Atenolol: Use with caution

The treatment of elevated blood pressure reduces the incidence of stroke and leads to a significant reduction in mortality and morbidity among patients with cardiovascular problems. Although the beta-blockers are among the most widely prescribed medications for blood pressure control, not all hypertensive patients show benefit from taking these drugs.

Studies have reported that the selective beta 1-blocker atenolol -at doses of 50 mg to 100 mg-produced higher cardiovascular mortality and stroke risk rates compared with other antihypertensives, such as losartan (Cozaar, Merck), metoprolol, and propranolol.

Losartan, while producing a similar reduction in blood pressure, was found to prevent more cardiovascular morbidity than atenolol. Furthermore, losartan-at doses of 50 mg to 100 mg-was found to be more effective than atenolol (at doses of 50 mg to 100 mg) in hypertensive patients with left ventricular hypertrophy (LVH), and it showed a higher reduction of new onset of atrial fibrillation as well as stroke risk.

Part of hypertension treatment involves an improvement of the impaired process of endothelium-dependent vasodilation. Nitric oxide (NO) is a relaxing factor that plays an important role in endothelium-dependent vasodilation. Patients with essential hypertension have reduced amounts of NO available for the endothelium-dependent vasodilation process. Thus, it is essential for antihypertensive agents to repair or improve this process.

Many antihypertensive drugs correct endothelial dysfunction of small arteries seen in hypertension, but this finding has not been seen for atenolol. Experimental studies done with atenolol have failed to show any improvements in endothelium-dependent vasodilation in response to either acetylcholine or bradykinin. On the other hand, a dihydropyridine calcium-channel blocker can reverse the damaged endothelium-dependent vasodilation mechanism.

The beneficial effect of beta-blockers after myocardial infarction has been well documented. However, atenolol fails that challenge as well. Studies involving beta-blockers have shown that after myocardial infarction, the administration of metoprolol and propranolol significantly prevented death in the long term, whereas atenolol showed no such preventive effect. Other studies compared treatments of atenolol versus placebo and led to results indicating no differences in all-cause mortality of MI.

An analysis of the chemical nature of these medical compounds can theoretically support these views. Atenolol is a hydrophilic compound that has very limited nervous system permeability, whereas propranolol and metoprolol are lipophilic compounds and penetrate the nervous system. As such, propranolol and metoprolol are more successful at reducing mortality rates. Beta-blockers of lipophilic nature were shown to increase vagal tone and offer cardioprotective characteristics-and, by increasing the vagal tone, prevent ventricular fibrillation from occurring-and thus ultimately decreasing the chances of acute myocardial ischemia.

Finally, the scientists conducting INVEST (International Verapamil-Trandolopril Study) suggest the usage of verapamil SR over atenolol in patients with hypertension who are at risk of depression. The study found that, after one year, patients taking verapamil SR improved their depressive symptoms compared with patients who were administered atenolol.

In conclusion, it is very important for pharmacists to use existing studies in the analysis of atenolol orders prescribed by physicians for patients with hypertension. This is especially the case for the population having coexisting medical complications such as depression or a post-MI condition.

References are available on request.

THE AUTHOR, who has experience working in the clinical and pharmaceutical fields, is a hospital-based pharmacy manager.