Ranolazine improves endothelial function in patients with stable coronary artery disease.
OBJECTIVE
We investigated the effect of ranolazine on endothelial-dependent vasodilatation (EDV), serum markers of endothelial dysfunction, and inflammation.


BACKGROUND
Endothelial dysfunction has been shown to be independently associated with the occurrence of cardiovascular events. We sought to investigate whether ranolazine, a novel antianginal medication with no effect on heart rate or blood pressure, improves endothelial function in patients with stable coronary artery disease (CAD).


METHODS
Twenty-seven patients with stable CAD were randomly assigned to either 1000 mg twice daily of ranolazine or to matching placebo for 6 weeks and then crossed over for an additional 6 weeks in a double-blind design. EDV was assessed using reactive hyperemia peripheral arterial tonometry (RH-PAT) at baseline, 6, and 12 weeks. Markers of endothelial dysfunction and inflammation were also evaluated.


RESULTS
After 6 weeks, treatment with ranolazine significantly increased the EDV RH-PAT index as compared with baseline (1.85+/-0.42 vs. 2.08+/-0.57, P = 0.037). EDV RH-PAT did not change while on placebo (1.69+/-0.35 vs. 1.78+/-0.41, P = 0.29). In addition, there was a significant drop in asymmetric dimethylarginine levels with ranolazine treatment (0.66+/-0.12 vs. 0.60+/-0.11 micromol/l, P = 0.02) and a near significant decrease in C-reactive protein levels (0.40+/-0.80 vs. 0.30+/-0.61 mg/dl, P = 0.05).


CONCLUSIONS
Ranolazine improves endothelial function, asymmetric dimethylarginine, and C-reactive protein levels in a group of patients with stable CAD. Our results suggest a novel mechanism of action of ranolazine.
Deshmukh
Smriti H
SH
Saint Vincent's Catholic Medical Center Manhattan, New York, New York 10011, USA.
Patel
Snehal R
SR
Pinassi
Elsa
E
Mindrescu
Catalin
C
Hermance
Eileen V
EV
Infantino
Michael N
MN
Coppola
John T
JT
Staniloae
Cezar S
CS
D000083:Acetanilides / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008365:Manometry; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D000069458:Ranolazine; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*
D000083:Acetanilides; D015415:Biomarkers; D002317:Cardiovascular Agents; D018836:Inflammation Mediators; D010879:Piperazines; C018524:N,N-dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine; D000069458:Ranolazine