Additivity of nebivolol/valsartan single‐pill combinations versus other single‐pill combinations for hypertension

Abstract

The single‐pill combination (SPC) comprising nebivolol (5 mg), a vasodilatory β1‐selective antagonist/β3‐agonist, and valsartan (80 mg), a renin‐angiotensin‐aldosterone system inhibitor, is the only Food and Drug Administration–approved β‐blocker/renin‐angiotensin‐aldosterone system inhibitor SPC for hypertension. Additive effects of four nebivolol/valsartan SPC doses (5 mg/80 mg, 5/160 mg, 10/160 mg, 10/320 mg nebivolol/valsartan) were compared with five Food and Drug Administration–approved non–β‐blocker/renin‐angiotensin‐aldosterone system inhibitor SPCs (aliskiren/hydrochlorothiazide, aliskiren/amlodipine, valsartan/amlodipine, aliskiren/valsartan, and telmisartan/amlodipine). Additivity is the ratio of placebo‐adjusted SPC blood pressure (BP) reduction to the placebo‐adjusted monotherapy component BP reduction sums. A weighted average of comparator scores was calculated and compared vs nebivolol/valsartan. Additivity ratio scores for nebivolol/valsartan SPCs (diastolic BP range: 0.735–0.866; systolic BP range: 0.717–0.822) were similar to the comparator weighted average (diastolic BP: 0.837; systolic BP: 0.825). Among the nebivolol/valsartan SPCs, 5/80 mg had the greatest additivity (diastolic BP: 0.866; systolic BP: 0.822). BP reduction contributions with monotherapy were similar for nebivolol/valsartan 5/80 mg SPC. Additivity scores for nebivolol/valsartan and select non–β‐blocker/renin‐angiotensin‐aldosterone system inhibitor SPCs were comparable.

Nebivolol/Valsartan: A Novel Antihypertensive Fixed-Dose Combination Tablet

“…Additionally, the FDA-approved dose was not included in primary end point results, making comparison to other FDCs difficult. Although Ishak et al 29 report that additivity scores in BP reductions achieved with nebivolol/valsartan FDCs are similar to those achieved in other FDCs, these data do not compare efficacy in numerical lowering of BP. No trials are available that compare nebivolol/valsartan head-to-head with other FDCs.…”

“…Although most data demonstrate that combination nebivolol/valsartan has greater clinical effect than either agent as monotherapy, it must be considered whether this combination offers a similar or greater benefit compared to other currently available antihypertensive combinations. Ishak et al 29 compared the additivity scores of nebivolol/valsartan to other combination antihypertensive agents in a retrospective, post hoc trial. 29 Additivity scores of >1 indicated synergistic effect, 1 indicated complete additivity, and <1 indicated partial additivity.…”

“…Ishak et al 29 compared the additivity scores of nebivolol/valsartan to other combination antihypertensive agents in a retrospective, post hoc trial. 29 Additivity scores of >1 indicated synergistic effect, 1 indicated complete additivity, and <1 indicated partial additivity. Varying doses of aliskiren/HCTZ, aliskiren/amlodipine, valsartan/amlodipine, aliskiren/valsartan, and telmisartan/amlodipine were used as 18 comparators with data gathered from 8-week trials with similar populations.…”

“…Although it did not achieve complete additivity, this score was similar to other products that demonstrated weighted averages of SBP (0.825; 95% CI = 0.786-0.867) and DBP (0.837; 95% CI = 0.794-0.883). 29…”