Ethnic Differences in Cardiovascular Drug Response

Abstract

In the early 1980s, clinical differences in response to the blood pressure (BP)-lowering effects of β-blockers and, to a lesser extent, diuretics were noted between ethnic groups. The most convincing evidence at that time came from a Veterans Affairs (VA) Cooperative Trial,1 which, along with other smaller studies, suggested that whites (those of European ancestry) had a better antihypertensive response to β-blockers than blacks (those of African ancestry), whereas blacks had a slight better response to diuretics than whites. Shortly after the first angiotensin-converting enzyme (ACE) inhibitor was approved in the mid-1980s, it was also recognized that whites responded more favorably to ACE inhibitors than did blacks. Over time, these differences in response became well accepted, such that ethnicity began to be used in helping to guide selection of antihypertensive drug therapy.2,3 Although the ethnic differences in response between β-blockers and ACE inhibitors in hypertension are perhaps the mostly widely recognized examples of ethnic differences in response to cardiovascular drugs, there are others. Pharmacogenetics is a field that seeks to unravel the genetic underpinnings of variable drug responses.4 Given the recognized ethnic differences in drug responses and the fact that many genetic polymorphisms differ in frequency on the basis of ethnicity/ancestry, questions about whether pharmacogenetics may also lead to an understanding of the ethnic differences in drug response are not surprising. The present review will summarize the most widely recognized examples of cardiovascular drugs with differential response by ethnicity and the evidence that pharmacogenetics data may aid in our understanding of these differences. Given that there are many examples in the literature of genetic associations that are not replicated, the pharmacogenetic examples discussed herein will come from those for which there is some evidence of replication or for which there have been multiple negative findings. In light …