Platelet Activity in Vascular Surgery and Cardiovascular Events (PACE)

Pathological and clinical studies have consistently demonstrated that abnormalities in thrombosis and hemostasis play a major role in the pathogenesis of atherosclerosis and atherothrombosis. Screening for abnormalities in thrombosis and hemostasis by measuring platelet activity, thrombin generation, and markers of coagulation have been proposed to identify individuals at high-risk for cardiovascular events, however, it remains a research tool not ready for implementation in standard care.

The proposed study will add to the growing understanding of platelet activity and markers of coagulation in cardiovascular disease; examine a comprehensive battery of platelet activity markers, thrombin generation, markers of coagulation, and inflammatory biomarkers in subjects undergoing vascular surgery; and will provide important data on the mechanism of increased platelet activity using micro RNA, RNA and DNA expression profiling. The study design is prospective and the main outcome measure is platelet activity measurements associated with short-term cardiovascular events in PAD patients

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; Peripheral Artery Disease; Critical Limb Ischemia

Detailed Description

The main aim is to determine whether preoperative platelet activity measurements are independently associated with short-term cardiovascular events in Peripheral artery disease (PAD) patients undergoing open non-emergent lower extremity vascular surgery. We will characterize the platelet phenotype in 350 PAD patients before vascular surgery and use Cox proportional hazard models to determine the independent association of the platelet phenotype with risk of cardiovascular events in the first 30 days after surgery.

Blood collection at three different time points (before surgery, following surgery while still in the hospital, and at the subjects' first return visit to the vascular surgeon following surgery) will allow us to assess the dynamic change in platelet activity, coagulation and inflammation during the perioperative period. We believe that markers of clotting and bleeding will change during the course of surgery, and that some of these markers may be used to help predict the likelihood of developing a clotting or bleeding event following surgery. The long-term goal is to develop a clinically useful assessment of platelet activity, thrombin generation, coagulation and inflammation for risk stratification that may ultimately serve as a target for therapeutic intervention.

• Study Type: Observational
• Enrollment (Actual): 246

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center and School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study's population will be obtained form NYU Langone Medical Center, Bellevue Hospital and the VA Hospital.

Description

Inclusion Criteria:

1. Subjects undergoing non emergent lower extremity revascularization
2. Use of aspirin within 48 hours prior to surgery
3. Age > 21 years of age
4. Able and willing to provide written informed consent for the study

Exclusion Criteria:

1. Use of any therapeutic anticoagulant
2. Use of any nonsteroidal antiinflammatory drug (ibuprofen, naproxen, etc.) within 72 hours
3. Thrombocytopenia (platelet count<100) or Thrombocytosis (platelet count>500)
4. Anemia (hemoglobin<9)
5. Any known hemorrhagic diathesis

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Platelet Hyperactivity; Subjects with platelet hyperactivity undergoing non emergent lower extremity revascularization.
No Platelet Hyperactivity; Subjects with no platelet hyperactivity undergoing non emergent lower extremity revascularization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients in Which Platelet Activity Measurements Were Associated With Short-term Cardiovascular Events	To determine whether preoperative platelet activity measurements are independently associated with short-term cardiovascular events in Peripheral artery disease (PAD) patients undergoing open non-emergent lower extremity vascular intervention. We will characterize the platelet phenotype in 350 PAD patients before vascular surgery and use Cox proportional hazard models to determine the independent association of the platelet phenotype with risk of cardiovascular events in the first 30 days after surgery.	30-days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between platelet activity measurements and long-term cardiovascular events in patients with established PAD	To determine whether platelet activity measurements are independently associated with long-term cardiovascular events in patients with established PAD. We will characterize the postoperative platelet phenotype following surgery and use Cox proportional hazards models to determine the independent association of the platelet phenotype with risk of long-term composite of myocardial infarction, stroke, or all-cause mortality with a mean follow-up of 2-years following vascular surgery.	Average follow-up of 5-years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
mRNA-microRNA co-expression profiles in patients with and without elevated platelet activity measurements	To investigate mRNA-microRNA co-expression profiles in patients with and without elevated platelet activity measurements. We will establish the relationship between differentially expressed microRNAs and their target mRNAs related to platelet activity and thus identify new diagnostic markers and potential therapeutic targets of increased platelet activity.	30-days

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Jeffrey Berger, MD, New York University Director of Cardiovascular Thrombosis

Publications and helpful links

General Publications

• Dann R, Hadi T, Montenont E, Boytard L, Alebrahim D, Feinstein J, Allen N, Simon R, Barone K, Uryu K, Guo Y, Rockman C, Ramkhelawon B, Berger JS. Platelet-Derived MRP-14 Induces Monocyte Activation in Patients With Symptomatic Peripheral Artery Disease. J Am Coll Cardiol. 2018 Jan 2;71(1):53-65. doi: 10.1016/j.jacc.2017.10.072.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): June 14, 2018
• Study Completion (Actual): June 14, 2018

Study Registration Dates

• First Submitted: January 22, 2014
• First Submitted That Met QC Criteria: April 3, 2014
• First Posted (Estimated): April 8, 2014

Study Record Updates

• Last Update Posted (Actual): August 20, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Vascular Surgery
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease Attributes; Atherosclerosis; Peripheral Vascular Diseases; Chronic Disease; Cardiovascular Diseases; Peripheral Arterial Disease; Chronic Limb-Threatening Ischemia
• Other Study ID Numbers: 14-00531; R01HL114978 (U.S. NIH Grant/Contract)