Rivaroxaban Plus Aspirin in Patients With Chronic Coronary Syndrome and High Ischemic Risk

Effectiveness and Safety of Low Dose Rivaroxaban Plus Aspirin in Patients With Chronic Coronary Syndrome and High Ischemic Risk

Registry to describe the impact in terms of effectiveness and safety of the combination treatment of rivaroxaban 2.5 mg twice daily with aspirin on clinical outcomes and practices in a real-life Dutch patient population that are at high risk of ischemic events.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease (CAD); Peripheral Arterial Disease (PAD)
• Intervention / Treatment: Drug: Rivaroxaban 2.5 MG [Xarelto]

Detailed Description

This study is a national multicentre (~15 sites), prospective, single-arm, observational study in patients treated with rivaroxaban 2.5mg bid on top of ASA75-100mg OD (N=1000). Female and male patients with a diagnosis of CCS and/or symptomatic PAD will be enrolled in the (outpatient) clinic after the decision for treatment with rivaroxaban 2.5mg bid, co-administered with acetylsalicylic acid has been made by the treating physician.

The primary effectiveness endpoint is a composite of:

• Major Adverse Cardiac Events (MACE including stroke, cardiovascular mortality and myocardial infarction)
• Clinically driven coronary, peripheral or carotid revascularization
• Stent thrombosis at one year

The primary safety endpoint is Major Bleeding at one year. These major bleeding complications are analysed according to the International Society on Thrombosis and Haemostasis (ISTH) criteria as a composite of fatal bleeding, symptomatic bleeding into a critical organ (such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome), bleeding causing a fall in haemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells.

The secondary endpoints will be:

• Occurrence (and date) of stroke
• Occurrence (and date) of myocardial infarction
• Occurrence (and date) of cardiovascular death
• Occurrence (and date) of coronary revascularization procedures (PCI, CABG).
• Occurrence (and date) of peripheral revascularization procedures.
• Occurrence (and date) of carotid revascularization procedures.
• Occurrence (and date) of minor bleeding complications (according to ISTH)

In addition, all bleeding events including minor bleedings according to ISTH definitions will be reported.

• Study Type: Observational
• Enrollment (Actual): 645

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • OLVG
  • Arnhem, Netherlands
    • Rijnstate Hospital
  • Den Bosch, Netherlands
    • Jeroen Bosch Hospital
  • Den Haag, Netherlands
    • Haaglanden Medisch Centrum
  • Den Haag, Netherlands
    • Hagaziekenhuis
  • Enschede, Netherlands
    • Medisch Spectrum Twente
  • Heerlen, Netherlands
    • Zuyderland Medical Center
  • Meppel, Netherlands
    • Isala Klinieken, location Meppel
  • Nieuwegein, Netherlands
    • St. Antonius Hospital
  • Tilburg, Netherlands
    • Elisabeth-Tweesteden Hospital
  • Venlo, Netherlands
    • VieCuri
  • Zwolle, Netherlands
    • Isala Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Female and male patients with a diagnosis of CCS and/or symptomatic PAD will be enrolled in the (outpatient) clinic within 4 weeks after the decision for treatment with rivaroxaban 2x2.5mg plus ASA (75-100mg) has been made by the investigator (according to label (indicated for the prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischemic events)) and who consent to participate in the study.

Description

Inclusion Criteria:

• Adult (≥18 years) patient.

• Diagnosis of CAD and/or PAD and high risk of ischemic events.

  • Patients at high risk of ischaemic events include the following:
  • CAD + PAD
  • CAD + Recurrent MI (Previous MI followed by second MI)
  • CAD + diabetes mellitus (all types)
  • CAD + chronic kidney disease with eGFR 30-59 ml/min/1.73 m2 (CKD-EPI formula)
  • CAD + heart failure (ejection fraction ≥30% - 50%) and New York Heart Association (NYHA) class I or II;)
  • CAD + CHA2DS2VaSc ≥ 3 (for men) or ≥ 4 (for women)
• Patients can only be enrolled in the study if the decision to treat with rivaroxaban plus ASA has been made by the treating physician in advance and independent of study inclusion, however within 4 weeks prior to study inclusion.
• Treatment according to local marketing authorization, with rivaroxaban 2.5 mg [BID] and 80mg ASA / 100mg Carbasalate calcium. Treatment of rivaroxaban started within 4 weeks prior or 4 weeks after study inclusion.
• Patients who are willing to participate in this study (signed informed consent).

Exclusion Criteria:

• Hypersensitivity/allergy and known contraindication to ASA/Carbasalate calcium or rivaroxaban

• Patients with recent major bleeding, active bleeding, or history with:

  • History of major clinical bleeding or known coagulopathy
  • History of intracerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke
  • Known severe liver dysfunction
• Patients that have received any organ transplant or await any organ transplant
• Patient with anemia (Hb < 6.0 mmol/L)
• Patient with active malignancy
• Patients with ejection fraction < 30% and/or New York Heart Association (NYHA) class III or IV
• Patients with eGFR < 30 ml/min/1.73m2 or undergoing dialysis
• Patients with liver failure accompanied with coagulopathy ( incl. Child-Pugh B and C)
• Patients with concomitant use of other anticoagulants or antiplatelet drugs
• Pregnant or lactating female
• Patients currently participating in another investigational drug or drug-coated device study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome Measures	The primary efficacy endpoint is a composite of 1) Major Adverse Cardiovascular Events (MACE), which is a composite endpoint of cardiovascular mortality, myocardial infarction and stroke, 2) clinically driven coronary, peripheral or carotid revascularization, and 3) stent thrombosis, that will be reported at 1 year. The primary safety endpoint is major bleeding according to the International Society on Thrombosis and Haemostatsis (ISTH) criteria that will be reported at 1 year. It is a composite of 1) fatal bleeding, 2) symptomatic bleeding into a critical organ (such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome), 3) bleeding causing a fall in haemoglobin level of 2 g/dL (1.24 mmol/L) or more, or 4) leading to transfusion of two or more units of whole blood or red cells.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome Measures	The secondary efficacy and safety endpoint is the incidence of individual endpoints, that will be reported at 1 year: Occurrence (and date) of stroke; Occurrence (and date) of myocardial infarction; Occurrence (and date) of cardiovascular death; Occurrence (and date) of coronary revascularization procedures (PCI, CABG).; Occurrence (and date) of peripheral revascularization procedures.; Occurrence (and date) of carotid revascularization procedures.; Occurrence (and date) of minor bleeding complications (according to ISTH)	one year

Collaborators and Investigators

• Sponsor: Maatschap Cardiologie Zwolle
• Collaborators: Diagram B.V.
• Investigators: Principal Investigator: Rik Hermanides, MD, PhD, Isala

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2020
• Primary Completion (Actual): September 13, 2023
• Study Completion (Actual): September 13, 2023

Study Registration Dates

• First Submitted: December 22, 2020
• First Submitted That Met QC Criteria: February 10, 2021
• First Posted (Actual): February 15, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Coronary Artery Disease (CAD); peripheral arterial disease (PAD); high ischemic risk
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Peripheral Arterial Disease; Peripheral Vascular Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Aspirin; Rivaroxaban
• Other Study ID Numbers: Dutch Rivaroxaban CCS Registry

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No