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Epidural spinal electrical stimulation for severe angina: a study of its effects on symptoms, exercise tolerance and degree of ischaemia.

The effectiveness of epidural spinal electrical stimulation has been studied in 14 patients with severe intractable angina unresponsive to standard therapies including bypass grafting. After implantation of the neurostimulator units the patients were assessed by a symptom questionnaire, treadmill exercise testing and right atrial pacing. There was a significant improvement of symptoms and GTN consumption fell markedly. With the neurostimulator on, exercise duration increased from a mean (CI) of 414 (153) to 478 (149) s, and total ST segment depression was less both at maximum exercise (7.1 (4.5) vs 5.6 (4.2) mm) and at 90% of the maximum control heart rate (3.5 (3.7) vs 2.6 (4.3) mm), with similar rate-pressure product at maximum exercise. With right atrial pacing the maximum heart rate reached before onset of angina was increased (143 (14) to 150 (7) b.min-1) and total ST segment depression was less at all heart rates. Benefit has persisted in some patients for over 2 years without any apparent adverse sequelae. Epidural spinal electrical stimulation is, therefore, an alternative therapy for some patients with intractable angina which has not responded to standard therapies.

Angina Pectoris↗

ECG changes and exercise tolerance in patients after myocardial infarction.

The aim of the study was to analyse the type of ECG changes in patients after acute myocardial infarction and to compare them with changes in their physical performance. The authors examined 218 patients with acute myocardial infarction after discharge from hospital. Resting ECG and step-wise graded exercise ECG test on a bicycle ergometer was carried out. The technique of examination was in accordance with WHO recommendations. Statistical evaluation was performed by the Wilcoxon-Mann-Whitney's U-test. The workload in patients showing ECG changes of "transmural" myocardial infarction was not different compared with that of persons with "non-ransmural" lesion (70.00 W versus 71.7 W). When evaluating the relation between the site of ECG changes and the workload, the authors found that the lowest tolerated workload was in cases where ECG changes suggested an extensive damage to the myocardium (53.5 W, p less than 0.05). The authors conclude that the extent of ECG changes after myocardial infarction is a better marker of the level of impairment of physical performance than patient classification to Q or non-Q types.

Electrocardiography↗

Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial.

CONTEXT: Many patients with chronic angina experience anginal episodes despite revascularization and antianginal medications. In a previous trial, antianginal monotherapy with ranolazine, a drug believed to partially inhibit fatty acid oxidation, increased treadmill exercise performance; however, its long-term efficacy and safety have not been studied in combination with beta-blockers or calcium antagonists in a large patient population with severe chronic angina. OBJECTIVES: To determine whether, at trough levels, ranolazine improves the total exercise time of patients who have symptoms of chronic angina and who experience angina and ischemia at low workloads despite taking standard doses of atenolol, amlodipine, or diltiazem and to determine times to angina onset and to electrocardiographic evidence of myocardial ischemia, effect on angina attacks and nitroglycerin use, and effect on long-term survival in an open-label observational study extension. DESIGN, SETTING, AND PATIENTS: A randomized, 3-group parallel, double-blind, placebo-controlled trial of 823 eligible adults with symptomatic chronic angina who were randomly assigned to receive placebo or 1 of 2 doses of ranolazine. Patients treated at the 118 participating ambulatory outpatient settings in several countries were enrolled in the Combination Assessment of Ranolazine In Stable Angina (CARISA) trial from July 1999 to August 2001 and followed up through October 31, 2002. INTERVENTION: Patients received twice-daily placebo or 750 mg or 1000 mg of ranolazine. Treadmill exercise 12 hours (trough) and 4 hours (peak) after dosing was assessed after 2, 6 (trough only), and 12 weeks of treatment. MAIN OUTCOME MEASURES: Change in exercise duration, time to onset of angina, time to onset of ischemia, nitroglycerin use, and number of angina attacks. RESULTS: Trough exercise duration increased by 115.6 seconds from baseline in both ranolazine groups (pooled) vs 91.7 seconds in the placebo group (P =.01). The times to angina and to electrocardiographic ischemia also increased in the ranolazine groups, at peak more than at trough. The increases did not depend on changes in blood pressure, heart rate, or background antianginal therapy and persisted throughout 12 weeks. Ranolazine reduced angina attacks and nitroglycerin use by about 1 per week vs placebo (P<.02). Survival of 750 patients taking ranolazine during the CARISA trial or its associated long-term open-label study was 98.4% in the first year and 95.9% in the second year. CONCLUSION: Twice-daily doses of ranolazine increased exercise capacity and provided additional antianginal relief to symptomatic patients with severe chronic angina taking standard doses of atenolol, amlodipine, or diltiazem, without evident adverse, long-term survival consequences over 1 to 2 years of therapy.

