Beneficial effects of long-acting nifedipine on coronary vasomotion abnormalities after drug-eluting stent implantation: The NOVEL study.

European Heart Journal

PubMedID: 27354043

Tsuburaya R, Takahashi J, Nakamura A, Nozaki E, Sugi M, Yamamoto Y, Hiramoto T, Horiguchi S, Inoue K, Goto T, Kato A, Shinozaki T, Ishida E, Miyata S, Yasuda S, Shimokawa H, NOVEL Investigators. Beneficial effects of long-acting nifedipine on coronary vasomotion abnormalities after drug-eluting stent implantation: The NOVEL study. Eur Heart J. 2016;37(35):2713-21.
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).