Clinical trial NCT00761969: Prevention of Ischemic Events in Patients With Peripheral Arterial Disease
Official title: Prevention of Ischemic Events in Patients With Peripheral Arterial Disease by the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Peripheral Arterial Disease
Keywords: peripheral arterial disease
secondary prevention
cardiovascular /atherothrombotic events
European guidelines
Cardiovascular disease prevention
Lead sponsor: KRKA
Sponsor class: INDUSTRY
Collaborators: name: University Medical Centre Ljubljana
name: University of Ljubljana School of Medicine, Slovenia
name: Krka, d.d., Novo mesto, Slovenia
First posted: 2008-09-30
Enrollment: 1455
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with stable, objectively confirmed PAD, recruited from primary care settings in Slovenia, Europe.

Control subjects of comparable age- and sex-distribution, without PAD, recruited from primary care settings in Slovenia, Europe.

Brief summary: The PID-PAB study aims to test the efficacy of the European Guidelines on Cardiovascular Disease Prevention in patients with peripheral arterial disease. Survival, the rate of major atherothrombotic events (myocardial infarction, stroke, critical limb ischemia) and the incidence of revascularization procedures will be compared between a group of patients with stable peripheral arterial disease (PAD) and age- and sex-matched control subjects without PAD. Both groups will be receiving up-to-date medical care according to their cardiovascular risk based on the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice. Yearly follow-up is planned for 5 years. The PID PAB study aims to test (a) whether stable PAD is still an adverse prognostic indicator in spite of contemporary preventive measures, and (b) to what extent do contemporary preventive measures improve the prognosis of patients with PAD in comparison to historic controls, representing the natural history of the disease.

Detailed description: The observational study Prevention of Ischemic Events in Patients with Peripheral Arterial Disease by the European Guidelines on Cardiovascular Disease Prevention (Slovenian acronym of the study: PID-PAB)aims to test the efficacy of the European Guidelines on Cardiovascular Disease Prevention in patients with peripheral arterial disease, who have an even higher mortality rate than patients with isolated coronary artery disease or cerebrovascular disease when left to the natural course of the disease. The PID-PAB study will compare the rates of survival, major atherothrombotic events (myocardial infarction, stroke, critical limb ischemia) and revascularization procedures between a group of patients with stable peripheral arterial disease (PAD) and a control group of age- and sex-matched subjects without PAD. Both groups will be receiving up-to-date medical care (including life-style advice and prescription of cardioprotective medication) according their cardiovascular risk based on the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice. PAB is defined by a reduced ankle-brachial pressure index of =\< 0.90, while absence of PAD is defined by palpable pedal pulses and a normal ankle-brachial index (0.91-1.30). Exclusion criteria are: age \< 40 or \> 80 years at inclusion, active cancer or other disease with a life expectancy of les than 5 years, any major atherothrombotic event in 30 days prior to enrollment, and pregnancy. All subjects will be followed annually for 5 years by comprehensive medical examinations. The settings of the study are primary care facilities in Slovenia, European Union. The target size of each group is 1000 subjects, i.e., 5000 patient years. The number of participating physicians-researchers is estimated at 100, with a goal for each physician to recruit 10 patients with PAD and 10 age- and sex-matched controls. The study is coordinated by a steering committee consisting of researchers from the Department of Vascular Diseases at the University of Ljubljana Medical Centre, Institute of Biomedical Informatics at the University of Ljubljana School of Medicine, Department of Family Medicine at the University of Ljubljana School of Medicine and the pharmaceutical company Krka, Slovenia, who is also the sponsor of the study. The protocol of the study has been approved by the Committee of Medical Ethics of the Republic of Slovenia.

