Key result
Plasma renin activity <0.65 ng/ml/hour predicted a greater systolic BP decrease to chlorthalidone than metoprolol in European Americans (by -15.9 mm Hg, P<0.0001), but not in African Americans.
Why the study?
Although plasma renin activity is a potential biomarker for personalizing antihypertensive therapy in European and African American hypertensives, the clinical utility of PRA-guided prescribing was incompletely understood.
Does baseline plasma renin activity predict systolic blood pressure response to different antihypertensive classes in European and African Americans with uncomplicated hypertension?
RCT (n=236)
Yes
Does baseline plasma renin activity predict systolic blood pressure response to different antihypertensive classes in European and African Americans with uncomplicated hypertension?
p-value: p=< 0.0001
Plasma renin activity is an effective predictive biomarker for personalizing antihypertensive selection in European Americans, but lacks clinical utility for guiding therapy in African Americans.
May support PRA-guided diuretic selection in low-renin European Americans; leaves open utility in African Americans pending randomized validation.
BACKGROUND: Interindividual variability in blood pressure (BP) response to antihypertensives has been reported. Although plasma renin activity (PRA) is a potential biomarker for personalizing antihypertensive therapy in European American (EA) and African American (AA) hypertensives, clinical utility of PRA-guided prescribing is incompletely understood. METHODS: Using systematic-phased approach, PRA's clinical utility was assessed. After categorizing by baseline PRA, clinic systolic BP (SBP) responses to metoprolol and chlorthalidone were compared in 134 EAs and 102 AAs enrolled in the Pharmacogenomics Evaluation of Antihypertensive Responses-2 (PEAR-2) trial. Receiver operating characteristic (ROC) analysis was conducted in EAs. Data from PEAR-2 AAs were used to estimate an optimal PRA cut point using multivariable linear regression models. The derived cut point in AAs was tested in a meta-analysis of 2 independent AA cohorts, and its sensitivity and specificity were assessed. RESULTS: EAs with PRA < 0.65 ng/ml/hour had a greater decrease in SBP to chlorthalidone than metoprolol (by -15.9 mm Hg, adjusted P < 0.0001), whereas those with PRA ≥ 0.65 ng/ml/hour had a greater decrease in SBP to metoprolol than chlorthalidone (by 3.3 mm Hg, adjusted P = 0.04). Area under ROC curve (0.69, P = 0.0001) showed that PRA can predict SBP response among EAs. However, we observed no association between PRA and SBP response in PEAR-2 AAs. Among independent AA cohorts, those with PRA ≥ 1.3 ng/ml/hour (PEAR-2-derived cut point) responded better to atenolol/candesartan than hydrochlorothiazide (meta-analysis P = 0.01). However, sensitivity of the derived cut point was 10%. CONCLUSIONS: PRA at the previously established 0.60-0.65 ng/ml/hour cut point is an effective predictive biomarker of BP response in EAs. However, we were unable to identify PRA cut point that could be used to guide antihypertensive selection in AAs. TRIAL REGISTRATION: NCT01203852, NCT00246519, NCT00005520.
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Mehanna et al. (2019) conducted an RCT in Uncomplicated hypertension (n=236). Metoprolol and chlorthalidone was evaluated on Clinic systolic BP (SBP) response (p=< 0.0001). Plasma renin activity <0.65 ng/ml/hour predicted a greater systolic BP decrease to chlorthalidone than metoprolol in European Americans (by -15.9 mm Hg, P<0.0001), but not in African Americans.
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