Beta‐blockers, hypertension, and stroke outcomes

Treatment of high blood pressure remains a cornerstone in stroke prevention, and beta‐blockers have now been used to treat hypertension and prevent strokes for almost 5 decades. The first beta‐blocker to be used in clinical medicine, propranolol, was originally invented to provide relief for patients with angina pectoris. It was specifically designed to block the beta adrenergic receptors of the heart, thus decreasing the myocardial oxygen demand.1 It was soon found, however, that the newly developed drug could also be used as a blood pressure lowering medication.2 Placebo‐controlled trials such as the landmark MRC trial3 demonstrated a reduced risk for stroke in hypertensive patients who used beta‐blockers. Indeed, the clinical usefulness of beta‐blockers led to its inventor, Sir James Black, being awarded with the Nobel Prize in Physiology or Medicine in 1988. However, modern hypertension trials have suggested that at similar attained blood pressure levels, beta‐blockers are actually less effective than angiotensin receptor blockers4 or calcium channel blockers,5 in terms of stroke prevention. The same picture has emerged from the most recent meta‐analysis on this topic,6 in which beta‐blocker use was associated with decreased risk for stroke compared with placebo, but beta‐blocker use was also associated with increased risk for stroke compared with renin angiotensin system inhibitors or calcium channel blockers. Several mechanisms have been proposed to explain this shortcoming of beta‐blockers: it has been suggested that beta‐blockers lower the central blood pressure to a lesser extent than the peripheral blood pressure,7 or that beta‐blockers lower the nocturnal blood pressure less effectively than other antihypertensive drugs.8 Nonetheless, since most patients with hypertension will ultimately require several drugs in order to lower their blood pressure below the treatment target, many patients with hypertension still use beta‐blockers today, and the possible influence of beta‐blockers on the long‐term outcome after stroke has remained a matter of debate.

In this issue of the journal, Eizenberg and coworkers present data from the National Acute Stroke Israeli (NASIS) registry. The aim of their analysis was to evaluate whether patients who used beta‐blockers prior to being admitted to hospital with a stroke had a poorer outcome than patients who did not use beta‐blockers prior to hospitalization for stroke. The authors found that among 1126 stroke patients, more than half (54.6%) used beta‐blockers, alone or as monotherapy, prior to the stroke admission. Expectedly, patients who reported that they had been using beta‐blockers prior to the stroke admission were more likely to have atrial fibrillation and previously diagnosed heart disease than were patients who did not use beta‐blockers prior to the stroke admission. Systolic blood pressure levels at admission did not differ between groups, but there were a larger proportion of patients with severe stroke among the patients who used a beta‐blocker prior to the admission. Despite this, patients who had used beta‐blockers were not at increased risk for death or poor functional outcome at the 3‐month follow‐up. The study represents an interesting approach in stroke research, in which not only traditional hard endpoints such as mortality and morbidity, but also long‐term functional outcomes, are reported as endpoints.

As pointed out by the authors, most patients in their study used antihypertensive drugs from several drug classes, a fact which makes it difficult to single out the effects attributable to one of the individual drugs. Although the authors report that atenolol is the most commonly used beta‐blocker in Israel, it would have been interesting to see more detailed data concerning which specific beta‐blockers were used by the patients in the present study, since there may be important differences between different beta‐blockers. This has been reported, for instance, regarding metabolic side effects such as the degree of impact on the glycemic control in patients with type 2 diabetes mellitus.9 Furthermore, some experimental data have suggested that novel beta‐blockers such as nebivolol, which also exhibits vasodilatory properties, lower the central blood pressure more effectively than atenolol.10 Interestingly, Eizenberg and co‐workers found that a larger proportion of patients in the beta‐blocker group presented with a severe stroke, a finding which may indeed, at least partially, be explained by an inferior central blood pressure lowering effect of beta‐blockers in general and of atenolol in particular.

The global incidence rates of stroke have remained fairly stable for 2 decades, but with more people surviving longer, we have also witnessed a remarkable increase regarding the total number of prevalent stroke survivors during the same period.11 Low‐ and middle‐income countries seem to be disproportionately affected by the increase in stroke burden, as measured by loss of disability‐adjusted life years. Therefore, it is appropriate to report not only stroke incidence, but also stroke severity and functional outcomes when hypertension treatment is evaluated in clinical research projects. The authors of the present study are to be congratulated for having contributed to this important and emerging field of hypertension research.

CONFLICT OF INTEREST

None.

Wijkman MO. Beta‐blockers, hypertension, and stroke outcomes. J Clin Hypertens. 2018;20:573–574. 10.1111/jch.13234