Antiangina ranolazine
Patients suffering from chronic angina experience repeated attacks of cardiac pain when insufficient oxygen reaches the heart. It is usually associated with exercise, and results from coronary artery disease, where plaque build-up in coronary arteries reduces the flow of blood through the heart. The standard drug treatment is with glyceryl trinitrate, or betablockers such as propanalol. In severe cases, the only other alternative is some form of surgery angioplasty or a bypass operation.
A new class of drugs being developed to treat angina is the partial fatty acid oxidation (pFOX) inhibitors. Animal studies showed that these could increase the efficiency of the heart's use of oxygen. The heart gets its energy from two sources: glucose and fatty acids. It can produce more energy per unit of oxygen by getting energy from glucose rather than fatty acids, and pFOX inhibitors shift the metabolism towards using glucose as an energy source.
Such a compound is being developed by CV Therapeutics. Ranolazine has now completed two pivotal Phase III studies, and shows great promise as an angina treatment. The first of these trials was a multinational randomised double blind placebo controlled crossover design study of its safety and efficacy.1 Ranolazine was given in doses of 500, 1,000 or 1,500mg, or a placebo, each for one week in random order over a total of four weeks, to 191 patients with chronic angina. Exercise times were prolonged by all three doses of ranolazine compared with placebo.
A second trial looked at ranolazine combined with background antianginal therapy. A total of 823 patients were assessed over 12 weeks.2 They were given background therapy of atenolol, diltiazem CD or amlodipine, and then randomised to twice daily doses of 750 or 1,000 mg of ranolazine or placebo. Symptom limited trough plasma concentration exercise times increased by an average of 116s, compared with 92s on placebo. Systolic blood pressure also decreased.
The most common side-effects observed during the trials were constipation, dizziness, nausea and asthaenia. Further studies are in progress.