Critical appraisal of amlodipine and olmesartan medoxomil fixed-dose combination in achieving blood pressure goals

Figures & data

Figure 1 Possible combinations between some classes of antihypertensive agents. Framed agents have shown clinical benefit in interventional trials. Reproduced with permission from 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(6):1105–1187. Copyright © 2007 Lippincott, Williams & Wilkins.

Abbreviation: ACE, angiotensin-converting enzyme.

Figure 2 Mean plasma concentration profiles of amlodipine (upper panel) and olmesartan (lower panel) after administration of single-pill amlodipine/olmesartan medoxomil 10/40 mg combination therapy and concomitant administration of the two drugs and single tablets. Reproduced with permission from Rohatagi S, Lee J, Shenouda M, et al. Pharmacokinetics of amlodipine and olmesartan after administration of amlodipine besylate and olmesartan medoxomil in separate dosage forms and as a fixed-dose combination. J Clin Pharmacol. 2008;48(11):1309–1322. Copyright © 2008 Sage Publications.

Figure 3 Complementary mechanisms by which ARBs and CCBs lower BP. ARBs block the effects of angiotensin II at the AT₁ receptor thus suppressing vasoconstriction. CCBs block the entry of calcium into cells allowing arterial smooth muscle to relax causing peripheral vasodilation. These complementary activities cause reductions in blood pressure. Reproduced with permission from Neutel JM. Complementary mechanisms of angiotensin receptor blockers and calcium channel blockers in managing hypertension. Postgrad Med. 2009;121(2):40–48. Copyright © 2009 JTE Multimedia, LLC.

Abbreviations: ARB, angiotension receptor blocker; CCB, calcium channel blocker; MOA, mechanism of action.

Figure 4 Least-squares mean (standard error) reduction in seated blood pressure (BP) after 8 weeks of treatment with placebo, amlodipine and olmesartan medoxomil monotherapy, and amlodipine + olmesartan medoxomil combination therapy in the COACH study. Amlodipine/olmesartan medoxomil is available as 5/20, 5/40, 10/20, and 10/40 mg fixed-dose combinations in the United States. Reproduced with permission from Chrysant S, Melino M, Karki S, Lee J, Heyrman R. The combination of olmesartan medoxomil and amlodipine besylate in controlling high blood pressure: COACH, a randomized, double-blind, placebo-controlled, 8-week factorial efficacy and safety study. Clin Ther. 2008;30(4):587–604. Copyright © 2008 Elsevier.

Abbreviations: SeDBP, seated diastolic BP; SeSBP, seated systolic BP.

Figure 5 Percentage of patients achieving BP goal in the COACH study. (Adapted with permission from Table III in Chrysant et al).³⁶

Abbreviations: AML, amlodipine; OM, olmesartan medoxomil.

Figure 6 Achievement of BP goal in patients with Stage 1 and 2 hypertension (upper panel) and based on prior antihypertensive exposure (lower panel) in the COACH study. Reproduced with permission from Oparil S, Lee J, Karki S, Melino M. Subgroup analyses of an efficacy and safety study of concomitant administration of amlodipine besylate and olmesartan medoxomil: evaluation by baseline hypertension stage and prior antihypertensive medication use. J Cardiovasc Pharmacol. 2009;54:427–436. Copyright © 2009 Lippincott, Williams & Wilkins.

Abbreviations: AML, amlodipine; HTN, hypertension; OM, olmesartan medoxomil.

Table 1 Randomized double-blind, parallel-group, multicenter studies assessing efficacy of AML/OM following AML or OM monotherapy

Study	Volpe et al 2009^Citation39			Barrios et al 2009^Citation40
N	1,017			722
BP inclusion criteria	SeDBP ≥ 100 mmHg, SeSBP ≥ 160 mmHg, and mean 24-hr DBP ≥ 84 mmHg with ≥30% of daytime DBP < 90 mmHg
Patient characteristics
Mean age, years	55.8			56.8
Aged ≥ 65 years (%)	21.5			27.0
Caucasian (%)	99.7			100
Males (%)	61.1			48.9
Diabetes mellitus (%)	7.2			8.0
Mean baseline SeBP	164/102 mmHg			171/104 mmHg
Open-label monotherapy	AML 5 mg (8 wks)			OM 20 mg (8 wks)
Efficacy of treatment from the end of monotherapy period to end of first 8-week randomized, double-blind phase
Change in mean BP and attainment of SeBP goal	Treatment (mg/day)	Change (mmHg)	Goal (%)	Treatment (mg/day)	Change (mmHg)	Goal (%)
<140/90 mmHg	AML 5	−9.7/−5.7	30	OM 20	−10.8/−7.6	28.5
(<130/80 mmHg for diabetes)	AML/OM 5/10	−13.2/−7.7	39	AML/OM 5/20	−16.1/−10.4	45.8
	AML/OM 5/20	−15.4/− 9.5	54	AML/OM 10/20	−16.7/−10.9	44.5
	AML/OM 5/40	−16.8/−9.6	51
Efficacy of treatment at end of second 8-week double-blind phase after dose titration
Change in mean BP and attainment of SeBP goal	Treatment (mg/day)	Change (mmHg)	Goal (%)	N/A
	AML/OM 5/0→5/20	−12.6/−8.2	38
<140/90 mmHg	AML/OM 5/10→5/20	−7.5/−5.6	28
(<130/80 mmHg for diabetes)	AML/OM 5/20→5/40	−10.6/−6.2	36
	AML/OM 5/40→10/40	−12.3/−8.2	47

Abbreviations: AML, amlodipine; BP, blood pressure; DBP, diastolic BP, OM, olmesartan medoxomil; SeBP, seated BP; SeDBP, seated DBP; SeSBP, seated SBP.

ChrysantSMelinoMKarkiSLeeJHeyrmanRThe combination of olmesartan medoxomil and amlodipine besylate in controlling high blood pressure: COACH, a randomized, double-blind, placebo-controlled, 8-week factorial efficacy and safety studyClin Ther200830458760418498909

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BarriosVBrommerPHaagUCalderonAEscobarCOlmesartan medoxomil plus amlodipine increases efficacy in patients with moderate-to-severe hypertension after monotherapy: a randomized, double-blind, parallel-group, multicentre StudyClin Drug Investig2009297427439

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