Antihypertensive Response to Thiazide Diuretic or Angiotensin Receptor Blocker in Elderly Hypertensives Is Not Influenced by Pretreatment Plasma Renin Activity
- 205 Downloads
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.
- 5.Mancia G, De Backer G, Dominiczak A, et al. 2007 guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25:1105–87.PubMedCrossRefGoogle Scholar
- 7.Aronow WS, Fleg JL, Pepine CJ, et al. ACCF/AHA 2011 expert consensus document on hypertension in the elderly a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents Developed in Collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension. J Am Coll Cardiol. 2011;57:2037–114.PubMedCrossRefGoogle Scholar
- 16.Duprez DA, Botha J, Charney AN, Prescott MF. Comparison of the efficacy of aliskiren-versus ramipril-based treatment regimens on plasma renin concentration and plasma renin activity in elderly patients with systolic hypertension. J Clin Hypertens. 2009;11:A154.Google Scholar
- 21.Meade TW, Imeson JD, Gordon D, Peart WS. The epidemiology of plasma renin. Clin Sci (Lond). 1983;64:273–80.Google Scholar