Effects of Ivabradine and Ranolazine in Patients With Microvascular Angina Pectoris

Study Questions:

What is the effect of ivabradine and ranolazine in patients with microvascular angina (MVA)?


The investigators randomized 46 patients with stable MVA (effort angina, positive exercise stress test [EST], normal coronary angiography, coronary flow reserve <2.5), who had symptoms inadequately controlled by standard anti-ischemic therapy, to ivabradine (5 mg twice daily), ranolazine (375 mg twice daily), or placebo for 4 weeks. The Seattle Angina Questionnaire (SAQ), EuroQoL scale, and EST were assessed at baseline and after treatment. Coronary microvascular dilation in response to adenosine and to cold pressor test and peripheral endothelial function (by flow-mediated dilation) were also assessed.


Both drugs improved SAQ items and EuroQoL scale compared with placebo (p < 0.01 for all), with ranolazine showing some more significant effects compared with ivabradine, on some SAQ items and EuroQoL scale (p < 0.05). Time to 1-mm ST-segment depression and EST duration were improved by ranolazine compared with placebo. No effects on coronary microvascular function and on flow-mediated dilation were observed with drugs or placebo.


The authors concluded that ranolazine and ivabradine may have a therapeutic role in MVA patients with inadequate control of symptoms in combination with usual anti-ischemic therapy.


This study suggests that ivabradine and ranolazine are reasonable choices in the treatment of MVA patients who continue to have chest pain episodes despite conventional anti-ischemic therapy. Overall, ranolazine seemed to show some more favorable effects on angina symptoms in this small trial. Despite the benefits on clinical endpoints, the study did not find any significant effect of either ranolazine and ivabradine on coronary microvascular function, suggesting that the clinical benefits of the two drugs were likely related to their primary mechanisms (i.e., the heart-rate-lowering effect for ivabradine and the improvement of left ventricular diastolic relaxation for ranolazine). The clinical benefits noted in this pilot study need to be validated in larger prospective trials.

Clinical Topics: Stable Ischemic Heart Disease, Chronic Angina

Keywords: Depression, Piperazines, Benzazepines, Microvascular Angina, Exercise Test

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