Aspirin and Thienopyridine Resistance in Peripheral Arterial Disease

The Effect of Aspirin and Thienopyridine Non-responsiveness on Outcomes in Peripheral Arterial Disease

This study evaluates the effects of Aspirin and thienopyridine resistance in relation to clinical cardiovascular outcomes as the genetic predictors of, and outcomes associated with aspirin and thienopyridine resistance in patients with peripheral arterial disease (PAD) currently remain unknown.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease; Clopidogrel, Poor Metabolism of

Detailed Description

Although anti-platelet therapy is a cornerstone of PAD treatment, the investigators know very little about the prevalence, genetic determinants and clinical relevance of aspirin and thienopyridine resistance in PAD patients. The investigators expect to report on the prevalence of, and impact on outcomes from aspirin and/or thienopyridine (eg. clopidogrel) resistance, in patients who undergo peripheral arterial angiography/interventions (including carotid angiography/interventions) and operations. This study will provide important information on the utility of testing for aspirin and thienopyridine resistance and improve understanding of the genetic and pathophysiologic basis of anti-platelet therapy resistance in patients with cardiovascular disease, including PAD. Most importantly, this study will serve as the basis for a subsequent randomized prospective trial of different treatment options in PAD patients with aspirin/thienopyridine resistance.

• Study Type: Observational
• Enrollment (Actual): 195

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients enrolled between August 2010 and September 2012, with angiographically documented PAD involving carotid or lower extremity arteries. Patients may have been treated surgically or endovascularly at the discretion of the primary physician.

Description

Inclusion Criteria:

• patient undergoing PAD (carotid or lower extremity) angiography or intervention
• greater than or equal to 18 years of age

Exclusion Criteria:

• patient unable to take aspirin and thienopyridine for any reason (not excluded if take at least one of either medication)
• hematocrit less than or equal to 30%
• hematocrit greater than or equal to 52%

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Aspirin responsive; The participant is shown to be responsive to platelet activity inhibition by aspirin, as determined by testing with VerifyNow
Aspirin non-responsive; The participant is shown to be non-responsive to platelet activity inhibition by aspirin, as determined by testing with VerifyNow
Clopidogrel responsive; The participant is shown to be responsive to platelet activity inhibition by clopidogrel, as determined by testing with VerifyNow
Clopidogrel non-responsive; The participant is shown to be responsive to platelet activity inhibition by clopidogrel, as determined by testing with VerifyNow

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clopidogrel non-responsiveness	Clopidogrel non-responsiveness was defined as patients with Plavix reaction units (PRU) ≥ 235	Immediate
Aspirin non-responsiveness	Aspirin non-responsiveness was defined as patients with aspirin reaction units (ARU) ≥ 550	Immediate
Composite of major adverse cardiovascular events	Composite of major adverse cardiovascular events including all-cause mortality, myocardial infarction, stroke, target vessel revascularization (TVR) and limb loss in patients who underwent extremity intervention.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic predictors of aspirin and clopidogrel non-responsiveness	Single nucleotide polymorphisms (SNP) were correlated to measures of aspirin and clopidogrel non-responsiveness	Immediate

Collaborators and Investigators

• Sponsor: University of California, Davis
• Investigators: Principal Investigator: khung keong, MD, Cardiovascular interventionalist

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2010
• Primary Completion (Actual): May 17, 2013
• Study Completion (Actual): December 20, 2013

Study Registration Dates

• First Submitted: May 25, 2017
• First Submitted That Met QC Criteria: May 31, 2017
• First Posted (Actual): June 5, 2017

Study Record Updates

• Last Update Posted (Actual): June 5, 2017
• Last Update Submitted That Met QC Criteria: May 31, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: genetics; clopidogrel; aspirin; peripheral arterial disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: 224399

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes