A randomized placebo-controlled study on the effect of nifedipine on coronary endothelial function and plaque formation in patients with coronary artery disease: the ENCORE II study.
OBJECTIVE
Endothelial dysfunction and plaque formation are features of atherosclerosis. Inhibition of L-type calcium channels or HMG-CoA pathway improves endothelial function and reduces plaque size. Thus, we investigated in stable coronary artery disease (CAD) the effects of a calcium antagonist on coronary endothelial function and plaque size.


RESULTS
In 454 patients undergoing PCI, acetylcholine (10(-6) to 10(-4) M) was infused in a coronary segment without significant CAD. Changes in coronary diameter were measured and an intravascular ultrasound examination (IVUS) was performed. On top of statin therapy, patients were randomized in a double-blind fashion to placebo or nifedipine GITS 30-60 mg/day and followed for 18-24 months. Blood pressure was lower on nifedipine than on placebo by 5.8/2.1 mmHg (P < 0.001) as was total and LDL cholesterol (4.8 mg/dL; P = 0.495), while HDL was higher (3.6 mg/dL; P = 0.026). In the most constricting segment, nifedipine reduced vasoconstriction to acetylcholine (14.0% vs. placebo 7.7%; P < 0.0088). The percentage change in plaque volume with nifedipine and placebo, respectively, was 1.0 and 1.9%, ns.


CONCLUSIONS
The ENCORE II trial demonstrates in a multi-centre setting that calcium channel blockade with nifedipine for up to 2 years improves coronary endothelial function on top of statin treatment, but did not show an effect of nifedipine on plaque volume.
Lüscher
Thomas Felix
TF
Department of Cardiology, Universitätsspital, Ramistrassee 100, CH-8091 Zürich, Switzerland. cardiotfl@gmx.ch
Pieper
Michael
M
Tendera
Michael
M
Vrolix
Mathy
M
Rutsch
Wolfgang
W
van den Branden
Frank
F
Gil
Robert
R
Bischoff
Karl-Otto
KO
Haude
Michael
M
Fischer
Dieter
D
Meinertz
Thomas
T
Münzel
Thomas
T
D000109:Acetylcholine; D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D018450:Disease Progression; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000009:adverse effects / Q000627:therapeutic use*; D014665:Vasodilator Agents; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology
D002121:Calcium Channel Blockers; D008055:Lipids; D014665:Vasodilator Agents; D009543:Nifedipine; D000109:Acetylcholine