Department of Internal Medicine, Division of Cardiology, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneun, South Korea.
Cardiovasc Ther. 2013 Jun;31(3):179-85. doi: 10.1111/j.1755-5922.2012.00312.x.
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.
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.
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.
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.
尽管血管痉挛性心绞痛（VSA）引起的心绞痛发作通常可以用硝酸酯类和钙通道阻滞剂（CCB）缓解或控制，但仍有一些患者即使使用更高剂量和联合用药也无法控制。西洛他唑是一种磷酸二酯酶 3 的选择性抑制剂，可增加细胞内环腺苷酸（cAMP）含量。cAMP 信号转导的刺激增加了冠状动脉中一氧化氮的产生。我们研究了西洛他唑是否可以改善常规治疗无法控制的 VSA 患者的心绞痛症状。
这是一项前瞻性、多中心、非随机研究。研究对象为 21 名 VSA 患者（男 13 名，年龄 57 ± 9 岁），他们在过去 1 周内至少有 2 次心绞痛发作，尽管使用了 CCB 和/或硝酸酯类等常规药物。在常规药物治疗的基础上加用西洛他唑 100mg，每日 2 次，治疗 2 周。患者在服用常规药物和西洛他唑的 2 周内记录心绞痛发作的频率，并记录心绞痛发作严重程度的数字评分，同时在评估时记录过去 1 周内的平均评分或总发作次数。使用 Wilcoxon 秩和检验，比较加用西洛他唑前后心绞痛发作频率和严重程度评分的变化。
在常规药物治疗的基础上加用西洛他唑后，心绞痛强度评分降低了 78.9%，心绞痛发作频率降低了 73.5%（P<0.001）。有 4 名患者（19%）因头痛等不良反应而被迫停用西洛他唑。
西洛他唑似乎是一种治疗常规药物治疗无效的 VSA 的有效方法。需要进一步进行前瞻性、随机、安慰剂对照研究来验证这一结果。
