Treatment of hypertension associated with stable angina pectoris: favourable interaction between new metoprolol formulation (OROS) and nifedipine.
This was a double-blind, within-patient, crossover study to evaluate the effects of a new formulation of metoprolol on blood pressure (BP) and myocardial ischemia. Twenty outpatients with mild to moderate essential arterial hypertension, chronic stable angina pectoris and positive exercise test, after a 2-week baseline placebo period, were randomized to receive long-acting metoprolol (OROS) 14/190 mg o.d., nifedipine SR 20 mg b.i.d. or their combination in a sequence of a 3 x 3 Latin square design. Two patients withdrew from the study (1 for adverse event during metoprolol and 1 for rise of BP during nifedipine). Nifedipine, metoprolol and their combination significantly reduced the weekly number of angina attacks and nitroglycerin consumption with respect to baseline. The total number of ischemic events (at 24-hour ECG monitoring) significantly decreased after each treatment with respect to baseline. Twenty-four hours mean systolic and diastolic BP were reduced by both nifedipine alone and metoprolol alone; the combination of the two drugs led to a further decrease in both systolic and diastolic BP. The duration of silent ischemic episodes was significantly reduced by nifedipine and combination but not by metoprolol. On the other hand 24 hours symptomatic attacks/patient were significantly reduced by beta-blocker and combination, but not by nifedipine. Metoprolol alone and administered with nifedipine caused a decrease, with respect to placebo baseline, in 24-hour mean heart rate (HR) and reduced the increase of HR and systolic BP at the onset of ST depression during symptomatic ischemic episodes. The effort time and time to ST = -1 mm at treadmill were significantly increased by treatment with nifedipine alone, with metoprolol alone and with their combination, but the combination was more effective than the individual therapies. ST depression at peak exercise was significantly reduced by each treatment. The slopes of correlations between the ST-segment variation and systolic BP, HR and rate-pressure product during exercise, significantly decreased after all treatments with respect to placebo baseline, more with the combination therapy than with nifedipine alone and metoprolol alone. In conclusion, based on our results the favourable interaction of metoprolol OROS and nifedipine given concomitantly, is likely to be due to a better control, respect to each individual therapy, of the pathogenetic mechanism of myocardia ischemia: BP and HR increases during exercise and during symptomatic ischemic episodes are controlled by the beta-blocker and coronary vasoconstriction during silent ischemia is prevented by the calcium-antagonist.
Di Somma
S
S
Cattedra di Medicina d'Urgenza e Pronto Soccorso, Facoltà di Medicina e Chirurgia, Università degli Studi Federico II, Napoli.
de Divitiis
M
M
Bertocchi
F
F
Carotenuto
A
A
Cudemo
G
G
Petitto
M
M
Napodano
M
M
de Divitiis
O
O
D000787:Angina Pectoris / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D018660:Blood Pressure Monitoring, Ambulatory; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002908:Chronic Disease; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D015716:Electrocardiography, Ambulatory; D005080:Exercise Test; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use*; D005996:Nitroglycerin / Q000627:therapeutic use; D012044:Regression Analysis; D014665:Vasodilator Agents / Q000627:therapeutic use
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D005996:Nitroglycerin; D008790:Metoprolol; D009543:Nifedipine