The efficacy and safety of triple vs dual combination of angiotensin II receptor blocker and calcium channel blocker and diuretic: a systematic review and meta-analysis

Abstract

Many hypertensive patients require ≥2 drugs to achieve blood pressure targets. This study aims to review and analyze the clinical studies conducted with dual or triple combination of angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics. Medical literature between January 1990 and April 2012 was reviewed systematically and data from eligible studies were abstracted. Data were analyzed using random-effects models. Of the 224 studies screened, 7563 eligible patients from 11 studies were included. Triple combinations of ARBs (olmesartan or valsartan), CCBs (amlodipine), and diuretics (hydrochlorothiazide) at any dose provided more blood pressure reduction in office and 24-hour ambulatory measurements than any dual combination of these molecules (P<.0001 for both). Significantly more patients achieved blood pressure targets with triple combinations (odds ratio, 2.16; P<.0001). Triple combinations did not increase adverse event risk (odds ratio, 0.96; P=.426). Triple combinations at any dose seem to decrease blood pressure more effectively than dual combination of the same molecules without any remarkable risk elevation for adverse events. Further prospective studies evaluating the efficacy and safety of triple combinations, especially in the form of single pills, are required.

Figure 1

Study selection flow diagram.

Figure 2

Funnel plots for systolic and diastolic blood pressure analyses. The observed studies are shown as open circles, and the observed point estimate of difference in mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of triple and dual combinations is shown as an open diamond. The 9 imputed studies are shown as filled circles, and the imputed point estimate of difference in mean SBP and DBP of triple and dual combinations is shown as a filled diamond.

Figure 3

Odds ratios for blood pressure control rate in dual and triple combination groups. ARB indicates angiotensin II receptor blocker (valsartan or olmesartan); CCB, calcium channel blocker (amlodipine); CI, confidence interval, odds ratio >1.0 favors triple combinations in terms of blood pressure target achieving. *Ratio of patients achieving blood pressure target <140/90 mm Hg. ^† P value for odds ratio, P<.05 means significant odds difference between dual and triple combination. ^‡The parameters for heterogeneity, P value for Q.

Figure 4

Odds ratios for adverse events in dual and triple combination groups. AE, adverse event; ARB, angiotensin II receptor blocker (valsartan or olmesartan); CCB, calcium channel blocker (amlodipine); CI, confidence interval, odds ratio<1.0 favors dual combinations in terms of adverse event ratio. *P values for odds ratio, P<.05 means significant odds difference between dual and triple combination. ^†The parameters for heterogeneity, P value for Q.