Routine protamine cut minor bleedings, but 83% of selective-arm patients never needed it
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POPular ACE TAVIStructural HeartOpen Access
Routine versus selective protamine administration after transcatheter aortic valve implantation
Christiaan Overduin
What happened
Routine protamine after TAVI cuts death or clinically relevant bleeding by ~37% versus selective use.
- risk difference −10.9 pts
- P<0.001
- n=966
- 18.5% vs 29.4%
Does this change practice?
What this trial adds
Experts see routine protamine after TAVI as a simple win on bleeding but flag that the earlier dataset was underpowered for thromboembolic safety, leaving full adoption an open question until the definitive trial confirms the benefit.
Published field read
The trial showed routine protamine cuts death and bleeding after transfemoral TAVI, and most experts accept the direction of the result. However, several voices note that earlier data reduced mainly minor bleedings and that the study was not powered to rule out thromboembolic risk. The live question is whether a confirmatory trial will settle the safety concern and move protamine into routine practice.
Still open
Questions raised in published commentaryExperts note the study was not powered to assess thromboembolic risk, leaving uncertainty about whether routine protamine could raise clotting events in a larger or longer-follow-up cohort.
Whether a confirmatory trial will replicate the benefit and settle the question of universal adoption remains open.
Context from published commentary. Source summaries are not a new guideline recommendation.
Who says what
Pieter A. Vriesendorp
Practice takeInterventional cardiologist, Maastricht University Medical CenterA confirmatory trial showing benefit should settle the question in favor of routine protamine
Original post ↗Gilbert Tang
Practice takeCardiac surgeon, Mount Sinai Health, New YorkMinor vascular complications are not benign, especially for low-surgical-risk patients wanting faster recovery
Original post ↗Show 1 more perspectivesShow fewer perspectives
Stefano GarzonResults readoutInterventional / Structural Cardiology · Hospital Israelita Albert Einstein
Less minor bleeding as expected, but no evidence yet for routine protamine use
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Full evidence
Why the trial, key points, tables, limitations, PICO, abstract, media & sources
Full evidence
Why the trial, key points, tables, limitations, PICO, abstract, media & sources
Why the trial?
Heparin reversal with protamine after TAVI varies widely between centres, balancing access-site bleeding against possible thrombotic risk with no randomised evidence to guide practice. POPular ACE TAVI compared routine against selective protamine administration.
Does routine protamine administration reduce the composite of all-cause death or clinically relevant bleeding in patients undergoing transfemoral TAVI compared to selective administration?
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Key Points
- To assess whether routine protamine administration is superior to selective administration in reducing bleeding and mortality in patients undergoing transfemoral transcatheter aortic valve implantation.
- Investigator-initiated, randomized, double-blind superiority trial conducted across 6 centers in the Netherlands and Belgium between November 2023 and September 2025 (N=966).
- Participants receiving transfemoral TAVI were randomly assigned to routine protamine administration upon procedural completion or selective administration (initial placebo, with protamine given only for ongoing bleeding after 10 minutes).
- The primary composite endpoint of all-cause death or clinically relevant bleeding occurred in 18.5% of the routine protamine arm versus 29.4% of the selective arm (risk difference 10.9 percentage points; p<0.001), predominantly driven by a reduction in VARC-3 type 1 bleeding.
- Thromboembolic event rates were approximately 4% in both study groups, while anaphylactic reactions occurred in 6 patients (1.3%) who received routine protamine.
- In the selective administration group, only roughly 18% of patients eventually required and received protamine.
Evidence details
What drove the result?
| Outcome | Routine | Selective |
|---|---|---|
| All-cause death or clinically relevant bleeding | 18.5% | 29.4% |
| Primary composite · risk difference 10.9 pp (p<0.001), driven mainly by VARC-3 type 1 bleeding | ||
Limitations & tradeoffs
Safety
Anaphylactic reactions occurred in 6 patients (1.3%) in the routine-protamine arm, while thromboembolic events were ~4% in both arms.
Design limitations
The composite was driven mainly by VARC-3 type 1 (minor) bleeding rather than death, and the follow-up duration and primary endpoint's ascertainment window are not reported in this conference-only record.
Statistical certainty
No per-arm event counts or confidence intervals are available.
Structured PICO
Does routine protamine administration reduce the composite of all-cause death or clinically relevant bleeding in patients undergoing transfemoral TAVI compared to selective administration?
