Perindopril, an ACE inhibitor, and amlodipine, a dihydropyridine calcium channel blocker, are established antihypertensive agents with complementary mechanisms of action. Recently, a once-daily, orally-administered, fixed-dose combination (FDC) of perindopril arginine plus amlodipine besylate (Prestalia®; hereafter referred to as perindopril/amlodipine FDC) was approved in the USA for the treatment of hypertension. This article reviews the efficacy and tolerability of perindopril/amlodipine FDC and briefly summarizes the agent’s pharmacologic properties. As demonstrated in short-term randomized controlled trials, perindopril/amlodipine FDC was significantly more effective in reducing blood pressure (BP) than monotherapy with either of the component drugs, and it appeared to be more effective than an up-titration scheme using valsartan and valsartan/amlodipine. The FDC agent was generally well tolerated, with the most common adverse events (peripheral edema, cough, headache, and dizziness) being consistent with the well-defined tolerability profiles of the individual component drugs. Furthermore, perindopril/amlodipine FDC was associated with a numerically lower incidence of peripheral edema compared with amlodipine monotherapy. Thus, perindopril/amlodipine FDC represents a useful option for the treatment of hypertension, including as initial therapy for patients likely to require multiple drugs to achieve their BP targets.
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World Health Organization. Global atlas on cardiovascular disease prevention and control. 2011. http://whqlibdoc.who.int/publications/2011/9789241564373_eng.pdf?ua=1. Accessed 10 Aug 2015.
Gillespie CD, Hurvitz KA. Prevalence of hypertension and controlled hypertension—United States, 2007–2010. MMWR Surveill Summ. 2013;62(Suppl 3):144–8.
Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206–52.
Valderrama AL, Gillespie C, Coleman King S, et al. Vital signs: awareness and treatment of uncontrolled hypertension among adults—United States, 2003-2010. MMWR Morb Mortal Wkly Rep. 2012;61:703–9.
Gradman AH, Basile JN, Carter BL, et al. Combination therapy in hypertension. J Clin Hypertens. 2011;13(3):146–54.
Neutel JM, Smith DHG. Hypertension management: rationale for triple therapy based on mechanisms of action. Cardiovasc Ther. 2013;31(5):251–8.
Bangalore S, Kamalakkannan G, Parkar S, et al. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med. 2007;120(8):713–9.
Gupta AK, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis. Hypertension. 2010;55(2):399–407.
US FDA. Prestalia (perindopril arginine and amlodipine) tablets: US prescribing information. 2015. http://www.fda.gov. Accessed 10 Aug 2015.
Elliott WJ. Rationale for a single-pill combination of perindopril arginine and amlodipine besylate. J Am Soc Hypertens. 2015;9(4):257–65.
Mourad J-J, Le Jeune S, Pirollo A, et al. Combinations of inhibitors of the renin-angiotensin system with calcium channel blockers for the treatment of hypertension: focus on perindopril/amlodipine. Curr Med Res Opin. 2010;26(9):2263–76.
Makani H, Bangalore S, Romero J, et al. Effect of renin-angiotensin system blockade on calcium channel blocker-associated peripheral edema. Am J Med. 2011;124(2):128–35.
Bahl VK, Jadhav UM, Thacker HP. Management of hypertension with the fixed combination of perindopril and amlodipine in daily clinical practice: results from the STRONG prospective, observational, multicenter study. Am J Cardiovasc Drugs. 2009;9(3):135–42.
Dahlöf B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005;366(9489):895–906.
Hatala R, Pella D, Hatalova K, et al. Optimization of blood pressure treatment with fixed-combination perindopril/ amlodipine in patients with arterial hypertension. Clin Drug Investig. 2012;32(9):603–12.
Nagy VL. Twenty-four-hour ambulatory blood pressure reduction with a perindopril/amlodipine fixed-dose combination. Clin Drug Investig. 2013;33(7):469–76.
Ruilope L, Schaefer A. The fixed-dose combination of olmesartan/amlodipine was superior in central aortic blood pressure reduction compared with perindopril/amlodipine: a randomized, double-blind trial in patients with hypertension. Adv Ther. 2013;30(12):1086–99.
Zhang Y, Ly C, Yannoutsos A, et al. Effect of a fixed combination of perindopril and amlodipine on blood pressure control in 6256 patients with not-at-goal hypertension: the AVANT’AGE study. J Am Soc Hypertens. 2013;7(2):163–9.
Elliott WJ, Whitmore J, Feldstein JD, et al. Efficacy and safety of perindopril arginine + amlodipine in hypertension. J Am Soc Hypertens. 2015;9(4):266–74.
Laurent S, Parati G, Chazova I, et al. Randomized evaluation of a novel, fixed-dose combination of perindopril 3.5 mg/amlodipine 2.5 mg as a first-step treatment in hypertension. J Hypertens. 2015;33(3):653–62.
Mancia G, Asmar R, Amodeo C, et al. Comparison of single-pill strategies first line in hypertension: perindopril/amlodipine versus valsartan/amlodipine. J Hypertens. 2015;33(2):401–11.
Hurst M, Jarvis B. Perindopril: an updated review of its use in hypertension. Drugs. 2001;61(6):867–96.
Macfadyen RJ, Lees KR, Reid JL. Perindopril: a review of its pharmacokinetics and clinical pharmacology. Drugs. 1990;39(Suppl 1):49–63.
Todd PA, Fitton A. Perindopril: a review of its pharmacological properties and therapeutic use in cardiovascular disorders. Drugs. 1991;42(1):90–114.
Abernethy DR. Amlodipine: pharmacokinetic profile of a low-clearance calcium antagonist. J Cardiovasc Pharmacol. 1991;17(Suppl 1):S4–7.
Haria M, Wagstaff AJ. Amlodipine: a reappraisal of its pharmacological properties and therapeutic use in cardiovascular disease. Drugs. 1995;50(3):560–86.
Murdoch D, Heel RC. Amlodipine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cardiovascular disease. Drugs. 1991;41(3):478–505.
Telejko E. Perindopril arginine: benefits of a new salt of the ACE inhibitor perindopril. Curr Med Res Opin. 2007;23(5):953–60.
US FDA. Aceon (perindopril erbumine) tablets: US prescribing information. 2015. http://www.fda.gov. Accessed 10 Aug 2015.
Faulkner JK, McGibney D, Chasseaud LF, et al. The pharmacokinetics of amlodipine in healthy volunteers after single intravenous and oral doses and after 14 repeated oral doses given once daily. Br J Clin Pharmacol. 1986;22(1):21–5.
Stopher DA, Beresford AP, Macrae PV, et al. The metabolism and pharmacokinetics of amlodipine in humans and animals. J Cardiovasc Pharmacol. 1988;12(Suppl 7):S55–9.
Beresford AP, McGibney D, Humphrey MJ, et al. Metabolism and kinetics of amlodipine in man. Xenobiotica. 1988;18(2):245–54.
James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507–20.
Fox KM, EUROPA Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362(9386):782–8.
Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA. 2004;292(18):2217–25.
During the peer review process, the manufacturer of perindopril/amlodipine FDC (Prestalia®) was offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
The preparation of this review was not supported by any external funding.
Conflicts of interest
Matt Shirley and Paul McCormack are salaried employees of Adis/Springer, are responsible for the content, and declare no relevant conflicts of interest.
The manuscript was reviewed by: T. H. Le Jemtel, Heart and Vascular Institute, Tulane University School of Medicine, New Orleans, LA, USA; D. M. Riche, School of Pharmacy, University of Mississippi, Jackson, MS, USA.
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Shirley, M., McCormack, P.L. Perindopril/Amlodipine (Prestalia®): A Review in Hypertension. Am J Cardiovasc Drugs 15, 363–370 (2015). https://doi.org/10.1007/s40256-015-0144-1
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