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Objectives. The Asymptomatic Cardiac Ischemia Pilot (ACIP) study was initiated to determine the feasibility of a large trial in evaluating the effects of treatment of ischemia on outcome (mortality and myocardial infarction). The study was designed to examine the effects of medical treatment to control angina compared with treatment strategies guided by ambulatory electrocardiographic (ECG) ischemia or coronary anatomy. Background. Treatments to suppress ischemia (asymptomatic and symptomatic) have not been evaluated in a large prospective, randomized trial. Before undertaking such a trial, issues about recruitment and treatment strategies must be addressed. Methods. The 618 enrolled patients had coronary artery disease suitable for revascularization, ischemia on stress test and asymptomatic ischemia on ambulatory ECG. Patients were assigned randomly to one of three treatment strategies: 1) angina-guided medical strategy with titration of anti-ischemic medication to relieve angina (angina-guided strategy); 2) angina-guided plus ambulatory ECG ischemia-guided medical strategy with titration of anti-ischemic medication to eliminate both angina and ambulatory ECG ischemia (ischemia-guided strategy); and 3) revascularization by angioplasty or bypass surgery (revascularization strategy). Results. Ambulatory ECG ischemia was no longer present at the week 12 visit in 39% of patients assigned to the angina-guided strategy, 41% of patients assigned to the ischemia-guided strategy and 55% of patients assigned to the revascularization strategy. All strategies reduced the median number of episodes and total duration of ST segment depression during follow-up ambulatory ECG monitoring. Revascularization was the most effective strategy. Treadmill test results were concordant with those of ambulatory ECG monitoring, lor most patients in the two medical strategies, angina was controlled with low to moderate doses of anti-ischemic medication, and the majority of patients (65%) in the revascularization strategy did not require medication for angina. Conclusions. This pilot study demonstrated that cardiac ischemia can be suppressed in 40% to 55% of patients with either low or moderate doses of medication or revascularization and that a large trial is feasible.

Objectives. We examined the antianginal and anti-ischemic effects of oral zatebradine, a direct sinus node inhibitor that has no blood pressure-lowering or negative inotropic effects in patients with chronic stable angina pectoris taking extended-release nifedipine.Background. Heart rate reduction is considered an important pharmacologic mechanism for providing anginal pain relief and anti-ischemic action in patients with chronic stable angina, suggesting a benefit for sinus node-inhibiting drugs.Methods. In a single-blind placebo run-in, randomized double-blind, placebo-controlled, multicenter study, patients already receiving extended-release nifedipine (30 to 90 mg once a day) were randomized to receive zatebradine (5 mg twice a day [n = 64]) or placebo (n = 60). All subjects had reproducible treadmill exercise-induced angina at baseline, and after randomization they performed a serial exercise test 3 h after each dose for 4 weeks.Results. Zatebradine reduced rest heart rate both at 4 weeks ([mean ± SEM] 12.9 ± 1.23 vs. 2.3 ± 1.6 [placebo] beats/min, p < 0.0001) and at the end of comparable stages of Bruce exercise (16.7 ± 1.2 vs. 3.4 ± 1.2 [placebo] beats/min, p < 0.0001). Despite the significant effects on heart rate at rest and exercise, there were no additional benefits of zatebradine from placebo baseline in measurements of total exercise duration, time to 1-mm ST segment depression or time to onset of angina. Subjects taking zatebradine also had more visual disturbances as adverse reactions.Conclusions. Zatebradine seems to provide no additional anti-anginal benefit to patients already receiving nifedipine, and it raises questions regarding the benefit of heart rate reduction alone as an antianginal approach to patients with chronic stable angina.

The Multi-Hospital Eastern Atlantic Restenosis Trial group obtained follow-up angiography in 510 patients with 598 successfully dilated coronary lesions who were enrolled in a controlled trial of the effects of a single dose of 1 g of methylprednisolone on restenosis after coronary angioplasty. The overall restenosis rate was 39.6%. The strongest univariate relations to the restenosis rate were found for lesion location (saphenous vein graft, 68%; left anterior descending artery, 45%; left circumflex artery and right coronary artery, 32%; p = 0.002); lesion length (≤4.6 mm, 33%; >4.6 mm, 45%; p = 0.001); percent stenosis before angioplasty (≤73%, 25%; >73%, 43%; p = 0.005), percent stenosis after angioplasty (≤21%, 33%; >21%, 46%; p = 0.017) and arterial diameter (