Polypill Effects on Sub Clinical Atherosclerosis (PESCA) Trial
Polypill Effects on Sub Clinical Atherosclerosis (PESCA) Trial
Medications that lower blood pressure and cholesterol are known to improve the shape and
 function of our blood vessels. These improvements include a reduction in the thickness of the
 wall of the carotid artery (the main artery that runs up the neck to supply the brain) and a
 reduction in the stiffness of arteries generally including the main central artery -the
 aorta. Such medications are in the polypill (the Red Heart Pill) that is being used in the
 UMPIRE Study. In UMPIRE, patients' reported adherence to taking the single, once daily
 polypill is being compared to adherence to medications taken as separate tablets (usual
 care).The aim of the PESCA sub-study is to see whether or not the polypill differs from
 'usual care' in its direct effects on blood vessels as shown by ultrasound examination of the
 carotid arteries and assessment of central (aortic) blood pressure.
PESCA is a substudy of the UMPIRE clinical trial which is evaluating a 'polypill' treatment
 strategy for subjects with established cardiovascular disease or at high risk. All PESCA
 subjects will have already been recruited to UMPIRE and randomised to taking either a single
 'polypill' (comprising low dose aspirin, a cholesterol-lowering statin, and one of two blood
 pressure lowering medicines) or their usual treatment consisting of similar medication in
 more than one separate tablets.

 PESCA will evaluate whether: 1) progression of atherosclerosis (fatty deposits which narrow
 the arteries and impair blood flow to vital organs); and 2) central systolic blood pressure
 (the pressure in the body's main artery, the aorta, when the heart pumps out blood), are
 reduced in 'polypill' recipients compared to those who continue their usual treatment.
 Atherosclerosis and central blood pressure are both strongly associated with increased risk
 of heart attacks and stroke. Atherosclerosis will be assessed by ultrasound scanning of the
 carotid (neck) arteries to look at thickness of the artery walls (carotid intima media
 thickness)and plaques(fatty deposits). Direct measurement of central blood pressure is
 impractical but it will be estimated using a computerised "pulsecor" device. This uses an
 inflatable cuff on the arm but provides a detailed recording of the pressure wave as the cuff
 is deflated which enables "pulsecor" to calculate central blood pressure. Results from both
 ultrasound and blood pressure investigations will be reviewed by investigators who do not
 know whether the subjects have been randomised to the polypill or their usual treatment.

 PESCA assessments will be conducted at 2 visits:baseline (as soon as possible after
 recruitment to the UMPIRE study); and at the end of both studies (which will coincide).

 Parallel studies are being undertaken in the three European sites (UK, Eire and Netherlands)
 participating in the UMPIRE trial with each site aiming to recruit 300 participants.
Patients must meet the inclusion criteria for the UMPIRE trial, and be consented to take
 part in the PESCA sub-study.

 Inclusion criteria

 Individuals are eligible for inclusion if all of the following criteria are satisfied:

 Adults (≥ 18 years) The participant is able to give informed consent. Established
 atherothrombotic cardiovascular disease (CVD) or high cardiovascular risk, defined as;

 -  History of coronary heart disease (myocardial infarction, stable or unstable angina
 pectoris, or coronary revascularisation procedure), or

 -  History of ischaemic cerebrovascular disease (ischaemic stroke or transient ischaemic
 attack), or

 -  History of peripheral vascular disease (peripheral revascularisation procedure or
 amputation due to vascular disease), or

 -  For individuals without established cardiovascular disease, a calculated 5 year CVD
 risk of 15% or greater (calculated using the 1991 Anderson Framingham risk equation
 with adjustments as defined by the New Zealand Guidelines Group recommendations) The
 trial Investigator considers that each of the polypill components are indicated at the
 doses in the Red Heart Pill The trial Investigator is unsure as to whether a
 polypill-based strategy or usual care is better.

 Exclusion criteria

 Individuals will NOT be eligible if one or more of the following criteria are satisfied:

 -  Contraindication to any of the components of the polypill (e.g. known intolerance to
 aspirin, statins, or ACE inhibitors; pregnancy or likely to become pregnant or
 breastfeeding women during the treatment period).

 -  The treating doctor considers that changing a participant's cardiovascular medications
 would put the participant at risk (e.g. symptomatic heart failure, high dose β-blocker
 required to manage angina or for rate control in atrial fibrillation, accelerated
 hypertension, severe renal insufficiency, a history of severe resistant hypertension).

 Other potential reasons for exclusion include:

 -  Known situation where medication regimen might be altered for a significant length of
 time, e.g. current acute cardiovascular event, planned coronary bypass graft
 operation.

 -  Unlikely to complete the trial (e.g. life-threatening condition other than
 cardiovascular disease) or adhere to the trial procedures or attend study visits (e.g.
 major psychiatric condition, dementia).