Early Mortality Rates After TAVR Halved in a Decade, With Some Gender Differences

SAN FRANCISCO, CA—Global 30-day mortality rates among men and women undergoing TAVR have decreased by more than half over the last decade, new research shows. However, significant gender differences persist in terms of a higher bleeding risk for women, a greater need for permanent pacemaker for men, and a slightly unequal decline in survival over time.

“These findings emphasize increased safety and can be used to reassure patients,” noted lead author Ronak Delewi, MD, PhD (University of Amsterdam, the Netherlands), in an email. “The higher risk of major or life-threatening bleeding in females undergoing TAVI emphasizes that special care should be taken to reduce or recognize [it early],” he added.

Delewi recently presented the findings, gathered by the CENTER collaboration, at TCT 2019.

The data, which were simultaneously published in the Journal of the American College of Cardiology, add to ongoing gender research in TAVR, which has documented the higher rate of early vascular and bleeding complications among women in the Society of Thoracic Surgeons/American College of Cardiology TVT Registry. However, both the PARTNER and PARTNER 2A trials have shown better long-term survival in women compared with men, while the PARTNER 2 S3 trial reported similar outcomes for men and women out to 1 year with newer-generation valves.

Commenting on the CENTER analysis, Ayman Elbadawi, MD (University of Texas Medical Branch, Galveston), told TCTMD it may “help to better characterize why women do worse in the short term.”

For example, Delewi and colleagues observed that, for women, bleeding risk was inversely correlated with body mass index (BMI), such that patients with lower BMI had more bleeding than those with higher BMI. That pattern was not observed in men, even at the lowest BMI tertile.

“It's just a hypothesis, but lower-BMI women may be more likely to have device missizing or be given a too-large device, which comes with higher risk of bleeding and vascular complications,” Elbadawi said. “It’s important to identify women at high risk and spend the time making sure the access is appropriate and bleeding complications are minimized as much as possible.”

Likewise, Delewi stressed that the data highlight the importance of appropriate imaging of the iliofemoral vasculature during TAVR work-up in women.

“However, there is little evidence on this topic,” he noted. “Future studies on anatomical and procedural predictors of access-site-related major and life-threatening bleeding, specified per gender, would provide aid in reducing bleeding.”

Mortality Decreasing Over Time, but Not Stroke

For the study, Delewi and colleagues examined details from the CENTER data set on 12,381 men and women who underwent transfemoral TAVR from 2007 through 2018 and who were enrolled in global registries or prospective studies (three national registries, two multicenter prospective registries, four single-center prospective registries, and one RCT).

Compared with men, women were more likely to have hypertension and an estimated glomerular filtration rate below 30 mL/min/ m², and they were less likely to have other traditional cardiovascular comorbidities. On both the logistic EuroSCORE and the EuroSCORE II, the risk of mortality for men and women was comparable; on the STS score, which includes female gender as a risk factor, predicted mortality was higher in women than men (P < 0.001).

In-hospital stroke and all-cause mortality were comparable in men and women. Similarly, at 30 days the rate of stroke was 2.3% in women and 2.5% in men (P = 0.53), and all-cause death was 5.9% in women and 5.5% in men (P = 0.17). However, the risk of life-threatening or major bleeding was significantly greater for women than for men (6.7% vs 4.4%; P < 0.001). Among those who experienced a serious bleeding event, women were more likely than men to die within 30 days (20.1% vs 14.4%; P = 0.09).

In analyses by valve type, major or life-threatening bleeding was higher in women compared with men with both early-generation valves (6.0% vs 2.7%; P < 0.001) and newer-generation valves (4.1% vs 2.2%; P = 0.01). Men had significantly higher rates of permanent pacemaker implantation than women, however, regardless of valve type. Rates of MI and new-onset A-fib were similar between men and women.

The researchers also looked at temporal trends by dividing treatment periods into three time frames (2007-2010, 2011-2014, and 2015-2018). The more recent period had the highest proportion of women and the lowest mortality rates for both men and women. However, whereas men saw a 60% decrease in mortality from the earliest to the latest time frames, the decrease was only 50% for women. Stroke rates remained consistent over the years for both genders, with no decline from the early to the more contemporary era.

Data Both Reassuring and Sobering

“These data are reassuring for improvements in devices and techniques facilitating reduction in procedural complications, as well as careful patient selection avoiding TAVR in prohibitive-risk patients in whom it is futile. Yet the stroke incidence is sobering, showing neither a decrease in females nor males,” Delewi and colleagues write.

“The lack of improvement in stroke is interesting,” Elbadawi agreed. “It's another area where I think we lack some insight and need more research to understand why that didn't improve despite mortality improving.”

To TCTMD, Delewi said the greater need for pacemakers in men independent of valve type is novel and that it, too, deserves further research.

“This is a very helpful study because it’s giving us feedback on real-world practice in TAVR,” Elbadawi said, adding that large, multinational cohort reports such as this add to the overall picture of how TAVR is evolving and where questions remain.