β blockers in hypertension and cardiovascular disease

Abstract

Are β blockers less protective in hypertensive patients?Results of ASCOT-BPLA (the Anglo-Scandinavian cardiac outcomes trial—blood pressure lowering arm) suggest that atenolol may be only marginally inferior to amlodipine.1 Its main lesson is that blood pressure must be tightly controlled, and patients taking β blockers (and diuretics) must be monitored so that cardiovascular risk factors are not adversely altered.ASCOT-BPLA randomised 19 257 high risk people with hypertension to amlodipine (adding perindopril) or atenolol (adding bendroflumethiazide). After 5.5 years, the primary end point, non-fatal myocardial infarction and cardiovascular death, was similar in the two groups (relative risk 0.90, 95% confidence interval 0.79 to 1.02; P=0.11). Several measures were lower with amlodipine: coronary end point (8% v 9%; 0.87, 0.79 to 0.96; P=0.007), stroke (3% v 4%; 0.77, 0.66 to 0.89; P=0.0003) and mortality (8% v 9%; 0.89, 0.81 to 0.99; P=0.02). Patients taking amlodipine had significantly lower blood pressure, as well as higher HDL (high density lipoprotein) cholesterol, and lower body mass index and concentrations of triglyceride, creatinine, and glucose. Multivariate adjustment for all these differences abolishes the difference in the cardiovascular event rate of the two groups.4Thus, rather than showing the inferiority of atenolol, ASCOT-BPLA shows the importance of rigorously controlling blood pressure and other risk factors to reduce clinical cardiovascular disease. Although statistically significant, the 1% reduction in coronary event, stroke, and total mortality is not inspiring; the number needed to treat (NNT) for a year to prevent one cardiovascular event is 220, and to prevent one death is 650.w1 With diuretic antihypertensive therapy to prevent heart failure NNT=48, and for the reduction in mortality with β blockers after myocardial infarction NNT=25-80.w2 w3Meta-analysesTwo large meta-analyses also question the value of β blockers in cardiovascular protection of hypertensive patients.2 3 These show that atenolol is inferior in reducing stroke and mortality, but non-atenolol β blockers may be equivalent to other antihypertensive drugs. Carlberg reviewed the effects of atenolol on cardiovascular outcomes in hypertensive patients aged 52-70 who were followed up for 4.6 years. In four studies comparing atenolol with placebo (6825 patients) there was no difference in total mortality (relative risk 1.01, 0.89 to 1.15), cardiovascular mortality (0.99, 0.83 to 1.18), myocardial infarction (0.99, 0.83 to 1.19), and stroke (0.85, 0.72 to 1.01). In five studies comparing atenolol with other antihypertensive agents (17 671 patients), despite equivalent reduction in blood pressure, atenolol treatment was associated with higher total mortality (1.13, 1.02 to 1.25), cardiovascular mortality (1.16, 1.00 to 1.34), and stroke (1.30, 1.12 to 1.50). Lindholm's meta-analysis was more comprehensive, reviewing 13 trials (105 951 patients) comparing β blockers with other antihypertensives and seven trials (27 433 patients) comparing β blockers with placebo. Overall, β blockers were inferior to other antihypertensives in preventing stroke (1.16, 1.04 to 1.30), but the results were different for atenolol and non-atenolol β blockers (table 1)⇓. Compared with other antihypertensive drugs, atenonol was associated with higher risk of stroke (1.26, 1.15 to 1.38) and total mortality (1.08, 1.02 to 1.14). Non-atenolol β blockers were not inferior to other antihypertensives in preventing stroke (1.20, 0.30 to 4.71), myocardial infarction (0.86, 0.67 to 1.11), and total mortality (0.89, 0.70 to 1.12). View this table: In this window In a new window Table 1 Incidence of stroke and myocardial infarction and total mortality in hypertensive patientsAtenololThe different pharmacokinetic properties of atenolol and non-atenolol β blockers may account for their different cardiovascular protective effects in older hypertensive patients. Good data now show that atenolol is inferior, but the data are not conclusive enough to require using a substitute in all patients. Before starting or continuing with atenolol, though, a cautious clinician would ask whether another β blocker could be used. Atenolol is hydrophilic, has minimal hepatic metabolism, and is excreted in the urine; its long half life allows once daily dosage.w4 It is inexpensive and has little interaction with drugs that are metabolised in the liver; these features account for its popularity. However, its pharmacokinetic profile can be disadvantageous in older patients with renal impairment, which slows clearance of atenolol.w5