We wished to assess the clinical safety and pharmacokinetics of ascending doses of a synthetic oligodeoxynucleotide (LR-3280) administered after coronary angioplasty. Antisense oligodeoxynucleotides designed to hybridize with target messenger ribonucleic acid (mRNA) in a complementary fashion to inhibit the expression of corresponding protein also have the ability to bind to extracellular growth factors. LR-3280 has been shown to reduce c-myc expression, inhibit growth and collagen biosynthesis in human vascular cells, and reduce neointimal formation in animal models of vascular injury. After successful percutaneous transluminal coronary angioplasty (PTCA), 78 patients were randomized to receive either standard care (n = 26) or standard care and escalating doses of LR-3280 (n = 52) (doses from 1 to 24 mg), administered into target vessel through a guiding catheter. Overall safety was evaluated by clinical adverse events, laboratory tests, and electrocardiograms. Patency was evaluated by quantitative coronary angiography. There were no clinically significant differences between treated and control patients. No adverse effects of LR-3280 on the patency of dilated coronary arteries were observed. Pharmacokinetic data revealed that peak plasma concentrations of LR-3280 occurred at 1 minute over the studied dose range and rapidly decreased after approximately1 hour, with little LR-3280 detected in the urine between 0-6 hours and 12-24 hours. The intracoronary administration of LR-3280 is well tolerated at doses up to 24 mg and produces no adverse effects in dilated coronary arteries. These results provide the basis for the evaluation of local delivery of this phosphorothioate oligodeoxynucleotide for the prevention of human vasculoproliferative disease.

Summary:In order to determine the natural evolution of different clinical types of "unstable angina", 167 patients were included in a prospective study. After angiography, 11 (6.5%) were excluded because they had no significant coronary lesions. The remaining 156 were sorted into different groups according to their clinical characteristics and were followed up for a period of 24 months at least. After that follow-up period, mortality and incidence of acute myocardial infarction (AMI) were as follows: angina of recent onset (Class III-IV NYHA): 8.5 % (3/35) and 34.2 % (12/35). Progressive angina: 7.4% (2/27) and 7.4% (2/27). Intermediate syndrome: 41.6% (10/24) and 37.5% (9/24).Prinzmetal's angina: 10% (1110) and 10% (1110). Post acute myocardial infarction angina: 35% (7/20) and 10% (2120). Acute persistent ischemia: 2.5% (1140) and 20% (8/40). Comparison of these figures pointed out significant differences (p < 0.001 for mortality and p < 0.03 for AMI incidence respectively).We conclude that it is clinically possible to identify different groups within the so-called unstable angina. Such a division not only allows for the creation of more homogeneous groups, but it contributes to a more rational

This investigation was undertaken to study the effects of beta-adrenergic blockade with timolol on infarct size and on the incidence of late ventricular tachycardia in patients with acute myocardial infarction of less than 6 hr of evolution. Patients were assigned randomly either to a placebo-treated group (98 patients) or to a timolol-treated group (102 patients). The patients were treated with 5.5 mg iv timolol (or matched placebo) as a bolus divided into four doses during the first 2 hr followed by 10 mg orally twice daily for 1 month. Cumulative total creatine kinase (CK) release, which reflects the amount of myocardial necrosis was 1677 +/- 132 IU/liter in the placebo group (n = 83) and 1274 +/- 73 IU/liter in the timolol group (n = 81, p less than .01), a 24% reduction. Cumulative release of CK-MB was 138 +/- 8 IU/liter in the placebo group and 106 +/- 8 IU/liter in the timolol group (p less than .01), a 23% reduction. Twenty-four hour Holter electrocardiograms were obtained on days 7, 14, 21, and 28 after the onset of the acute myocardial infarction in 80 patients in the placebo group and 82 patients in the timolol group. The incidence of ventricular tachycardia was lower in the timolol than in the placebo group (7 vs 16 patients, p = .05). We conclude that early administration of intravenous timolol followed by oral treatment in patients with acute myocardial infarction reduces infarct size as assessed by CK and CK-MB serum activity, and decreases the occurrence of late ventricular tachycardia.