Routine Protamine Use Enhances Hemostasis and Reduces Vascular Complications After TAVI: ACE-PROTAVI Trial

Transfemoral transcatheter aortic valve implantation is a minimally invasive procedure used to replace a damaged or diseased aortic valve in the heart. Vascular complications following transfemoral TAVI continue to be a significant source of procedure-related complications. Routine use of protamine to reverse anticoagulation at the end of transfemoral TAVI may help decrease these complications, although there is limited data available.

To evaluate the efficacy and safety of routine protamine administration after transfemoral TAVI, scientists conducted an ACE-PROTAV randomized clinical trial.

For this trial, Pieter A. Vriesendorp, Heart Centre, The Alfred Hospital, Melbourne, Australia, and the team recruited 410 patients from 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. Eligible patients were randomized 1:1 between routine protamine administration and placebo. Out of 410 patients, 199 patients were in the protamine group and 211 in the placebo group. Measurements were done using odds ratios(ORs)

The study results reveal:

• 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 who received protamine administration at the start of the procedure experienced a higher rate of successful hemostasis (97.9% in 188 of 192 patients) compared to those who received a placebo (91.6% in 186 of 203 patients), with an absolute risk difference of 6.3%
• The median time to hemostasis (TTH) was shorter for those given protamine upfront, with a median of 181 seconds (IQR 120-420) compared to 279 seconds (IQR 122-600) for the placebo group.
• Routine administration of protamine led to a lower risk of the composite outcome in the protamine group (5.2% in 10 of 192 patients) compared to the placebo group (12.8% in 26 of 203 patients), with an odds ratio of 0.37.
• This reduction was mainly due to a lower rate of minor vascular complications in the protamine group. Additionally, no adverse events were linked to the use of protamine.

“The advantages of protamine were evident in decreased minor vascular complications, shorter procedural time, and reduced post-procedural hospital stay for patients who received routine protamine compared to those who received a placebo,” researchers concluded.

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