Acetanilides↗

Increased exercise tolerance after nitroglycerin oral spray: a new and effective therapeutic modality in angina pectoris.

The prophylactic antianginal efficacy of nitroglycerin (NTG) oral spray was assessed in 20 patients with angiographically documented coronary disease and stable angina pectoris. The evaluation was by a randomized crossover trial involving treadmill exercise testing. On study day 1, a control treadmill exercise test was performed, followed 30 minutes later by a second exercise test 2 minutes after administration of either placebo (group A, 10 patients) or NTG spray 0.8 mg (group B, 10 patients). One week later, on study day 2, the patients again underwent control treadmill exercise testing followed by a second exercise test after either NTG spray (group A) or placebo (group B). NTG spray delayed the onset of anginal pain during exercise by a mean of 100 +/- 64 seconds (p less than 0.001) in 13 patients and prevented pain entirely in seven. Placebo did not significantly delay the appearance of angina and prevented chest pain in only one patient. NTG spray increased treadmill exercise duration by 31% before the onset of angina (p less than 0.001); placebo did not significantly alter the duration of exercise. NTG spray abolished in six patients and delayed in 14 patients the onset of exercise-induced ST-segment depression of 1 mm (p less than 0.001). Patients achieved a higher heart rate at peak exercise with NTG spray, and yet the maximal exercise-induced ST-segment depression of 2.1 +/- 1.0 mm during the control study declined to 1.3 +/- 0.9 mm on NTG spray (p less than 0.001). Placebo had no effect on exercise ST-segment depression. These data indicate that the oral NTG spray is an effective prophylactic for exercise-induced angina.

Administration, Oral↗

Effects of bepridil on exercise tolerance in chronic stable angina: a double-blind, randomized, placebo-controlled, crossover trial.

Bepridil, a calcium antagonist with a half-life of approximately 42 hours, was compared with placebo in a double-blind, randomized, crossover trial. Thirteen men (average age 62 years) with exercise-related angina pectoris and a positive exercise test (modified Bruce protocol) were studied. In the group as a whole, bepridil (400 mg once a day) caused an increased total exercise time (2.6 +/- 1.8 minutes, mean +/- standard deviation), time to onset of angina (3.3 +/- 1.6 minutes), time to 1 mm of ST-segment depression (2.2 +/- 2.3 minutes), time to 2 mm of ST-segment depression (2.4 +/- 1.4 minutes) and total work load achieved (1.8 +/- 1.4 kpm) compared with the preceding placebo phase (all p less than 0.05). Frequency of angina and nitroglycerin consumption were low and did not change significantly during bepridil therapy. Comparison of the 3 placebo periods (run-in, double-blind and washout) did not reveal a change in any measurement except time to onset of angina, suggesting no training effect or change in patient status. Adverse effects were common in patients taking both placebo and bepridil, but only 2 patients had adverse effects (dizziness) with bepridil that necessitated discontinuation of therapy. Similarity of the double product (systolic blood pressure X heart rate) at the end of exercise suggests a decrease in myocardial oxygen demand as the primary mode of action. This study suggests that bepridil is a promising agent for the treatment of exercise-induced myocardial ischemia.

Aged↗

Effects of atenolol and diltiazem on exercise tolerance and ambulatory ischaemia.

Twenty-five normotensive patients with stable angina, angiographically documented coronary disease and normal left ventricular function were randomized to a crossover study comparing atenolol 100 mg x 1, sustained-release diltiazem 120 mg x 2, and their combination. A maximal symptom limited bicycle exercise test and a 24-h ambulatory electrocardiographic (ECG) monitoring were performed at the end of each treatment period. Exercise duration was increased equally in the different treatment groups. Time to onset of 1-mm ST-segment depression was longer with atenolol (P < 0.02) and combination therapy (P < 0.01) than with diltiazem. The maximal ST-segment depression was decreased with atenolol (P < 0.05) and combination therapy (P < 0.02), whereas, time to onset of angina was prolonged only with combination therapy (P < 0.03). The number of ischaemic episodes during ambulatory monitoring was lower with atenolol and combination therapy than with diltiazem (P < 0.01). The difference between atenolol and diltiazem was mainly due to lower ischaemic activity with atenolol between 06:00 h and 12:00 h (P < 0.05). Anginal frequency (P < 0.01) and nitroglycerin consumption (P < 0.05) were lower with combination therapy than with monotherapy. Thus, while comparable effects were achieved on clinical variables, atenolol appeared to be more effective than diltiazem, reducing myocardial ischaemia during exercise and ambulatory monitoring. With combination therapy, both clinical and electrocardiograph signs of ischaemia were improved.

Adult↗