Aliskiren and amlodipine in the management of essential hypertension: meta-analysis of randomized controlled trials

Abstract

Background: Aliskiren is a novel renin-angiotensin aldosterone system (RAAS) inhibitor, the combination therapy of aliskiren and amlodipine for blood pressure control have been reported recently. The primary objective of this analysis is to review recently reported randomized controlled trials (RCTs) to compare antihypertensive effects and adverse events between mono (amlodipine or aliskiren alone) and combination therapy of both medicines.

Methods: Databases for the search included Pubmed, Embase and the Cochrane Central Register of Controlled Trials. Revman v5.0 statistical program was used to analyze the data. Weighted mean differences (WMD) with a 95% confidence interval (CI) were used for the calculation of continuous data, and relative risk (RR) with a 95% CI was used for dichotomous data.

Results: We analyzed the data from 7 RCTs for a total of 6074 participants in this meta-analysis. We found that the aliskiren/amlodipine combination therapy had a stronger effect in lowering blood pressure as compared with the monotherapy using aliskiren (SBP: WMD = -10.42, 95% CI -13.03∼-7.82, P<0.00001; DBP: WMD = -6.60, 95% CI -7.22∼-5.97, P<0.00001) or amlodipine (SBP: WMD = -4.85, 95% CI -6.88∼-2.81, P<0.00001; DBP: WMD = -2.91, 95% CI -3.85∼-1.97, P<0.00001). No differences were found in terms of adverse events between combination therapy and monotherapy, except for the rates of peripheral edema and hypokalaemia which were significantly lower in the combination therapy than in the amlodipine monotherapy (RR = 0.78, 0.66∼0.92, P = 0.004; RR = 0.51, 0.27∼0.97, P = 0.04). Similar antihypertensive effects were found in both obese (body mass index > = 30 kg/m(2)) hypertensive and non-obese (body mass index <30 kg/m(2)) hypertensive patients. Moreover, there was no difference with the blood pressure lowering or adverse effects with regards to the combination therapy in both subgroups.

Conclusion: We found that aliskiren/amlodipine combination therapy provided a more effective blood pressure reduction than monotherapy with either drug without increase in the occurrence of adverse events.

Figure 1. PRISMA flow diagram.

Figure 2. Forest plot of BP reduction efficacy of aliskiren/amlodipine 300/10 mg/d and 300 mg/d aliskiren.

(a) Comparison of change in systolic blood pressure (SBP), diastolic blood pressure (DBP) (b).

Figure 3. Forest plot of BP reduction efficacy of aliskiren combined with amlodipine and amlodipine monotherapy at any doses.

(a) Comparison of change in systolic blood pressure (SBP); (b) Comparison of change in diastolic blood pressure (DBP).

Figure 4. Forest plot of BP reduction efficacy of 150 mg/d aliskiren combined with amlodipine and 10 mg/d amlodipine monotherapy.

(a) Comparison of change in systolic blood pressure (SBP); (b) Comparison of change in diastolic blood pressure (DBP).

Figure 5. Forest plot of BP reduction efficacy of 300 mg/d aliskiren combined with amlodipine and 10 mg/d amlodipine.

(a) Comparison of change in systolic blood pressure (SBP). (b) Comparison of change in diastolic blood pressure (DBP).

Figure 6. Forest plot of BP reduction efficacy and safety of aliskiren/amlodipine and amlodipine in obese patients and non-obese patients.

(a) Comparison of change in systolic blood pressure (SBP). (b) Comparison of change in diastolic blood pressure (DBP). (c) Comparison of adverse events incidence.

Figure 7. Forest plot of BP reduction efficacy of aliskiren/amlodipine combination therapy in obese patients and that in non-obese patients.

(a) Comparison of change in systolic blood pressure (SBP). (b) Comparison of change in diastolic blood pressure (DBP).