Antihypertensive Response to Thiazide Diuretic or Angiotensin Receptor Blocker in Elderly Hypertensives Is Not Influenced by Pretreatment Plasma Renin Activity
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Renin profiling has been proposed as a method to guide antihypertensive drug selection. This prespecified post-hoc analysis examined the influence of baseline plasma renin activity (PRA) on blood pressure (BP) responses.
A 16-week, randomized, double-blind, prompted-titration trial evaluated initial valsartan (V)/hydrochlorothiazide (HCTZ) combination therapy versus initial HCTZ or V monotherapy in individuals aged ≥70 years with systolic hypertension. Sitting PRA was measured at baseline, Week 4, and Week 16. Subjects were stratified into 2 groups for analysis: low renin (baseline PRA <0.65 ng/mL/h) or normal-high renin (baseline PRA ≥0.65 ng/mL/h).
PRA data were available in 322/384 subjects: 178 had low PRA and 144 had normal-high PRA. At Week 4, V/HCTZ was more effective than HCTZ or V at reducing mean sitting systolic BP (MSSBP), independent of baseline PRA, with reductions of −16.9, −12.6, and −9.5 mmHg, respectively, in low-renin subjects and −19.4, −11.5, and −8.6 mmHg in normal-high renin subjects. Baseline PRA was similar in responders (subjects not uptitrated at Week 4) and nonresponders (subjects uptitrated at Week 4). In responders, the reactive rise in PRA at Week 4 was related to change in MSSBP, with the greatest increases in PRA observed in the V/HCTZ group. Higher baseline PRA was associated with a greater reactive rise in PRA.
Baseline PRA is not a useful guide to the BP responses of initial combination V/HCTZ in elderly individuals with systolic hypertension.
Key wordsValsartan Hydrochlorothiazide Plasma renin activity Hypertension Blood pressure Elderly
Funding statement/industry support:
This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
The authors wish to thank Michael S. McNamara, MS, and Mary A. Tom, PharmD, of Oxford PharmaGenesis Inc. for assistance in preparing the methods, results, figures, and tables. This assistance was funded by Novartis Pharmaceuticals Corporation. The authors express their appreciation to Colleen Faller of Novartis Pharmaceuticals Corporation for expert assistance in project management (ClinicalTrials.gov identifier: NCT00698646).
Consultancies: Gilead. Speakers’ Bureau: Novartis Pharmaceuticals Corporation, Daiichi-Sankyo, Takeda, AstraZeneca, Gilead, Abbott, Kowa. Grant support: none. Stock ownership/financial interests: none.
Speakers’ Bureau: Novartis Pharmaceuticals Corporation, Forest, Pfizer, Merck. Advisory Board: Novartis Pharmaceuticals Corporation, Pfizer, Abbott. Grant support: Novartis Pharmaceuticals Corporation, Roche. Stock ownership/financial interests: none.
Consultancies: Novartis Pharmaceuticals Corporation, Takeda, Daiichi-Sankyo. Grant support: Novartis Pharmaceuticals Corporation, GlaxoSmithKline, Merck. Stock ownership/financial interests: none.
D Purkayastha, DH Zappe, and R Samuel
Employees of Novartis Pharmaceuticals Corporation.
JL Izzo Jr
Consultancies: Boehringer-Ingelheim, Forest Laboratories, Novartis Pharmaceuticals Corporation, Daiichi-Sankyo, Takeda. Grant support: GlaxoSmithKline, Novartis Pharmaceuticals Corporation. Stock ownership/financial interests: none.
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