Efficacy and safety of the single pill combination of amlodipine 10 mg plus valsartan 160 mg in hypertensive patients not controlled by amlodipine 10 mg plus olmesartan 20 mg in free combination.

BACKGROUND AND OBJECTIVE For patients with moderate hypertension (grade 2, defined as systolic blood pressure [SBP] 160-179 mmHg and/or diastolic blood pressure [DBP] 100-109 mmHg), current guidelines recommend initial combination therapy and rapid dose-adjustment to achieve blood pressure goal. In this study we investigated the efficacy and tolerability of the single pill combination of amlodipine 10 mg plus valsartan 160 mg (A 10 + Val 160) in patients not controlled by the free combination of amlodipine 10 mg plus olmesartan 20 mg (A 10 + O 20). METHODS In this prospective, open-label, non-randomized trial, 257 patients with mean sitting DBP of 100-109 mmHg at trough entered a 4 week treatment phase with A 10 + O 20 in free combination once daily. Patients in whom DBP remained uncontrolled were switched in a second 4 week treatment phase to A 10 + Val 160. The primary efficacy variable was the reduction in DBP at week 8 compared to week 4 in the intent-to-treat population. RESULTS In the total cohort, baseline SBP/DBP of 164.2 +/- 9.8/103.6 +/- 2.1 mmHg decreased by 19.2 +/- 12.4/14.1 +/- 7.4 mmHg at week 4. In patients who did not achieve BP control (n = 175), subsequent treatment with A 10 + Val 160 for 4 weeks reduced SBP from 149.6 +/- 11.1 at week 4 by 7.9 mmHg at week 8 (95% CI: 6.1-9.6, p < 0.0001) and DBP from 93.4 +/- 3.9 mmHg by 9.1 mmHg (95% confidence interval: 8.1-10.2, p < 0.0001). The combination of A 10 + Val 160 was well tolerated, and the observed adverse events (15.3% of patients in phase 2) were consistent with the known drug profiles. CONCLUSIONS In a study designed to reflect typical clinical practice, in patients not controlled by the free combination of A 10 + O 20, the single pill combination of A 10 + Val 160 produced a statistically and clinically significant additional BP reduction and was well tolerated. Potential limitations of the design (open-label, non-controlled design, short term treatment) have to be taken into account.