Efficacy of Cilostazol on Uncontrolled Coronary Vasospastic Angina: A Pilot Study

BACKGROUND Although an angina attack by vasospastic angina (VSA) can usually be relieved or controlled with nitrates and calcium channel blockers (CCBs), there are some patients who cannot be controlled even by higher doses and combinations of these drugs. Cilostazol is a selective inhibitor of phosphodiesterase 3 that increases intracellular cyclic adenosine monophosphate (cAMP) contents. A stimulation of cAMP signal transduction increases coronary nitric oxide production. We examined whether cilostazol improved angina symptoms in patients with VSA uncontrolled by conventional treatment. METHODS This study was conducted in a prospective, multicenter, nonrandomized manner. The subject consisted of 21 patients (13 men, 57 ± 9 year-old) who were diagnosed with VSA and had at least two angina attacks during the past 1 week despite of conventional medications such as CCBs and/or nitrates. They took cilostazol 100 mg twice daily for 2 weeks in addition to the conventional medications. The patients recorded the frequency of angina attack and wrote down the numeric rating scale of a "severity of angina attack" while taking conventional medications and cilostazol for 2 weeks, and also recorded an averaged scale or total number of event during the last week at the time of the assessment. Using the Wilcoxon rank-sum test, we compared the changes in the scores of frequency and severity of angina attack before and after adding cilostazol to the conventional medications. RESULTS After adding cilostazol to the conventional medications, there were 78.9% relative reduction of the score of angina intensity and 73.5% of angina frequency (P < 0.001). There were four patients (19%) who were forced to stop cilostazol due to headache as an adverse event. CONCLUSIONS Cilostazol appears to be an effective therapy in VSA uncontrolled with conventional medical treatment. A further prospective, randomized, placebo-controlled study will be needed to validate this result.