Addition of candesartan to lisinopril reduced diastolic blood pressure by an additional 1.7 mm Hg compared to up-titration of lisinopril in patients with uncontrolled hypertension.
RCT (n=1,096)
Double-blind
1:1
Yes
Does the addition of candesartan to lisinopril reduce blood pressure more effectively than up-titration of lisinopril in patients with uncontrolled hypertension?
In patients with hypertension uncontrolled on 20 mg lisinopril, adding 32 mg candesartan or doubling the lisinopril dose to 40 mg both provide safe, additional blood pressure reduction, with combination therapy showing slightly greater efficacy.
Mean Difference: -1.7 (95% CI -2.8–-0.7)
Absolute Event Rate: -8.21% vs -6.49%
The AMAZE (A Multicenter Trial Using Atacand and Zestril vs. Zestril to Evaluate the Effects on Lowering Blood Pressure) program included two identical studies sponsored by AstraZeneca LP. The oral form of candesartan is candesartan cilexetil; for simplicity, the term "candesartan" is used throughout this manuscript. Two identical multicenter, randomized, double-blind studies were performed to determine if addition of the angiotensin receptor blocker candesartan was more effective in lowering blood pressure than up-titration of lisinopril. Hypertensive patients (N=1,096) who were uncontrolled on lisinopril 20 mg daily were randomized (1:1) to receive either 8 weeks of high-dose lisinopril (40 mg) or the addition of candesartan (16 mg) for 2 weeks followed by 32 mg for 6 weeks. Study 1 (n=538) demonstrated decreases in trough sitting systolic/diastolic blood pressures at Week 8 by 6.2/5.9 mm Hg, respectively, for the lisinopril up-titration treatment group and by 11.6/8.3 mm Hg, respectively, for the lisinopril plus candesartan treatment group (p<0.01 in comparing both blood pressures reductions between the two treatment groups). Corresponding results for Study 2 (n=558) are reductions of 8.7/6.2 mm Hg and 9.5/7.4 mm Hg, respectively, for each of the two treatment groups. For Study 2, comparisons of systolic/diastolic blood pressures between the two treatment groups were not statistically significantly different (p=0.51/p=0.08, respectively). Post hoc pooled analysis (N=1,096) demonstrated a slightly greater blood pressure reduction with lisinopril plus candesartan compared with lisinopril (3.1/1.7 mm Hg). A 95% confidence interval limit for the difference in least squares mean change from baseline in systolic blood pressure between the two treatment groups is -4.8 to -1.5 and is -2.8 to -0.7 in mm Hg for diastolic blood pressure. The blood pressure control rates (<140/<90 mm Hg) were 42.7% and 36.9%, respectively. Both treatment regimens were well tolerated in all groups. In conclusion, for hypertensive patients not controlled by lisinopril 20 mg once daily, addition of candesartan (32 mg once daily) or doubling the dose of lisinopril provides safe, additional reduction of blood pressure.
Izzo et al. (2004) conducted an RCT in Essential hypertension (n=1,096). Candesartan plus lisinopril vs. Lisinopril 40 mg daily was evaluated on Mean change in trough sitting diastolic blood pressure from baseline to Week 8 (MD -1.7 mm Hg, 95% CI -2.8 to -0.7). Addition of candesartan to lisinopril reduced diastolic blood pressure by an additional 1.7 mm Hg compared to up-titration of lisinopril in patients with uncontrolled hypertension.