Efficacy and Safety of the Extemporaneous Combination Nebivolol/Amlodipine in Patients with Hypertension Uncontrolled on Monotherapy: The BOTTICELLI Study.

Hypertension is the leading cause of cardiovascular disease, and its complications are preventable with blood pressure (BP)-lowering treatment. Combination treatment with 2 or more antihypertensive agents achieves sustained BP reductions. Nebivolol (NEB), a highly β1-selective beta-blocker with vasodilating properties, and amlodipine (AML), a dihydropyridine calcium channel blocker, are widely prescribed as monotherapies or in combination. To evaluate efficacy and safety of extemporaneous combination at fixed doses of NEB/AML in adults with hypertension uncontrolled on monotherapy. This phase 4, open-label, multicentre study enrolled adults with hypertension uncontrolled on monotherapy. After 4-week run-in on NEB 5 mg or AML 5 mg, patients with uncontrolled BP initiated NEB/AML 5/5 mg. Those still uncontrolled after 4 weeks were up-titrated to NEB/AML 5/10 mg, while controlled patients continued NEB/AML 5/5 mg for the full 8-week period. The primary endpoint was the change from baseline in mean sitting DBP after 8 weeks of treatment. Secondary endpoints included the change from baseline in mean sitting SBP, the proportion of patients achieving guideline-recommended BP targets, and safety. A total of 301 patients, mean age 52.1 (± 8.5) years, entered the run-in period; of these, 276 completed the study, with 182 achieving goal BP on NEB/AML 5/5 mg and 94 up-titrated to NEB/AML 5/10 mg. Overall, mean sitting DBP decreased by -15.2 (± 8.3) mmHg and SBP by -24.2 (± 11.8) mmHg (both p<0.001) over the treatment period. At study end, 63.0% of patients achieved BP <130/80 mmHg. NEB/AML dose regimens were well tolerated, and no serious treatment-emergent adverse events were reported. This study adds to the existing evidence supporting the efficacy and safety of the NEB/AML combination at two dose levels in managing hypertension and bringing patients at target goal.