Routine Protamine Use Enhances Hemostasis and Reduces Complications After TAVI, ACE-PROTAVI Trial Finds

"In the ACE-PROTAVI randomized clinical trial involving 410 patients across three Australian hospitals, routine administration of protamine after TAVI resulted in a higher rate of successful hemostasis and a lower incidence of vascular complications compared to placebo," the researchers reported in JAMA Cardiology.

Vascular complications following transfemoral TAVI continue to be a significant source of procedure-related morbidity. Routine use of protamine to reverse anticoagulation at the end of transfemoral TAVI has the potential to reduce these complications, though evidence on its effectiveness is limited. To fill this knowledge gap, Pieter A. Vriesendorp, Heart Centre, The Alfred Hospital, Melbourne, Australia, and colleagues aimed to evaluate the safety and efficacy of routine protamine administration after transfemoral TAVI.

The ACE-PROTAVI trial was an investigator-initiated, double-blind, placebo-controlled randomized clinical trial conducted at three Australian hospitals from December 2021 to June 2023, with a follow-up period of one year. Patients eligible for transfemoral TAVI, as determined by a multidisciplinary heart team, were included in the study.

Participants were randomly assigned in a 1:1 ratio to receive either routine protamine administration or a placebo. The coprimary outcomes were the rate of hemostasis success and the time to hemostasis (TTH). These outcomes were analyzed as categorical variables using a χ2 test or as continuous variables, presented as means (SD) or medians (IQR), depending on their distribution.

The major secondary outcome was a composite measure of all-cause death, major and minor bleeding complications, and major and minor vascular complications occurring after 30 days.

The following were the key findings of the study:

• The study population comprised 410 patients: 199 patients in the protamine group and 211 in the placebo group. The median patient age in the protamine group was 82 years, and 68 of 199 patients receiving protamine (34.2%) were female. The median patient age in the placebo group was 80 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 (97.9%) than patients in the placebo group (91.6%; absolute risk difference, 6.3%); in addition, patients receiving up-front protamine had a shorter median TTH (181 seconds versus 279 seconds).
• Routine protamine administration led to a reduced risk of the composite outcome in the protamine group (5.2%) versus the placebo group (12.8%; OR, 0.37). This difference was predominantly driven by the difference in the prevalence of minor vascular complications.
• There were no adverse events associated with protamine use.

In the ACE-PROTAVI randomized clinical trial, routine protamine administration improved the rate of hemostasis success and reduced the time to hemostasis. Additionally, patients who received protamine experienced fewer minor vascular complications, shorter procedural times, and reduced post-procedural hospital stays versus those who received a placebo.

Reference:

Vriesendorp PA, Nanayakkara S, Heuts S, et al. Routine Protamine Administration for Bleeding in Transcatheter Aortic Valve Implantation: The ACE-PROTAVI Randomized Clinical Trial. JAMA Cardiol. Published online August 14, 2024. doi:10.1001/jamacardio.2024.2454