Effect of niacin ER/lovastatin on claudication symptoms in patients with peripheral artery disease.
In patients with peripheral artery disease (PAD), statins may improve the symptoms of claudication. The Intermittent Claudication Proof of Principle (ICPOP) study tested the hypothesis that the combination of extended release niacin plus lovastatin would improve exercise performance in patients with PAD and claudication compared with a diet intervention. A phase 3 double-blind, parallel-group, multi-center, 28-week multi-national study evaluated subjects with a history of claudication who had an ankle-brachial index (ABI) < or = 0.90, a reproducible peak treadmill walking time (PWT) of 1-20 minutes, and a low-density lipoprotein (LDL)-cholesterol level < 160 mg/dl (< 4.1 mmol/l). Subjects were randomly assigned to low-dose niacin 1000 mg plus lovastatin 40 mg (low niacin-statin), high-dose niacin 2000 mg plus lovastatin 40 mg (high niacin-statin), or diet intervention (diet). The co-primary efficacy endpoint of percent change in PWT and claudication onset time (COT) at 28 weeks was assessed using a graded treadmill protocol. At completion, 385 subjects were analyzed for safety and 370 subjects were analyzed for efficacy. The primary efficacy analysis showed no statistical significance for overall treatment effect at week 28 for the co-primary endpoint of PWT and COT. The PWT component of the primary endpoint increased 26.5% on diet, 37.8% on high niacin-statin (p = 0.137) and 38.6% on low niacin-statin (p = 0.096). Flushing as the most common event leading to discontinuation and treatment was associated with increases in liver enzymes, fasting blood glucose concentration and a decrease in platelet count.
Hiatt
William R
WR
Section of Vascular Medicine, Division of Geriatrics, University of Colorado Denver School of Medicine, Denver, CO 80203, USA. Will.Hiatt@UCHSC.edu
Hirsch
Alan T
AT
Creager
Mark A
MA
Rajagopalan
Sanjay
S
Mohler
Emile R
ER
Ballantyne
Christie M
CM
Regensteiner
Judith G
JG
Treat-Jacobson
Diane
D
Dale
Rita A
RA
Rooke
Thom
T
D000368:Aged; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D005080:Exercise Test; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D007383:Intermittent Claudication / Q000175:diagnosis / Q000178:diet therapy / Q000188:drug therapy*; D008148:Lovastatin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage* / Q000009:adverse effects; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000178:diet therapy / Q000188:drug therapy*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
D003692:Delayed-Action Preparations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014665:Vasodilator Agents; D009525:Niacin; D008148:Lovastatin