The British Heart Foundation older patients with non-ST SEgmeNt elevatIOn myocaRdial infarction Randomized Interventional TreAtment Trial The BHF SENIOR-RITA Trial working together as Newcastle Academic Health Partners

Trial Summary Multi-centre study involving 30 NHS sites (England, Scotland, Wales and [Northern Ireland to include]) Patients over 75 years admitted with Type 1 NSTEMI 5 Year follow up, 10 years collecting HES & ONS data Total Recruitment target: 2300 patients over 3 years

Timelines Open to recruitment: September 2016 36 month recruitment period Interventional arm: Coronary angiography and coronary revascularisation within 7 days of randomisation Recruitment end date: 30th September 2019 End of trial: 30th September 2029

Regulatory approvals REC favourable ethical opinion (UK): 3rd August 2016 HRA Approval (England): 8th August 2016

Background: Our Population is Ageing..... ONS 2012

Burden of Coronary Disease in Older Patients Patients >70 years represent over half of all myocardial infarctions Average age of first non ST elevation MI (NSTEMI) is 70 years Yet fewer older patients receive contemporary care MiNAP Database 2012-2013 Eur Heart J 2014; 35(23):1551-8

Frail versus Non-Frail p=0.28 Frail older patients with NSTEMI have a significantly higher mortality at one year * p=<0.0001 p=0.48 p=0.74 Eur J Prev Cardiol 2014 21(10):1216-24

Representation of Older Patients In Clinical Trials/Registries Patients >75 years account for 9% of trial participants! 32% trials actively excluded participants >75 years! JAMA. 2001;286(6):708-713

Current Problem NHS/Economy Older patients are under represented in clinical trials – patients aged ≥75 years are excluded from clinical trials (9% of all patients enrolled in trials) Existing guidelines (ESC, NICE) on invasive care are based on younger age group (mean age 62 years) Advanced care including revascularisation and pharmacotherapy are under utilised in older patients Frail, comorbid, cognitively impaired patients presenting with NSTEMI have not been previously studied in clinical trials Heart 2016 2016 Mar;102(6):416-24

The BHF SENIOR-RITA Whether the beneficial effects of revascularisation will be demonstrated in frail older patients with co-morbidities presenting with NSTEMI is unknown and will be investigated SENIOR-RITA specifically aims to investigate all-comer older patients with NSTEMI high-risk co-morbid frail older patients and those with cognitive impairment who normally would be denied invasive care due to underlying co-morbidity and in whom there is lack of evidence currently in the management of NSTEMI.

The BHF SENIOR-RITA Study Setting and Flow Chart n=2300 Multicentre prospective randomised controlled trial of invasive versus conservative management 30 NHS centres with on and offsite cardiac catheter lab facilities throughout the UK

The BHF SENIOR-RITA: Primary Objective To determine if a routine invasive strategy reduces overall one-year cardiovascular death and non-fatal myocardial infarction compared with a conservative treatment strategy in older patients (≥75 years) with NSTEMI.

The BHF SENIOR-RITA: Secondary Objective(s) To determine the impact of a routine invasive strategy compared with a conservative strategy on: All-cause, cardiovascular and non-cardiovascular death rates Recurrent myocardial infarction Hospitalisation for heart failure Urgent coronary revascularisation Recurrent hospitalisation for myocardial infarction Stroke Bleeding (BARC 2) Procedural complications (including death, MI, major bleeding (BARC definition), 25% increase in serum creatinine concentration from baseline, need for renal replacement therapy, stroke) Length of time spent at home Fried and Rockwood frailty scores Quality of Life using EQ-5D-5L and quality adjusted life years (QALY) Costs to the NHS and personal social services Incremental cost per QALY gained at 1 year

The BHF SENIOR-RITA Eligibility Criteria Inclusion Criteria Aged ≥75 years Type 1 NSTEMI during index hospitalisation Exclusion Criteria STEMI or unstable angina, cardiogenic shock Neither the patient nor the consultee able to provide written informed consent Previous inclusion in the SENIOR-RITA trial Inability to undergo invasive coronary angiography, such as no vascular access site, or absolute contraindication to coronary revascularisation.

The BHF SENIOR-RITA: Consent Patients with ability to provide informed consent: Patients will be provided with the PIS to read Informed consent will be obtained from patients Patients unable to provide informed consent: Some patients with cognitive impairment will be able to provide informed consent. In patients who lack the capacity to provide informed consent, identify and approach a consultee as defined by the Mental Capacity Act (2005). The consultee will be provided with the PIS and an information sheet for consultees and where appropriate, asked to sign the consultee declaration form

The BHF SENIOR-RITA: Schedule of Events   V1 Postal V2 V3 V4 V5 V6 V7 Event In-patient with NSTEMI 30 days ±14 days 3-months ±14 days 6-month ±14 days 1 year 2 year ± 28 days 3 year ±28 days 4 year ± 28 days 5 year ± 28 days Eligibility X Informed Consent Fried and Rockwood Frailty Score Required pre- randomisation Montreal Cognitive Assessment Randomize (Web) Patient Demographics, Baseline Admission Data Medical History, Risk Factors, Co-morbidities Baseline ECG Baseline Bloods (FBC, urea, creatinine, glucose, lipids, peak troponin) Angiography/Procedural Data Concomitant Medications Evaluate End-points Either Clinic or Post or Telephone or ONS, HES EQ-5D-5L Patient and Proxy NHS & PSS Utilisation† X† X‡ Time and Travel Questions

Recruitment Target Update The BHF SENIOR-RITA: Recruitment Target Update

Please think of SENIOR RITA for all >75 NSTEMI cases Please do get in touch with Newcastle CTU SENIOR RITA Trial Team with any questions relating to the trial With all your help we can achieve our target!!!

Key Contacts: Newcastle CTU Trial Manager Jaki Begum Jaki.Begum@newcastle.ac.uk Tel. 0191 208 8753 Trial Administrator Carol Shields Carol.shields@newcastle.ac.uk Trial Secretary Laura Robertson Laura.Robertson@newcastle.ac.uk Tel. 0191 208 2526 Database Manager Jonathan Pritchard Jonathan.Pritchard@newcastle.ac.uk