PCSK9 inhibitor therapy and guideline treatment targets for cardiovascular disease and familial hypercholesterolaemia. (14th October 2021)

• Record Type: Journal Article
• Authors: Suresh, A; Theodoraki, A; Ward, E; Feher, M D
• Is Part Of: European heart journal. Volume 42(2021)Supplement 1
• Publication Date: 2021-10-14
• Subjects: Lipid-Lowering Agents; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehab724.2945
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Background: Updated trial data on the benefits of low-density lipoprotein cholesterol (LDL-C) reduction on cardiovascular outcomes have been incorporated into 2019 ESC/EAS guidelines and 2020 UK-based NICE guidance. Treatment targets for secondary cardiovascular disease (CVD) prevention are LDL-C <1.4mmol/L (ESC/EAS) and non-high-density lipoprotein <2.5mmol/L (equates to LDL-C <1.8mmol/L; NICE). Guidelines also recommend ≥50% LDL-C reduction in patients with CVD or Familial Hypercholesterolaemia (FH). Targets are often not achieved with oral statin +/− ezetimibe due to reduced efficacy or tolerability, warranting a switch to PCSK9 inhibitor therapy. However, there is limited data on whether this achieves LDL-C targets for both CVD and FH in real world clinical practice. Purpose: To assess attainment of LDL-C treatment targets using PCSK9 inhibitor mono- or combination therapy in routine clinical care for patients with FH or CVD. Methods: Observational study in a single specialist lipid clinic, using retrospective case note review of patients prescribed PCSK9 inhibitor therapy according to NICE guidelines until February 2021. Anonymised clinical, demographic and biochemical data before and after commencement of PCSK9 inhibitor therapy were collected. Primary outcomes were attainment of guideline-defined LDL-C treatment targets: LDL-C <1.8 mmol/L, LDL-C <1.4mmol/L and ≥50% LDL-C reduction. Results: A total of 55 patients (mean age 60.8±12.9 years, 58% male) on PCSK9 inhibitor therapy (98% alirocumab, 2% evolocumab; mean treatment duration 1.7±1.3 years) were identified. PCSK9 inhibitor therapy was commenced due to drug intolerance to statins (89%), ezetimibe (36%) and fenofibrate (25%). In patients with FH (n=18), 78%, 56% and 33% of patients achieved targets of ≥50% LDL-C reduction, LDL-C <1.8 mmol/L and LDL-C <1.4 mmol/L on treatment, respectively. In CVD patients (n=49), 84%, 51% and 27% achieved the same targets respectively (Table 1). In patients on PCSK9 inhibitor monotherapy (n=19), 21% and 5% achieved LDL-C targets <1.8 mmol/L and <1.4 mmol/L respectively, whereas in those on PCSK9 inhibitor + two or more additional oral lipid-lowering therapies, 87% and 60% achieved the same targets respectively (Table 2). Conclusions: Most patients with FH or CVD achieve an LDL-C reduction of ≥50% from baseline with PCSK9 inhibitor therapy, however fewer achieve the LDL-C targets of <1.8 mmol/L or <1.4 mmol/L. Patients on PCSK9 inhibitor monotherapy are unlikely to reach LDL-C <1.8 mmol/L and <1.4mmol/L targets, whereas PCSK9 inhibitor combination therapies are more likely to do so. Additional lipid-lowering drugs are required with PCSK9 inhibitor therapy in most patients to reach guideline LDL-C targets. Funding Acknowledgement: Type of funding sources: None.