ß-Blockers for Hypertensives Without Other Comorbidities: Going, Going . . . Gone?

Time does not go by slowly. In only 2½ years, it will 40 years since I graduated from medical school. During my residency in medicine, and for a generation after, ß-blockers were among first choices for lowering blood pressure. Now it seems that ß-blockers have evolved into disreputable antihypertensives.

What’s changed over a generation?

Dr Franz Messerli has waged a tireless campaign against ß-blockers for hypertensive therapy. Elliott and Childers¹ chose 7 of Dr Messerli’s publications in their annotated bibliography, addressing the question whether ß-blockers should be considered first-line drugs in the treatment of otherwise uncomplicated (that is, without other indications such as ischemic heart disease) essential hypertension.¹

Let’s unpack the arguments from this important paper.¹

The first article that questioned the efficacy and safety of ß-blockers as antihypertensives was a meta-analysis (7 trials with 27,433 enrollees comparing a ß-blocker with placebo).² Stroke prevention afforded by ß-blockers was suboptimal (half of that expected and 16% higher than any other antihypertensive used).

Elliott and Childers also looked at another meta-analysis (N=6825) that specifically addressed atenolol.³ Atenolol’s suspected inferiority as an antihypertensive has become a recurrent theme. Although blood pressure lowering was the same with atenolol as with other agents, patients taking atenolol experienced a higher mortality and stroke rate.

Elliott and Childers reviewed 4 theories explaining why atenolol may confer additional vascular risk. One has been used frequently and deserves expansion. Atenolol lowers blood pressure more in the arm (brachial artery) than it does in the central circulation (aorta). Central or aortic hypertension is a documented risk for multiple cardiovascular end points. Central blood pressure is what the heart and brain “feel.” Atenolol appears to affect pulse wave velocities and reflected pressure waves more than other medications based on its unique chronotropic and inotropic ß-blocker properties.

Since ß-blockers also increase insulin resistance, they may substitute one vascular risk (diabetes) for another (hypertension). In the COMET trial (N=1511), carvedilol was superior to metoprolol in regard to rising HbA1c.⁴

The authors’ conclusions are essential to a synthesis.¹ The final answer is not in yet. Elliott and Childers highlighted the fact that ß-blockers are a large and heterogeneous group of medications. Within the group, however, atenolol is associated with lower rates of prevention in all 6 cardiovascular end points studied.

Newer ß-blockers such as nebivolol, which has additional vasodilator actions, may change the negative cardiovascular profile associated with ß-blocker use for hypertension. The negative profile as it stands now may lead to a change in recommendations regarding ß-blockers when JNC-8 is published. First line may become fourth line.          

References:
1. Elliott WJ, Childers WK. Should ß blockers no longer be considered first-line therapy for the treatment of essential hypertension without comorbidities? Curr Cardiol Rep. 2011 Sep 7; [Epub ahead of print].
2. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analyis. Lancet. 2005;366:1545-1553.
3. Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: is it a wise choice? Lancet. 2004;364:1684-1689.
4. Poole-Wilson PA, Swedberg K, Cleland JGF; COMET Investigators. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet. 2003;362:7-13.