Time does not go by slowly. In only 2 ½ years, it will 40 years since I graduated from medical school. During my residency in medicine, and for a generation after, beta-blockers were among first choices for lowering blood pressure. Now it seems that beta-blockers have evolved into disreputable antihypertensives.
What’s changed over a generation?
Dr Franz Messerli has waged a tireless campaign against beta-blockers for hypertensive therapy. Elliot and Childers1 chose 7 of Dr Messerli’s publications in their annotated bibliography, addressing the question whether beta-blockers should be considered first-line drugs in the treatment of otherwise uncomplicated (that is, without other indications like 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 beta-blockers as anti-hypertensives was a meta-analysis (7 trials with 27,433 enrollees comparing a beta-blocker to placebo).2 Stroke prevention afforded by beta-blockers was suboptimal (half of that expected and 16% higher than any other antihypertensive used).
Elliot and Child also looked at another meta-analysis (N=6,825) that specifically addressed atenolol(Drug information on atenolol).3 Atenolol’s suspected inferiority as an antihypertensive has become a recurrent theme. Although blood pressure lowering was the same with atenolol as compared to 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 beta-blocker properties.
Since beta-blockers also increase insulin resistance, they may substitute one vascular risk (diabetes) for another (hypertension). In the COMET trial (N=1,511), carvedilol(Drug information on carvedilol) was superior to metoprolol(Drug information on metoprolol) in regard to rising HbA1c.4
The authors’ conclusions are essential to a synthesis.1 The final answer is not in yet. Elliot and Childers highlighted the fact that beta-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-point studied.
Newer beta-blockers like nebivolol(Drug information on nebivolol), which has additional vasodilator actions, may change the negative cardiovascular profile associated with beta-blocker use for hypertension. The negative profile as it stands now may lead to a change in recommendations regarding beta-blockers when JNC-8 is published. First line may become fourth line.
1. Elliott WJ, Childers WK. Should beta-blockers no longer be considered first-line therapy for treatment of essential hypertension without comorbidities? Curr Cardiol Rep. 2011; epub 07 September 2011.
2. Lindholm LH, Carlberg B, Samuelsson O. Should beta-blockers remain first choice in the treatment of primary hypertension? 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, for the 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.