Abstract 13004: Intensive Lipid-Lowering Therapy by Pitavastatin Ameliorates Coronary Hypercontraction After Stenting, the CONTRACTION Study
Background: Use of drug-eluting stents has raised new concerns including delayed re-endothelialization and coronary hypercontraction (HC), which may result in coronary adverse events. We hypothesized that intensive lipid lowering therapy by pitavastatin, a new strong statin, may ameliorate HC after coronary stenting through inhibition of Rho-associated kinase (ROCK) that controls contractility in vascular smooth muscle and eNOS expression in vascular endothelium, and tested our hypothesis in the CONTRACTION study with a randomized controlled design.
Methods and Results: During Dec. 2007 through Dec. 2010, we recruited 113 patients who were planned to undergo follow-up coronary angiogram 6-9 month after percutaneous coronary stenting. In 73 subjects without restenosis, we examined coronary responses to intracoronary acetylcholine (5, 15, 50 μ g/artery) and found that 55 (75%) subjects exhibited coronary HC defined as >50% angiographical contraction with one of angina pectoris, ischemic ECG changes, or lactate production in the coronary sinus (CS) blood. Forty-one subjects with coronary HC were randomly assigned to pitavastatin treatment (LDL-C 99±25 to 74±15 mg/dL, P<0.01, HDL-C 43±12 to 45±13 mg/dL, P<0.05) or control statin treatment (LDL-C 106±31 to 87±21 mg/dL, P<0.05, HDL-C 51±14 to 51±13 mg/dL, NS). After 119±20 days, we re-examined responses to intracoronary acetylcholine in 34 subjects and found that pitavastatin treatment was significantly more effective to ameliorate HC [6/17 (36%) subjects on pitavastatin treatment, 1/17 (6%) on control treatment, P<0.05 by Fisher's exact test]. The use of pitavastatin was associated with inhibition of ROCK activity determined as phosphorylation levels of myosin binding subunit MYPT1 (-16% vs. +10% after pitavastatin and control treatment, respectively, P<0.05) in the CS blood leukocytes, and reduction in NO2/NO3 levels (-12±3 μ mol/L, P<0.05 from the baseline) in the CS blood.
Conclusion: Intensive lipid-lowering therapy by pitavastatin effectively ameliorates coronary HC after stenting. The effect of pitavastatin may be associated with regulation of coronary artery contractility through ROCK and improvement of NO bioavailability. (Clinical trial registry: UMIN000000888)
- © 2011 by American Heart Association, Inc.