Circ: Blacks treated with fibrinolysis or PPCI at higher risk of bleeding
Rajendra H. Mehta, MD, MS, of the Duke Clinical Research Institute in Durham, N.C., and investigators in the National Registry of MI (NRMI) observed that previous studies have suggested bleeding rates are higher among blacks than whites treated with fibrinolysis, and that bleeding was associated with poor outcomes among blacks. They added that these studies were limited, though. They also noted that differences in the risk of bleeding and outcomes in black and white patients undergoing PPCI was unknown because the clinical trials had enrolled insufficient numbers of black participants.
Using NRMI data, the researchers designed a retrospective analysis of 93,684 black and white patients with STEMI treated with either fibrinolysis or PPCI within 12 hours of their first arrival at one of 1,138 sites between July 2000 and December 2006. The patients were stratified by primary reperfusion strategy (fibrinolysis or PPCI) and then stratified again by race.
Their objectives were to assess the impact of race on moderate to severe bleeding in either reperfusion strategy and to evaluate the relationship of race and moderate to severe bleeding with in-hospital mortality and whether it differed by type of reperfusion.
They used multivariable logistic regression analyses to evaluate differences in rates of in-hospital bleeding and mortality. They found that bleeding rates were higher among blacks compared with whites in both reperfusion strategies. The bleeding rate in black and white STEMI patients treated with fibrinolysis was 10.9 percent and 10.3 percent, respectively, and the bleeding rate in black and white STEMI patients treated with PPCI was 10.3 percent and 7.8 percent, respectively.
Overall, bleeding was higher in blacks with any reperfusion therapy, at 10.6 percent vs. 9.1 percent for whites.
In both groups, bleeding was associated with a higher mortality risk, and there was no overall difference by race in in-hospital mortality with or without bleeding for either reperfusion strategy.
“We found that despite younger age and higher body mass index (the two most important predictors of bleeding), African Americans treated with fibrinolysis had a higher risk of bleeding requiring interventions,” Mehta and colleagues wrote. They added theirs was the first study to show that racial differences in bleeding extended to patients undergoing PPCI. “Even among PPCI treated patients, bleeding was significantly higher in African Americans (1.33 times) that was independent of underlying GPIIb/IIIa [glycoprotein IIb/IIIa] use.”
They wrote that their results, based on a large, community-based cohort, confirmed previous studies that found higher bleeding rates among blacks treated with fibrinolysis and suggested a higher bleeding risk in black patients treated with PPCI as well. “This raises the possibility that perhaps other patient and/or race-specific and/or genetic differences beyond that leading to enhanced fibrinolysis may play an important role in the increased bleeding risk seen in African Americans.”
They proposed that strategies to reduce bleeding should be considered for both reperfusion strategies, which might have an impact on clinical outcomes. The also recommended that registry studies and clinical trials include a broad representation of ethnic groups.
They pointed out that their study was observational with limitations including missing data and potential unmeasured confounding that “may have accounted for some or all of the variations in bleeding.“ In an accompanying editorial, Robert P. Giugliano, MD, SM, of Brigham and Women’s Hospital in Boston, and a member of the TIMI Study Group, noted that their caution was appropriate.
“[T]he reasons why African Americans with STEMI treated with reperfusion therapy have higher rates of bleeding are likely complex and multifactorial,” Giugliano wrote. “To get to the next level of understanding, more details on the types of bleeding, analysis of alternative bleeding definitions and collection of additional confounding factors that are known to be associated with bleeding (e.g., combination antithrombotic therapy, excess dosing of antithrombotics, baseline hemoglobin and presence of peripheral vascular diseases) are needed.”
He argued that the use of registry data to explore causal relationships and the addition of a variable such as race in analyses, among other things, was problematic. “[T]he authors have overextended their data, speculating that higher rates of bleeding in African Americans may explain higher long-term mortality observed in other datasets,” Giugliano wrote.
In conclusion, he agreed with Mehta et al that a focus on understanding and preventing bleeding in blacks and other high-risk patient groups was needed.