Vascular Medicine

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Register here to gain access to SAGE's 500+ Journals Online

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brass, E. P
Right arrow Articles by Hiatt, W. R
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brass, E. P
Right arrow Articles by Hiatt, W. R
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Vascular Medicine, Vol. 11, No. 3, 141-145 (2006)
DOI: 10.1177/1358863x06069513

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

Eric P Brass

Department of Medicine, Harbor-UCLA Center for Clinical Pharmacology, Torrance, CA, USA, ebrass{at}ucla.edu

William R Hiatt

Department of Medicine, Section of Vascular Medicine, University of Colorado Health Sciences Center, Colorado Prevention Center, Denver, CO, USA

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.

Key Words: claudication • clinical trials • morbidity • mortality • peripheral arterial disease

References

  • Hiatt WR. Medical treatment of peripheral arterial disease and claudication . N Engl J Med 2001; 344: 1608-1621 .[Free Full Text]
  • McDermott MM, Mehta S, Liu Ket al. Leg symptoms, the ankle-brachial index, and walking ability in patients with peripheral arterial disease . J Gen Intern Med 1999; 14: 173-181 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Hiatt WR, Hirsch AT, Regensteiner JG, Brass EP. Clinical trials for claudication. Assessment of exercise performance, functional status, and clinical end points. Vascular Clinical Trialists . Circulation 1995; 92: 614-621 .[Free Full Text]
  • Brass EP, Lewis RJ, Lipicky R, Murphy J, Hiatt WR. Risk assessment in drug development for symptomatic indications: a framework for the prospective exclusion of unacceptable cardiovascular risk . Clin Pharmacol Ther 2006; 79: 165-172 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Criqui MH, Langer RD, Fronek Aet al. Mortality over a period of 10 years in patients with peripheral arterial disease . N Engl J Med 1992; 326: 381-386 .[Abstract]
  • Dormandy J, Heeck L, Vig S. The natural history of claudication: risk to life and limb . Semin Vasc Surg 1999; 12: 123-137 .[Medline] [Order article via Infotrieve]
  • Muluk SC, Muluk VS, Kelley MEet al. Outcome events in patients with claudication: a 15-year study in 2777 patients . J Vasc Surg 2001; 33: 251-257; discussion 257-58.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee . Lancet 1996; 348: 1329-1339 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Ostergren J, Sleight P, Dagenais Get al. Impact of ramipril in patients with evidence of clinical or subclinical peripheral arterial disease . Eur Heart J 2004; 25: 17-24 .[Abstract/Free Full Text]
  • Dawson DL, Cutler BS, Meissner MH, Strandness DE Jr. Cilostazol has beneficial effects in treatment of intermittent claudication: results from a multicenter, randomized, prospective, double-blind trial . Circulation 1998; 98: 678-686 .[Abstract/Free Full Text]
  • Money SR, Herd JA, Isaacsohn JLet al. Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease . J Vasc Surg 1998; 27: 267-274; discussion 274-75.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Beebe HG, Dawson DL, Cutler BSet al. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial . Arch Intern Med 1999; 159: 2041-2050 .[Abstract/Free Full Text]
  • Brevetti G, Diehm C, Lambert D. European multicenter study on propionyl-L-carnitine in intermittent claudication . J Am Coll Cardiol 1999; 34: 1618-1624 .[Abstract/Free Full Text]
  • Lievre M, Morand S, Besse B, Fiessinger JN, Boissel JP. Oral Beraprost sodium, a prostaglandin I(2) analogue, for intermittent claudication: a double-blind, randomized, multicenter controlled trial. Beraprost et Claudication Intermittente (BERCI) Research Group . Circulation 2000; 102: 426-431 .[Abstract/Free Full Text]
  • Dawson DL, Cutler BS, Hiatt WRet al. A comparison of cilostazol and pentoxifylline for treating intermittent claudication . Am J Med 2000; 109: 523-530 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Hiatt WR, Regensteiner JG, Creager MAet al. Propionyl-L-carnitine improves exercise performance and functional status in patients with claudication . Am J Med 2001; 110: 616-622 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • McGrath C, Robb R, Lucas AJet al. A randomised, double blind, placebo-controlled study to determine the efficacy of immune modulation therapy in the treatment of patients suffering from peripheral arterial occlusive disease with intermittent claudication . Eur J Vasc Endovasc Surg 2002; 23: 381-387 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Lederman RJ, Mendelsohn FO, Anderson RDet al. Therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (the TRAFFIC study): a randomised trial . Lancet 2002; 359: 2053-2058 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Rajagopalan S, Mohler ER 3rd, Lederman RJet al. Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication . Circulation 2003; 108: 1933-1938 .[Abstract/Free Full Text]
  • Mohler ER 3rd, Hiatt WR, Olin JW, Wade M, Jeffs R, Hirsch AT. Treatment of intermittent claudication with beraprost sodium, an orally active prostaglandin I2 analogue: a double-blinded, randomized, controlled trial . J Am Coll Cardiol 2003; 41: 1679-1686 .[Abstract/Free Full Text]
  • Hiatt WR, Klepack E, Nehler Met al. The effect of inhibition of acyl coenzyme A-cholesterol acyltransferase (ACAT) on exercise performance in patients with peripheral arterial disease . Vasc Med 2004; 9: 271-277 .[Abstract/Free Full Text]
  • Hiatt WR, Hirsch AT, Cooke JP, Olin JW, Brater DC, Creager MA. Randomized trial of AT-1015 for treatment of intermittent claudication. A novel 5-hydroxytryptamine antagonist with no evidence of efficacy . Vasc Med 2004; 9: 18-25 .[Abstract/Free Full Text]
  • Gresele P, Migliacci R, Di Sante G, Nenci GG. Effect of cloricromene on intermittent claudication. A randomized, double-blind, placebo-controlled trial in patients treated with aspirin: effect on claudication distance and quality of life. CRAMPS Investigator Group. Cloricromene Randomized Arteriopathy Multicenter Prospective Study . Vasc Med 2000; 5: 83-89 .[Abstract/Free Full Text]
  • Castano G, Mas R, Roca Jet al. A double-blind, placebo-controlled study of the effects of policosanol in patients with intermittent claudication . Angiology 1999; 50: 123-130 .[ISI][Medline] [Order article via Infotrieve]
  • Nenci GG, Gresele P, Ferrari G, Santoro L, Gianese F. Treatment of intermittent claudication with mesoglycan - a placebo-controlled, double-blind study . Thromb Haemost 2001; 86: 1181-1187 .[ISI][Medline] [Order article via Infotrieve]
  • Messa GL, Gelso E. Heparan sulfate in the treatment of intermittent claudication: results of a randomized, double-blind, placebo-controlled multicenter trial . Drugs Exp Clin Res 2002; 28: 37-48 .[ISI][Medline] [Order article via Infotrieve]
  • Strandness DE Jr, Dalman RL, Panian Set al. Effect of cilostazol in patients with intermittent claudication: a randomized, double-blind, placebo-controlled study . Vasc Endovascular Surg 2002; 36: 83-91 .[Abstract/Free Full Text]
  • Packer M, Carver JR, Rodeheffer RJet al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group . N Engl J Med 1991; 325: 1468-1475 .[Abstract]
  • Burns P, Wilmink T, Fegan C, Bradbury AW. Exercise in claudicants is accompanied by excessive thrombin generation . Eur J Vasc Endovasc Surg 2003; 26: 150-155 .[CrossRef][ISI][Medline] [Order article via Infotrieve]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brass, E. P
Right arrow Articles by Hiatt, W. R
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brass, E. P
Right arrow Articles by Hiatt, W. R
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?