Dovepress investigating the efficacy of ranolazine to improve angina relief and exercise performance and duration. MARISA (Monotherapy Assessment of Ranolazine In Stable Angina), a double blind, placebo-controlled study, investigated the effect of three different doses of ranolazine (500, 1000 or 1500 mg, each administered twice daily) on total exercise duration in 191 patients with angina-limited exercise. All doses of ranolazine were well tolerated and effective in reducing angina frequency and increasing exercise duration (by 94, 103 and 116 seconds, P , 0.005 compared with placebo) when used as monotherapy.19 The ERICA (Antianginal Efficacy of Ranolazine When Added to Treatment With Amlodipine) trial addressed whether ranolazine decreased the symptoms of angina in stable coro- nary patients who had persistent symptoms even with the use of maximum recommended doses of amlodipine. The popula- tion in this study consisted of 565 stable patients with known coronary disease taking maximal amlodipine doses and having three or more anginal attacks per week. Patients were random- ized to ranolazine 1000 mg versus placebo twice daily for six weeks. The results showed that ranolazine in combination with amlodipine reduced the frequency of angina compared with amlodipine alone (mean anginal attacks per week 2.88 versus 3.31, P = 0.028; average weekly nitroglycerin consumption 2.03 versus 2.68, P = 0.014).9 CARISA (Combination Assessment of Ranolazine In Stable Angina), a randomized three-group parallel, double- blind placebo-controlled study, had the primary aim of compar- ing the effects of ranolazine 750 mg or 1000 mg versus placebo on treadmill exercise duration in 823 patients with persistent symptoms of chronic angina despite use of maximum doses of atenolol, amlodipine, or diltiazem. This trial demonstrated the ability of ranolazine to improve exercise capacity (exercise duration increased by 115.6 seconds from baseline in both ranolazine groups versus 91.7 seconds in the placebo group, P = 0.01) and increase time to the onset of angina on the back drop of these standard antianginal medications.22 The most recent investigation, the MERLIN-TIMI 36 trial, evaluated the efficacy and safety of ranolazine in 6560 patients with non-ST segment elevation acute coronary syndromes. Although the primary endpoint of the study was not met (reduction of a composite of cardiovascular death, myocardial infarction, and recurrent ischemia in the ranolazine arm compared with standard treatment) the inci- dence of recurrent ischemia was significantly lower in the ranolazine group compared with standard treatment (13.9% versus 16.1%; hazards ratio 0.8, 95% confidence interval 0.76–0.99).7 Vascular Health and Risk Management 2011:7 extended-release ranolazine in stable angina Overall, ranolazine has been well tolerated in the studies of patients with chronic stable angina and acute coronary syndromes. The most common side effects of ranolazine consistently observed across these trials, in particular with higher doses, were constipation, dizziness, nausea, headache, asthenia, and peripheral edema.9,19,22 However, in the MARISA and CARISA trials, ranolazine was shown to increase the QTc, but without evidence of effect on QT dispersion or torsades de pointes.19,22 The larger MERLIN trial in patients with acute coronary syndrome confirmed the safety of ranolazine in a higher-risk ischemic population, showing no increase in torsades de pointes or other life-threatening arrhythmias.8 Syncope and postural hypotension have occurred in patients taking high doses (up to 2000 mg) of ranolazine.19,22 However, Holter monitoring during the first seven days of treatment in the MERLIN trial showed no evidence of arrhythmias associated with these side effects, and in fact revealed a reduction in both tachyar- rhythmias and bradyarrhythmias in the ranolazine treatment arm.8 In general, most side effects from ranolazine treatment can be avoided by starting ranolazine with the lowest avail- able dose and titrating the dose upward based on efficacy and tolerability. Although the MERLIN-TIMI 36 trial does not support the use of ranolazine in patients with acute coronary syndrome to reduce subsequent death or myocardial infarction during follow-up, data from the trial confirmed the safety profile and tolerability of ranolazine and provided additional support for ranolazine as an antianginal drug in chronic angina. Ranola- zine offers a second option for intensification of antianginal therapy in case first-line agents fail.7,13 Quality of life and economic impact Despite advances in medical and interventional technologies, millions of people continue to experience angina symptoms. This not only translates into a dramatic worsening in their qual- ity of life, but also represents a major public health problem.27,28 Thus, patient-centered health status assessment that measures patient symptoms and function, as well as quality of life, is becoming an increasingly common outcome measure.27,28 Different health status/quality of life indicators have been used in recent studies of ranolazine,7,9 among them, the Seattle Angina Questionnaire, the Rose dyspnea scale, the Medical Outcomes Study 12-item Short Form (SF)-12, and the EuroQol-5D questionnaire.28 The Seattle Angina Questionnaire surveys patients on 19 items that measure five clinically important dimensions about health in patients with coronary artery disease, ie, angina frequency, angina stability, submit your manuscript | www.dovepress.com Dovepress 537