Date of Approval:
It has been well documented that patients with elevated levels of cholesterol are at increased risk of cardiovascular events such as heart attack and stroke. One particular component of cholesterol known as low density lipoprotein cholesterol (LDL-C) has been shown to be most closely associated with the increased risk of cardiovascular events. Statins and other cholesterol-lowering therapies therefore aim to reduce LDL-C as this has been shown to reduce cardiovascular events. However, some patients fail to reduce LDL-C to what are considered ‘safe’ levels despite being treated with the highest doses of existing treatments. Recent trials have reported that a new therapy known as Inclisiran may be effective at targeting these people who do not respond well to existing treatment. In this study we wish to use the Clinical Practice Research Datalink to select three groups of patients at risk of cardiovascular event who also have evidence of high LDL-C levels. These groups are i) those who have already had a cardiovascular event ii) those who have other risk factors associated with cardiovascular events and iii) those with familial hypercholesterolemia; a condition where the patient has very high LDL-C levels which are difficult to reduce with current treatments. We then wish to profile these patients in terms of their age and gender and other demographic information, other conditions they may have, their existing treatment patterns and impact of this treatment on their LDL-C levels. This will help in providing information about the population that could benefit from new treatments including Inclisiran.
Low density lipoprotein cholesterol (LDL-C) has been strongly associated with cardiovascular disease (CVD) and coronary heart disease (CHD) risk. It has been demonstrated that reducing LDL-C may halt the progression of atherosclerotic plaque and thus reduce the incidence of atherosclerotic cardiovascular disease (ASCVD). Inclisiran is a long-acting, subcutaneously delivered, synthetic siRNA directed against PCSK9 messenger RNA that is conjugated to triantennary GalNAc carbohydrates for targeted delivery to the liver. The ORION randomized clinical trials demonstrated increased efficacy of inclisiran versus placebo in reducing LDL-C. In this retrospective, descriptive study we aim to use the Clinical Practice Research Datalink to conduct a retrospective, descriptive study of the patient groups eligible for the Orion. Three non-mutually exclusive patient cohorts with i) ASCVD, ii) ASCVD-risk equivalent (based on presence of Type 2 diabetes, familial hypercholesterolemia or a baseline Framingham risk score indicative of 20% chance of 10 year cardiovascular event), iii) familial hypercholesterolemia will be extracted. From these study sets those with evidence of hypercholesterolemia based on either clinical diagnosis, LDL-C test results or prescription of lipid-lower therapy will form the three study cohorts. The primary objective is to describe the demographics, clinical characteristics, baseline biochemistry and baseline lipid lowering regimens of these cohorts. Secondary objectives are to assess initial cholesterol-lowering treatment patterns in terms of dose changes, switching, adding discontinuation and re-initiation and to understand how treatment patterns relate to changes in LDL-C levels over time. Linked data from the Hospital Episode Statistics admitted patient care dataset will also be used to ascertain both exposures and descriptive disease and surgical procedure outcomes.
Health Outcomes to be Measured:
Patient demographics; cardiovascular comorbidities; baseline cholesterol-lowering therapy, baseline biochemistry, therapy change, LDL-C change.
Christopher Morgan - Chief Investigator - Pharmatelligence Limited
Christopher Morgan - Corresponding Applicant - Pharmatelligence Limited
Raquel Lahoz - Collaborator - NOVARTIS
Thomas Berni - Collaborator - Pharmatelligence Limited