The PID PAB study aims to answer the questions:

1. Is stable PAD is still an adverse prognostic indicator in spite of contemporary preventive measures?
2. To what extent do contemporary preventive measures improve the prognosis of patients with PAD in comparison to historic controls (described in earlier reports on the natural history of PAD ? We expect to still find a significant difference in the rate of cardiovascular events between patients with PAD and their peers without PAD, but we hypothesize that contemporary preventive measures will strongly attenuate the adverse prognosis of PAD regarding survival and major atherothrombotic events in comparison to the natural history of the disease.

Eligibility criteria: Inclusion Criteria:

1. Patients with PAD: ankle-brachial pressure index \<= 0.90
2. Controls: palpable pedal pulses, ankle-brachial pressure index 0.91-1.30

Exclusion Criteria:

1. Age \< 40 or \> 80 years at inclusion
2. Malignancy with a life expectancy \< 5 years
3. Atherothrombotic event within a month before inclusion (acute coronary syndrome, stroke or documented transient ischemic attack, critical limb ischemia)
4. pregnancy

Primary outcomes:
measure: Incidence of Major Cardiovascular Events
timeFrame: 5 years:
Secondary outcomes:
measure: Incidence of Revascularization Procedures
timeFrame: 5 years
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: Department of Vascular Diseases, University of Ljubljana Medical Center
Study officials:
affiliation: Dept of Vascular Diseases, University of Ljubljana Med Ctr
name: Ales Blinc, MD, DSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR, McCann TJ, Browner D. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992 Feb 6;326(6):381-6. doi: 10.1056/NEJM199202063260605.
citation: Newman AB, Shemanski L, Manolio TA, Cushman M, Mittelmark M, Polak JF, Powe NR, Siscovick D. Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study Group. Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):538-45. doi: 10.1161/01.atv.19.3.538.
citation: Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, Krook SH, Hunninghake DB, Comerota AJ, Walsh ME, McDermott MM, Hiatt WR. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001 Sep 19;286(11):1317-24. doi: 10.1001/jama.286.11.1317.
citation: Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86. doi: 10.1136/bmj.324.7329.71.
citation: Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002 Jul 6;360(9326):7-22. doi: 10.1016/S0140-6736(02)09327-3.
citation: Heart Outcomes Prevention Evaluation Study Investigators; Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000 Jan 20;342(3):145-53. doi: 10.1056/NEJM200001203420301.
citation: De Backer G, Ambrosioni E, Borch-Johnsen K, Brotons C, Cifkova R, Dallongeville J, Ebrahim S, Faergeman O, Graham I, Mancia G, Manger Cats V, Orth-Gomer K, Perk J, Pyorala K, Rodicio JL, Sans S, Sansoy V, Sechtem U, Silber S, Thomsen T, Wood D; Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J. 2003 Sep;24(17):1601-10. doi: 10.1016/s0195-668x(03)00347-6. No abstract available.
citation: Giampaoli S, Capewell S, Shelley E, Allender S, Briggs A, Jorgensen T, Labarthe D, Marques-Vidal P, Stegmayr B, Verschuren WM, Zdrojewski T. Foreword. Eur J Cardiovasc Prev Rehabil. 2007 Dec;14 Suppl 3:S1. doi: 10.1097/01.hjr.0000296928.40040.b0. No abstract available.
citation: Blinc A, Kozak M, Sabovic M, Bozic Mijovski M, Stegnar M, Poredos P, Kravos A, Barbic-Zagar B, Stare J, Pohar Perme M. Survival and event-free survival of patients with peripheral arterial disease undergoing prevention of cardiovascular disease. Int Angiol. 2017 Jun;36(3):216-227. doi: 10.23736/S0392-9590.16.03731-7. Epub 2016 Jun 22.
citation: Blinc A, Kozak M, Sabovic M, Bozic M, Stegnar M, Poredos P, Kravos A, Barbic-Zagar B, Pohar Perme M, Stare J; PID-PAB Investigators. Prevention of ischemic events in patients with peripheral arterial disease design, baseline characteristics and 2-year results an observational study. Int Angiol. 2011 Dec;30(6):555-66.