La raza negra un predictor independiente de la trombosis de stent farmacoactivo después de su colocación
Black race an independent predictor of stent thrombosis after DES placement
Por Fran Lowry
Theheart.org
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Washington, DC – Black race is an independent risk factor for developing stent thrombosis after implantation of a drug-eluting stent (DES).
The finding, published August 30, 2010 in Circulation, goes against the more widespread belief that poor compliance, lower socioeconomic status, and other demographic factors are responsible for the poor outcomes after DES placement in African Americans.
“We have to understand exactly why this is happening,” senior author Dr Ron Waksman (Washington Hospital Center, Washington, DC). “The popular answer was that this was an issue of compliance, that black patients are sicker, that there are some other confounders. But within our population, we looked into that, and it was not a compliance issue. This was the real deal.”
The investigators, led by Dr Sara D Collins (Washington Hospital Center), compared 1594 black patients who underwent DES implantation with 5642 nonblack patients in a retrospective analysis. Most (65.7%) were men, and the average age at presentation was 65 (range 52-78) years. The median household income was significantly lower in blacks than in whites ($44 197 vs $60 838, p<0.001). In addition, blacks were younger and were more likely to have a history of hypertension, diabetes mellitus, chronic renal insufficiency, and congestive heart failure.
Blacks more compliant with clopidogrel than whites
Angiographic success was high in both groups (97.9% for blacks and 98.2% for nonblacks).
Blacks were more likely to be taking clopidogrel at the time of stent thrombosis than were nonblacks, although this difference did not reach statistical significance (87.5% vs 77.8%; p=0.068).
Blacks were nearly three times more likely to develop stent thrombosis than nonblacks. After 30 days, the rates were 1.71% vs 0.59%; at one year, they were 2.25% vs 0.79%; at two years, they were 2.78% vs 1.09%; and at three years, they were 3.67% vs 1.25%.
In a multivariate analysis, black race emerged as an independent predictor of early stent thrombosis at 30 days and persisted as an independent predictor of late stent thrombosis beyond 30 days.
Asked what he thinks is going on with African American patients, Waksman said he and his team have a working hypothesis that this population may have a genetic polymorphism that makes them less responsive to clopidogrel.
“This is just speculation, and this study did not include any genomic data. At our center, we take care of a large population of African Americans, and I think we have to understand exactly why this is happening,” he said.
In the meantime, “Physicians and patients need to be aware that this is happening, and it’s not necessarily a compliance issue. This may be a consideration to take into account in the decision to place a drug-eluting stent. What are the other options for these patients? If it is a question of a polymorphism, that may address the issue, but we don’t know for sure at the moment. That was the purpose in publishing this study, to increase awareness and to continue to search for an answer.”
Health disparities likely due to a number of factors
Dr Mauro Moscucci (University of Miami Miller School of Medicine, FL) agrees that genetics probably has a role in the disparity. But, he told, other factors may also be at play.
“I disagree that the authors necessarily ruled out all other possibilities, including compliance with clopidogrel,” he said. A more valid way of assessing compliance would be to use the medication-possession ratio [MPR]—defined as the sum of days’ supply of medication divided by 365—to measure adherence.
“If the patient is supposed to be on the medication for one year, the total numbers of prescription multiplied by the numbers of days should be 365 days, so the MPR should be 1. If it is less than 1, it means that there have been some gaps in taking the medication. Some recent registry analyses that have been presented on an abstract level have shown that there are, in fact, differences in the MPR across different ethnic groups,” Moscucci said.
Also, socioeconomic factors may still have been of some importance. “They looked at median income, which is certainly a way to look at socioeconomic status, but I think it would have been worthwhile to know more. Studies looking at subacute stent thrombosis have shown that being on minimum wage or being unemployed is also associated with an increased risk,” Moscucci said.
Nevertheless, there does seem to be some underlying genetic differences in the way blacks and whites metabolize clopidogrel, he noted. “As the authors nicely state in their discussion, there has been a lot of interest in different genes that code enzymes that metabolize clopidogrel. There has been a lot of interest in the CYP2C19 gene and reduced-function alleles. There are some data to suggest that African Americans and Asians tend to have a higher frequency of reduced-function alleles compared with whites.”
It is likely that the health disparities are due to a combination of factors, he said. “Some are socioeconomic, some are probably genetic, and it is going to be our role now to start digging more into those factors, trying to identify what we can correct. If it is genetic, we can address it perhaps with genetic testing to identify low responders and then use different medications to reduce the risk of subacute stent thrombosis. But the socioeconomic factors would be difficult to address, especially now in the current economic situation.”
Weighing in with his comments about the study, Dr Oscar C Marroquin (University of Pittsburgh Medical Center, PA) said the fact that the study was retrospective is an important limitation. “Given this, confounding variables not included in their adjusted model could account for the observed findings.”
He, too, feels that the role that socioeconomic status might have played in the outcome cannot be completely discounted. Finally, the study reports on outcomes in patients receiving so-called “first-generation” DES. “Whether these observations can be extrapolated to patients who receive newer-generation DES is unknown.”
Despite these limitations, Marroquin feels that the study observations are important. “They should be viewed as hypothesis-generating, rather than conclusive. As the study authors suggest, further study of race genetics/pharmacogenomics and their impact on responsiveness to dual antiplatelet therapy to potentially explain these findings is warranted.”
Fuente:
1.   Collins SD, Torguson R, Gaglia MA, et al. Does black ethnicity influence the development of stent thrombosis in the drug-eluting stent era? Circulation 2010; DOI:10.1161/CIRCULATIONAHA.109.907998.Available at:http://circ.ahajournals.org.