Major Bleeds Late After TAVR Not Only Frequent But Portend Worse Outcomes

Major bleeding complications are relatively common from 30 days to 1 year after TAVR and are associated with greater risks of mortality and other adverse outcomes, according to a study published in the December 23, 2014, issue of the Journal of the American College of Cardiology.

“The study clearly illustrates that we need to optimize the antiplatelet and antithrombotic treatment of these patients,” co-author Philippe Généreux, MD, of Columbia University Medical Center (New York, NY), told TCTMD in a telephone interview. “But I think we need more studies and trials to determine what will be the best treatment after TAVR, given the high-risk population.”

Take Home: Major Bleeds Late After TAVR Not Only Frequent But Portend Worse Outcomes

To look at the impact of late major bleeding complications, the researchers, led by Martin B. Leon, MD, also of Columbia University Medical Center, examined data from 2,401 patients who survived at least 30 days after undergoing TAVR as part of the randomized PARTNER trial (both cohorts) or the randomized and nonrandomized continued-access registries. All patients received either the 23- or 26-mm version of the Sapien valve (Edwards Lifesciences).

Major bleeds were defined as those that caused death, a new hospitalization, or permanent disability; prolonged hospitalization ≥ 24 hours because of treatment; or required pericardiocentesis, a procedure for repair or hemostasis, or transfusion of more than 3 units of blood within a 24-hour period.

From 30 days to 1 year, major late bleeding complications occurred in 5.9% of patients at a median of 132 days after the procedure. The most common types of bleeds were gastrointestinal (40.8%), neurological (15.5%), or trauma- or fall-related (7.8%).

On multivariate analysis, the researchers identified 4 independent predictors of major late bleeds:

  • Moderate or severe aortic paravalvular leak at 30 days
  • A-fib or flutter at baseline or 30 days
  • Greater LV mass at 30 days
  • Low baseline hemoglobin

Patients who had major late bleeding complications were more likely to have adverse clinical outcomes from 30 days to 1 year after TAVR (table 1). Renal failure requiring dialysis also was more common in patients with late bleeding (3.9% vs 1.5%; P = .02).

 Table 1. Clinical Outcomes 30 Days to 1 Year Post-TAVR: Major Bleeding vs No Major Bleeding

After further adjustment for clinical, echocardiographic, and procedural factors, as well as outcomes, major bleeding remained strongly associated with mortality between 30 days and 1 year (adjusted HR 3.83; 95% CI 2.62-5.61).

Long-term Prognosis Comes Into Focus

Prior studies have established the association between early bleeding complications after TAVR and worse clinical outcomes, but this analysis extends that relationship to bleeds that occur among patients who survive for at least 30 days, according to Dr. Généreux.

“Although much attention initially focused on the improvement of acute outcomes (advances in device technologies, optimization of implantation techniques, and enhanced operator experience), leading to a dramatic reduction in periprocedural complications, this study demonstrates that reducing later adverse events (such as [major late bleeding complications]) is also crucial if long-term prognosis is to be improved,” he and his co-authors write.

The findings underscore the need for a more individualized approach to antiplatelet and antithrombotic therapy after TAVR, Dr. Généreux said, adding that trials will need to explore different strategies in specific subtypes of patients, such as those with A-fib.

He noted that the ARTE trial, which compares aspirin with or without clopidogrel after TAVR, will provide some answers, although it excludes patients who need chronic anticoagulation therapy.

The unexpected finding that moderate or severe paravalvular leak was associated with major late bleeding complications opens up the possibility that treatment might be tailored based on the severity of the leak, Dr. Généreux suggested.

Confirmation of Results Required

In an accompanying editorial, Dhruv S. Kazi, MD, MSc, MS, of San Francisco General Hospital (San Francisco, CA), highlights some of the limitations of the analysis, including the possibility of confounding by unobserved factors.

“For instance, in what appears to be a major oversight in the design of the original studies, data about anticoagulant use (a predictor of bleeding complications) were not prospectively collected,” he notes.

In addition, Dr. Kazi writes, although the strength of the relationship between major bleeds and mortality suggests “the association is real,” whether it is causal remains to be determined in future randomized trials.

Nevertheless, the findings could have important clinical implications if they are ultimately reproduced, he says.

“Since the introduction of TAVR, an intense focus on technological and procedural improvements has substantially reduced periprocedural bleeding. These findings argue that bleed-reduction strategies must also be extended to the first year postprocedure,” he writes. “In the future, nested clinical trials or well-designed observational analyses must examine the impact of improved patient selection and the effectiveness of pre- or postprocedure bleed-reduction interventions on long-term outcomes after TAVR.”

Note: Drs. Leon and Généreux and another co-author are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 


Sources:
1. Généreux P, Cohen DJ, Mack M, et al. Incidence, predictors, and prognostic impact of late bleeding complications after transcatheter aortic valve replacement. J Am Coll Cardiol. 2014;64:2605-2615.
2. Kazi DS. From innovation to implementation: optimizing long-term outcomes after TAVR [editorial]. J Am Coll Cardiol. 2014;64:2616-2618.

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Disclosures
  • The PARTNER trial was funded by Edwards Lifesciences.
  • Dr. Généreux reports receiving speaker fees from Edwards Lifesciences.
  • Dr. Leon reports receiving travel reimbursements from Edwards Lifesciences related to his activities as an unpaid member of the PARTNER Executive Committee.
  • Dr. Kazi reports no relevant conflicts of interest.

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