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

ANTIPLATELET TREATMENT IN ACUTE CORONARY SYNDROMES. SAFETY AND EFFICACY OF ANTIPLATELET SWITCHING Safety and Efficacy of Ticagrelor vs Clopidogrel in Patients With Acute Coronary Syndrome

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).

Study Overview

• Status: Unknown
• Conditions: Acute Coronary Syndromes
• Intervention / Treatment: Drug: Clopidogrel; Drug: Ticagrelor

Detailed Description

To date, there are still a paucity of data on the medium- and long-term safety and efficacy outcomes of new antiplatelet agents, namely Ticagrelor and Prasugrel, compared to Clopidogrel in a real-world ACS setting.

The ARIAM-Andalusia multicentre Registry, and the CREA-ARIAM multicentre Registry (ClinicalTrials.gov Identifier: NCT02500290; Fundación Pública Andaluza Progreso y SaludIdentifier: FPS-AAS-2014-01), are two Real World Evidence (RWE) studies aimed to investigate real-world practice on antiplatelet treatment in patients with ACS in Andalusia (Western Spain).

Our group are interested in performing a retrospective observational pilot analysis using data from patients with ACS admitted to cardiovascular intensive care units in Andalusia (Spain), who were prospectively included in the ARIAM-Andalusia multicentre Registry, and the CREA-ARIAM multicentre Registry (ClinicalTrials.gov Identifier: NCT02500290; Fundación Pública Andaluza Progreso y Salud-Identifier: FPS-AAS-2014-01) between 2014 and March 2019. The main findings from the RWE study revealed a consistent net clinical benefit of Ticagrelor vs Clopidogrel resulted in a significant reduction of short-term all-cause mortality favored Ticagrelor. In this scenario, after baseline imbalance adjustment using propensity score matching (PSM) and IPTW (inverse probability of treatment weight) methods, the net clinical benefit with Ticagrelor persisted. Preliminary results of the above mentioned study have been presented as an oral communication at the Annual Scientific Meeting of the Spanish Society of Cardiology (Madrid, October 2017).

The aim of this new pilot study suggested is to describe the efficacy and safety of Ticagrelor vs Clopidogrel after the first 30 days from hospital discharge and up to 1 year follow-up.

• Study Type: Observational
• Enrollment (Actual): 1900

Contacts and Locations

Study Locations

• Spain
  • Sevilla, Spain
    • Hospital Universitario Virgen Macarena
  • Sevilla, Spain, 41092
    • Fundación Pública Progreso y Salud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with ACS in a real world setting

Description

Inclusion Criteria:

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.

Exclusion Criteria:

• 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.
• Pregnancy, breast-feeding, or intend to become pregnant during the study period population should be always considered as exclusion criterion.
• 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; 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; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thrombolysis in Myocardial Infarction (TIMI)	Bleeding criteria	During 2 months
BARC definition	Bleeding criteria	During 2 months
Major Adverse Cardiac and Cerebrovascular Events (MACCE)	Defined as the composite of all-cause mortality, myocardial infarction (MI), target lesion revascularization (TLR), stent thrombosis and stroke or TIA at 1-year follow-up after the index ACS admission.	During 2 months
All-cause mortality	Component of MACCE	During 2 months
Myocardial infarction	Component of MACCE	During 2 months
Target lesion revascularization	Component of MACCE	During 2 months
Stent thrombosis	Component of MACCE	During 2 months
Stroke	Component of MACCE	During 2 months
Net clinical benefit/Net Adverse Clinical Event (NACE):	Defined as the composite of the efficacy (Major Adverse Cardiac and Cerebrovascular Events-MACCE) and safety (BARC type≥ 2 bleeding episodes according to the Bleeding Academic Research Consortium (BARC) definition for bleeding) outcomes at 1 year after the index ACS.	During 2 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2019
• Primary Completion (Actual): November 1, 2019
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: January 14, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Actual): November 16, 2020
• Last Update Submitted That Met QC Criteria: November 10, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: FPS-AAS-2019-01 (ESR-17-13127)

Drug and device information, study documents

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