Late Post-TAVR Bleeding Linked With Significant Mortality Risks: PARTNER Analysis

December 18, 2014

NEW YORK, NY — Nearly 6% of patients undergoing transcatheter aortic-valve replacement (TAVR) will experience a late major bleeding complication, and these bleeding events are associated with a significantly increased risk of death, according to a new analysis of the PARTNER study[1].

Between 30 days and one year, major late bleeding complications occurred in 142 of 2401 patients (5.9%) undergoing TAVR, the most common complication being gastrointestinal bleeds, neurological bleeds, and bleeding resulting from a traumatic fall. Individuals with late bleeding were nearly four times more likely die between 30 days and 1 year, report investigators.

"The magnitude of impact is surprising," said lead investigator Dr Philippe Généreux (Columbia University Medical Center/New York Presbyterian Hospital). "When a patient has a late bleed, one after 30 days, about 40% end up dying compared with 10% of those who don't have a bleeding complication. When patients have atrial fibrillation and have a bleed, they have a 50% chance of dying. The impact of bleeding in this [overall] population is very, very important and relatively frequent at 6%."

The study, published in December 23, 2014 issue of the Journal of the American College of Cardiology, also identified significant predictors of late bleeding. These included the presence of low hemoglobin levels at baseline, atrial fibrillation or flutter at baseline, the presence of a moderate or severe paravalvular leak at 30 days, and a larger left ventricular mass at 30 days.

Types of Bleeding Beyond 30 Days

The median time between the procedure and the late major bleeding event was 132 days. Gastrointestinal bleeding occurred in 40.8% of patients, neurological bleeding occurred in 15.5% of patients, and falls or trauma were responsible for bleeding in 7.8% of patients. Access-site bleeding related to the procedure occurred in 2.1% of patients.

To heartwire , Généreux said previous data from PARTNER, as well as from other groups, suggested the majority of bleeding occurred within 30 days of the TAVR procedure. These periprocedural bleeds were typically related to the procedure or were the result of vascular complications. Early bleeding is known to be associated poor clinical outcomes, he said, but data were limited on the incidence and prognosis of bleeding events that occurred beyond 30 days.

For bleeding occurring between 30 days and 1 year, Généreux said such complications are most likely related to the patient's baseline health and susceptibility to bleeding complications. TAVR patients tend to be sick, older, and are often treated with multiple drugs, including antithrombotic agents.

"Is the late bleeding related more to the TAVR?" asked Généreux. "I would say it's difficult to say, but it's probably most likely related to patient predisposition. But we can say that in certain cases, the procedure might induce a vulnerability. They might have a minor stroke or asymptomatic stroke that converts into bleeding in the future."

In an editorial[2], Dr Dhruv Kazi (San Francisco General Hospital, CA) points out that correlation is not causation, so some caution should be exercised when interpreting observational analyses. As Généreux told heartwire , though, evidence from other fields, including PCI and surgery, suggests the association between bleeding and mortality is causal.

Regarding the four predictors of major late bleeding in PARTNER, baseline hemoglobin levels and the presence of atrial fibrillation/flutter make sense. Increased left ventricular mass might be a marker of end-organ damage resulting from hypertension. Future studies will be needed to confirm the association between moderate and severe paravalvular leak and late major bleeding, writes Kazi.

Future Studies, Such as the ARTE Trial

To heartwire , Généreux said the analysis was designed to raise awareness about the problems of late bleeding following TAVR. "I think now we're in an era where we're trying to optimize care of the patient, such as we did with early care with all the improvements in the catheter, the technique, and operator experience," he said. "Now we're trying to refine and tailor the treatment for this population."

One such trial looking at how to best manage TAVR patients is the ongoing ARTE trial led by Dr Josep Rodés-Cabau (Laval University, Quebec, QC). Following TAVR, patients will be randomized to antithrombotic treatment with aspirin 80 mg or aspirin 80 mg and clopidogrel 75 mg for the prevention of MI, ischemic stroke, death, and life-threatening major bleeding.

In his editorial, Kazi says that if these PARTNER findings are reproduced in other cohorts, the results suggest strategies designed to reduce bleeding must extend throughout the first year postprocedure. "Following on the impressive reductions in procedural complications, the focus must shift to improving long-term outcomes," he writes. "Small refinements in the TAVR protocol could yield valuable clinical and economic dividends by reducing delayed complications."

Généreux has received speaker’s fees from Edwards Lifesciences. Disclosures for the coauthors are listed in the article.

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