Telomerase activator TA-65MD® in patients with ACS (TACTIC)

INTERVENTION: Design and patient population: The TACTIC trial will be a single site, double blinded randomised placebo controlled pilot trial. The study will take place at The James Cook University Hospital where the patients' routine care for a heart attack would normally take place under the care of consultant cardiologists in the research team. A total of 90 heart attack patients with a diagnosis of coronary heart disease will be recruited to the study. The patient journey: Potentially eligible patients will be identified by the local research team, given a patient information sheet to read, allowed time and opportunity to ask the research team any questions they have before being asked to give written informed consent. Once consent has been given the patient will have their medical history checked and their blood pressure measured to confirm eligibility. Eligible patients will have the following baseline assessments: 1. Blood sample for exposure to the cytomegalovirus 2. Blood sample for blood glucose 3. Blood sample for high sensitivity C Reactive Protein and N‐terminal pro‐brain natriuretic peptide markers of inflammation and heart failure respectively 4. Blood sample for research bloods to measure CD8 T cell ageing (primary endpoint) 5. Blood sample for research bloods to measure immune cell ageing (secondary endpoints), telomere length, and telomerase activity 6. Blood sample to obtain plasma to measure oxidative stress 7. Blood sample to obtain stored serum for further research (with specific consent) 8. Echocardiogram (heart scan) 9. Endothelial function 10. Physical assessment for height and weight 11. Record of patients' medications Once all of these assessments have been performed the patient may be randomised All patients will have been successfully treated for their heart attack prior to randomisation to either the test arm (TA65MD) or the placebo control arm with 45 patients in each arm. Once the patient has been randomised they may begin taking their CONDITION: Specialty: Cardiovascular Disease, Primary sub‐specialty: Atherothrombosis; UKCRC code/ Disease: Cardiovascular/ Ischaemic heart diseases ; Circulatory System PRIMARY OUTCOME: Immunosenescence determined by flow cytometry (FACS) after 1 year of treatment. The proportion of terminally differentiated CD8+ effector memory cells (%CD8+ TEMRA 'aged') will be calculated from the total number of peripheral blood CD8+ T‐lymphocytes in each blood sample; Timepoint(s): End of the study. INCLUSION CRITERIA: 1. Able to give written informed consent 2. Patients aged 65 or over with an index presentation of an acute coronary syndrome* within the previous 6 months 3. Successfully completed revascularisation** or managed medically following ACS 4. Angiographic evidence of coronary heart disease (at least one major epicardial vessel stenosis =70%) 5. More than 24 hours after presentation with the index event *Acute coronary syndrome (ACS) defined as either a non ST elevation acute coronary syndrome (NSTEMI), or ST elevation MI (STEMI) only. **PCI/angioplasty (eligible the following day) or surgery (eligible 3 months later) SECONDARY OUTCOME: 1. Leukocyte Telomere Length measured at baseline, 6 months and 1 year; short leukocyte telomere length is a predictor of cardiovascular mortality ; 2. CD8 T‐cell telomere length measured at baseline, 6 months and 1 year; short telomere length is a predictor of cardiovascular mortality, and CD8 telomere length is significantly reduced in patients with coronary heart disease and post myocardial infarction. Isolated peripheral blood mononuclear cells (PBMCs) will be FACS sorted to purify CD8 cells.; 3. The proportion of senescent (CD28‐) CD4+ T‐lymphocytes measured at baseline, 6 months and 1 year and calculated from the total number of CD4+ T‐lymphocytes in each PBMC sample. CD28‐ CD4+ T‐lymphocytes have been shown to be significantly increased in patients with acute coronary syndrome; 4. The proportion of senescent (CD28‐) CD8+ T‐lymphocytes measured at baseline, 6 months and 1 year and calculated from the total number of CD8+ T‐lymphocytes in each PBMC sample ; 5. Microvascular Endothelial Function assessed by measuring flow‐mediated dilation (FMD) using finger plethysmography (EndoPat) at baseline, 6 months and 1 year of treatment. Using plethysmography at the fingertips of both hands, the EndoPAT system (Itamar Medical Ltd., Caesarea, Israel) will calculate an index of pulse wave amplitude after cuff occlusion to before occlusion of the test arm divided by the same ratio of the control arm, namely the reactive hyperemic index (RHI). FMD has been shown to be compromised in patients with diabetes as well as with coronary artery disease. It is a predictor of adverse clinical outcome. Endothelial dysfunction is seen as the initial step in atherogenesis. ; 6. Systemic inflammation measured by high sensitivity C‐reactive protein (hsCRP) at baseline, 6 months and 12 months of treatment; 7. Heart failure and cardiac function assessed by transthoracic echocardiography (TTE) at baseline and 12 months of treatment, and the pro natriuretic peptide NT‐proBNP biomarker at baseline, 6 months and 12 months of treatment. Together these measures determine myocardial function, hypertrophy (left ventricular wall thickness), strain (NT‐proBNP), and global longitudinal strain, reflecting the pathophysiological targets of heart failure; 8. Telomerase activity assessed at baseline, 6 and 12 months following treatment using the TRAP assay. This provides an indication of drug effect; 9. Oxidative stress measured at baseline, 6 and 12 months following treatment using the TBARS colorimetric assay (Oxford Biomedical Research) with frozen plasma. TBARS is an established assay to quantify lipid peroxides. Additionally, the trialists will evaluate whether treatment with TA‐65MD® leads to parallel activation of canonical and non‐canonical pathways, measuring oxidative stress and endothelial function over time and correlating this with telomere length dynamics and telomerase activity.; 10. The effect of CMV seropositivity at baseline will be correlated with study outcomes using an exploratory analysis; 11. Adherence to the study drugs determined by counts of returned capsules and packaging at each dispensing visit; 12. Adverse events recorded from the time of randomisation to withdrawal or the last study visit. All cause death, stroke and myocardial infarction will also be combined to provide a composite outcome