DES Patients Who Bleed After Hospital Discharge Face Higher Mortality Risk

Postdischarge bleeding after DES implantation, regardless of the need for transfusion, is frequent and strongly predicts 2-year mortality in a relatively unselected PCI population, according to post hoc analysis of the ADAPT-DES study published in the September 1, 2015, issue of the Journal of the American College of Cardiology. Bleeding is associated with both clinical and pharmacologic factors.

“Because bleeding after hospital discharge following [PCI] occurs more frequently and has a greater impact on mortality than myocardial infarction, physicians should carefully consider the trade-off between risks of ischemic and bleeding events to individualize the duration and intensity of antiplatelet therapy,” write researchers led by Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY). Take Home: DES Patients Who Bleed After Hospital Discharge Face Higher Mortality Risk

“More research is needed to develop safer antithrombotic strategies to reduce the risk of hemorrhagic complications after deployment of drug-eluting coronary stents, especially in patients at high risk of bleeding,” they add.

ADAPT-DES was a prospective registry designed to examine the association between platelet reactivity and stent thrombosis after DES implantation. It enrolled 8,582 patients who underwent successful procedures at 11 centers in the United States and Europe from January 2008 to September 2010. All were treated with aspirin indefinitely, with clopidogrel recommended for at least a year. All but 5 patients survived to hospital discharge.

Overall, 6.2% of patients had clinically significant postdischarge bleeding, defined as TIMI major or minor bleeding, GUSTO severe or moderate bleeding, ACUITY major bleeding, or any bleeding requiring medical attention. Of the bleeding events, 10.5% occurred within 30 days, 48.2% occurred from 30 days to less than 1 year, and 41.3% occurred between 1 and 2 years.

Most bleeds (61.7%) originated in the GI tract, and 31.4% were treated with blood transfusion.

Predictors Established

After multivariate adjustment, several factors independently predicted postdischarge bleeding, including older age, PAD, lower baseline hemoglobin, lower platelet reactivity at baseline, warfarin use at discharge, and the presence of calcified lesions or bifurcations (table 1).

Table 1. Multivariate Predictors of Postdischarge Bleeding

DES Patients Who Bleed After Hospital Discharge Face Higher Mortality Risk

Postdischarge bleeding was associated with substantially higher rates of 2-year all-cause mortality (13.0% vs 3.2%; P < .0001), a difference that remained after multivariate adjustment (adjusted HR 5.03; 95% CI 3.29-7.66). The magnitude of that relationship was greater than for any other mortality predictors, including postdischarge MI (adjusted HR 1.92; 95% CI 1.18-3.32).

Mortality risk was elevated regardless of whether postdischarge bleeding was accompanied by transfusion (adjusted HR 4.71; 95% CI 2.76-8.03) or not (adjusted HR 5.27; 95% CI 3.32-8.35). However, patients with both bleeding and transfusion had the highest rates of all-cause and cardiac mortality.

Multiple Potential Links Between Bleeding, Mortality

According to Dr. Stone and colleagues, the strong association between postdischarge bleeding and mortality likely results from multiple factors. These include:

  • Bleeding results in reductions in circulating blood volume and oxygen-carrying capacity, which in turn predisposes to hypotension and greater risks of ischemia and arrhythmias
  • Discontinuing dual antiplatelet therapy (DAPT) to manage bleeding has been associated with particularly high risks of thrombotic events
  • Stopping other critical medications to manage hypotension after a bleed and failing to restart them can increase risk of poor outcomes
  • Red-blood-cell transfusions have been tied to systemic vasoconstriction, activation of inflammatory pathways, apoptosis, increased platelet aggregation, and thrombosis

The fact that the relationship was comparable regardless of transfusion suggests “that it is the deleterious effects of bleeding itself (perhaps in concert with essential medication discontinuation) rather than transfusions that may affect prognosis,” the authors write.

Optimal DAPT Duration Remains Uncertain

Debate continues about whether shorter or longer DAPT duration is ideal following DES implantation, with some evidence suggesting that mortality is lower with shorter treatment.

“Nonetheless, some patients at high risk for thrombotic events, such as those with prior MI, might still benefit from more potent and prolonged DAPT,” the authors note.

Tailoring both the duration and intensity of DAPT based on an individual patient’s bleeding and ischemic risks should improve outcomes, Dr. Stone and colleagues add, noting that some of the risk factors for postdischarge bleeding they identified have also been tied to ischemic events (ie, older age and PAD), whereas others are unique (ie, lower baseline hemoglobin and concomitant use of warfarin).

In an accompanying editorial, Samin K. Sharma, MD, and Usman Baber, MD, MS, of the Icahn School of Medicine at Mount Sinai (New York, NY), say the findings “reinforce the need to reliably estimate not just short, but also long-term risks for both bleeding and ischemic events after PCI, a necessary process to inform clinical decisions regarding DAPT duration.”

However, doing so can be challenging, and improved methods for evaluating long-term risks of both outcomes are needed, they add.

Moving forward, the results of the study will have implications for the use of DAPT after PCI, Drs. Sharma and Baber observe.

“Although the focus approximately 10 years ago was clearly towards longer DAPT durations for most patients, the pendulum has now shifted towards a more nuanced and individualized approach that incorporates risks for both bleeding and thrombosis,” they write. “Within this context, the identification of risk factors for late bleeding after PCI is an important first step towards developing and validating risk models that may identify patients most likely (or unlikely) to realize any benefit from a longer DAPT duration.”

These models will need to be implemented into practice to improve processes of care, and a combination of strategies to lower both in-hospital and postdischarge bleeding complications “will allow us to achieve more efficient, safer, and ultimately, better care for our patients after PCI,” the editorialists conclude.

Note: Dr. Stone and several coauthors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.


Sources: 
1. Généreux P, Giustino G, Witzenbichler B, et al. Incidence, predictors, and impact of post-discharge bleeding after percutaneous coronary intervention. J Am Coll Cardiol. 2015;66:1036-1045.

2. Sharma SK, Baber U. The shifting pendulum for DAPT after PCI: balancing long-term risks for bleeding and thrombosis [editorial]. J Am Coll Cardiol. 2015;66:1046-1049.

Disclosures:

  • Dr. Baber and Stone report no relevant conflicts of interest.
  • Dr. Sharma reports serving on the speakers bureaus of Abbott Vascular, Boston Scientific, Cardiovascular Systems, and Terumo Medical.

Related Stories:

Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

Read Full Bio

Comments