Isradipine: has similar antianginal efficacy to nifedipine •••

Results from preclinical studies have suggested that isradipine [PN 200110; Sandoz] may have selective properties; namely coronary vasodilator activity and electrophysiological properties, that make it an attractive antianginal agent. A randomised double-blind crossover study was therefore conducted to compare the efficacy of isradipine and nifedipine in the treatment of 33 patients with chronic stable angina. After a 2-week placebo washout period, patients randomly received isradipine 2.5-7.5mg tid or nifedipine 10-30mg tid in titrated doses for 4 weeks. Patients were then crossed over to the alternate treatment for 4 weeks after a l-week placebo washout period. Thereafter, 29 patients received open label isradipine 7.5mg tid for a mean period of 14.6 months.

Both isradipine and nifedipine significantly reduced systolic and diastolic BP and increased heart rate at rest compared with baseline. There were no significant differences between the 2 treatment groups with respect to haemodynamic effects. Total exercise time significantly increased from 447 seconds at baseline to 581 seconds after isradipine compared with 578 seconds after nifedipine. Anginal frequency decreased from 20 episodes in 2 weeks at baseline to 12 and 9 per fortnight after isradipine and nifedipine, respectively. Nitroglycerin consumption decreased from 11 tablets in 2 weeks to 8 (NS) and 6 per fortnight (p < 0.05), respectively. There were no significant differences between the 2 treatment groups in these parameters. During fOllOW-Up, on withdrawal of isradipine therapy, 5/14 patients experienced a moderate increase in angina, 5 had moderately severe angina, 3 experienced very severe angina, 1 patient died suddenly and 1 experienced no change. Adverse effects included dizziness or vertigo (17 patients receiving nifedipine vs 7 receiving isradipine), fatigue or lethargy (11 vs 5), nervousness or shaking (10 vs 3), nausea or abdominal discomfort (11 vs 7), oedema (8 vs 5), tachycardia or palpitation (7 vs 1) and leg pains or cramps (6 vs 7). Two nifedipine recipients experienced side effects that necessitated withdrawal from treatment.

Thus, isradipine and nifedipine appear to have similar antianginal efficacy but ' __ . I.radlplne I. better tolerated and produce. fewer and Ie •• • evere adver.e reaction. than n"edlplne'. Pool PE. Seagren SC, Sale AF American Journal 01 MediCine 84 (Suppl 38) 62-66. Mar 1988 .,"

... and appears more potent than diltiazem A randomised double-blind study compared the

antihypertensive efficacy of isradipine with that of diltiazem in 95 patients with essential hypertension (sitting diastolic BP > 100mm Hg). Following a 3-week placebo run-in, patients received either isradipine 2.5mg bid (n = 47) titrated biweekly up to 10mg bid If required for BP control (sitting diastolic ~ 90mm Hg), or diltiazem 30mg tid (48) titrated up to 120mg lid.

4 INPHARMA' 6 Aug 1988

After 10 weeks, the BP of evaluable patients had decreased significantly by 26/18mm Hg with Isradipine and by 16/15mm Hg with diltiazem. The reduction In systolic BP was greater with Isradiplne than with diltiazem (p < 0.01). Treatment was discontinued because of lack of efficacy In 0 vs 5 isradipine and diltiazem recipients, respectively HR decreased significantly amongst dlltiazem but not isradipine recipients 80

vs 81"10 of isradipine- and diltiazem-treated patients achieved a decrease in sitting diastolic BP of ~ 10mm Hg after 10 weeks of active treatment. 70 vs 62"10 of isradipine and diltiazem recipients reported ~ 1 adverse reaction, Most frequently, adverse reactions in isradipine . recipients were oedema, swollen legs and flushing. These were generally mild but 4 patients discontinued treatment because of adverse reactions Diltiazem recipients reported angina, atrial fibrillation, collapse and dizziness, necessitating withdrawal in 2 patients.

The authors concluded that, at the doses used in this study, isradipine is generally well tolerated and a more potent antihypertensive agent than diltiazem.

Vermeulen A Wester A Willemse PFA. Lustermans FAT. Stegeman CJ, el al American Journal of MediCine 84 (Suppl 38) 42-45. Mar 1988 " ..

0156-2703/88/0806-0004/050100/0 CD ADIS Press