Aliskiren – renin inhibitor for hypertension management Review article
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Published:
Dec 31, 2008
Keywords:
aliskiren, hypertension, renin-angiotensin-aldosterone system, renin inhibitors
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Abstract
The renin-angiotensin-aldosterone system (RAAS) has long been recognized to play a significant role in hypertension pathophysiology. Certain agents that modify the RAAS can control blood pressure and improve cardiovascular outcomes. One of them is renin, monospecific enzyme that catalyzes the rate-limiting step in the synthesis of angiotensin II. Renin inhibitors block the RAAS at the highest level, and might thus offer a novel approach for pharmacotherapy of arterial hypertension. Aliskiren is the first orally active, low molecular weight, non-peptide renin inhibitor, that has progressed to treatment of arterial hypertension. In patients with hypertension aliskiren produces dose-dependent blood pressure reduction. Its antihypertensive potency is approximately equivalent to that of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics. Aliskiren given with an angiotensin receptor blocker, produces significant additional blood pressure reduction, when combined with diuretics, its fully additive effect in therapy of arterial hypertension is seen. Therefore aliskiren may be an effective alternative in blood pressure reduction.
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Postuła , M., Szlufik , S., Jagiełło , E., & Pomianowska , A. (2008). Aliskiren – renin inhibitor for hypertension management. Cardiology in Practice, 2(4), 170-175. Retrieved from https://journalsmededu.pl/index.php/kwp/article/view/1676
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Copyright: © Medical Education sp. z o.o. This is an Open Access article distributed under the terms of the Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). License (https://creativecommons.org/licenses/by-nc/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
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References
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3. Cheng J.W.M.: Aliskiren: Renin Inhibitor for Hypertension Management. Clin. Therapeutics 2008, 30(1): 31-47.
4. Gradman A.H., Pinto R., Kad R.: Current concepts: renin inhibition in the treatment of hypertension. Current Opinion in Pharmacology 2008, 8:120-126.
5. Swedberg K., Cleland J., Dargie H. et al.: Guidelines for the diagnosis and treatment of chronic heart failure. Executive summary (update 2005): the Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur. Heart J. 2005, 26: 1115-1140.
6. Swedberg K., Cleland J., Dargie H., Drexler H., Follath F., Komajda M., Tavazzi L., Smiseth O.A., Gavazzi A., Haverich A., Hoes A., Jaarsma T., Korewicki J., Lévy S., Linde C., Lopes-Sendon J.L., Nieminen M.S., Piérard L., Remme W.J.: Guidelines for the diagnosis and treatment of chronic heart failure: full text (update 2005) The Task Force for the diagnosis and treatment of CHF of the European Society of Cardiology.
7. 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) Journal of Hypertension 2007, 25: 1105-1187.
8. Guidelines for the diagnosis and treatment of chronic heart failure: full text (update 2005).The Task Force for the diagnosis and treatment of CHF of the European Society of Cardiology.
9. Guidelines for the diagnosis and treatment of chronic heart failure: full text (update 2005) The Task Force for the diagnosis and treatment of CHF of the European Society of Cardiology.
10. Guidelines for the diagnosis and treatment of chronic heart failure: full text (update 2005) The Task Force for the diagnosis and treatment of CHF of the European Society of Cardiology.
11. Azizi M., Webb R., Nussberger J., Hollenberg N.K.: Renin inhibition with aliskiren: where are we now and where are we going? J. Hypertens. 2006, 24: 243-256.
12. Vaidyanathan S., Valencia J., Kemp C. et al.: Lack of pharmacokinetic interactions of aliskiren, a novel direct renin inhibitor for the treatment of HTN, with the antihypertensives amlodipine, valsartan, hydrochlorothiazide (HCTZ) and ramipril in healthy volunteers. Int. J. Clin. Pract. 2006, 60: 1343-56.
