January 22, 2008JAMA
Pharmacogenetic Association of the NPPA T2238C Genetic Variant With Cardiovascular Disease Outcomes in Patients With Hypertension
Why the study?
Does the NPPA T2238C or G664A genetic variant modify the effect of chlorthalidone versus other antihypertensive medications on cardiovascular disease outcomes in patients with hypertension?
Population
38,462 participants with hypertension from ALLHAT, a multicenter randomized clinical trial conducted in the…
Comparison
Diuretic (chlorthalidone; n = 13,860) vs Calcium antagonist, angiotensin-converting…
Design
Cohort, randomly assigned
Follow-up
mean 4.9 years
Authors
Discussion
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Member takes
Implication
NPPA T2238C may modify chlorthalidone versus amlodipine effects on CHD; hypothesis-generating and requires prospective validation before clinical use.
Structured PICO
Does the NPPA T2238C or G664A genetic variant modify the effect of chlorthalidone versus other antihypertensive medications on cardiovascular disease outcomes in patients with hypertension?
P
Population
38,462 participants with hypertension from ALLHAT, a multicenter randomized clinical trial conducted in the United States and Canada.
I
Intervention
Diuretic (chlorthalidone; n = 13,860)
C
Comparator
Calcium antagonist (amlodipine; n = 8174), angiotensin-converting enzyme inhibitor (lisinopril; n = 8233), or alpha-blocker (doxazosin; n = 8195)
O
Outcome
Coronary heart disease (CHD), defined as fatal CHD or nonfatal myocardial infarction (mean follow-up, 4.9 years)hard clinical
The NPPA T2238C genetic variant modifies the efficacy of antihypertensive medications, suggesting that minor C allele carriers may benefit more from diuretics while TT allele carriers may benefit more from calcium channel blockers.
Cite This Study
Lynch et al. (2008) studied this question.