Safety and Efficacy of Ticagrelor vs Clopidogrel in Patients With Acute Coronary Syndrome

NCT04630288 | Unknown

• 1 other identifier: FPS-AAS-2019-01 (ESR-17-13127)
• Study Type: observational
• Target: 1,900
• Locations: 1 country
• Sites: 2

Brief Summary

Multicenter post-approval observational retrospective cohort study in routine clinical practice (Real World Evidence Study) to assess the 1-year safety profile associated with ticagrelor and clopidogrel therapy in a contemporary reprospective cohort of patients who survived the initial 30-day period after the index hospitalization for acute coronary syndrome (ACS).

Conditions

Acute Coronary Syndromes

Outcome Measures

Primary Outcomes (1)

• Major bleeding

  Defined as BARC type≥ 3 according to the Bleeding Academic Research Consortium (BARC) definition at 1-year follow-up after the index ACS.

  During 2 months

Secondary Outcomes (9)

• Thrombolysis in Myocardial Infarction (TIMI)

  During 2 months

• BARC definition

  During 2 months

• Major Adverse Cardiac and Cerebrovascular Events (MACCE)

  During 2 months

• All-cause mortality

  During 2 months

• Myocardial infarction

  During 2 months

Study Arms (2)

Clopidogrel

Clopidogrel is a prodrug that requires metabolic activation in two stepsby hepatic CYP450 enzymes to produce the active metabolite that inhibits platelet aggregation. The active metabolite of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet P2Y12 receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Consequently, due to the irreversible binding to the P2Y12 receptor,platelets exposed to clopidogrel's active metabolite are affected for the remainder of their lifespan (about 7 to 10 days) and recovery of normal platelet function occurs at a rate consistent with the normal platelet turnover. Clopidogrel was approved by the European Commission on 15 July 1998 for the secondary prevention of atherothrombotic events in adult patients with ACS.

Drug: Clopidogrel

Ticagrelor

Ticagrelor is a nucleoside analogue member of the chemical class cyclopentyltriazolopyrimidines (CPTP), which is a selective and reversible ADP- receptor antagonist acting on the platelet P2Y12 receptor. This prevents the binding of ADP to the receptor which attenuates plateletactivation and aggregation.The drug was approved by the European Commission on December 3, 2010, for the prevention of thrombotic events (cardiovascular death, myocardial infarction and stroke) in patients with ACS (unstable angina, non ST elevation Myocardial Infarction \[NSTEMI\] or ST elevation Myocardial Infarction \[STEMI\]) including patients managed medically, and those who are managed with percutaneous coronary intervention (PCI) or coronary artery by-pass grafting (CABG).

Drug: Ticagrelor

Interventions

Clopidogrel DRUG

Describe the safety of Ticagrelor vs Clopidogrel use, in patients with ACS in terms of major bleeding between 30 days and one year after the index ACS event. An ITT approach and IPCW method to adjust for change of initial treatment will be used for the analysis.

Clopidogrel

Ticagrelor DRUG

Describe the safety of Ticagrelor vs Clopidogrel use, in patients with ACS in terms of major bleeding between 30 days and one year after the index ACS event. An ITT approach and IPCW method to adjust for change of initial treatment will be used for the analysis.

Ticagrelor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with ACS in a real world setting

You may qualify if:

• All-comers ACS population (with or without ST segment elevation, including unstable angina) with:
• A recent CCU admission (patients included in the ARIAM-CREA study within 1 week from the index ACS admission between March 1, 2015 to March 31, 2018), irrespective of either the initial management (invasive or non-invasive) or the revascularization procedure (PCI with stenting or CABG) discharged on DAPT including either Ticagrelor or Clopidogrel and have survived the first 30-day follow-up period from the index ACS event and could complete a 12-month follow-up.

You may not qualify if:

• Age \< 18 years.
• Subjects who died in the first 30-day follow-up period from the index ACS event, including those who died during the index admission.
• A medical condition likely to limit survival to less than 1 year.
• Any factors judged by the local investigators to be likely to limit adherence to pharmacological treatment.
• Failure to obtain informed consent from participant.
• Currently enrolled in an interventional clinical research trial involving an investigational product (drug) or device
• Not available for follow-up over a minimum of 365 days, e.g. no fixed home address.
• Non-ACS diagnosis at discharge, i.e., acute myocarditis, Takotsubo syndrome, pulmonary thromboembolism or acute aortic syndromes.
• Myocardial infarction secondary to an ischaemic imbalance or type 2 myocardial infarction (Third Universal Definition of MI), in instances of myocardial injury with necrosis, where a condition other than CAD contributes to an imbalance between myocardial oxygen supply and/or demand, i.e., anaemia, sepsis, tachyarrhythmias, hypotension, heart failure…
• Patients not discharged on dual antiplatelet therapy (DAPT) consistent on low dose of ASA plus a P2Y12platelet receptor inhibitor (Clopidogrel or Ticagrelor)
• Patient discharged on DAPT including Prasugrel as the P2Y12 inhibitor drug.
• Hypersensitivity to ticagrelor or any of the excipients.
• Active pathological bleeding.
• History of intracranial haemorrhage (ICH).
• Severe hepatic impairment.

Sponsors & Collaborators

• Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud: lead

Study Sites (2)

Fundación Pública Progreso y Salud

Seville, 41092, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

Related Publications (1)

• Almendro-Delia M, Blanco-Ponce E, Carmona-Carmona J, Arboleda Sanchez JA, Rodriguez Yanez JC, Soto Blanco JM, Fernandez Garcia I, Castillo Caballero JM, Garcia-Rubira JC, Hidalgo-Urbano RJ. Comparative Safety and Effectiveness of Ticagrelor versus Clopidogrel in Patients With Acute Coronary Syndrome: An On-Treatment Analysis From a Multicenter Registry. Front Cardiovasc Med. 2022 May 27;9:887748. doi: 10.3389/fcvm.2022.887748. eCollection 2022.

  PMID: 35711382 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Clopidogrel; Ticagrelor

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2020
• First Posted: November 16, 2020
• Study Start: July 2, 2019
• Primary Completion: November 1, 2019
• Study Completion: December 31, 2020
• Last Updated: November 16, 2020

Record last verified: 2020-11

Locations

ES (2)