P
Population
966 patients undergoing transfemoral TAVI.
I
Intervention
Routine protamine administration at the end of the TAVI procedure.
C
Comparator
Selective administration (placebo first, with protamine only for ongoing bleeding after 10 minutes).
O
Outcome
Composite of all-cause death or clinically relevant bleeding.composite
Main Result
Absolute Risk Reduction: 10.9
Absolute Event Rate: 18.5% vs 29.4%
Absolute Risk Reduction: 10.9%
p-value: p=<0.001
Routine administration of protamine after transfemoral TAVI significantly reduces bleeding complications without increasing thromboembolic risk compared to a selective administration strategy.
Discussion
No takes yet. Share an insight, caveat, or question.
Expert reaction
What experts said about POPular ACE TAVI
ESC Congress 2026
Expert labels are toward POPular ACE TAVI's result, from named public quotes (n=1). As of Sep 1, 2026.
Where experts stand
Experts see routine protamine after TAVI as a simple win on bleeding but flag that the earlier dataset was underpowered for thromboembolic safety, leaving full adoption an open question until the definitive trial confirms the benefit.
The trial showed routine protamine cuts death and bleeding after transfemoral TAVI, and most experts accept the direction of the result. However, several voices note that earlier data reduced mainly minor bleedings and that the study was not powered to rule out thromboembolic risk. The live question is whether a confirmatory trial will settle the safety concern and move protamine into routine practice.
2 takes classified by contention axis so far — the map appears as more land.
Still unclear
Experts note the study was not powered to assess thromboembolic risk, leaving uncertainty about whether routine protamine could raise clotting events in a larger or longer-follow-up cohort. Whether a confirmatory trial will replicate the benefit and settle the question of universal adoption remains open.
Key expert perspectives
PAPieter A. VriesendorpInterventional cardiologist, Maastricht University Medical CenterPractice takeSep 1
A confirmatory trial showing benefit should settle the question in favor of routine protamine
Vriesendorp stated that if a follow-up study also shows a beneficial effect, the issue can be put to rest and everyone should use protamine.
Distilled from their postOriginal post
Routine protamine cut minor bleedings, but 83% of selective-arm patients never needed it
Thamman highlights that routine protamine decreased minor bleedings after TAVI but points out that operators in the selective arm did not feel the need for protamine in almost 83% of patients. She notes the study was not powered to assess thromboembolic risk.
Distilled from their postX post
GTGilbert TangCardiac surgeon, Mount Sinai Health, New YorkPractice takeSep 1
Minor vascular complications are not benign, especially for low-surgical-risk patients wanting faster recovery
Tang argues that minor vascular issues matter clinically because they slow mobilization, particularly in low-surgical-risk patients who expect a quick recovery.
Distilled from their postOriginal post
Implication
Routine protamine reversal after TAVI reduces death or bleeding; supports immediate adoption as standard and closes a prior evidence gap.
Abstract
POPular ACE TAVI was an investigator-initiated, randomised, double-blind superiority trial that enrolled 966 patients undergoing transfemoral TAVI at 6 centres in the Netherlands and Belgium between November 2023 and September 2025. Patients were randomised to routine protamine administration at the end of the procedure or selective administration (placebo first, with protamine only for ongoing bleeding after 10 minutes). The primary composite of all-cause death or clinically relevant bleeding occurred in 18.5% with routine protamine versus 29.4% with selective administration (risk difference 10.9 percentage points; p<0.001), driven mainly by a reduction in VARC-3 type 1 bleeding. Anaphylactic reactions occurred in six patients (1.3%) given routine protamine; thromboembolic event rates were low and comparable at roughly 4% in both arms. In the selective arm, protamine was given to only about 18% of patients. Presented by Christiaan Overduin in Hot Line 7 at ESC Congress 2026; no simultaneous journal publication. Sources: herzmedizin.de (DGK) and ESC 365 (presentation 335391).
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
Christiaan Overduin (2026) conducted an RCT in transfemoral TAVI (n=966). Routine protamine administration vs. Selective administration was evaluated on composite of all-cause death or clinically relevant bleeding (risk difference 10.9 percentage points, p=<0.001). Routine protamine administration after TAVI reduced all-cause death or clinically relevant bleeding compared to selective administration (risk difference 10.9 percentage points; p<0.001).