13. Dieterle W., Corynen S., Vaidyanathan S., Mann J.: Pharmacokinetic interactions of the oral renin inhibitor aliskiren with lovastatin, atenolol, celecoxib and cimetidine. Int. J. Clin. Pharmacol. Ther. 2005, 43: 527-35.
14. Dieterich H., Kemp C., Vaidyanathan S., Yeh C.: Pharmacokinetic interaction of the oral renin inhibitor aliskiren with hydrochlorothiazide in healthy volunteers (abstr). Clin Pharmacol. Ther 2006, 79 (supl.): P12.
15. Dieterich H., Kemp C., Vaidyanathan S., Yeh C.: Aliskiren, the first in a new class of orally effective renin inhibitors, has no clinically significant drug interactions with digoxin in healthy volunteers (abstr). Clin. Pharmacol. Ther. 2006, 79 (supl.): P64.
16. Dieterle W., Corynen S., Mann J.: Effect of the oral renin inhibitor aliskiren on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects. Br. J. Clin. Pharmacol. 2004, 58: 433-6.
17. Tekturna (package insert). East Hanover, NJ: Novartis Pharmaceuticals Corporation, 2007.
18. Allikmets K. 2007. Aliskiren – an orally active renin inhibitor. Review of pharmacology, pharmacodynamics, kinetics, and clinical potential in the treatment of hypertension. Vasc. Health and Risk Management, 3(6): 809-815.
19. Oh B.H., Mitchell J., Herron J.R. et al.: Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-h blood pressure control in patients with hypertension. J Am. Coll. Cardiol. 2007, 49: 1157-63.
20. Pool J., Gradman A., Kolloch R., Meyers M.J., Cai J., Satlin A., Prescott M.F.: Aliskiren, a novel renin inhibitor, provides longterm suppression of the rennin system, when used alone or in combination with hydrochlorothiazide in the treatment of hypertension. Eur. Heart. J. 2006, 27(supl.): 119.
21. Gradman A.H., Schmieder R.E., Lins R.L. et al.: Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation 2005, 111: 1012-8.
22. Villamil A., Chrysant S.G., Calhoun D. et al.: Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J. Hypertens. 2007, 25: 217-26.
23. Oparil S., Yarows S.A., Patel S. et al.: Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomized double-blind trial. Lancet 2007, 370: 221-9.
24. Stanton A., Jensen C., Nussberger J., O’Brien E.: Blood pressure lowering in essential hypertension with oral renin inhibitor, aliskiren. Hypertension 2003, 42: 1137-1143.
25. Gradman A.H., Kad R.: 2008 Renin Inhibition in Hypertension. JACC 51(5): 519-28.
26. Andersen K., Weinberger M.H., Egan B., Constance C.M., Ali M.A., Jin J., Keefe D.L.: Aliskiren-based therapy lowers blood pressure more effectively than ramipril-based therapy in patients with hypertension: a 6-month, randomized, double blind trial. J. Am. Coll. Cardiol. 2007, 49(supl. A): A371.
27. Uresin Y., Taylor A., Kilo C. et al.: Aliskiren, a novel renin inhibitor, has greater BP lowering than ramipril and additional BP lowering when combined with ramipril in patients with diabetes and hypertension (abstr). J. Hypertens. 2006, 24(supl.): 4-82.
28. Jordan J., Engeli S., Boye S.W. et al.: Direct renin inhibition with aliskiren in obese patients with arterial hypertension. Hypertension 2007, 49: 1047-55.
29. Munger M.A., Drummond W., Essop M.R. et al.: Aliskiren as add-on to amlodipine provides significant additional blood pressure lowering without increased oedema associated with doubling the amlodipine dose (abstr). Eur. Heart. J. 2006, 27 (supl.): 117.
30. McMurray J.: Aliskiren observation of heart failure treatment ALOFT – a 12 week safety evaluation of aliskiren 150 mg vs. placebo when added to standard therapy for stable heart failure. In Oral presentation in Hotline I session at European Society of Cardiology Congress 2007.
