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CLINICAL RESEARCH: VASCULAR DISORDER

Effects of a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor, Fluvastatin, on Coronary Spasm After Withdrawal of Calcium-Channel Blockers

Hirofumi Yasue, MD^_*,_*, Yuji Mizuno, MD^_*, Eisaku Harada, MD^_*, Teruhiko Itoh, MD^_*, Hitoshi Nakagawa, MD^_*, Masafumi Nakayama, MD, Hisao Ogawa, MD, Shinji Tayama, MD, Takasi Honda, MD, Seiji Hokimoto, MD, Shuichi Ohshima, MD, Youichi Hokamura, MD^||, Kiyotaka Kugiyama, MD^¶, Minoru Horie, MD^#, Michihiro Yoshimura, MD^_**, Masaki Harada, MD, Shiroh Uemura, MD, Yoshihiko Saito, MD for the SCAST (Statin and Coronary Artery Spasm Trial) Investigators

^_* Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, Kumamoto, Japan
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
Division of Cardiology, Cardiovascular Center, Saiseikai Kumamoto Hospital, Kumamoto, Japan
Division of Cardiology, Kumamoto Central Hospital, Kumamoto, Japan
^|| Division of Cardiology, Kumamoto City Hospital, Kumamoto, Japan
^¶ Second Department of Internal Medicine, Yamanashi University School of Medicine, Yamanashi, Japan
^# Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Shiga, Japan
^_** Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
First Department of Internal Medicine, Nara Medical University, Nara, Japan.

Manuscript received August 14, 2007; revised manuscript received November 26, 2007, accepted December 2, 2007.

^_* Reprint requests and correspondence: Dr. Hirofumi Yasue, Kumamoto Aging Research Institute, 6-8-1, Yamamuro, Kumamoto City 860-8518, Japan. (Email: yasue{at}juryo.or.jp).

Objectives: The purpose of this study was to determine whether a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) suppresses coronary spasm.

Background: Coronary spasm is associated with endothelial dysfunction. Statins have been shown to improve endothelial function.

Methods: This was a prospective, randomized, open-label, end point study. Sixty-four patients who had no significant organic coronary stenosis and in whom coronary spasm was induced by intracoronary injection of acetylcholine (ACh) were randomly assigned to fluvastatin 30 mg/day plus the conventional calcium-channel blocker (CCB) therapy (31 patients, statin group) or the conventional CCB therapy (33 patients, nonstatin group). After 6 months of treatment, the intracoronary injection of ACh was repeated and the coronary spasm was assessed.

Results: Coronary spasm was suppressed in 16 of the 31 patients (51.5%, p < 0.0001) of the statin group and in 7 of the 33 patients (21.2%, p = 0.0110) of the nonstatin group after 6 months of treatment. Thus, the number of patients with ACh-induced coronary spasm was significantly reduced in the statin group as compared with the nonstatin group (51.6% vs. 21.2%, p = 0.0231) after 6 months of treatment.

Conclusions: The addition of fluvastatin 30 mg/day to the conventional CCB therapy for 6 months significantly reduced the number of patients with ACh-induced coronary spasm as compared with the conventional CCB therapy. Thus, a statin (fluvastatin) may possibly be a novel therapeutic drug for coronary spasm.

Abbreviations and Acronyms   ACh = acetylcholine   CCB = calcium-channel blocker   ECG = electrocardiogram   LCA = left coronary artery   LDL = low-density lipoprotein   NO = nitric oxide   RCA = right coronary artery   ROCK = RhoA-associated kinase

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