BERN, SWITZERLAND — A novel study that looked beyond the access-site bleeding complications that garnered much attention in the early days of transcatheter aortic valve replacement (TAVR) reveals that nearly one in three patients experience bleeding up to 5 years after TAVR.
In addition, mortality rates rose steadily from 49% in patients without a bleed to 59% with access-site bleeding and 73% with non–access-site bleeding, largely gastrointestinal and pericardial bleeds.
Non–access-site bleeding carried a 56% increased risk for death compared with access-site bleeding in the multivariate analysis (hazard ratio [HR] 1.56; 95% CI 1.12–2.18).
"In the domain of PCI, there is ample evidence supporting such an association. However, since vascular access requires larger sheath sizes in TAVR than PCI, one may expect a similar magnitude of effect between the two types of bleeding events in TAVR patients,” lead author Dr Raffaele Piccolo (Bern University Hospital, Switzerland) told theheart.org | Medscape Cardiology in an email.
"Surprisingly, our results consistently replicate those observed in the setting of PCI," said Piccolo.
The article was published in the current issue of the JACC: Cardiovascular Interventions.
In an accompanying editorial, Drs George Dangas and Roxana Mehran (Icahn School of Medicine, Mount Sinai Medical Center, New York, NY) describe the observed bleeding rates as "astonishing."
Not only did 31% of the 926 consecutive patients (mean age 82.4 years; 53% female) experience a bleeding event, but in 24.4% the bleeding was life-threatening or major.
"This isn't a trivial number, and it may even be that these events are underreported because we know that once these patients leave the hospital and go back to other physicians, the reported outcomes of out-of-hospital bleeding are always very difficult to ascertain," Mehran said in an interview.
"If we are to add important antiplatelets or anticoagulants to avoid a valve thrombosis or embolic event, we're going to have to fine-tune that against the bleeding complications, so that's an important end point to look at," she added.
The editorialists note wide variability in post-TAVR antiplatelet and anticoagulant therapy despite this being a single-center registry but also cite as limitations the lack of extensive data on therapy during follow-up and difficulty in ascertaining events.
The 926 patients underwent TAVR from 2007 through 2014 and were prospectively followed for an average of 2.75 years in the Bern TAVR registry. Use of single-antiplatelet therapy increased from 10% at 1 month to 57% at 5 years, and oral anticoagulants from 7% to 21%, while over the same period, dual-antiplatelet use dropped from 60% to 7% and oral anticoagulants plus single- or dual-antiplatelets from 22% to 6%. Notably, antithrombotic therapy during follow-up was not associated with postdischarge, non–access-site bleeding events in univariate or multivariate analysis.
Overall, about 40% of non–access-site bleeding events occurred more than 30 days after the index TAVR. Among 285 patients who had bleeding, a recurrent event occurred in 53 cases, or nearly 20%.
Compared with no bleeding, the adjusted risk of mortality was significantly higher with access-site bleeding (HR 1.34; 95% CI 1.01–1.76) and non–access-site bleeding (HR 2.08; 95% CI 1.60–2.71).
Chronic kidney disease and Society of Thoracic Surgeons (STS) score were independent correlates of non–access-site bleeding, reflecting the greater burden of age and coexisting comorbidities over time rather than in the immediate aftermath of TAVR.
Importantly, non–access-site bleeding raised the risk of death more than 1.5-fold compared with access-site bleeding in 746 patients who underwent transfemoral TAVR, prompting the investigators to comment that "use of this route of access may not suffice to offset the detrimental effects of bleeding complications."
Both the investigators and editorialists commented that while selection of oral antithrombotic therapy is critical in the mid- and long-range period after TAVR, there is a paucity of robust randomized data to inform clinical decision-making.
Piccolo said results of ongoing trials like GALILEO, POPULAR TAVI, and ATLANTIS will importantly inform the clinical management of antithrombotic therapy in TAVR patients and that "future trials should be designed to take into account the time course of bleeding (early vs late), patient profile (atrial fibrillation, coronary artery disease), and the risk of valve thrombosis."
Given her druthers, Mehran said, "I'd like to test in the high-risk patient population whether or not we even need clopidogrel or aspirin. I'd love to see us drop aspirin because I think aspirin is a big culprit here and everyone is afraid of doing that."
Piccolo has received a research grant from the Veronesi Foundation. Disclosures for the coauthors are listed in the paper. Dangas has received teaching/lecture fees from Bayer and Janssen and is an unpaid consultant for Bayer and Daiichi-Sankyo. Mehran has reported numerous relationships with industry including serving as a consultant for Medscape.
Medscape Medical News © 2017
Cite this: Bleeding Common Years After TAVR, and Deadly - Medscape - Jul 20, 2017.