African-Americans Have Higher Bleeding Rates After Reperfusion for STEMI

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Compared with their Caucasian counterparts, African-American patients with ST-segment elevation myocardial infarction (STEMI) have a higher risk of bleeding following reperfusion with either fibrinolysis or primary percutaneous coronary intervention (PCI), researchers report in a study published online March 14, 2012, ahead of print in Circulation.

Rajendra H. Mehta, MD, of Duke Clinical Research Institute (Durham, NC), and colleagues analyzed bleeding and mortality in 5,109 African-Americans and 88,575 Caucasians with STEMI who received either fibrinolysis or primary PCI at centers participating in the National Registry of Myocardial Infarction (NRMI) between 2000 and 2006.

Regardless of reperfusion strategy, African-Americans had a higher overall rate of bleeding than Caucasians (10.6% vs. 9.1%; P = 0.0026).

In patients receiving fibrinolysis, rates of bleeding requiring intervention were similar between African-Americans and Caucasians, while among those receiving primary PCI, bleeding rates were higher in African-Americans. The same racial difference was seen with regard to transfusion use. Additionally, in the primary PCI group, bleeding was more frequent in African-Americans compared with Caucasians regardless of glycoprotein (GP) IIb/IIIa inhibitor use (tables 1 and 2).

Table 1. In-Hospital Bleeding: Fibrinolysis

Table 2. In-Hospital Bleeding: Primary PCI

Overall, the adjusted odds ratio for bleeding in African-Americans compared with Caucasians was 1.35 (95% CI 1.13-1.60) regardless of reperfusion strategy. An interaction between race and treatment emerged in the multivariable logistic regression model for bleeding in the overall population (P < 0.001).

With adjustment, African-Americans were about 20% more likely to bleed than Caucasians after receiving fibrinolysis (OR 1.21; 95% CI 1.02-1.43; P = 0.0269), while the risk of bleeding in African-Americans was about one-third higher after undergoing primary PCI (OR 1.33; 1.13-1.55; P < 0.0001).

No Mortality Difference In-hospital

In-hospital mortality was similar between African-Americans and Caucasians treated with either fibrinolysis (OR 0.99; 95% CI 0.70-1.40) or primary PCI (OR 1.05; 95% CI 0.76-1.46). Although patients with bleeding were more likely to die than those with no bleeding, there was no mortality difference between African-Americans and Caucasians specifically among patients with bleeding who received either fibrinolysis (2.5% vs. 3.9%; P = 0.3331) or primary PCI (2.0% vs. 2.9%; P = 0.1006).

Dr. Mehta told TCTMD in a telephone interview that the main message of the findings is that clinical trial data should not be extrapolated to populations beyond those involved in the trials.

“The efficacy and safety of drugs in clinical trials that largely involve white patients may not necessarily apply to minorities,” he said. “The signals are there. These are not randomized data, but we used adequate methods to account for all the measured confounders.”

Dr. Mehta said he believes the finding is genuine since his group has shown at least twice before that African-Americans have higher bleeding risk than Caucasians with fibrinolytic therapy and have now extended those findings to primary PCI.

Bleeding Risk Likely Multifactorial

In an editorial accompanying the study, Robert P. Giugliano, MD, SM, of Brigham and Women’s Hospital (Boston, MA), writes that a number of factors may explain racial and ethnic differences in response to certain agents, including:

• Genetic factors that determine drug exposure (eg, differences in absorption, distribution, metabolism, elimination)
• Intrinsic factors (eg, age, gender, weight, renal and/or hepatic function)
• Extrinsic influences (eg, diet, concomitant medications and nontraditional therapies, environmental exposures, cultural factors)
• Combinations of genetic, intrinsic, and extrinsic factors

According to Dr. Giugliano, it has been known for over 2 decades that African-Americans have higher rates of bleeding with fibrinolytic therapy, “possibly related to a more pronounced fall in fibrinogen observed after 5 hours.”

He also points out that the study raises an interesting question about the causal relationship between bleeding and mortality. If African-Americans had more bleeding, and bleeding is associated with a significant increase in mortality, he states, why is there no accompanying higher mortality rate in African-Americans?

Dr. Mehta and colleagues believe that the apparent discrepancy may be explained by the higher long-term mortality rates for African-Americans, as have been observed in other studies. Dr. Giugliano believes that suggestion is overextending the present data.

Important and Timely

In a telephone interview with TCTMD, Deepak L. Bhatt, MD, MPH, of Brigham and Women's Hospital (Boston, MA), said the new analysis adds to one performed by his own group several years ago when he was with the Cleveland Clinic (Cleveland, OH). That study found that after PCI, African-Americans had similar short-term rates of death or MI compared with whites but a trend toward worse long-term outcomes (Chen MS, et al. Am J Med. 2005;118:1019-1025).

“I think this is a terrific analysis addressing a very important question,” Dr. Bhatt said. “It really corroborates our single-center observation that there is a risk that seems to be specific to African-Americans with respect to bleeding.”

Dr. Bhatt said that “the core finding is really quite robust in this analysis,” but the key question is what to do about it.

He added that use of radial access for primary PCI and bivalirudin should be considered in African-American patients as strategies to reduce bleeding risk.

“You could make the argument, as others have, that those should be considered in anyone at high risk of bleeding,” he added.

Dr. Bhatt concluded that while there is a need to do further studies specific to African-Americans, the body of research for this group is far greater than that for Latinos or Asians. Like Dr. Mehta, he said future research should focus on looking across a wider range of ethnicities and races to try to pinpoint those at higher risk for bleeding as well as ischemic events.

Sources:

1. Mehta, RH, Parsons L, Rao SV, et al. Association of bleeding and in-hospital mortality in African American and Caucasian patients with ST elevation myocardial infarction receiving reperfusion. Circulation. 2012;Epub ahead of print.
2. Giugliano RP. Relationships between race, bleeding, and mortality in coronary reperfusion. Circulation. 2012;Epub ahead of print.

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