Abstract 19079: Major Room for Intensification of Statin Therapy in Patients With Severe Familial Hypercholesterolemia or Cardiovascular Disease Before Initiation of PCSK9 Inhibitors

Introduction: PCSK9 inhibitors are indicated for patients with severe familial hypercholesterolemia (FH) or cardiovascular disease (CVD) not reaching ideal LDL-cholesterol levels despite maximum dose of statins. The prevalence of severe FH and CVD in the general population, and how statin therapy is implemented in these patients, are critical to anticipate the costs associated with the prescription of PCSK9 inhibitors.Methods: We studied 6,717 adults aged 35-75 years from a prospective population-based cohort study in Switzerland. At baseline, prevalence of severe FH was defined according to the latest position statement of the International Atherosclerosis Society Severe FH Panel. Severe FH was diagnosed if untreated LDL-cholesterol levels were u003e 400 mg/dL, or u003e 310 mg/dL with one additional cardiovascular risk factor, or u003e 190 mg/dL with two cardiovascular risk factors. Pre-existing CVD was defined as a history of coronary heart disease, stroke or peripheral artery disease. At 5-year, we assessed eligibility for PCSK9 inhibitors defined as unmet LDL-cholesterol goals despite use of rosuvastatin 20mg, atorvastatin 40mg, simvastatin 40mg, or higher doses. Achievement of LDL-cholesterol goals were 50% reduction from baseline, or less than 100 mg/dL or 70 mg/dL, for patients with severe FH or CVD, respectively.Results: Severe FH was diagnosed in 295 (4.4%) patients out of whom 27 had pre-existing CVD, whereas 403 patients (6.0%) had CVD without criteria for severe FH so that, altogether, 698 patients (10.4%) were included in the analysis. After a mean follow-up period of 5.5 years, 47 of these patients (6.7%) had died, 160 (22.9%) refused to attend the follow-up visit, and 14 (2.0%) had missing LDL-cholesterol measurement. Among the remaining 477 patients, 54 (11.3%) achieved optimal LDL-cholesterol goals, 235 (49.3%) were using statins, 75 (15.7%) had high-dose statins, and 23 (4.8%) were eligible for PCSK9 inhibitors.Conclusions: In this population-based sample, a vast majority of patients who meet the diagnostic criteria for severe FH or CVD have sub-optimal statin therapy. A major effort in improving use and intensification of statin dosage is required before prescription of PCSK9 inhibitors can be initiated.