Will up-titration or combination with bisoprolol help to better control hypertension in amlodipine users?

Blood Pressure Control in Patients Resistant to Monotherapy

Guidelines from European professional societies recommend that patients who fail to achieve good blood pressure (BP) control should preferably be given combination therapy of low doses of 2 antihypertensives with different and complementary mechanisms of action, rather than increasing the monotherapy dose to the maximum possible daily dose. In the randomized controlled trial (RCT) BA5-A5, combined treatment with 5 mg of the selective calcium channel blocker (CCB) amlodipine and 5 mg of the selective beta-blocker (BB) bisoprolol was shown to be superior to monotherapy with 5 mg of amlodipine in patients with uncontrolled hypertension.

However, no clinical study directly compared the effectiveness of the maximum dose of amlodipine with switching the patient to combination therapy at a low dose. The authors of the presented analysis aimed to fill this gap.

Methodology and Goals of the Analysis

The aim of the analysis was to compare changes in systolic (sBP) and diastolic blood pressure (dBP) values from baseline to those achieved by patients after 8 weeks of treatment. In this context, patients received either a low-dose combination of 5 mg of amlodipine with 5 mg of bisoprolol, or amlodipine alone, titrated up to a maximum of 10 mg daily.

The two treatment options mentioned were compared indirectly, simulated (STC – simulated treatment comparison), using individual patient data (IPD) from an RCT in which participants received either 5 mg of amlodipine, or a combination of 5 mg amlodipine with 5 mg bisoprolol, and aggregated data (AgD) from a published RCT, which evaluated the results of using amlodipine at doses of 10 vs. 5 mg. The RCT with IPD was used to create models for assessing how patients might respond to the combination if they were more similar to participants in the RCT with AgD. In this indirect comparison, a dose of 5 mg amlodipine was used as the anchor.

Results

Effectiveness data from a total of 261 patients from the RCT with AgD, who received 10 mg amlodipine, and 178 patients from the RCT with IPD, who received the low-dose combination, were included in the analysis. The average age of subjects in the 10 mg amlodipine arm was 54.3 years (standard deviation [SD] 10.6), and in the combination arm, it was 57.1 years (SD 13.7). There were fewer diabetics among the 10 mg amlodipine users (8.7% vs. 18.8%), and the baseline mean sBP/dBP was 149.3 (SD 12.0)/96.5 (SD 4.7) versus 148.8 (SD 8.2)/90.2 (SD 7.6) mmHg.

The final model for sBP and dBP included the following variables: baseline sBP, baseline dBP, duration of hypertension, age, concomitant diabetes, gender, smoking history (only in the final model for sBP), and BMI (only in the final model for dBP). The average values whereby the results of combination therapy differed from up-titration after 8 weeks were −1.6 mmHg (standard error [SE] 1.9) for sBP and −3.3 mmHg (SE 1.3) for dBP.

Conclusion

In the indirect comparison described above, a more pronounced reduction in dBP was observed with low-dose combination therapy than with up-titration of amlodipine from 5 to 10 mg. There was no significant difference for sBP.

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Sources: 
1. Foch C., Feifel J., Gottwald-Hostalek U. 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. Curr Med Res Opin 2022 Apr; 38 (4): 587–593, doi: 10.1080/03007995.2022.2030112. 
2. Williams B., Mancia G., Spiering W. et al; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018; 39 (33): 3021–3104, doi: 10.1093/eurheartj/ehy339.