BACKGROUND:

Despite major advances, TAVR is still associated with procedure-related vascular and bleeding complications, that have a significant impact on mortality. Recent studies have shown that heparin antagonization using protamine resulted in significantly lower bleeding rates in patients undergoing TAVR as compared to those without heparin reversal. However, there are only limited data on the safety of protamine administration regarding thromboembolic complications including in-stent thrombosis in TAVR patients who have had a recent percutaneous coronary intervention (PCI). Accordingly, daily practice varies from selective to routine administration of protamine.

PURPOSE:

The aim of this multicentre study was to evaluate the safety and efficacy of protamine in patients who have had a recent PCI undergoing subsequent TAVR. 

METHODS: 

Our study cohort included 1838 consecutive patients undergoing TAVI with next-generation heart valves between January 2017 and October 2020. Of the patients included, 173 (9.4%) had a recent PCI (≤30 days), 319 (17.4%) had an intermediately (≥30 days) and 303 (16.5%) a previously performed PCI (≥6 months). The indication for protamine administration was left to the discretion of the operator. The primary endpoint was a composite of one-year all-cause mortality and myocardial infarction at 30 days. Key secondary end points included 30-day mortality and VARC-3-defined complications.

RESULTS:

The overall study population had a mean age of 81.1±6.2 years and was at intermediate surgical risk (EuroScore II: 5.5±4.9%). The baseline characteristics were well balanced between the PCI groups. Among patients with recent PCI, 134 (77.5%) patients received protamine for heparin reversal during the TAVR procedure. In the group of patients with intermediately and previously performed PCI 258 (80.9%) and 249 (82.2%) patients received protamine, respectively. In the recent PCI group, the occurrence of the primary endpoint was comparable between patients with protamine administration (24.6%) as compared to patients without heparin reversal (30.8%, p=0.53), Figure 1. Similarly, among patients with intermediately as well as previously performed PCI, the rates of the primary endpoint were comparable irrespective of protamine administration (20.1 vs 16.4%, p=0.59; 17.3 vs 27.7%, p=0.08, respectively), Figure 2 and 3. Moreover, among all three groups, the incidence of myocardial infarction at 30 days after TAVR was low and comparable between patients with and without heparin reversal (p>0.50). Overall, protamine administration was associated with decreased life-threatening bleeding (3.2 vs 9.4%, p<0.01) as well as major vascular complications (4.4 vs 7.9%, p=.02). Regarding safety endpoints, no overall differences were observed in the incidence of stroke between patients with protamine administration as compared to those without heparin reversal (1.5 vs 2.9%, p=0.13).

CONCLUSION:

Protamine administration for heparin reversal during the TAVR procedure did not increase the rate of myocardial infarction or one-year mortality in patients who have had a recently or intermediately performed PCI. Overall, heparin reversal using protamine resulted in significantly lower rates of life-threatening bleeding and major vascular complications, without increasing the incidence of thromboembolic events, such as stroke. Further sufficiently powered randomized trials are needed to validate the results of this study.

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