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

• Published in: Journal of the American College of Cardiology Vol. 51; no. 18; pp. 1742 - 1748
• Main Authors: Yasue, Hirofumi, Mizuno, Yuji, Harada, Eisaku, Itoh, Teruhiko, Nakagawa, Hitoshi, Nakayama, Masafumi, Ogawa, Hisao, Tayama, Shinji, Honda, Takasi, Hokimoto, Seiji, Ohshima, Shuichi, Hokamura, Youichi, Kugiyama, Kiyotaka, Horie, Minoru, Yoshimura, Michihiro, Harada, Masaki, Uemura, Shiroh, Saito, Yoshihiko
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 06.05.2008; Elsevier Science; Elsevier Limited
• Subjects: Acetylcholine - pharmacology; Adult; Aged; Aged, 80 and over; Angina pectoris; Biological and medical sciences; Calcium Channel Blockers - therapeutic use; Cardiology; Cardiology. Vascular system; Cardiovascular; Cholesterol; Coronary Angiography; Coronary heart disease; Coronary Vasospasm - drug therapy; Coronary Vasospasm - physiopathology; Coronary vessels; Coronary Vessels - drug effects; Coronary Vessels - pathology; Endothelium - drug effects; Endothelium - physiopathology; Fatty Acids, Monounsaturated - therapeutic use; Female; Fluvastatin; Heart; Heart attacks; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Indoles - therapeutic use; Internal Medicine; Male; Medical sciences; Middle Aged; Nitric Oxide; Older people; Prospective Studies; Risk Factors; Treatment Outcome; NO; RCA; CCB; ROCK; LDL; ACh; ECG; LCA; nitric oxide; RhoA-associated kinase; left coronary artery; low-density lipoprotein; right coronary artery; electrocardiogram; acetylcholine; calcium-channel blocker; Enzyme; Calcium antagonist; Coronary artery; Cardiovascular disease; Coronary heart disease; Coenzyme; Fluvastatin; Treatment withdrawal; Calcification; Spasm; Inhibitor; Oxidoreductases; Circulatory system; Cardiology; Reductase
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2007.12.049

Effects of a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor, Fluvastatin, on Coronary Spasm After Withdrawal of Calcium-Channel Blockers Hirofumi Yasue, Yuji Mizuno, Eisaku Harada, Teruhiko Itoh, Hitoshi Nakagawa, Masafumi Nakayama, Hisao Ogawa, Shinji Tayama, Takasi Honda, Seiji Hokimoto, Shuichi Ohshima, Youichi Hokamura, Kiyotaka Kugiyama, Minoru Horie, Michihiro Yoshimura, Masaki Harada, Shiroh Uemura, Yoshihiko Saito, for the SCAST (Statin and Coronary Artery Spasm Trial) Investigators Sixty-four patients in whom coronary spasm was induced by intracoronary injection of acetylcholine were randomly assigned to fluvastatin 30 mg/day plus the conventional therapy (31 patients, statin group) or the conventional therapy (33 patients, nonstatin group) for 6 months of treatment. There was a significant reduction in the number of patients with acetylcholine-induced coronary spasm in the statin group as compared with the nonstatin group after 6 months of treatment (51.6% vs. 21.2%, p = 0.0231). Thus, a statin (fluvastatin) may possibly be used as a novel drug for the treatment of coronary spasm. The purpose of this study was to determine whether a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) suppresses coronary spasm. Coronary spasm is associated with endothelial dysfunction. Statins have been shown to improve endothelial function. 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. 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. 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.