Effects of metoprolol succinate extended release vs. amlodipine besylate on the blood pressure, heart rate, and the rate-pressure product in patients with hypertension

Ambulatory monitoring of the blood pressure (BP) and heart rate allows for the assessment of the 24-hour rate-pressure product (RPP), a close correlate of myocardial oxygen demand, both in the untreated state and while on antihypertensive therapy. To evaluate the clinical effects of metoprolol succinate extended release (ER) tablets (100 mg titrated to 200 mg for clinic BP >140/90 mm Hg) vs. amlodipine (5 mg titrated to 10 mg for clinic BP >140/90 mm Hg) on the 24-hour and early morning hemodynamic parameters, we performed a double-blind crossover trial that included 8 weeks of active treatment, 4 weeks of placebo washout, and 8 weeks of active crossover treatment using 24-hour ambulatory blood pressure (ABP) measurements. Patients were included if they were untreated, had hypertension based on both clinic (140 to 179/90 to 109 mm Hg) and ABP recordings (>135/85 mm Hg while awake), and were 18 to 65 years of age. Patients enrolled in the trial (n = 35) had a mean age of 55 ± 7 years, 24-hour mean BP of 148/91 ± 11/7 mm Hg, heart rate (HR) of 76 ± 10 beats/minute, and a RPP of 11,230 ± 1717 mm Hg·beats·minute). In the early morning period (6 am to 10 am), baseline BP was 155/98 ± 11/7 mm Hg and the RPP was 12,084 ± 1752 mm Hg·beats·minute. The 24-hour diastolic blood pressure (DBP), HR, and RPP were lowered to a greater extent by metoprolol succinate compared with amlodipine. Additionally, changes from baseline in early morning DBP, HF, and RPP were lowered to a significantly greater extent by metoprolol (mean dose, 124 ± 44 mg daily) compared with amlodipine (mean dose, 7.2 ± 2.5 mg daily) (P = .02 for DBP and P < .0001 for HR and the RPP). The incident rates of adverse events were low and similar for the two treatment groups. These data demonstrate that metoprolol succinate ER induced greater reductions in early morning BP, HR, and FPP than amlodipine in middle-aged patients with Stages 1 and 2 hypertension. These findings have clinical implications for patients with hypertension and coronary heart disease.