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Ranolazine Versus Atenolol for Chronic Angina Pectoris - Ranolazine Versus Atenolol for Chronic Angina Pectoris
Description:
The goal of the trial was to evaluate ranolazine and atenolol compared with placebo among patients with chronic angina and symptom-limited exercise.
Study Design
Study Design:
Patients Enrolled: 158
Mean Patient Age: Age 41-77 years (mean 59)
Female: 11
Patient Populations:
Presence of one of the following: evidence of coronary artery disease (documented medical history of myocardial infarction or significant coronary artery disease); symptoms that supported the diagnosis of chronic angina and a bicycle or modified Bruce’s protocol treadmill exercise electrocardiogram that showed ≥1 mm ST-segment depression 3-9 minutes after the start of exercise; or documented improvement in anginal symptoms and ST-segment depression during exercise testing after administration of standard antianginal medical therapy
Primary Endpoints:
Time to onset of angina
Secondary Endpoints:
Time to 1 mm ST-segment depression and total exercise duration
Drug/Procedures Used:
Patients enrolled in the trial discontinued beta-blocker therapy during a seven- to 10-day run-in period, during which time they underwent exercise testing. Patients were then randomized in a double-blind, crossover manner to 400 mg of immediate-release ranolazine three times daily, 100 mg/day of atenolol, or placebo, each administered for one week. At the end of each treatment week, patients underwent exercise testing.
Concomitant Medications:
Calcium channel blockers (54%), long-acting nitrates (11%), and both drugs (4%)
Principal Findings:
Time to angina was 51 seconds longer with ranolazine versus placebo (p<0.001) and 39.5 seconds longer with atenolol versus placebo (p<0.001). Time to angina with ranolazine was 11.4 seconds longer than atenolol, although the difference was not statistically significant (p=0.18). Increase in exercise duration was also longer with both ranolazine and atenolol versus placebo (37.1 seconds [p<0.001] and 16.0 seconds [p<0.04], respectively), while ranolazine was also longer than atenolol (21.1 seconds, p=0.006). Time to ST depression was longer with both ranolazine and atenolol versus placebo (52.6 seconds and 51.0 seconds, respectively, p<0.001 for each), but there was no difference between the two active therapies (p=0.86).
Blood pressure and heart rate at rest and at maximal exercise were significantly lower with atenolol compared with ranolazine and placebo. There was no significant difference in blood pressure or heart rate at rest, or in heart rate at maximal exercise for ranolazine compared with placebo. However, systolic blood pressure at maximal exercise was slightly but significantly higher for ranolazine compared with placebo (184 mm Hg vs. 179 mm Hg, p<0.05).
Cardiac work as measured by rate-pressure product was significantly lower with atenolol compared to placebo or ranolazine both at rest and at maximal exercise. There was no difference between ranolazine and placebo in cardiac work by rate-pressure product.
Adverse events were reported in 29% of patients during the ranolazine phase, 25% during the atenolol phase, and 17% during the placebo phase. There were no significant changes observed in QTc, PR, or QRS intervals.
Interpretation:
Among patients with chronic angina and symptom-limited exercise, treatment with ranolazine and treatment with atenolol were associated with prolonged time free of exercise-induced angina and ST depression and prolonged exercise duration compared with placebo. Additionally, treatment with ranolazine was associated with longer exercise duration compared with atenolol, without decreases in blood pressure or heart rate. The improvements in exercise parameters with ranolazine were not attenuated by decreased cardiac work, as was the case with atenolol. Similar improvements in exercise parameters were observed with ranolazine compared with placebo in the MARISA and CARISA trials.
References:
Rousseau MF, Pouleur H, Cocco G, Wolff AA. Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris. Am J Cardiol 2005;95:311-316.
Keywords: Coronary Artery Disease, Myocardial Infarction, Enzyme Inhibitors, Blood Pressure, Piperazines, Electrocardiography, Heart Rate, Exercise Test
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