Review of mortality and cardiovascular event rates in patients enrolled in clinical trials for claudication therapies

被引:41
作者
Brass, Eric P.
Hiatt, William R.
机构
[1] Harbor UCLS Ctr Clin Pharmacol, Dept Med, Torrance, CA 90502 USA
[2] Univ Colorado, Hlth Sci Ctr, Dept Med, Sect Vasc Med, Denver, CO 80262 USA
[3] Colorado Prevent Ctr, Denver, CO USA
关键词
claudication; clinical trials; morbidity; mortality; peripheral arterial disease;
D O I
10.1177/1358863x06069513
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Pharmacological and non-pharmacological interventions to improve function and quality of life in patients with claudication are being evaluated in clinical research trials. An important component of clinical development programs is assessing the safety of the intervention and monitoring for adverse impact of the therapy on research participants. The conduct of both of these safety assessments is facilitated by the ability to estimate the anticipated rates of cardiovascular events and death in the target population. To obtain estimates of these rates, data were abstracted from randomized, double-blind, placebo-controlled trials performed in patients with claudication and designed to show functional improvement, and which have been published since 1990. Patient-year exposures and the number of deaths, serious adverse events and cardiovascular serious adverse events in the placebo arms of these trials were tabulated, and summed event rates calculated. The mortality rate was 1.9 deaths per hundred patient-years (27 deaths observed in 1446 patient-years). The mortality rate in claudication trials is lower than that reported in natural history studies. Cardiovascular serious adverse events in claudication trials were observed at a rate of 8.5 per hundred patient-years (65 events in 762 patient-years). Thus, cardiovascular morbidity and mortality should be expected in clinical trials enrolling claudicants. The current analyses provide benchmark data for ensuring that development programs are large enough to allow meaningful safety conclusions, and to assist in data and safety monitoring of these trials.
引用
收藏
页码:141 / 145
页数:5
相关论文
共 29 条
[1]   A new pharmacological treatment for intermittent claudication:: Results of a randomized, multicenter trial [J].
Beebe, HG ;
Dawson, DL ;
Cutler, BS ;
Herd, JA ;
Strandness, DE ;
Bortey, EB ;
Forbes, WP .
ARCHIVES OF INTERNAL MEDICINE, 1999, 159 (17) :2041-2050
[2]   Risk assessment in drug development for symptomatic indications: A framework for the prospective exclusion of unacceptable cardiovascular risk [J].
Brass, EP ;
Lewis, RJ ;
Lipicky, R ;
Murphy, J ;
Hiatt, WR .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2006, 79 (03) :165-172
[3]   European multicenter study on propionyl-L-carnitine in intermittent claudication [J].
Brevetti, G ;
Diehm, C ;
Lambert, D .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1999, 34 (05) :1618-1624
[4]   Exercise in claudicants is accompanied by excessive thrombin generation [J].
Burns, P ;
Wilmink, T ;
Fegan, C ;
Bradbury, AW .
EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY, 2003, 26 (02) :150-155
[5]   A double-blind, placebo-controlled study of the effects of policosanol in patients with intermittent claudication [J].
Castaño, G ;
Más, R ;
Roca, J ;
Fernández, L ;
Illnait, J ;
Fernández, JC ;
Selman, E .
ANGIOLOGY, 1999, 50 (02) :123-130
[6]   MORTALITY OVER A PERIOD OF 10 YEARS IN PATIENTS WITH PERIPHERAL ARTERIAL-DISEASE [J].
CRIQUI, MH ;
LANGER, RD ;
FRONEK, A ;
FEIGELSON, HS ;
KLAUBER, MR ;
MCCANN, TJ ;
BROWNER, D .
NEW ENGLAND JOURNAL OF MEDICINE, 1992, 326 (06) :381-386
[7]   A comparison of cilostazol and pentoxifylline for treating intermittent claudication [J].
Dawson, DL ;
Cutler, BS ;
Hiatt, WR ;
Hobson, RW ;
Martin, JD ;
Bortey, EB ;
Forbes, WP ;
Strandness, DE .
AMERICAN JOURNAL OF MEDICINE, 2000, 109 (07) :523-530
[8]   Cilostazol has beneficial effects in treatment of intermittent claudication - Results from a multicenter, randomized, prospective, double-blind trial [J].
Dawson, DL ;
Cutler, BS ;
Meissner, MH ;
Strandness, DE .
CIRCULATION, 1998, 98 (07) :678-686
[9]  
Dormandy J, 1999, Semin Vasc Surg, V12, P123
[10]   A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) [J].
Gent, M ;
Beaumont, D ;
Blanchard, J ;
Bousser, MG ;
Coffman, J ;
Easton, JD ;
Hampton, JR ;
Harker, LA ;
Janzon, L ;
Kusmierek, JJE ;
Panak, E ;
Roberts, RS ;
Shannon, JS ;
Sicurella, J ;
Tognoni, G ;
Topol, EJ ;
Verstraete, M ;
Warlow, C .
LANCET, 1996, 348 (9038) :1329-1339