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Title: Ranolazine Concurrent with Antianginals Reduces Frequency of Angina, Increases Exercise Capacity of Patients with Chronic Angina

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JAMA 2004;291:309-316.
01/21/2004 09:02:00 AM
By Joene Hendry

Patients taking atenolol, amlodipine, or diltiazem for chronic angina experienced a reduction in angina frequency and nitroglycerine consumption, as well as an increased exercise capacity when also taking ranolazine, according to the findings of a 3-group parallel, double-blind, multicentre trial. "Ranolazine affords additional anti-anginal and anti-ischaemic efficacy in patients with severe chronic angina who remain symptomatic while taking standard doses of atenolol, amlodipine, or diltiazem, with minimal haemodynamic effects and without evident adverse long-term survival consequences over 1 to 2 years of therapy," writes Bernard R. Chaitman, MD, St. Louis University Health Sciences Center, Missouri, United States, and colleagues for the Combination Assessment of Ranolazine In Stable Angina (CARISA) Investigators. The researchers randomised 823 adults, with confirmed coronary artery disease and a minimum of 3 months of exertional angina, to receive twice daily ranolazine at either 750 mg or 1000 mg, or matching placebo for 12 weeks. The investigators determined change in treadmill exercise duration, time to onset of angina and ischaemia, nitroglycerine use, and the number of angina attacks over the course of treatment. Baseline data showed an average of 4.5 angina attacks per week and nearly as many nitroglycerine uses in the study group. With treatment, weekly angina attacks occurred a mean of 2.5 times in the 750 mg and 2.1 times in the 1000 mg ranolazine groups compared with 3.3 times in the placebo group, as well as a corresponding reduction in nitroglycerine use. Treadmill exercise at 12 hours after dosing (trough levels) increased from baseline by a pooled time of 115.6 seconds in the ranolazine groups compared with 91.7 seconds in the placebo group. Treadmill exercise at 4 hours after dosing (peak levels) increased from baseline by 99.4 seconds in the 750 mg and 91.5 seconds in the 1000 mg ranolazine groups compared with 65.4 seconds in the placebo group. Overall, adverse events occurred in 31.2% of the 750 mg and 32.7% of the 1000 mg ranolazine groups compared with 26.4% of the placebo group. The most common dose-related adverse effects included constipation, dizziness, nausea, and asthenia. The authors conclude that ranolazine therapy "may be particularly useful in patients who cannot tolerate the initiation or upward titration of currently available antianginal drugs because of their depressive effects on blood pressure and heart rate."

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