In a recent double blind, placebo controlled trial (STELLA study), Shin et al (1) assessed the efficacy and safety of cilostazol, a selective inhibitor of phosphodiesterase-3, for the treatment of vasospastic angina pectoris. Cilostazol is known to have strong vasodilator effects but this is the first large randomized study assessing therapeutic role of this new agent in patients with coronary artery spasm. The STELLA trial was conducted in 10 teaching hospitals in South Korea between October 2011 and July 2012 (ClinicalTrials.gov number, NCT01444885). Patients were included if they had newly diagnosed vasospastic angina (<3 months from onset of symptoms), spontaneous or ergonovine induced coronary artery spasm ( >90% coronary lumen diameter reduction during spasm at angiography) associated with chest pain and transient ischaemic ST segment changes (ST elevation or depression). Fifty patients with documented vasospastic angina who experienced episodes of chest pain despite treatment with amlodipine (5mg/day) were randomly given treatment with cilostazol (up to 200 mg/day) or placebo for 4 weeks. Frequency and severity of the episodes of angina were recorded by the patients in ad hoc diaries. All patients graded their chest pain episodes using a scale from 0 (very mild pain) to 10 (extremely severe). The primary study endpoint was the reduction of the incidence of chest pain episodes. Forty-nine patients (25 in the cilostazol group, 24 in the placebo group) constituted the study group. The authors reported a reduced incidence of weekly episodes in the cilostazol group compared with the placebo group (66.5±88.6% vs 17.6±140.1%, respectively, p=0.009). Pain severity was also reduced (−2.8±0.4 vs −1.1±0.4, respectively; p=0.003), and a larger proportion of patients were chest pain-free in the cilostazol group compared with the control group (76.0% vs 33.3%, respectively; p=0.003). Of interest, no major side effects were reported in the group receiving cilostazol.
This study by Shin et al (1) is of clinical interest as its results seem to indicate that cilostazol may be a useful adjunct to our current pharmacological armamentarium for the management of patients with coronary artery spasm whose symptoms cannot be properly controlled with the use of conventional treatments i.e. amlodipine. Another interesting finding, in addition to the efficacy of cilostazol in reducing the incidence of chest pain in this patient population, is the absence of major side effects with the use of this agent.
Despite the promising results, there are important issues that need to be addressed by future studies, including for example whether findings in this small investigation can be confirmed in larger studies involving multi-ethnic patient groups and whether the effects of this agent will be sustained over longer periods of time. The effect of cilostazol may be limited to patients in who endothelial dysfunction is responsible for coronary spasm but may not be suitable for the management of coronary spasm triggered by other mechanisms. The long term safety of cilostazol also needs further assessment, in addition to establishing whether its antiplatelet effects play any major role in this patient population. Undoubtedly and despite the unknown issues mentioned above, the cardiovascular community will follow with great interest any further developments in relation to the role of cilostazol in the treatment of coronary artery spasm. The indication of this agent could be even extended to coronary microvascular spasm and microvascular angina.
Shin E-S et al.Heart 2014; 100:1531–1536. doi:10.1136/heartjnl-2014-305986