A Double‐Blind Comparison of Metoprolol CR/ZOK 50 mg and Atenolol 50 mg Once Daily for Uncomplicated Hypertension

In a double‐blind study with parallel groups, the clinical bioequivalence of the antihypertensive effect of metoprolol CR/ZOK (controlled release formulation) 50 mg and atenolol 50 mg in ordinary tablets given once daily for uncomplicated hypertension was investigated. Clinical bioequivalence was defined as difference in blood pressure reduction less than 8 mmHg. The study involved 195 patients, 98 on metoprolol CR/ZOK and 97 on atenolol. All patients were taken off antihypertensive therapy during a 2‐week placebo run‐in period. Thereafter the patients were randomly allocated to metoprolol CR/ZOK 50 mg or atenolol 50 mg for 4 weeks. In patients with a diastolic blood pressure remaining above 90 mmHg, the dose was increased to 100 mg daily of the respective drug. After 4 weeks treatment with 50 mg of the two therapies, blood pressure and heart rate was significantly reduced in both treatment groups. At this dose, clinical bioequivalence was found regarding both blood pressure and heart rate reductions. After 8 weeks of therapy (100 mg doses given to 31 in the metoprolol group and 43 in the atenolol group), clinical bioequivalence according to stated definition was found for blood pressures and heart rate reductions, although the reductions of systolic and diastolic blood pressures at rest as well as diastolic blood pressure during exercise were significantly greater in the metoprolol group. In an evaluation of the responder rate after the 8 weeks of treatment, 89% of the patients in the metoprolol CR/ZOK group and 74% in the atenolol group (P < .05) had a diastolic blood pressure reduction to 90 mmHg or less. In conclusion, metoprolol CR/ZOK 50 mg and atenolol 50 mg in a dosage once daily was shown to be clinically bioequivalent. After doubling the dose in those patients who did not respond with a reduction of diastolic blood pressure to 90 mmHg or less on the 50 mg doses, blood pressure reduction was greater in the metoprolol group, although within the limits of defined clinical bioequivalence. Antihypertensive response rate was higher with metoprolol CR/ZOK than atenolol treatment.