Anti-platelet therapy in the elderly with Non ST elevation acute coronary syndrome and CRUSADE score of at least 31
Conditions
Interventions
clopidogrel versus ticagrelor/prasugrel in patients aged at least 75 year with CRUSADE score of at least 31. At 3 months and 12 months patients will also be requested to fill out questionnaires to ass
Sponsors
St. Antonius teaching hospital
Eligibility
Inclusion criteria
Inclusion criteria: 1) At least 75 years of age. 2) Hospitalization for NSTEMI or unstable angina (UA), according to the following definitions NSTEMI (Non-ST-elevation myocardial infarction) will be defined as detection of a rise and/or fall of cardiac biomarker values [preferably cardiac troponin (cTn)] with at least one value above the 99th percentile upper reference limit (URL) and with at least one of the following: - Symptoms of ischaemia. - New or presumed new significant ST-segment–T wave (ST–T) changes other than ST-segment elevation. - Development of pathological Q waves in the ECG. - Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. - Identification of an intracoronary thrombus by angiography or autopsy. UA (unstable angina) will be defined as acute onset of chest pain consistent with symptoms of ischaemia without rise in cardiac biomarker values, which may or may not be consistent with ECG changes suggesting ischaemia. Diagnosis of UA and NSTEMI should be made by decisional doctor. 3) A CRUSADE bleeding risk score of at least 31
Exclusion criteria
Exclusion criteria: Exclusion criteria 1) Contraindication to P2Y12 inhibitors i.e. clopidogrel, prasugrel or ticagrelor: - Hypersensitivity to the active substance or to any of the excipients - History of intracranial bleeding or active pathological bleeding such as peptic ulcer or intracranial haemorrhage - Moderate to severe (Child-Pugh C) hepatic disfunction. - Concomitant use of ticagrelor with strong CYP3A4 inhibitors (e.g. itraconazol, voriconazol, ketoconazol, erytromycine, clarithromycine, rifampicine, nefozodon, lopinavir, ritonavir en atazanavir) 2) Unable or unwilling to give informed consent or have a life expectancy of less than one year 3) Active malignancy with increase in bleeding risk, in the investigator’s opinion. 4) Having received thrombolytic therapy within the previous 24 hours or oral anticoagulants during the previous 7 days. 5) Severe renal function impairment needing dialysis. 6) Confirmed or persistent severe hypertension (Systolic Blood Pressure (SBP) > 180 mmHg and/or Diastolic Blood Pressure (DBP) >110 mmHg) at randomization. 7) Contraindication to anticoagulation or at increased bleeding risk, at the investigator’s opinion, i.e. because of active malignancy. 8) Cardiogenic shock (SBP ≤ 80mmHg for >30 mins) or needing Intra-Aortic Balloon Pump (IABP) at presentation. 9) History of major surgery, severe trauma, fracture or organ biopsy within 90 days prior to randomisation. 10) Clinically significant out of range values for platelet count or haemoglobin at screening, in the investigator’s opinion. 11) ACS under dual antiplatelet therapy, e.g. aspirin with a P2Y12 inhibitor; clopidogrel, prasugrel, ticagrelor. 12) Patients either homozygous or heterozygous carriers of a CYP2C19*2 or *3 allele if known at time of randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The first primary endpoint is the occurrence of any bleeding episode at 30 days and 1 year after diagnosis and second primary endpoint is the net clinical benefit at 30 days and 1 year after diagnosis. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary safety endpoints are the number of patients with (non-)CABG-related major bleeding, major bleeding, minor bleeding, life threatening bleeding, fatal bleeding, intracranial bleeding and bleed requiring transfusion or the number of patients with combination of these endpoints at 30 days and 1 year after diagnosis. Different bleeding classifications will be used, i.e. TIMI, PLATO, GUSTO and BARC bleeding scales to make the study comparable to previous and future publications Secondary net clinical benefit endpoints are the number of patients who either died from any cause other than vascular or bleeding causes, died from vascular causes, died from bleeding causes (= fatal bleeding), developed recurrent myocardial infarction, stroke, unstable angina, trans ischemic attack, other arterial thrombosis, PLATO major and minor bleeding or the number of patients with combinations of these endpoints at 30 days and at one year after diagnosis. Secondary efficacy endpoints are the number of patients who either died, died from cardiovascular death, from cerebrovascular death, developed recurrent MI, stent thrombosis, underwent urgent target vessel revascularisation (TVR), hospitalization for ACS, developed stroke or the number op patients with combinations of these endpoints at 30 days and at one year after diagnosis. Secondary endpoints in terms of quality of life are measurements obtained with EuroQol 5D and SF36 questionnaires. Tertiary endpoints would be the evaluation of genetic variants on the response to clopidogrel and prasugrel or ticagrelor in terms of efficacy and safety in a candidate gene approach, Genome Wide Association Study or (next generation) sequencing | — |
Contacts
Public ContactV.H.M. Deneer
St. Antonius Hospital Dept Clinical Pharmacy PO Box 2500
Outcome results
None listed