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Antihypertensive Response to Thiazide Diuretic or Angiotensin Receptor Blocker in Elderly Hypertensives Is Not Influenced by Pretreatment Plasma Renin Activity

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Abstract

Purpose

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.

Methods

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).

Results

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.

Conclusions

Baseline PRA is not a useful guide to the BP responses of initial combination V/HCTZ in elderly individuals with systolic hypertension.

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Acknowledgments

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).

Disclosures

HS Weintraub

Consultancies: Gilead. Speakers’ Bureau: Novartis Pharmaceuticals Corporation, Daiichi-Sankyo, Takeda, AstraZeneca, Gilead, Abbott, Kowa. Grant support: none. Stock ownership/financial interests: none.

DA Duprez

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.

WC Cushman

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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Authors and Affiliations

  1. New York University School of Medicine, New York, NY, USA

    Howard S. Weintraub

  2. University of Minnesota, Minneapolis, MN, USA

    Daniel A. Duprez

  3. University of Tennessee, Memphis, TN, USA

    William C. Cushman

  4. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

    Dion H. Zappe, Das Purkayastha & Rita Samuel

  5. State University of New York at Buffalo, Buffalo, NY, USA

    Joseph L. Izzo Jr

  6. NYU Center for the Prevention of Cardiovascular Disease, New York University School of Medicine, New York, NY, 10016, USA

    Howard S. Weintraub

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  1. Howard S. Weintraub
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  2. Daniel A. Duprez
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  6. Rita Samuel
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  7. Joseph L. Izzo Jr
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Correspondence to Howard S. Weintraub.

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Weintraub, H.S., Duprez, D.A., Cushman, W.C. et al. Antihypertensive Response to Thiazide Diuretic or Angiotensin Receptor Blocker in Elderly Hypertensives Is Not Influenced by Pretreatment Plasma Renin Activity. Cardiovasc Drugs Ther 26, 145–155 (2012). https://doi.org/10.1007/s10557-011-6365-x

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  • DOI: https://doi.org/10.1007/s10557-011-6365-x

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