|
||||||
|
|
|
|
|||||||||||
|
|||||||||||||
| ||||||||||||||||||||||||||||||||||||||
Physicians who have steered clear of confronting racial health careinequities may be in for a reality check if the combination of isosorbidedinitrate and hydralazine (BiDil, NitroMed)—the first medicationcarrying a race-specific indication—receives Food and DrugAdministration (FDA) approval for use in black patients with heartfailure.
Availability of this so-called "ethnic drug" will press thequestion of whether it represents a marketing maneuver involving thepharmaceutical industry, the patent system, and the FDA, or a critical steptoward eliminating racial disparities in cardiac care.
Three years have passed since the Institute of Medicine published itslandmark report, Unequal Treatment, documenting the problem of racialand ethnic disparities in healthcare.1 Despite theensuing proliferation of "call-to-action" agendas, currentestimates indicate that more than 80,000 black Americans die annually as aresult of the continuing health caredivide.2
Contributing to this toll is mortality from heart failure, which occurs twoand a half times more frequently in blacks than in whites. Diabetes conferseven greater risk for heart failure and a worse prognosis.
To date, focusing on long-term and difficult-to-measure solutions such asexpanding insurance coverage and heightening cultural sensitivity has donelittle to raise the awareness of individual practitioners with respect toracial disparities in healthcare.3 If approved,BiDil almost certainly will move the issue of health disparities squarely intothe clinic, where race-centered conversations remain largelytaboo.
|
EVOLUTION OF A CONTROVERSY
Retrospective analyses of three major heart studies—theVasodilator-Heart Failure Trial (V-HeFT) I, the V-HeFT II, and the Studies ofLeft Ventricular Dysfunction—formed the basis of the FDA new drugapplication forBiDil.4–6The orally administered combination of two older drugs, isosorbide dinitrateand hydralazine, lost favor in the treatment of heart failure after theangiotensin-converting enzyme (ACE) inhibitor enalapril (Vasotec, Merck)proved superior.
Later review of the data suggested, however, that ACE inhibitors might notbe as effective in blacks as in whites. This difference is attributed, atleast in part, to less robust bioavailability of nitric oxide andrenin-angiotensin activity in black patients—conditions alleviated byBiDil.
The potential value of combined isosorbide dinitrate and hydralazineemerged in the 1980s, when Jay N. Cohn, MD, of the University of MinnesotaSchool of Medicine demonstrated that the combination drug had some effect inthe treatment of heart failure. Although trial results were not strong enoughto win FDA approval, NitroMed, Inc., a company specializing in nitricoxide–enhancing medications, subsequently licensed the drug. NitroMed'sreanalysis of Cohn's data revealed marked improvement in the subset ofpatients who were black, prompting reapplication to the FDA for arace-specific indication. In early 2001, the agency notified NitroMed that apositive confirmatory trial of the drug in blacks with heart failure wouldprovide sufficient basis for marketing approval.
Accordingly, NitroMed and the Association of Black Cardiologists (ABCardio)sponsored the African-American Heart Failure Trial (A-HeFT), in which 1,050black patients with New York Heart Association (NYHA) class III or class IVheart failure were randomized to receive either BiDil or placebo in additionto standardtherapy.7
Although completion of the trial was not expected until 2005, theindependent data and safety monitoring board unanimously recommended earlytermination due to the significantly higher mortality rate in the placebogroup (10.2%) compared with the BiDil group (6.2%). In other words, the 43%improvement in survival associated with BiDil was so significant that it wasdeemed unethical to withhold the drug from patients in the placebo group.NitroMed submitted these dramatic results to the FDA in November 2004 and isexpecting approval of BiDil this year.
Results of A-HeFT were published in the New England Journal ofMedicine and presented at the 2004 meeting of the American HeartAssociation (AHA), where Malcolm Taylor, MD, chairman of the ABCardioCommittee on Heart Failure, noted: "African Americans sufferdisproportionately from heart failure and until A-HeFT have beenunderrepresented in heart-failure trials. A-HeFT represents a significant stepforward in addressing thesedisparities."8
Yet even as Taylor and many others hailed the good news about BiDil,critics such as Jonathan Kahn, PhD, JD, a law professor at Hamline University,and Troy Duster, PhD, a sociologist at New York University, expressed concernthat race-specific marketing may encourage "racial profiling" inmedicine and succeed only in widening the caregap.9,10"The pervading message will be that BiDil is for blacks, and that a lotof people whom it might help might not get it," Kahn wrote. "Thedeeper message is that blacks are different at the biological level, becausethis is a drug that works at the molecular level."