31. Sealey J.E., Laragh J.H.: Aliskiren, the first renin inhibitor for treating hypertension: reactive renin secretion may limit its effectiveness. Am. J. Hypertens. 2007, 20: 587-97.
2. Fox K., Alonso Garcia M.A., Ardissino D., Buszman P., Camici P.G., Crea F., Daly C., De Backer G., Hjemdahl P., Lopez-Sendon J., Marco J., Morais J., Pepper J., Sechtem U., Simoons M., Thygesen K. (Authors/Task Force Members): Guidelines on the management of stable angina pectoris. Executive summary: the Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology: ESC Committee for Practice Guidelines (CPG): Priori S.G., Blanc J.J., Budaj A., Camm J., Dean V., Deckers J., Dickstein K., Lekakis J., McGregor K., Metra M., Morais J., Osterspey A., Tamargo J., Zamorano J.L. Document Reviewers: Zamorano J.L., Andreotti F., Becher H., Dietz R., Fraser A., Gray H., Hernandez Antolin R.A., Huber K., Kremastinos D.T., Maseri A., Nesser H.J., Pasierski T., Sigwart U., Tubaro M., Weis M. European Heart Journal 2006.
3. Cheng J.W.M.: Aliskiren: Renin Inhibitor for Hypertension Management. Clin. Therapeutics 2008, 30(1): 31-47.
4. Gradman A.H., Pinto R., Kad R.: Current concepts: renin inhibition in the treatment of hypertension. Current Opinion in Pharmacology 2008, 8:120-126.
5. Swedberg K., Cleland J., Dargie H. et al.: Guidelines for the diagnosis and treatment of chronic heart failure. Executive summary (update 2005): the Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur. Heart J. 2005, 26: 1115-1140.
6. Swedberg K., Cleland J., Dargie H., Drexler H., Follath F., Komajda M., Tavazzi L., Smiseth O.A., Gavazzi A., Haverich A., Hoes A., Jaarsma T., Korewicki J., Lévy S., Linde C., Lopes-Sendon J.L., Nieminen M.S., Piérard L., Remme W.J.: Guidelines for the diagnosis and treatment of chronic heart failure: full text (update 2005) The Task Force for the diagnosis and treatment of CHF of the European Society of Cardiology.
7. 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) Journal of Hypertension 2007, 25: 1105-1187.
8. Guidelines for the diagnosis and treatment of chronic heart failure: full text (update 2005).The Task Force for the diagnosis and treatment of CHF of the European Society of Cardiology.
9. Guidelines for the diagnosis and treatment of chronic heart failure: full text (update 2005) The Task Force for the diagnosis and treatment of CHF of the European Society of Cardiology.
10. Guidelines for the diagnosis and treatment of chronic heart failure: full text (update 2005) The Task Force for the diagnosis and treatment of CHF of the European Society of Cardiology.
11. Azizi M., Webb R., Nussberger J., Hollenberg N.K.: Renin inhibition with aliskiren: where are we now and where are we going? J. Hypertens. 2006, 24: 243-256.
12. Vaidyanathan S., Valencia J., Kemp C. et al.: Lack of pharmacokinetic interactions of aliskiren, a novel direct renin inhibitor for the treatment of HTN, with the antihypertensives amlodipine, valsartan, hydrochlorothiazide (HCTZ) and ramipril in healthy volunteers. Int. J. Clin. Pract. 2006, 60: 1343-56.
13. Dieterle W., Corynen S., Vaidyanathan S., Mann J.: Pharmacokinetic interactions of the oral renin inhibitor aliskiren with lovastatin, atenolol, celecoxib and cimetidine. Int. J. Clin. Pharmacol. Ther. 2005, 43: 527-35.
