An anchored simulated treatment comparison of uptitration of amlodipine compared with a low-dose combination treatment with amlodipine 5 mg/bisoprolol 5 mg for patients with hypertension suboptimally controlled by amlodipine 5 mg monotherapy

Objective To compare changes in systolic and diastolic blood pressures (SBP, DBP) from baseline to following 8 weeks of treatment with a low dose combination of amlodipine 5 mg plus bisoprolol 5 mg versus up titration to the maximum daily dose of amlodipine 10 mg, in hypertensive patients uncontrolled by amlodipine 5 mg. Methods Individual patient data (IPD) from a randomized clinical trial (RCT) comparing the combination versus amlodipine 5 mg (EudraCT Number: 2019-000751-13) and aggregated data (AgD) from a published RCT comparing amlodipine 10 mg versus amlodipine 5 mg were utilized in an anchored simulated treatment comparison (STC). The RCT with IPD was used to create models assessing how patients might respond to the combination if they were more comparable to those patients in the RCT with AgD. A population-adjusted indirect comparison of the treatment strategies was then conducted, using amlodipine 5 mg as an anchor. Results In the efficacy analyses, a total of 261 patients were included in the amlodipine 10 mg arm of the RCT with AgD; and a total of 178 patients in the low-dose combination arm of the RCT with IPD. Respectively, in the Amlodipine 10 mg arm and in the low-dose combination arm, the mean age was 54.3 years-old (Standard deviation [SD] 10.6), and 57.1 years-old (13.7); 8.7% and 18.8% of patients were diabetics; and the mean baseline SBP/DBP was 149.3 (12.0)/96.5 (4.7) mmHg, and 148.8 (8.2)/90.2 (7.6) mmHg. The final model for SBP and DBP included the following variables: baseline SBP, baseline DBP, duration of hypertension, age, concomitant diabetes, sex, smoking history (final model for SBP only), and body mass index (final model for DBP only). Mean treatment differences (standard error [SE]) at 8 weeks between the combination and uptitration were -1.6 mmHg (1.9) for SBP; and -3.3 mmHg (1.3) for DBP. Conclusion In this indirect comparison, a more important decrease was observed in DBP with the low-dose combination as compared to the alternative therapeutic approach of up-titration from amlodipine 5 mg to amlodipine 10 mg. No meaningful difference was seen for SBP.