Ryuji Tsuburaya1, Jun Takahashi1, Akihiro Nakamura2, Eiji Nozaki2, Masafumi Sugi3, Yoshito Yamamoto3, Tetsuya Hiramoto4, Satoru Horiguchi5, Kanichi Inoue6, Toshikazu Goto7, Atsushi Kato8, Tsuyoshi Shinozaki9, Eiko Ishida1, Satoshi Miyata1, Satoshi Yasuda10, Hiroaki Shimokawa11. 1. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. 2. Iwate Prefectural Central Hospital, Morioka, Iwate, Japan. 3. Iwaki Kyoritsu General Hospital, Iwaki, Japan. 4. Oosaki Citizen Hospital, Osaki, Japan. 5. Hiraka General Hospital, Yokote, Japan. 6. South Miyagai Medical Center, Ookawara, Japan. 7. Yamagata Prefectural Central Hospital, Yamagata, Japan. 8. Sendai Open Hospital, Sendai, Japan. 9. Sendai Medical Center, Sendai, Japan. 10. National Cerebral and Cardiovascular Center, Osaka, Japan. 11. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan shimo@cardio.med.tohoku.ac.jp.
Abstract
AIMS: It is widely known that drug-eluting stents (DES) induce coronary vasomotion abnormalities. We have previously demonstrated that chronic treatment with long-acting nifedipine suppresses coronary hyperconstricting responses induced by the first-generation DES (e.g. sirolimus- and pacritaxel-eluting stents) through inhibition of vascular inflammation in pigs. To examine whether this is also the case with the second-generation DES (everolimus-eluting stents, EES) in humans, the most widely used DES in the world, we conducted a prospective, randomized, multicentre trial, termed as the NOVEL Study. METHODS AND RESULTS: We evaluated 100 patients with stable angina pectoris who underwent scheduled implantation of EES in the left coronary arteries. They were randomly assigned to receive either conventional treatments alone or additionally long-acting nifedipine (10-60 mg/day) (n = 50 each). After 8-10 months, 37 patients in the control and 38 in the nifedipine group were examined for coronary vasoreactivity to intracoronary acetylcholine (ACh) by quantitative coronary angiography after 48-h withdrawal of nifedipine. Coronary vasoconstricting responses to ACh were significantly enhanced at the distal edge of EES compared with non-stented vessel (P = 0.0001) and were significantly suppressed in the nifedipine group compared with the control group (P = 0.0044). Furthermore, the inflammatory profiles were also improved only in the nifedipine group, which evaluated by serum levels of high-sensitivity CRP (P = 0.0001) and adiponectin (P = 0.0039). CONCLUSIONS: These results indicate that DES-induced coronary vasomotion abnormalities still remain an important clinical issue even with the second-generation DES, for which long-acting nifedipine exerts beneficial effects associated with its anti-inflammatory effects. TRIAL REGISTRATION: This study is registered at the UMIN Clinical Trial Registry (UMIN-CTR; ID=UMIN000015147). Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIMS: It is widely known that drug-eluting stents (DES) induce coronary vasomotion abnormalities. We have previously demonstrated that chronic treatment with long-acting nifedipine suppresses coronary hyperconstricting responses induced by the first-generation DES (e.g. sirolimus- and pacritaxel-eluting stents) through inhibition of vascular inflammation in pigs. To examine whether this is also the case with the second-generation DES (everolimus-eluting stents, EES) in humans, the most widely used DES in the world, we conducted a prospective, randomized, multicentre trial, termed as the NOVEL Study. METHODS AND RESULTS: We evaluated 100 patients with stable angina pectoris who underwent scheduled implantation of EES in the left coronary arteries. They were randomly assigned to receive either conventional treatments alone or additionally long-acting nifedipine (10-60 mg/day) (n = 50 each). After 8-10 months, 37 patients in the control and 38 in the nifedipine group were examined for coronary vasoreactivity to intracoronary acetylcholine (ACh) by quantitative coronary angiography after 48-h withdrawal of nifedipine. Coronary vasoconstricting responses to ACh were significantly enhanced at the distal edge of EES compared with non-stented vessel (P = 0.0001) and were significantly suppressed in the nifedipine group compared with the control group (P = 0.0044). Furthermore, the inflammatory profiles were also improved only in the nifedipine group, which evaluated by serum levels of high-sensitivity CRP (P = 0.0001) and adiponectin (P = 0.0039). CONCLUSIONS: These results indicate that DES-induced coronary vasomotion abnormalities still remain an important clinical issue even with the second-generation DES, for which long-acting nifedipine exerts beneficial effects associated with its anti-inflammatory effects. TRIAL REGISTRATION: This study is registered at the UMIN Clinical Trial Registry (UMIN-CTR; ID=UMIN000015147). Published on behalf of the European Society of Cardiology. All rights reserved.