Cardiovascular Drugs and Therapy 4: 413-418, 1990 9 Kluwer Academic Publishers, Boston. Printed in U.S.A.
A Multicenter Comparison of Isradipine and Prazosin for Treatment of Essential Hypertension S t e p h e n L. Swartz,~ L e o n a r d M. G o n a s u n , 2 R.G. M c A l l i s t e r Jr, 3 Udho T h a d a n i 4 1West Roxbury/Brockton VA Medical Center, MA; 2Sandoz Research Institute, East Hanover, N J; J VA Medical Center, Lexington, K Y; aOklahoma University Health Sciences Center, Oklahoma City, OK, USA
Summary.
Isradipine is a dihydropyridine calcium-entry blocking agent with pronounced vasodilator activity and no significant cardiac effects at clinical doses, a desirable profile for an a n t i h y p e r t e n s i v e drug. Prazosin, a post-junctional alpha-adrenoceptor b l o c k i n g agent, m a y produce a similar h e m o d y n a m i c pattern. T h e r e f o r e , we compared the effects of isradipine (2.5-10 mg bid) with those of p r a z o s i n (2-8 m g bid) in 83 patients with established essential hypertension, using a randomized, double-blind, parallel-group design. Patients received a placebo for 3 - 5 w e e k s , then either isradipine or prazosin over a 6-week titration period, followed by a 4-week plateau phase. During the plateau period, isradipine t h e r a p y lowered sitting blood pressure more effectively than did the administration of p r a z o s i n : Mean systolic B P fell 16.7 versus 8.1 m m H g (p < 0.001) and mean diastolic BP was reduced 15.6 versus 12.6 m m H g (p < 0.01). In the dosing range used (while also noting that prazosin is o c c a s i o n a l l y titrated up to doses of 30 mg qd), 83r~ of isradipine-treated patients had at least a 10 m m H g reduction in diastolic BP, compared with 64c~ of prazosin-treated patients (p - 0.05, F E T ) . T a c h y p h y l a x i s did not occur with either drug. The rate of occurrence of side effects w a s similar in both treatment groups; the most common adverse event seen with isradipine was headache (20c/~) and with p r a z o s i n , d i z z i n e s s (19c5). K e y W o r d s . c a l c i u m c h a n n e l blockers, isradipine
Essential hypertension is usually associated with increased peripheral vascular resistance. Since calcium influx is a major determinant of intraeellular calcium levels, which in turn regulate vascular smooth muscle contraction, calcium-channel blockers have been used successfully in treating patients with hypertension. The chemical heterogeneity of the calcium-blocking drugs suggests that these agents may preferentially inhibit the calcium channel at different sites (i.e., cardiac muscle, vascular smooth nmsele, sinoatrial and atrioventrieular node cells). A new dihydropyridine calcium antagonist, isradipine, appears to be particularly attractive in the treatment of hypertension because of its high selectivity for vascular smooth muscle compared with cardiac muscle [1].
In this report we described the results of a randomized, double-blind multicenter study desigqled to compare the safety and efficacy of isradipine with prazosin, an alphat blocker, in patients with mild to moderate hypertension. Prazosin was chosen as the comparison drug because of its similar hemodynamie profile as an agent producing peripheral vasodilation [2].
Methods Patient selection This was a multicenter trial in which all patients who were entered had stable essential hypertension with drug-free sitting diastolic blood pressure (BP) levels of >95 m m H g and
A Multicenter Comparison of Isradipine and Prazosin for Treatment of Essential Hypertension S t e p h e n L. Swartz,~ L e o n a r d M. G o n a s u n , 2 R.G. M c A l l i s t e r Jr, 3 Udho T h a d a n i 4 1West Roxbury/Brockton VA Medical Center, MA; 2Sandoz Research Institute, East Hanover, N J; J VA Medical Center, Lexington, K Y; aOklahoma University Health Sciences Center, Oklahoma City, OK, USA
Summary.
Isradipine is a dihydropyridine calcium-entry blocking agent with pronounced vasodilator activity and no significant cardiac effects at clinical doses, a desirable profile for an a n t i h y p e r t e n s i v e drug. Prazosin, a post-junctional alpha-adrenoceptor b l o c k i n g agent, m a y produce a similar h e m o d y n a m i c pattern. T h e r e f o r e , we compared the effects of isradipine (2.5-10 mg bid) with those of p r a z o s i n (2-8 m g bid) in 83 patients with established essential hypertension, using a randomized, double-blind, parallel-group design. Patients received a placebo for 3 - 5 w e e k s , then either isradipine or prazosin over a 6-week titration period, followed by a 4-week plateau phase. During the plateau period, isradipine t h e r a p y lowered sitting blood pressure more effectively than did the administration of p r a z o s i n : Mean systolic B P fell 16.7 versus 8.1 m m H g (p < 0.001) and mean diastolic BP was reduced 15.6 versus 12.6 m m H g (p < 0.01). In the dosing range used (while also noting that prazosin is o c c a s i o n a l l y titrated up to doses of 30 mg qd), 83r~ of isradipine-treated patients had at least a 10 m m H g reduction in diastolic BP, compared with 64c~ of prazosin-treated patients (p - 0.05, F E T ) . T a c h y p h y l a x i s did not occur with either drug. The rate of occurrence of side effects w a s similar in both treatment groups; the most common adverse event seen with isradipine was headache (20c/~) and with p r a z o s i n , d i z z i n e s s (19c5). K e y W o r d s . c a l c i u m c h a n n e l blockers, isradipine
Essential hypertension is usually associated with increased peripheral vascular resistance. Since calcium influx is a major determinant of intraeellular calcium levels, which in turn regulate vascular smooth muscle contraction, calcium-channel blockers have been used successfully in treating patients with hypertension. The chemical heterogeneity of the calcium-blocking drugs suggests that these agents may preferentially inhibit the calcium channel at different sites (i.e., cardiac muscle, vascular smooth nmsele, sinoatrial and atrioventrieular node cells). A new dihydropyridine calcium antagonist, isradipine, appears to be particularly attractive in the treatment of hypertension because of its high selectivity for vascular smooth muscle compared with cardiac muscle [1].
In this report we described the results of a randomized, double-blind multicenter study desigqled to compare the safety and efficacy of isradipine with prazosin, an alphat blocker, in patients with mild to moderate hypertension. Prazosin was chosen as the comparison drug because of its similar hemodynamie profile as an agent producing peripheral vasodilation [2].
Methods Patient selection This was a multicenter trial in which all patients who were entered had stable essential hypertension with drug-free sitting diastolic blood pressure (BP) levels of >95 m m H g and
