High levels of low-density lipoprotein cholesterol (LDL-C), often referred to as ‘bad cholesterol’, are associated with an increased risk of cardiovascular events such as heart attacks and strokes. LDL-C can be reduced by certain medications including drugs called statins but despite taking high level doses of these therapies some patients still fail to reduce their LDL-C levels below recommended levels and thus remain at increased risk of cardiovascular events. People with a condition called familial hypercholesterolaemia have extremely high levels of LDL-C and, as a result, it is difficult to reduce their LDL-C levels to what is considered a safe level. A new drug called Inclisiran has been tested in clinical trials and been shown to reduce LDL-C levels in patients whose LDL-C was high despite being treated with other drugs. In this study, we wish to use the Clinical Practice Research Datalink to select a group of patients who either have familial hypercholesterolaemia or who have had a previous cardiovascular event and high levels of LDL-C. We then wish to describe these patients in terms of their age and gender, the other medical conditions they have and the other drugs that they have been taking. We then want to see how many of these people have new cardiovascular events or die either from a cardiovascular event of from any cause. This study will be important in helping to identify the size of the population that could potentially benefit from treatment with Inclisiran.
Low density lipoprotein cholesterol (LDL-C) has been strongly associated with cardiovascular disease and coronary heart disease risk. Clinical trials have demonstrated that reducing LDL-C with pharmaceutical interventions such as statins has been shown to be associated with reduced incidence of atherosclerotic cardiovascular disease (ASCVD). However, a large proportion of patients with elevated LDL-C have been shown to be refractory to conventional cholesterol lowering regimens. Patients with familial hypercholesterolemia are particularly difficult to manage due to genetically high baseline LDL-C levels. Inclisiran is a subcutaneously delivered therapy that has been shown in clinical trials to reduce refractory LDL-C in patients with atherosclerotic cardiovascular disease and familial hypercholesterolaemia. Novartis are interested in understanding these populations in terms of demography, comorbidity and risk of cardiovascular risk. In this study we wish to conduct a non-interventional, non-comparative, retrospective study using the Clinical Practice Research Datalink (CPRD). We will also use linked data from the Hospital Episode Statistics admitted patient care dataset to ascertain both exposures and outcomes. Three cohorts of patients with elevated LDL-C will be selected, those with either i) familial hypercholesterolemia, ii) history of atherosclerotic cardiovascular disease (coronary heart disease, cerebrovascular disease or peripheral arterial disease) or iii) atherosclerotic cardiovascular risk equivalent based on either comorbidity (type II diabetes or familial hypercholesterolemia) or Framingham score >20. These cohorts will not be mutually exclusive. We then wish to describe these cohorts in terms of demographics, cardiovascular and non-cardiovascular comorbidity, baseline biochemistry and baseline therapy profile. Crude rates of mortality, major adverse cardiovascular events (MACE) will be calculated by person year at risk and stratified by age, gender and baseline LDL-C category. A multi-state parametric model will then be constructed to estimate the transition probabilities between different disease states relating to MACE and non-cardiovascular mortality.
Revascularization; Unstable angina; Non-fatal myocardial infarction; Non-fatal stroke; Cardiovascular death; Non-cardiovascular death.
Christopher Morgan - Chief Investigator - Pharmatelligence Limited t/a Human Data Sciences
Christopher Morgan - Corresponding Applicant - Pharmatelligence Limited t/a Human Data Sciences
Adeline Durand - Collaborator - Novartis Pharmaceuticals UK Limited
David Trueman - Collaborator - Source Health Economics
Raquel Lahoz - Collaborator - NOVARTIS
Thomas Berni - Collaborator - Pharmatelligence Limited t/a Human Data Sciences
Thomas Berni - Collaborator - Pharmatelligence Limited t/a Human Data Sciences
HES Admitted Patient Care;ONS Death Registration Data