Why fixed-dose combinations in hypertension?
 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
Barrios V, Escobar C. Integrated Blood pressure Control. 2010:3 11-19.
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.
Risk of cardiovascular events reduced
in important trials
ADVANCE1
PROGRESS2
ACCOMPLISH3,4
Active group vs control
Active group vs control
Excess risk observed in the hydrochlorothiazide** arm
when combined with an ACE inhibitor
**HCTZ+ benazepril versus amlodipine + benazepril
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.
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, Makani
H, 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.