Beta-blockers Plus: A Fixed-dose Combination Quiz

Combinations of fixed-dose antihypertensive agents have become popular in the treatment of high blood pressure. This is a spot-check quiz on features, benefits, and the dual MOA of one specific combination.

1. Which of the following choices is/are correct in regard to coadministering antihypertensives from two different classes (you may choose more than one answer):

A. Combining 2 antihypertensive agents from different classes will lower blood pressure more than maximizing a single agent (proceeding with escalating doses of monotherapy).

B. When combinations are used, there are fewer adverse events than with escalating doses of single agents.

C. Patient medication adherence is improved with fixed-dose combination agents.

D. Available fixed-dose combination formulations are proven pharmacologically compatible.

Answer, discussion, and next question>>

Answer: All are correct  

There is evidence to support the contention that adding a second compatible agent to a single drug regimen lowers blood pressure more than increasing the dose of the first agent.^1,2 Benefits in terms of fewer adverse events and compliance can be realized.¹ Most of us are familiar with combinations such as ACEIs/ARBS with a diuretic or a dihydropyridine calcium channel blocker with an ARB.

Let’s look at a newer combination that has proven to be an attractive option-nebivolol and valsartan.

2. Choose the one correct statement from the options below:

A. Nebivolol is a unique beta-blocker that combines highly selective B₁-adrenergic receptor antagonism with alpha-receptor antagonism.

B. Nebivolol combines B₁-receptor antagonism with a nitric-oxide-dependent vasodilator action.

C. Nebivolol works in combination with valsartan by accentuating valsartan’s blockade of the angiotensin II receptor.

D. Nebivolol’s actions are similar to those of atenolol, another beta-blocker.

Answer and discussion>>

Correct statement is: B. Nebivolol combines B₁-receptor antagonism with a nitric-oxide-dependent vasodilator action.

Nebivolol combines B₁ selective receptor antagonism with a nitric oxide dependent vasodilatation. These actions compliment or add to the ARB effect of valsartan, but do not accentuate them specifically at the receptor level. Although the highest approved individual daily doses of nebivolol and valsartan are 40 mg and 320 mg, respectively, the fixed-dose formulation containing 20 mg and 320 mg respectively of these 2 drugs achieved a greater reduction in both systolic and diastolic blood pressures than maximizing either agents’ dose as montherapy.¹ Other publications support these data.³

I need to stress why nebivolol is unique as beta-blocker. Nebivolol lowers central aortic and central pulse pressures as a result of its action to increase nitric oxide. Atenolol does not lower either.³

Reliance on the “older” one-dimensional beta-blockers (ie, atenolol) is declining in favor of agents identified as “beta blockers plus,” that is, beta blockade combined with a second action such as alpha blockade (via carvedilol) or nitric oxide dependent vasodilatation (via nebivolol). One such agent, nebivolol, combines nicely in a single pill with valsartan and has been shown to decrease blood pressure effectively and safely.

References

1. Giles TD, Weber MA, Basile J, et al. Efficacy and safety of nebivolol and valsartan as fixed-dose combination in hypertension: a randomized, multicentre study. Lancet. 2014;383:1889-1898.

Wald DS, Morris JK, Bestwick JP, et al. Combination therapy versus monotherapy in reducing blood pressure: a meta-analysis on 11,000 participants from 42 trials. Am J Med. 2009; 22:290-300.

Sander GE, Giles TD. Nebivolol and valsartan as a fixed-dose combination for the treatment of hypertension. Expert Opin Pharmacother. 2015;16:763-770.