14. Dieterich H., Kemp C., Vaidyanathan S., Yeh C.: Pharmacokinetic interaction of the oral renin inhibitor aliskiren with hydrochlorothiazide in healthy volunteers (abstr). Clin Pharmacol. Ther 2006, 79 (supl.): P12.
15. Dieterich H., Kemp C., Vaidyanathan S., Yeh C.: Aliskiren, the first in a new class of orally effective renin inhibitors, has no clinically significant drug interactions with digoxin in healthy volunteers (abstr). Clin. Pharmacol. Ther. 2006, 79 (supl.): P64.
16. Dieterle W., Corynen S., Mann J.: Effect of the oral renin inhibitor aliskiren on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects. Br. J. Clin. Pharmacol. 2004, 58: 433-6.
17. Tekturna (package insert). East Hanover, NJ: Novartis Pharmaceuticals Corporation, 2007.
18. Allikmets K. 2007. Aliskiren – an orally active renin inhibitor. Review of pharmacology, pharmacodynamics, kinetics, and clinical potential in the treatment of hypertension. Vasc. Health and Risk Management, 3(6): 809-815.
19. Oh B.H., Mitchell J., Herron J.R. et al.: Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-h blood pressure control in patients with hypertension. J Am. Coll. Cardiol. 2007, 49: 1157-63.
20. Pool J., Gradman A., Kolloch R., Meyers M.J., Cai J., Satlin A., Prescott M.F.: Aliskiren, a novel renin inhibitor, provides longterm suppression of the rennin system, when used alone or in combination with hydrochlorothiazide in the treatment of hypertension. Eur. Heart. J. 2006, 27(supl.): 119.
21. Gradman A.H., Schmieder R.E., Lins R.L. et al.: Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation 2005, 111: 1012-8.
22. Villamil A., Chrysant S.G., Calhoun D. et al.: Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J. Hypertens. 2007, 25: 217-26.
23. Oparil S., Yarows S.A., Patel S. et al.: Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomized double-blind trial. Lancet 2007, 370: 221-9.
24. Stanton A., Jensen C., Nussberger J., O’Brien E.: Blood pressure lowering in essential hypertension with oral renin inhibitor, aliskiren. Hypertension 2003, 42: 1137-1143.
25. Gradman A.H., Kad R.: 2008 Renin Inhibition in Hypertension. JACC 51(5): 519-28.
26. Andersen K., Weinberger M.H., Egan B., Constance C.M., Ali M.A., Jin J., Keefe D.L.: Aliskiren-based therapy lowers blood pressure more effectively than ramipril-based therapy in patients with hypertension: a 6-month, randomized, double blind trial. J. Am. Coll. Cardiol. 2007, 49(supl. A): A371.
27. Uresin Y., Taylor A., Kilo C. et al.: Aliskiren, a novel renin inhibitor, has greater BP lowering than ramipril and additional BP lowering when combined with ramipril in patients with diabetes and hypertension (abstr). J. Hypertens. 2006, 24(supl.): 4-82.
28. Jordan J., Engeli S., Boye S.W. et al.: Direct renin inhibition with aliskiren in obese patients with arterial hypertension. Hypertension 2007, 49: 1047-55.
29. Munger M.A., Drummond W., Essop M.R. et al.: Aliskiren as add-on to amlodipine provides significant additional blood pressure lowering without increased oedema associated with doubling the amlodipine dose (abstr). Eur. Heart. J. 2006, 27 (supl.): 117.
30. McMurray J.: Aliskiren observation of heart failure treatment ALOFT – a 12 week safety evaluation of aliskiren 150 mg vs. placebo when added to standard therapy for stable heart failure. In Oral presentation in Hotline I session at European Society of Cardiology Congress 2007.
31. Sealey J.E., Laragh J.H.: Aliskiren, the first renin inhibitor for treating hypertension: reactive renin secretion may limit its effectiveness. Am. J. Hypertens. 2007, 20: 587-97.