[Study of the general and topical tolerance of Trinipatch and its clinical efficacy in the therapy of chronic stable angina in 5078 coronary disease patients]. / Etude de la tolérance générale et locale de Trinipatch, et de son efficacité clinique dans le traitement de l'angor chronique stable chez 5078 patients coronariens.

Nitrates still play an important role in the treatment of coronary heart disease after more than hundred years of use in this indication. Following oral administration, they undergo intense gastric hydrolysis, and are largery destroyed by the first-pass effect. The development of an attenuation phenomenon of the therapeutic effect has been frequently reported during continuous treatments at fixed doses. Percutaneous administration of nitroglycerin due to the development of transdermal devices palliates these various obstacles. Trinipatch is a small, transparent, matricial, monolayer patch with an absorption promoter, marketed in two dose-strengths (5 mg/24 h and 10 mg/24 h) by Laboratoires Synthelabo. Its systemic and local safety and clinical efficacy were studied by 383 private cardiologists and 2,294 general practitioners in 5,079 coronary patients, between the ages of 19 and 91 years, in two open, multicentre trials lasting 3 months. The systemic safety, assessed by adverse event reporting, was good. 2.7% of patients experienced adverse events, but only 0.3% of patients presented a serious adverse event. The effects most frequently encountered were vasodilator effects. A very good stability of cardiovascular parameters was observed, with no reflex tachycardia. The local safety, evaluated by the Draize scale, was also satisfactory; after 1 month and 3 months of treatment, 6.6% and 5.7% of patients presented erythema, usually isolated and moderate. The clinical efficacy was evaluated by subjective criteria in the 740 patients included by cardiologists. A significant reduction of the number of angina attacks and the numbers of doses of nitroglycerin was observed. The percentage of pain-free patients increased from 18.2% at the start of the study to 76% at the end of the trial. These two trials confirmed the good systemic and local safety and clinical efficacy of Trinipatch.

[Comparison of the antispastic effect of Bi-Tildiem 120 mg and Tildiem 60mg]. / Comparaison de l'effet anti-spastique du Bi-Tildiem 120 mg et du Tildiem 60 mg.

Diltiazem (Tildiem 60 mg) is a calcium channel blocker with demonstrated efficacy and safety in the treatment of stable angina pectoris and spastic angina. The sustained release formulation of diltiazem, allowing two daily doses (Bi-Tildiem 120 mg), is already marketed in France for the treatment of stable angina. It was therefore interesting to evaluate the efficacy and safety of this form, administered in two daily doses, in coronary spasm, versus the classical formulation, Tildiem 60 mg, given at the same daily dose, i.e. 240 mg, in three divided doses per day. We conducted a single-centre, randomized, double-blind, cross-over clinical study in twelve patients, eleven men and one woman, between the ages of 42 and 70 years, presenting with angina and normal coronary arteries and spasm documented by a positive methylergonovine (Methergin) test. They were divided into two groups of six patients receiving either Tildiem followed by Bi-Tildiem, or Bi-Tildiem followed by Tildiem. The characteristics of the two groups were comparable at the time of the selection visit. The methylergonovine test, used to assess the efficacy of the two treatments, was improved by Tildiem and Bi-Tildiem compared to the placebo test (p = 0.001 and 0.002), without any significant difference between Tildiem and Bi-Tildiem: an improvement was obtained in 11/12 and 10/12 patients, respectively. No deterioration of the test was observed with Tildiem or Bi-Tildiem compared to placebo. The coronary symptoms and blood diltiazem levels were similar with Tildiem and Bi-Tildiem. The results confirmed the safety of Bi-Tildiem. A single adverse effect was attributed to treatment: an episode of mild insomnia. No serious adverse effect were observed and none of the patients discontinued the study. The efficacy and safety of Tildiem and Bi-Tildiem are comparable in the treatment of spastic angina.

[Antihypertensive efficacy and tolerability of diltiazem and enalapril, alone or in combination. DESG. Diltiazem Enalapril Study Group]. / Efficacité antihypertensive et tolérance du diltiazem et de l'énalapril, en monothérapie et lors de leur association. DESG. Diltiazem Enalapril Study Group.

OBJECTIVES: Since conversion enzyme inhibitors and calcium inhibitors may have synergic actions, we evaluated the antihypertensive effect and tolerance of prolonged-release diltiazem (300 mg/d) and enalapril (20 mg/d). METHODS: A double blind study included 176 patients with mild to moderate hypertension. Diltiazem was given to 89 (44 males, 45 females, mean age 49.91 +/- 10.50 years, mean resting diastolic arterial pressure 103 +/- 5 mmHg) and 87 (49 males, 38 females, mean age 51.37 +/- 12.13 years, mean resting diastolic arterial pressure 103 +/- 5 mmHg) received enalapril. Single drug therapy was given for 6 weeks and then continued for another 8 weeks in responders. At the end of the first 6-week period non-responders were given a combination regimen (diltiazem 300 mg and enalapril 20 mg). RESULTS: After 6 weeks of single drug therapy, 48 patients in the diltiazem group (61.5%) and 53 in the enalapril group (65.4%) had normal blood pressures which remained normal at the end of the trial 8 weeks later in 36 (76%) and 42 (82%) respectively. After 8 weeks of combined regimen 15 of the 24 non-responders (68%) to single drug diltiazem therapy had normal blood pressures as did 18 of the 23 non-responders (78%) to enalapril alone. Tolerance evaluated clinically, biologically and electrocardiographically was comparable to reports in the literature. CONCLUSION: Delayed prolonged-release diltiazem 300 mg and enalapril 20 mg thus had equivalent antihypertensive effects and were equally well tolerated. Combination therapy increased effectiveness without inducing any additional side effects.