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

Eur Heart J. 2016 Sep 14;37(35):2713-21. doi: 10.1093/eurheartj/ehw256. Epub 2016 Jun 28.


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).

Keywords: Calcium channel blockers; Coronary spasm; Drug-eluting stents.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Coronary Disease
  • Drug-Eluting Stents*
  • Everolimus
  • Humans
  • Nifedipine
  • Prospective Studies
  • Sirolimus
  • Treatment Outcome


  • Everolimus
  • Nifedipine
  • Sirolimus

Associated data

  • UMIN-CTR/UMIN000015147