Routine Versus Selective Protamine Administration to Reduce Bleeding Complications After Transcatheter Aortic Valve Implantation

POPular ACE TAVI

Patient / Population Intervention / Exposure Comparison Outcome

In 966 patients undergoing transfemoral TAVI, routine protamine after the procedure reduced death or bleeding at 30 days compared with selective protamine.

N

1,000patients

Design

investigator-initiated, multicentre (6 sites, Netherlands and Belgium), double-blind, placebo-controlled RCT; 1:1 routine vs selective protamine, stratified by site and antithrombotic therapy; 30-day follow-up

Endpoint

composite of all-cause mortality or clinically relevant bleeding (VARC-3 type 1–4) within 30 days after TAVI

Relevance

2Important — one of several pillars.

ResultDeath or clinically relevant bleeding at 30 days: risk difference −10.9 percentage points (95% CI −17.0 to −4.8; P < 0.001) in favour of routine protamine. The difference is carried by minor bleeding (type 1: −10.9 points, 95% CI −16.8 to −5.1). Anaphylaxis was more frequent with routine protamine: +1.3 points (95% CI 0.2 to 3.0; P = 0.01).

Overduin C, et al. Presented at ESC Congress 2026, Hot Line 7, 30 August.

Discussion & critique

Reversing heparin before pulling a large-bore sheath removes about one bleeding event in nine, which is a large effect for a cheap drug given at the end of a routine procedure. The whole of that effect sits in VARC type 1 bleeding — the minor kind, an ooze or a haematoma rather than a transfusion — so the composite reads stronger than the clinical gain is. Against it stands anaphylaxis in 1.3% more patients, rare but the one complication that can be worse than the bleeding avoided; the trade is favourable on average and worth naming in the consent.