Effects of dihydropyridines and their combination with aspirin on blood pressure and circadian platelet activity in patients with essential hypertension.
The objective of this double-blind study was: 1) to evaluate and compare the effects of treatment with two dihydropyridines--isradipine and nitrendipine--on basal and circadian blood pressure and on 24-h platelet activity; and 2) to investigate the influence of low-dose aspirin on the antihypertensive, antiplatelet (antiaggregatory) efficacy of dihydropyridines. After a 4-week placebo period, 39 patients with mild-to-moderate essential hypertension were treated for 8 weeks, according to a double-blind design, with either isradipine at 2.5 mg/day (n = 20) or nitrendipine at 10 mg/day (n = 19). After this treatment period, aspirin at 100 mg/day was added to both treatments for a further 8 weeks. At week 0 (after placebo), week 8 (after dihydropyridines), and week 16 (after dihydropyridines + aspirin), blood pressure, plasma levels of beta-thromboglobulin (beta-TG) and platelet aggregation induced by serotonin (5-HT) were measured six times a day (at 5:30 AM, 9:00 AM, noon, 3:30 PM, 7:00 PM, and 11:30 PM). Both isradipine and nitrendipine significantly lowered basal and circadian blood pressure with no differences in antihypertensive efficacy between them. Low doses of aspirin did not interfere with the antihypertensive efficacy of either agent. All patients exhibited increased platelet activity after the placebo period in the form of increased beta-TG levels with circadian changes. The steepest increase in beta-TG was observed during the morning hours until midday. Treatment with the dihydropyridines inhibited platelet aggregability, shifting the beta-TG curve toward lower values. Addition of aspirin to nitrendipine produced a significant decrease and flattening of the beta-TG curve, whereas the combination of aspirin and isradipine was accompanied by a partial increase in plasma beta-TG levels. In conclusion, treatment with dihydropyridines alone or in combination with low-dose aspirin can prevent circadian increases in platelet activity in patients with essential hypertension.
Tison
P
P
Department of Clinical Pharmacology, Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic.
Ulicna
L
L
Jakubovska
Z
Z
Oravcova
J
J
Fetkovska
N
N
D000328:Adult; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D002940:Circadian Rhythm; D004095:Dihydropyridines / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D017275:Isradipine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009568:Nitrendipine / Q000627:therapeutic use
D004095:Dihydropyridines; D009568:Nitrendipine; D001241:Aspirin; D017275:Isradipine