Why fixed-dose combinations in hypertension?

Barrios V, Escobar C. Integrated Blood pressure Control. 2010:3 11-19.

Combination therapy is needed when monotherapy does not attain blood pressure objectives and as a first-line treatment in high-risk patients.

2007 and 2009 updates of European hypertension guidelines

Advantages of a fixed-dose combination:Increased antihypertensive efficacy+ lower incidence of adverse events

+ improved compliance

ACE inihibitor + diuretic combination is very beneficial throughout the cardiovascular continuum, as demonstrated by the perindopril/indapamide combination

Superior LVMI reduction with perindopril/indapamide

versus enalapril

Effect of the combination perindopril/indapamide (2 mg/0.625 mg up to 8 mg/2.5 mg)and enalapril (10 mg up to 40 mg/daily) on left ventricular mass index (g/m2).

Data from the PICXEL study.

Barrios V, Escobar C. Integrated Blood pressure Control. 2010:3 11-19.

AER reduction greater with perindopril/indapamide

versus enalapril

Effect of the combination perindopril/indapamide (2 mg/0.625 mg up to 8 mg/2.5 mg)and enalapril (10 mg up to 40 mg/daily) on urinary albumin excretion (% of change from

baseline). Data from the PREMIER study.

Barrios V, Escobar C. Integrated Blood pressure Control. 2010:3 11-19.

1. ADVANCE Collaborative Group. Lancet. 2007;370:829-840. 2. PROGRESS Collaborative Group. Lancet. 2001;358:1033-1041. 3. Jamerson K, Weber MA, Bakris GL, et al; ACCOMPLISH trial investigators. N Engl J Med. 2008;359:2417-2428. 4. Bakris GL, Sarafi dis PA, Weir MR, et al; ACCOMPLISH Trial investigators. Lancet. 2010;375:1173-1181.

Risk of cardiovascular events reducedin important trials

ADVANCE1

Active group vs control

PROGRESS2

Active group vs control

ACCOMPLISH3,4

Excess risk observed in the hydrochlorothiazide** arm when combined with

an ACE inhibitor

**HCTZ+ benazepril versus amlodipine + benazepril

Indapamide differs from thiazide diuretics

Indapamide Hydrochlorothiazide

Metabolically neutral1,2 Increases risk of diabetes8

Protects against stroke3-5

Protects the heart3-6

Reduces microalbuminuria7

Reduces total mortality3-5

1. Ambrosioni E, Safar M, Degautec J-P, et al. J Hypertens. 1998;16:1677-1684. 2. Akram J, Sheikh UE, Mahmood M, Donnelly R. Curr Med Res Opin. 2007;23:2929-2936. 3. Messerli FH, MakaniH, Benjo A, Romero J, Alviar C, Bangalore S. J Am Coll Cardiol. 2011;57:590-600. 4. Gaciong Z, Symonides B. Expert Opin Pharmacother. 2010;11:2579-2597. 5. Beckett NS, Peters R, Fletcher AE, et al. N Engl J Med. 2008;358:1887-1898. 6. Gosse P, Sheridan DJ, Zannad F, et al. J Hypertens. 2000;18:1465-1475. 7. Marre M, Garcia J, Kokot F, et al. J Hypertens. 2004;22:1613-1622. 8. Pepine CJ, Handberg EM, Cooper-DeHoff R, et al. JAMA. 2003;290:2805-2816.