The Risk of Major Bleeding With Novel Anti-platelets: A Comparison of Ticagrelor With Clopidogrel in a Real World Population of 5000 Patients Treated for Acute Coronary Syndrome (ROBOT-ACS)

A retrospective real world analysis of bleeding events with ticagrelor compared to clopidogrel in ACS patients.

Study Overview

• Status: Completed
• Conditions: Bleeding; Acute Coronary Syndrome; Ticagrelor; Clopidogrel; Novel Anti-platelets
• Intervention / Treatment: Drug: Ticagrelor

Detailed Description

Major bleeding after myocardial infarction portends a poor outcome. A balance is required between potency of platelet inhibition and risk of bleeding. Ticagrelor provides faster and more effective platelet inhibition than Clopidogrel. In the PLATO trial Ticagrelor reduced the incidence of cardiovascular death, myocardial infarction and stroke compared to Clopidogrel after ACS (acute coronary syndrome). Although there was no difference in overall bleeding there was more non-CABG related major bleeding with Ticagrelor. It has since been recommended, in addition to aspirin, in treatment of moderate-high risk ACS by both ESC (European Society of Cardiology) and NICE (National Institute for Clinical Excellence). There has been widespread adoption as first line therapy in UK hospitals. There remains potential concern about bleeding in a "real world" population compromising more high risk patients; particularly more elderly and female, than those in PLATO. The investigators intend to perform a large "real world" comparison of bleeding risk with Ticagrelor compared to Clopidogrel in a UK ACS population. The investigators plan an observational cohort study of patients presenting with ACS at 5 district general hospitals in Merseyside and Cheshire. The investigators will collect data retrospectively on 2500 patients treated with Clopidogrel prior to the guideline change and 2500 treated with Ticagrelor thereafter. The primary end point will be incidence of BARC 3-5 (Bleeding Academic Research Consortium) and PLATO major bleeding.

• Study Type: Observational
• Enrollment (Actual): 5225

Contacts and Locations

Study Locations

• United Kingdom
  • Liverpool, United Kingdom, L97AL
    • University Hospital Aintree

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All-comers treated for ACS above the age of 18 with either clopidogrel or ticagrelor

Description

Inclusion Criteria:

1. Patient commenced on clopidogrel for ACS prior to change of ACS guidelines, or tiacgrelor for same indication afterwards.

Exclusion Criteria:

1. Patient already taking the drug in question (clopidogrel or ticagrelor) prior to the ACS event
2. Patients under 18 years of age
3. Patients in whom the drug is stopped during the same hospital admission due to clinical judgement dictating that it is no longer indicated (this does not apply to patients in whom a bleeding event is the precipitant for stopping the drug)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Clopidogrel Group; Those patients treated with clopidogrel for ACS (before new guideline implementation)
Ticagrelor Group; Those patients treated with ticagrelor for ACS (after new guideline implementation)	Drug: Ticagrelor; No intervention- purely observational; Other Names: Clopidogrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of major bleeding defined by both BARC (3-5) and PLATO definitions	bleeding event	12 months from treatment starting

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of minor bleeding as defined by BARC and PLATO	Minor bleeding	12 months from treatment starting
Incidence of gastrointestinal bleeding	GI bleeding	12 months from treatment starting
Incidence of intracranial bleeding	intracranial bleeding	12 months from treatment starting
Rate of major adverse cardiovascular events; myocardial infarction, stroke and cardiovascular death	MACE/ischaemic events	12 months from treatment starting
Mortality	all cause mortality	12 months from treatment starting

Collaborators and Investigators

• Sponsor: Liverpool University Hospitals NHS Foundation Trust
• Collaborators: Liverpool Heart and Chest Hospital NHS Foundation Trust; Countess of Chester NHS Foundation Trust; St Helens & Knowsley Teaching Hospitals NHS Trust
• Investigators: Principal Investigator: Aleem Khand, MBChB MRCP, University Hospital Aintree

Publications and helpful links

General Publications

• Mullen L, Meah MN, Elamin A, Aggarwal S, Shahzad A, Shaw M, Hasara J, Rashid M, Fisher M, Ali T, Patel B, Ding WY, Grainger R, Heseltine T, Kirmani BH, Obeidat M, Kasolo Y, Thatchil J, Khand A. Risk of Major Bleeding With Potent Antiplatelet Agents After an Acute Coronary Event: A Comparison of Ticagrelor and Clopidogrel in 5116 Consecutive Patients in Clinical Practice. J Am Heart Assoc. 2021 Apr 20;10(8):e019467. doi: 10.1161/JAHA.120.019467. Epub 2021 Apr 9.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): June 1, 2016
• Study Completion (ACTUAL): June 1, 2016

Study Registration Dates

• First Submitted: June 26, 2015
• First Submitted That Met QC Criteria: June 29, 2015
• First Posted (ESTIMATE): June 30, 2015

Study Record Updates

• Last Update Posted (ACTUAL): June 9, 2022
• Last Update Submitted That Met QC Criteria: June 6, 2022
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Hemorrhage; 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: 680/15

Drug and device information, study documents

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