The novel phosphodiesterase inhibitor NM-702 improves claudication- limited exercise performance in patients with peripheral arterial disease

被引:30
作者
Brass, Eric P.
Anthony, Richard
Cobb, Frederick R.
Koda, Isao
Jiao, Jenny
Hiatt, William R.
机构
[1] Harbor UCLA Med Ctr, Ctr Clin Pharmacol, Dept Med, Torrance, CA 90502 USA
[2] Catalyst Pharmaceut Res Inc, Pasadena, CA USA
[3] Nissan Chem Amer, Pasadena, CA USA
[4] Durham VA Med Ctr, Durham, NC USA
[5] Univ Colorado, Div Geriatr, Boulder, CO 80309 USA
[6] Univ Colorado, Div Cardiol, Boulder, CO 80309 USA
[7] Colorado Prevent Ctr, Denver, CO USA
关键词
D O I
10.1016/j.jacc.2006.07.064
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVES The current study tested the hypothesis that NM-702 improves treadmill exercise performance in peripheral arterial disease patients with claudication-limited exercise performance. BACKGROUND Patients with claudication experience significant disability, owing to their exercise limitation. Therapeutic options to improve exercise performance in these patients are limited. NM-702 is a novel drug that inhibits phosphodiesterase as well as thromboxane A, synthase. METHODS This study was a randomized, multi-center, placebo-controlled, double-blind trial. Patients were randomized to receive 24 weeks of twice-daily treatment with either placebo (intent to treat population, n = 130), 4 mg NM-702 (n = 126), or 8 mg NM-702 (n = 130). RESULTS After 24 weeks of treatment, 8 mg NM-702 was associated with a statistically significant increased peak walking time on a graded treadmill as compared with placebo (p = 0.004). Peak walking time after 24 weeks was increased by 17.1 +/- 49.0% in the placebo arm, 22.1 +/- 60.1% in the 4-mg NM-702 arm, and 28.1 +/- 50.5% in the 8-mg NM-702 arm. NM-702 at the 8-mg dose for 24 weeks was associated with statistically significant improvements in the treadmill claudication onset time as compared with placebo. In addition, as compared with placebo, NM-702 improved the physical component and physical functioning scores of the Medical Outcomes Study 36-Item Short Form and the walking distance and stair climbing domains of the Walking Impairment Questionnaire. NM-702 was generally well tolerated, but adverse events typical of vasodilators were common. CONCLUSIONS NM-702 used for 24 weeks by patients with claudication was associated with improvements in laboratory- and ambulatory-based exercise performance.
引用
收藏
页码:2539 / 2545
页数:7
相关论文
共 12 条
[1]   A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure [J].
Cohn, JN ;
Goldstein, SO ;
Greenberg, BH ;
Lorell, BH ;
Bourge, RC ;
Jaski, BE ;
Gottlieb, SO ;
McGrew, F ;
DeMets, DL ;
White, BG .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (25) :1810-1816
[2]   EXERCISE REHABILITATION PROGRAMS FOR THE TREATMENT OF CLAUDICATION PAIN - A METAANALYSIS [J].
GARDNER, AW ;
POEHLMAN, ET .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1995, 274 (12) :975-980
[3]  
GARDNER AW, 1991, MED SCI SPORT EXER, V23, P402
[4]   CLINICAL-TRIALS FOR CLAUDICATION - ASSESSMENT OF EXERCISE PERFORMANCE, FUNCTIONAL STATUS, AND CLINICAL END-POINTS [J].
HIATT, WR ;
HIRSCH, AT ;
REGENSTEINER, JG ;
BRASS, EP .
CIRCULATION, 1995, 92 (03) :614-621
[5]   EFFECT OF DIAGNOSTIC-CRITERIA ON THE PREVALENCE OF PERIPHERAL ARTERIAL-DISEASE - THE SAN-LUIS VALLEY DIABETES STUDY [J].
HIATT, WR ;
HOAG, S ;
HAMMAN, RF .
CIRCULATION, 1995, 91 (05) :1472-1479
[6]   Drug therapy - Medical treatment of peripheral arterial disease and claudication. [J].
Hiatt, WR .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (21) :1608-1621
[7]  
Ikegawa Ruriko, 1995, Japanese Journal of Pharmacology, V67, p274P
[8]  
McDermott MM, 2001, JAMA-J AM MED ASSOC, V286, P1599
[10]   EFFECT OF ORAL MILRINONE ON MORTALITY IN SEVERE CHRONIC HEART-FAILURE [J].
PACKER, M ;
CARVER, JR ;
RODEHEFFER, RJ ;
IVANHOE, RJ ;
DIBIANCO, R ;
ZELDIS, SM ;
HENDRIX, GH ;
BOMMER, WJ ;
ELKAYAM, U ;
KUKIN, ML ;
MALLIS, GI ;
SOLLANO, JA ;
SHANNON, J ;
TANDON, PK ;
DEMETS, DL .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 325 (21) :1468-1475