Update on β‐Blockers in Hypertension

Atenolol, a cardioselective β‐blocker, is the most widely prescribed β‐blocker for the treatment of hypertension in the United States. ¹ Atenolol has been used in hypertension studies as a standard treatment and has been compared with various other agents. Recently, several large hypertension studies using atenolol have reported less favorable patient outcomes when compared with other agents, most especially among older patients. ² , ³ Yet substantial data for a broad range of patient populations and risk groups have established that β‐blockers significantly reduce cardiovascular morbidity and mortality in patients with hypertension and concomitant conditions like coronary artery disease. ¹ These discordant findings have called into question the indication for using β‐blockers in uncomplicated hypertension. ⁴ , ⁵ Why might this be so, and are all β‐blockers tarred with the same brush as atenolol?

Briefly, 2 investigations (the Losartan Intervention For Endpoint reduction in hypertension study [LIFE] ² and the Anglo‐Scandanavian Cardiac Outcomes Trial [ASCOT] ³ ) were performed in older patients with hypertension and high cardiovascular risk comparing an atenolol‐based and a losartan‐ ² or amlodipine‐based treatment regimen. ³ Nearly identical BP reduction was achieved in both studies with the different medications but, despite this, the outcomes favored the comparator drug in both studies. This finding has now been verified (for atenolol) in several other studies and with other (non‐atenolol) β‐blockers. ⁴ In ASCOT, ³ the blood pressure difference between the β‐blocker and the calcium channel blocker group over the first few months of the trial, although small, may have accounted for at least some of the differences in cardiovascular outcome.

As we know, β‐blockers are a heterogeneous class of drugs. Newer agents such as carvedilol, which has some β‐blocker action, and the highly cardioselective agent nebivolol, ⁶ which is under review but not approved in the United States, have been shown to have an improved hemodynamic profile when compared with atenolol. Carvedilol (in the United States) may be a reasonable alternative when a β‐blocker is considered for use in uncomplicated hypertension.

Several reasons may explain the less favorable outcomes with β‐blocker therapy. These include some adverse metabolic effects (lowering of high‐density lipoprotein cholesterol and an increased risk of developing diabetes), possible better efficacy with twice‐daily dosing with atenolol, and less effective reduction of central aortic compared with brachial blood pressures. ⁷

In our hypertension practice, we now recommend that β‐blockers not be considered as first‐line therapy in uncomplicated hypertension, especially in older patients. In patients who are already on atenolol as part of their regimen, we discuss either leaving atenolol in their regimen at a twice‐daily dose or raise the issue of switching to either another antiadrenergic β‐blocking agent (like carvedilol) or to a different class of antihypertensive medication on a case‐by‐case basis.