1. 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
2. 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.
3. 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.
4. 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 reduced
in 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
5. 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.
6. 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.
Notas del editor
Most patients with hypertension need at least 2 antihypertensive agents to achieve blood pressure goals.
Many clinical trials have demonstrated the benefits of the fixed combination perindopril/indapamide in the treatment of hypertension. The aim of this presentation is to update the published data on the efficacy and safety of this fixed combination.
In the PICXEL study, the left ventricular mass index decreased by 13.6 ± 23.9 g/m2 with perindopril/indapamide (P<0.0001 vs baseline) and 3.9 ± 23.9 g/m2 with enalapril (P<0.005 vs baseline and P<0.0001 between groups).
The effects of the combination perindopril/indapamide on kidney disease have also been assessed. Combination therapy produced greater reductions in systolic and diastolic BP (-3.0, P=0.012 and -1.5, P=0.019, respectively) and AER (-42% vs -27%, P = 0.002) than enalapril (Figure 3). The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups.
Relevant controlled, randomized clinical trials such as ADVANCE, PROGRESS or HYVET have importantly shown that treatment with perindopril/indapamide reduces cardiovascular outcomes in different contexts, such as the diabetic population, a history of cerebrovascular disease, or the elderly.
The ACCOMPLISH trial showed that not all antihypertensive fixed combinations have the same impact on cardiovascular outcomes. In this trial, the benazepril–amlodipine combination was superior to benazepril–hydrochlorothiazide in reducing cardiovascular events in a hypertensive population with a high proportion of patients with diabetes and obesity.
It should be kept in mind that in this situation a thiazide may worsen glucose and lipid profiles and this could influence outcomes. However, indapamide does not have these deleterious effects on lipid and glucose profiles. Although both indapamide and thiazides are diuretics, their mechanisms of action differ, as do their clinical benefits in terms of vascular protection.