Duster contends that because A-HeFT enrolled only blacks, the study revealslittle about racial distinctions. Moreover, he says the decision to design arace-specific trial was primarily a matter of economics: The original patentwould have expired in 2007, but the race-specific patent will give NitroMedcontrol over the profits from BiDil until 2020.
Some observers worry that racial labeling may feed into physicians'unexamined assumptions about group behaviors and distract attention fromenvironmentalinfluences.11 As aresult, the effort to alleviate health disparities could have the paradoxicaleffect of reinforcing the health care divide.
Yet according to Clyde W. Yancy, MD, a member of the A-HeFT SteeringCommittee, this is less likely to occur if the health care community movesbeyond the limiting concept of "race-based" medicine. "If weallow this paradigm to stand, then we will have failed thescientific-discovery process," says Yancy, associate dean of clinicalaffairs at St. Paul University Hospital/UT Southwestern Medical Center inDallas. "The real strength of the utility of nitric oxide upregulationis its exposure of a novel mechanism of disease progression."
The A-HeFT investigators recognize that BiDil might work well for groupsother than blacks and, conversely, that it might not work well for all blackswith heart failure. Consequently, a genetics sub-study is under way toidentify factors beyond race and ethnicity that might determine treatmentresponse. In the meantime, BiDil may offer an at-risk underserved population"renewed hope," Yancy says. "Remember, this is adramatically effective treatment for heart failure. That is the real news ofthe day."
THE CLINICAL PERSPECTIVE
Yancy says most physicians have been aware that not all drugs work equallywell in all patients, and he predicts there will be a "sense ofrelief" in that this higher-risk population may benefit from a noveltherapy.
According to Stephen Brunton, MD, director of faculty development at theCabarrus Family Medicine Residency Program in Harrisburg, N.C., BiDil poses nospecial dilemma from a clinical standpoint. "We've dealt with thisalready with respect to ACE inhibitors, which don't work as well in blackpatients with hypertension," Brunton says.
Yet Eugene Wright Jr., MD, medical director at Cape Fear Valley HealthSystem in Fayetteville, N.C., expects BiDil to raise as many questions as itanswers, especially given the impracticality of sophisticated genome analysisin the clinic. "My gut reaction is that this is great, but the questionwill be, `How do you define race?' In this multicultural society, thedefinition will often be subjective, based on the examiner." 
References
2. Satcher D, Fryer GE, McCann J, et al.: Trends: What if we wereequal? A comparison of the black-white mortality gap in 1960 and 2000.Health Aff 24:459–464, 2005.
3. Lavizzo-Mourey R, Jung M: Fighting unequal treatment: The RobertWood Johnson Foundation and a quality-improvement approach to disparities.Circulation 111:1208–1209, 2005.
4. Dries DL, Exner DV, Gersh BJ, et al.: Racial differences in theoutcome of left ventricular dysfunction. N Engl J Med 340: 609–616, 1999.
5. Carson P, Ziesche S, Johnson G, et al.: Racial differences inresponse to therapy for heart failure: Analysis of the vasodilator-heartfailure trials. J Card Fail 5:178–187, 1999.[Medline]
6. Exner DV, Dries DL, Domanski MJ, et al.: Lesser response toangiotensin-converting-enzyme inhibitor therapy in black as compared withwhite patients with left ventricular dysfunction. N Engl JMed 344:1351–1357, 2001.
7. Taylor Al, Ziesche S, Yancy C, et al.: Combination of isosorbidedinitrate and hydralazine in blacks with heart failure. N Engl JMed 351:2049–2057, 2004.
8. Medical Study News: BiDil demonstrates significant improvement insurvival rates in African American heart failure patients. November 9, 2004.www.news-medical.net/?id=6202.
9. Kahn J: How a drug becomes "ethnic": Law, commerce, andthe production of racial categories in medicine. Yale J HealthPolicy Law Ethics 4:1–46, 2004.[Medline]
10. Duster T: Race and reification in science.Science 307:1050–1051, 2005.
11. Sankar P, Cho MK, Condit CM, et al.: Genetic research and healthdisparities. JAMA 291:2985–2989, 2004.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
| ||||||||||||||||||||||||||||||||||||||
|
||||||
|
| DOC News | Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |
