What is the clinical evidence from this study?

Study design: Observational. Population: Acute myocardial infarction (n=40087). Intervention: Major bleeding vs. No major bleeding. Primary outcome: Hospital mortality (HR 1.9, 95% CI 1.6 to 2.2).

What does this research mean for the field?

Major bleeding in acute myocardial infarction is associated with increased hospital mortality but not postdischarge mortality, and this risk is much lower than reported in randomized controlled trials, suggesting bleeding is often a marker for higher baseline risk rather than a direct cause of adverse outcomes. Novelty: ClaimNovelty.CONTRADICTORY. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

November 19, 2007

Does Comorbidity Account for the Excess Mortality in Patients With Major Bleeding in Acute Myocardial Infarction?

Key Result

Major bleeding in acute myocardial infarction was associated with increased hospital mortality (HR 1.9; 95% CI 1.6-2.2) but not postdischarge mortality (HR 0.8; 95% CI 0.6-1.0).

Study Design

Type

Observational (n=40,087)

Multicenter

Yes

Structured PICO

Does major bleeding increase hospital and postdischarge mortality in real-world patients with acute myocardial infarction?

Population

40,087 patients with acute myocardial infarction enrolled in the Global Registry of Acute Coronary Events (GRACE)

Intervention

Major bleeding

Comparator

No major bleeding

Outcome

Hospital mortality and postdischarge mortalityhard clinical

Major bleeding in real-world AMI patients is associated with increased hospital mortality, though the risk is lower than reported in RCTs and often serves as a marker for higher baseline risk.

Main Result

Effect estimate: HR 1.9 (95% CI 1.6 to 2.2)

Abstract

BACKGROUND: Analyses from randomized controlled trials suggest that bleeding in patients with acute myocardial infarction is associated with poor outcomes. Because these data are not generalizable to all patients with acute myocardial infarction, we sought to better understand the scope of this problem in a "real-world" setting. METHODS AND RESULTS: We examined the frequency of major bleeding in 40,087 patients with acute myocardial infarction enrolled in the Global Registry of Acute Coronary Events. Regression analyses were used to examine the association between patient and treatment characteristics, bleeding, and hospital and postdischarge outcomes. Major bleeding occurred in 2.8% of patients. These patients were older, more severely ill, and more likely to undergo invasive procedures. Patients with bleeding were more likely to die during hospitalization (hazard ratio, 1.9; 95% confidence interval, 1.6 to 2.2) but not after discharge (hazard ratio, 0.8; 95% confidence interval, 0.6 to 1.0) than patients who did not bleed. Continuation of antithrombotic therapies after day 1 was lower in patients who experienced early bleeding. Moreover, in patients who bled, hospital mortality was increased in those who discontinued aspirin, thienopyridines, or low-molecular-weight heparins. CONCLUSIONS: Major bleeding occurred in 1 in 35 patients with acute myocardial infarction; these patients accounted for approximately 10% of all hospital deaths. Nevertheless, risk of hospital mortality associated with bleeding was much lower than reported in randomized controlled trials. These data suggest that although bleeding may be causally related to adverse outcomes in some patients in the real-world setting, it is often merely a marker for patients at higher risk for adverse outcomes.