Title: Rivaroxaban for preventing major cardiovascular events in people with coronary or peripheral artery disease [ID1397]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of rivaroxaban within its marketing authorisation for preventing atherothrombotic events in people with coronary or peripheral artery disease at high risk of ischaemic events.

Lay abstract: Coronary heart disease (CHD) also known as coronary artery disease or ischaemic heart disease is narrowing (stenosis) of the coronary arteries as a result of a build-up of fatty material in artery walls to form a plaque (also known as atheroma), which results in an insufficient supply of oxygen to the heart muscle. If the atheroma ruptures, it can cause a blood clot (thrombus), a condition referred to as atherothrombosis, which may block blood flow to heart muscles causing a heart attack (myocardial infarction). Sometimes blood clots may dislodge and travel in the blood stream (embolism) and block blood flow to the brain causing a stroke. Risk factors for CHD include smoking, a diet high in saturated fat, high levels of low-density lipoprotein cholesterol, high blood pressure, diabetes, being overweight or obese, lack of exercise, age, gender and family history.(1) People who survive a cardiovascular event are at high-risk of recurrence or developing further cardiovascular disease. CHD is one of the leading causes of death in England, accounting for over 53,000 deaths each year and over 66,000 in 2016. 1.8 million people in England have CHD. Incidence of CHD increases with age and is higher among men than women. Mortality and morbidity rates also vary by socio-economic group, geographic area and ethnicity.(2) Similarly to CHD, peripheral arterial disease (PAD) is caused by atherosclerosis in which narrowed arteries reduce blood flow to the limbs (PAD usually develops in the legs, but other arteries may be involved). Many people with peripheral arterial disease have no symptoms. However, some people develop a painful ache in their legs when they walk, which usually disappears after a few minutes rest. In severe cases some people may develop critical limb ischaemia, which can result in tissue loss, ulceration and gangrene. The process of atherosclerosis that causes peripheral arterial disease can also lead to serious and potentially fatal problems such as heart attacks and stroke.(3) Risk factors for PAD include smoking, diabetes and high blood pressure or cholesterol. The presence of PAD has been shown to identify people who are at increased risk of cardiac and cerebrovascular morbidity and mortality.(3) Approximately 348,000 people in England are living with PAD. The incidence of PAD increases with age and population studies have found that about 20% of people aged over 60 years have some degree of PAD. Over 9,000 people in England died from diseases of the arteries, arterioles and capillaries, including PAD, in 2016.(2) NICE clinical guideline 172 for the secondary prevention of atherothrombotic events for people following a myocardial infarction recommends exercise, dietary changes and help to stop smoking for people who smoke. It also recommends that everyone who has an acute myocardial infarction should be offered treatment with a combination of an angiotensin-converting enzyme inhibitor, dual antiplatelet therapy (aspirin plus a second antiplatelet agent), a beta-blocker and a statin. The guideline recommends that aspirin should be offered indefinitely after a myocardial infarction. NICE technology appraisal guidance 420 also recommends ticagrelor in combination with aspirin for people who had a myocardial infarction and who are at high risk of a further event. Ticagrelor should be offered for a maximum of 3 years. NICE clinical guideline 172 also recommends clopidogrel monotherapy as an alternative for people with aspirin hypersensitivity. People with lower limb PAD are considered separately in NICE clinical guideline 147. The recommendations align with NICE clinical guideline 172 and additionally recommend clopidogrel as an option to prevent occlusive vascular events, in line with NICE technology appraisal guidance 210. References 1. NHS Choices (2016) Cardiovascular disease. Accessed March 2018. Available at: http://www.nhs.uk/conditions/Cardiovascular- disease/Pages/Introduction.aspx 2. British Heart Foundation (2018) Cardiovascular disease statistics 2018. Accessed March 2018. Available at: https://www.bhf.org.uk/research/heart-statistics/heart-statistics- publications/cardiovascular-disease-statistics-2018 3. NHS Choices (2016) Peripheral arterial disease. Accessed March 2018. Available at: https://www.nhs.uk/conditions/peripheral-arterial-disease-pad/

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR