Anticoagulation for the Prevention of Arterial Thrombosis in Ambulatory Patients with Cancer: A Systematic Review

Lead Investigator: Marc Carrier, University of Ottawa
Title of Proposal Research:  Anticoagulation for the Prevention of Arterial Thrombosis in Ambulatory Patients with Cancer: A Systematic Review
Vivli Data Request: 7823
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Thrombosis (clots) associated with cancer is a major cause of complications and deaths among patients with cancer. The risk of artery-related clots (such as strokes, heart attacks and clots in leg arteries) are perceived to be high among patients on anti-cancer therapies. However, current evidence on whether anticoagulants (or blood-thinners) can prevent arterial clots in this population is unknown. This is a crucial topic, as current guidelines recommend use of preventive blood-thinners among patients starting anti-cancer therapies for prevention of blood clots in the vein systems (such as those involving the legs or lungs) among high-risk patients, but no recommendations current exist on whether the same dose and type of blood-thinning medications should be used for the prevention of artery-related clots. In 2018, 9.8 million people globally are estimated to have started anti-cancer therapy, and this represents a large evidence gap in the care of patients with cancer.

We will undertake a systematic search of the literature and identify all high-quality studies (such as clinical trials) in which patients starting anti-cancer therapy were randomly assigned to receive a blood-thinner or no blood-thinner. This is known as a systematic review of literature. We will then combine the data from all included studies to analyze rates of artery-related clots (such as strokes, heart attacks and clots in leg arteries), as well as risks of bleeding (a known complication of blood-thinners) and overall deaths. This is known as a meta-analysis. If a study included patients with or without anti-cancer therapy, we would attempt to only include patients that received anti-cancer therapy. This study will provide key insights into whether blood-thinners currently recommended for prevention of vein-related clots are also effective in prevention artery-related clots.

Statistical Analysis Plan:

We will extract the following data from all included studies:

  • Study information and characteristics: author, publication year, study design
  • Participant characteristics: number of patients included, % females, mean/median age, distribution of cancer sites (including solid tumour vs. lymphoma), stage (local vs. advanced) and treatments, % taking anti-platelets at baseline, number of patients lost to follow-up, adherence rate to assigned treatment
  • Baseline ATE risk factors, including % of participants with pre-existing coronary artery disease, ischemic stroke, peripheral artery disease, smoking.
  • Intervention/comparator characteristics: Type and dose of anticoagulant agent, duration of therapy, follow-up period.
  • Arterial thrombosis, safety outcomes (major/non-major bleeding), all-cause mortality

We will synthesize results from included studies in Microsoft Excel 2016 . The primary unit of analysis will be at the level of individuals randomized. In the event of more than two treatment groups, we will aggregate intervention groups Heterogeneity between studies will be assessed using the I² test.  Forest plots will be generated and inspected for each outcome. We will use a random-effects model to derive odds ratios (ORs) or relative risk (RR) as appropriate, with calculation of 95% confidence intervals (CIs). If the level of heterogeneity is unacceptable, a meta-analysis will not be attempted and a descriptive analysis will instead be pursued. Reasons for heterogeneity will be investigated and reported in subgroup analyses. We will not impute missing data for any of the outcomes. We will contact authors for missing outcome data and status of ongoing trials, as needed.

Where possible, subgroup analyses will be performed for ATE subtypes; targeted molecules vs. immunotherapy vs. conventional chemotherapy; aspirin use (daily versus not), stage (local versus advanced), dose of therapy (prophylactic, intermediate, and therapeutic dose), disease site (solid tumor versus lymphoma); inclusion of multiple treatment groups, duration of follow-up; and duration of therapy.

Requested Studies:

A Randomized, Controlled Trial to Evaluate the Effects of Nadroparin on Survival and Disease Progression in Patients With Advanced Malignancies of the Lung, Pancreas, or Prostate
Data Contributor: GlaxoSmithKline
Study ID: NCT00312013
Sponsor ID: FRX106365

A Multinational, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AVE5026 in the Prevention of Venous Thromboembolism (VTE) in Cancer Patients at High Risk for VTE and Who Are Undergoing Chemotherapy
Data Contributor: Sanofi
Study ID: NCT00694382
Sponsor ID: EFC6521

Public Disclosures:

  1. Mallity, C., Collins, E., Siegal, D., Wang, T., Carrier, M. and Xu, Y., 2023. IMPACT OF ANTICOAGULANTS FOR ARTERIAL THROMBOEMBOLISM PREVENTION AMONG AMBULATORY CANCER PATIENTS BY PRIMARY TUMOUR SITE: SYSTEMATIC REVIEW AND META-ANALYSIS. Canadian Journal of Diabetes, 47(7), pp.S209-S210. doi: 10.1016/j.jcjd.2023.10.390
  2. Mallity, C., Collins, E., Siegal, D., Wang, T., Carrier, M. IMPACT OF ANTICOAGULANTS FOR ARTERIAL THROMBOEMBOLISM PREVENTION AMONG AMBULATORY CANCER PATIENTS BY PRIMARY TUMOUR SITE: SYSTEMATIC REVIEW AND META-ANALYSIS. Canadian Journal of Cardiology, Volume 39, Issue 10, S252 – S253. doi: 10.1016/j.cjca.2023.06.405