Cilostazol was approved by FDA (food and drug administration) in 1999 for intermittent claudication. What made it known to cardiologists is the Cilostazol for Restenosis Trial (CREST) . In recent years, it was found out that cilostazol had many other uses. Koji and his colleagues reported that cilostazol was effective and safe to be applied in patients with three-degree atrioventricular block for a short-term . Cilostazol was also reported to reduce ST segment elevation, thus acting to diminish the action potential notch and suppress the substrate and trigger for ventricular tachycardia/fibrillation (VT/VF), which made it a candidate for brugada syndrome treatment . The CREST (Cilostazol for Restenosis Trial) released in 2005, showed that administration of cilostzaol together with aspirin and clopidogrel significantly lower binary restenosis rate . It seems that cilostazol is a promising drug, while still based on the mechanism, it showed some side-effects, like ventricular arrhythmias, haemorrhage, interaction with other drugs or food and many more. In our case, A 68-year-old male patient diagnosed acute myocardial infarction without histories of arrythmias developed a severe premature ventricular contractions (PVCs) while taking cilostazol and the PVCs decreased significantly after cilostazol discontinuation. So the PVCs are obviously related to cilostazol and probably the safety of cilostazol in patients having a history of myocardial infarction or malignant arrhythmias should be reevaluated.
General history: A 68-year-old male patient, complaining persistent chest pain for 18 hours, was admitted to our hospital.
Previous medical history: totally 5 coronary stents were implanted in 2007 and 2008, respectively; there are no histories of drinking or smoking.
Physical examination: Respiratory rate: 18 times/min; heart rate: 84 beats/min; blood pressure: 120/76 mmHg. No other positive signs were detected.
Electrocardiography (ECG): Sinus rhythm, heart rate: 84 beats/min; In II, III, AVF leads, ST segments elevation, diminished R waves and abnormal Q waves were seen.
Echocardiography: Left atrium: 39 mm, left ventricle: 49 mm, ejection fraction: 58%.
Blood test: K+: 3.67 mmol/L; Na+: 142.2 mmol/L; Cl-: 105.8 mmol/L; Ca++: 2.08 mmol/L; UREA: 5.1 mmol/L; AST: 155 U/L; CK: 1624 U/L; CKMB: 151 U/L; LDH: 385 U/L; HBDH: 348 U/L; TBIL: 26.3 ummo/L; others were normal.
Aspirin, clopidogrel and atorvastatin were administrated and immediate coronary angiography was performed, which showed thrombi in the distal right coronary artery. After given tirofiban, the thrombi was dissolved and the patient was discharged with prescription of oral cilostazol (100 mg, Bid). While one week later, he felt palpitation and 24-hour ECG showed PVCs, more than 27000 beats/24 hours (Figure 1). Cilostazol was discontinued and metoprolol (25 mg, Tid) was applied. 24-hour ECG after one week showed PVCs, 600 beats/24 hours (Figure 2).
Figure 1. ECG after oral cilostazol for one week showed premature ventricular contractions (PVCs), more than 27000 beats/24 hours.
Figure 2. ECG one week after discontinuation of cilostazol showed PVCs, 600beats/24 hours.
Cilostazol, a phosphodiesterase (PDE) III inhibitor, which was first approved in Japan and 3 years later in the US is long used for intermittent claudication . Based on its mechanism and tissue specifities, it mainly affect cardiac monocytes, vascular smooth vessels and platelets, therefore cilostazol is far more than just an antithrombotic agent.
Cilostazol is widely used in the treatment of three-degree atrioventricular block, Brugada syndrome and post percutaneous coronary intervention [1-3]. CREST (Cilostazol for Restenosis Trial) released in 2005, first showed that administration of cilostzaol together with aspirin and clopidogrel significantly lower binary restenosis rate without increasing major complications . Cilostazol was also administrated in high risk patients implanted with drug-eluting stents . Some Korean colleagues used cilostazol in patients having acute myocardial infarction (AMI) and still an exciting result was achieved . It is thought a promising drug with little side effects till recent years, different voices came up. It was reported that cilostazol increased the incidence of ventricular arrhythmias and the mean number of episodes in infarcted animals. Barta et al found the same thing not only in infarcted but also in normal animals under epinephrine challenged test . These bring up a question, whether it is worthwhile to take the risk having cilostazol? While it was not significant in the CREST , so further studies should be carried out to evaluate the safety of cilostazol in infracted patients.
In our case, cilostazol is a compensatory way to treat coronary thrombi. During taking cilostazol, the patient developed PVCs. Since he didn’t have any histories of arrhythmias and after discontinuation of cilostazol, the PVCs decreased significantly, the arrhythmia is highly associated with cilostazol. It made us feel a little nervous that every year ventricular arrhythmias kills thousands of patients having acute myocardial infarction (AMI) throughout the world. And clinical drugs either offer exogenous or enhance endogenous cAMP are forbidden in AMI patients. CREST showed a decrease in binary restenosis in patients receiving stents without differences in bleeding, rehospitalization, target-vessel revascularization, myocardial infarction, or death . While the patients recruited in this study are with stable angina or unstable angina or silent myocardial ischemia. So further studies including broad spectrum of patients should be carried out. Even though, we still should be careful to apply cilostazol in patients having a history of myocardial infarction or malignant arrhythmias.
We thank Lili Mao who collected all the information of the patients.
Conflicts of Interest
All authors don’t have conflicts of interest.
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© 2012, Zhong L., Gao Y., Li X., Wei S.
© 2012, Russian Open Medical Journal
Received 31 July 2012, Revised 31 October 2012, Accepted 20 November 2012.
Correspondence to Shipeng Wei. Address: Department of Cardiology, the 4th Clinical Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin, 150001, China. Tel: +86 (451) 82579351. E-mail: Shipengwei@yahoo.com.