Combined Renin Inhibition/Beta-blockade

Summary

Antihypertensive drug treatment is effective in only about 50% of patients. One mechanism responsible for treatment failure is a drug related stimulation of the renin-angiotension-aldosterone-system (RAAS). Several classes of medications that treat hypertension by blocking the RAAS system have been developed. However, the kidney responds to these drug treatments by producing greater amounts of renin. This high level of renin can reduce the effectiveness of some of these medications, ultimately causing the blood pressure to rise. This is one reason why blood pressure can be difficult to control in a certain percentage of patients. The hypothesis to be tested in the proposed study is that beta-adrenergic blockade (β-blockade), when superimposed upon aliskiren, a drug that competitively inhibits plasma renin activity (PRA) but stimulates the release of renin by the kidneys (plasma renin concentration \[PRC\]), can suppress the reactive increase in PRC that occurs during aliskiren monotherapy. The primary aim of this study is to measure plasma renin concentration (PRC) and plasma renin activity (PRA) levels during renin inhibition with aliskiren and combined renin inhibition/β-blocker treatment to determine whether the addition of a β-blocker attenuates the rise in plasma renin concentration (PRC). A secondary aim is to determine whether combined treatment further suppresses PRA and blood pressure.

Timeline

Start

2008-11

Primary completion

2010-05

Completion

2010-05

Publications

• Background Staessen JA, Li Y, Richart T. Oral renin inhibitors. Lancet. 2006 Oct 21;368(9545):1449-56. doi: 10.1016/S0140-6736(06)69442-7.
• Results Nussberger J, Wuerzner G, Jensen C, Brunner HR. Angiotensin II suppression in humans by the orally active renin inhibitor Aliskiren (SPP100): comparison with enalapril. Hypertension. 2002 Jan;39(1):E1-8. doi: 10.1161/hy0102.102293.
• Results Sealey JE, Laragh JH. Aliskiren, the first renin inhibitor for treating hypertension: reactive renin secretion may limit its effectiveness. Am J Hypertens. 2007 May;20(5):587-97. doi: 10.1016/j.amjhyper.2007.04.001.
• Results Oparil S, Yarows SA, Patel S, Fang H, Zhang J, Satlin A. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet. 2007 Jul 21;370(9583):221-229. doi: 10.1016/S0140-6736(07)61124-6.
• Results Blumenfeld JD, Sealey JE, Mann SJ, Bragat A, Marion R, Pecker MS, Sotelo J, August P, Pickering TG, Laragh JH. Beta-adrenergic receptor blockade as a therapeutic approach for suppressing the renin-angiotensin-aldosterone system in normotensive and hypertensive subjects. Am J Hypertens. 1999 May;12(5):451-9. doi: 10.1016/s0895-7061(99)00005-9.

Drugs

Indications