]; absolute risk difference, 6.3%; 95% CI, 2.0%-10.6%; P = .006); in addition, patients receiving up-front protamine had a shorter median (IQR) TTH (181 [120-420] seconds vs 279 [122-600] seconds; P = .002). Routine protamine administration resulted in a reduced risk of the composite outcome in the protamine group (10 of 192 [5.2%]) vs the placebo group (26 of 203 [12.8%]; OR, 0.37; 95% CI, 0.1-0.8; P = .01). This difference was predominantly driven by the difference in the prevalence of minor vascular complications. There were no adverse events associated with protamine use.

Conclusions and relevance: In the ACE-PROTAVI randomized clinical trial, routine administration of protamine increased the rate of hemostasis success and decreased TTH. The beneficial effect of protamine was reflected in a reduction in minor vascular complications, procedural time, and postprocedural hospital stay duration in patients receiving routine protamine compared with patients receiving placebo.

Trial registration: anzctr.org.au Identifier: ACTRN12621001261808.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Vriesendorp reported personal fees from Abbott Vascular and Boehringer Ingelheim outside the submitted work. Dr Chandrasekhar reported speaking fees from Boston Scientific, Medtronic, and Amgen outside the submitted work. Dr Stub reported grants from the Cabrini Foundation during the conduct of the study; grants from the Australian National Health and Medical Research Council (NHMRC) and the National Heart Foundation of Australia (NHF) outside the submitted work; and serving on medical advisory boards for Edwards Lifesciences, Medtronic, and Anteris. Dr Walton reported grants from the Fox Foundation outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Flowchart of Patient Inclusion
Figure 2.
Figure 2.. Primary End Points
Error bars indicate 95% CIs.
See this image and copyright information in PMC

References

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