In-Hospital Bleeding, Mortality Linked Long After NSTEMI

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Elderly patients with non-ST-segment elevation myocardial infarction (NSTEMI) who experience in-hospital major bleeding have higher mortality both within the first month and as late as 3 years after discharge. However, the relationship does not appear causative, with bleeding serving only as a marker of underlying risk, according to a large observational study published online March 5, 2012, ahead of print in the European Heart Journal.

Renato D. Lopes, MD, PhD, of Duke University Medical Center (Durham, NC), and colleagues looked at 32,895 NSTEMI patients aged 65 years or older who were treated between November 2001 and December 2006. The researchers paired patient-level data from the CRUSADE registry with Medicare claims records to examine the relationship between bleeding and mortality over time.

Association vs. Causation

In all, 39.8% of patients underwent PCI during hospitalization and 59.5% did not. In-hospital major bleeding occurred in 11.9% of the overall cohort, 12.4% of PCI patients, and 11.6% of those who did not undergo PCI.

Bleeding was more likely in women and in patients with comorbidities including hypertension, diabetes, peripheral artery disease, heart failure, stroke, and prior intervention. Patients who bled had higher baseline serum creatinine and lower creatinine clearance as well as lower baseline hematocrit. Use of unfractionated heparin or glycoprotein IIb/IIIa inhibitors during the first 24 hours of hospitalization also was associated with higher bleeding rates.

Cumulative mortality rates were higher at 30 days, 1 year, and 3 years for patients who had major bleeding during index hospitalization and survived to discharge (table 1).

Table 1. Mortality Rates After In-Hospital Major Bleeding

The association between in-hospital major bleeding and mortality, which was strongest in the first 30 days, persisted even after adjustment for baseline characteristics, discharge antiplatelet medications, cardiac catheterization, and PCI use (table 2).

Table 2. Effect of In-Hospital Major Bleeding on Mortality

Beyond 3 years, the relationship attenuates in the overall population (adjusted HR 1.14; 95% CI 0.99-1.31; P = 0.0595) but not in patients who underwent PCI (adjusted HR 1.25; 95% CI 1.01-1.54; P = 0.0404).

“Despite a probable early hazard related to bleeding, the longer duration of risk in patients who bleed casts doubt on its causal relationship with long-term mortality,” Dr. Lopes and colleagues write. “Rather, major bleeding likely identifies patients with an underlying risk for mortality.”

Major bleeds are “most likely a marker of residual unmeasured comorbidity (ie, bone marrow suppression, frailty, infection, malignancy, malnutrition, etc),” they say.

In the short term, mortality “could be a direct consequence of a hemodynamically significant bleeding event or subsequent anemia,” the researchers note, adding that patients may also experience higher risk when antiplatelet drugs are temporarily stopped after a bleeding event. For example, the current analysis found that “PCI patients who bled were slightly less likely to receive clopidogrel at discharge.”

Moreover, “it remains to be seen whether preventing bleeding in this at-risk population will translate into improved long-term outcomes,” they conclude.

Study Details

Major bleeding was defined as meeting 1 of the following criteria:

• Absolute hematocrit drop ≥ 12% units (38.4% of bleeds)
• Intracranial hemorrhage (0.5%)
• Witnessed retroperitoneal bleed (1.5%)
• Baseline hematocrit ≥ 28% plus transfusion (71.8%)
• Baseline hematocrit < 28% plus transfusion and a witnessed bleed (3.6%)

 

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Source:
Lopes RD, Subherwal S, Holmes DN, et al. The association of in-hospital major bleeding with short-, intermediate-, and long-term mortality among older patients with non-ST-segment elevation myocardial infarction. Eur Heart J. 2012;Epub ahead of print.

 

 

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