The Proliferation REduction with Vascular ENergy Trial (PREVENT)

PREVENT was the first prospective, randomized placebo-controlled study of intracoronary beta radiotherapy with (32)P. A total of 105 patients with de novo or restenotic lesions, treated by stenting or balloon angioplasty, received 0 (control), 16, 20, or 24 Gy to a depth of 1 mm beyond the lumen surface. Rates of restenosis (50% diameter stenosis or more) were significantly lower in radiotherapy patients at the target site (8% compared with 39%, P = 0.012) and at the target site plus adjacent segments (22% compared with 50%, P = 0.018). Stenosis adjacent to the target site and late thrombotic events reduced the overall clinical benefit of radiotherapy

Randomized placebo-controlled trial of amlodipine in vasospastic angina

AbstractObjectives. This study was designed to assess the efficacy and safety of amlodipine, a long-acting calcium channel blocker, in patients with vasospastic angina.Background. Previous studies have established the value of short-acting calcium channel blockers in the treatment of coronary spasm.Methods. Fifty-two patients with well documented vasospastic angina were entered into the present study. After a single-blind placebo run-in period, patients were randomized (in a double-blind protocol) to receive either amlodipine (10 mg) or placebo every morning for 4 weeks. Twenty-four patients received amlodipine and 28 received placebo. All patients were given diaries in which to record both the frequency, severity, duration and circumstances of anginal episodes and their intake of sublingual nitroglycerin tablets.Results. The rate of anginal episodes decreased significantly (p = 0.009) with amlodipine treatment compared with placebo and the intake of nitroglycerin tablets showed a similar trend. Peripheral edema was the only adverse event seen more frequently in amlodipine-treated patients. No patient was withdrawn from the double-blind phase of the study because of an adverse event. Patients who completed the double-blind phase as responders to amlodipine or as nonresponders to placebo were offered the option of receiving amlodipine in a long-term, open label extension phase. During the extension, the daily dose of amlodipine was adjusted to 5 or 15 mg if needed and the rate of both anginal episodes and nitroglycerin tablet consumption showed statistically significant decreases between baseline and final assessment.Conclusion. This study suggests that amlodipine given once daily is efficacious and safe in the treatment of vasospastic angina

Effects of transluminal coronary angioplasty on left ventricular systolic and diastolic function at rest and during exercise

The left ventricular global and regional systolic function, ventricular volumes, and peak diastolic filling rate (PDFR) were studied in 30 patients with coronary artery disease, before and 2 to 5 days after transluminal coronary angioplasty (PTCA), utilizing equilibrium radionuclide angiography at rest and during exercise. At rest, the global ejection fraction (EF) was unchanged before (60 ± 9%) and after PTCA (62 ± 10%). During exercise, global EF increased from 59 ± 11% pre PTCA to 67 ± 10 post PTCA (p \u3c 0.001). Twenty-two patients had abnormal EF response to exercise pre PTCA, versus seven post PTCA (p \u3c 0.001). Improvements in exercise regional EF paralleled the changes in global EF. End-systolic volume was unchanged at rest but decreased significantly with exercise post PTCA (60 ± 36 ml pre vs 49 ± 32 ml post PTCA, p \u3c 0.01). At rest, the PDFR was unchanged post PTCA (2.4 ± 0.9 end-diastolic volume (EDV)/sec pre vs 2.5 ± 0.8 EDV/sec post). During exercise, PDFR increased from 2.1 ± 0.7 EDV/sec pre PTCA to 2.5 ± 0.7 EDV/sec post PTCA (p \u3c 0.02). In conclusion, in patients with coronary artery disease, successful PTCA improves global and regional systolic function during exercise. Diastolic function is improved during exercise, a fact not previously demonstrated. © 1985

Activation of the complement system by recombinant tissue plasminogen activator

Recent trials have shown that recombinant tissue plasminogen activator (rt-PA) is an effective thrombolytic agent in patients with acute myocardial infarction. Because rt-PA converts plasminogen to plasmin, which is known to activate complement in vitro, we tested the hypothesis that rt-PA can induce in vivo activation of complement. Studies were performed in 12 patients with acute myocardial infarction. Six control patients had patent coronary arteries and did not receive rt-PA; these patients had normal values of the components of the complement system C4a (409 ± 111 ng/ml) and C5a (8.8 ± 1.8 ng/ml) with a slight elevation of C3a (204 ± 6.6 ng/ml) in samples collected before coronary arteriography (253 ± 25 minutes after onset of pain). After coronary arteriography, there was a slight decrease in the values of C4a (224 ± 37 ng/ml), C5a (7.3 ± 1.3 ng/ml) and C3a (164 ± 35 ng/ml).The remaining six patients had complete coronary occlusion and received rt-PA (80 to 150 mg intravenously). In this treated group, before coronary arteriography the values of C4a (406 ± 51.6 ng/ml) and C5a (8.1 ± 1.9 ng/ml) were normal, and those of C3a were slightly elevated (250 ± 76 ng/ml). All complement values obtained before rt-PA were similar to those in the untreated group. However, after administration of rt-PA (but before any angiographically detectable reperfusion), there was a striking ihcrease in C4a (2,265 ± 480 ng/ml; p < 0.01), C3a (600 ± 89 ng/ml; p < 0.05) and C5a (30.0 ± 4.5 ng/ml; p < 0.05).Thus, rt-PA causes an immediate, marked activation of complement in patients with acute myocardial infarction. Measurement of plasma anaphylatoxin levels may be a useful means of assessing the activity of rt-PA, and the degree of complement activation might reflect the extent of thrombolysis. The significance of rt-PA-induced complement activation with respect to the extent of ischemic injury remains to be determined, but it is conceivable that the anaphylatoxin release might limit the otherwise beneficial effects of rt-PA