By Kathryn Litten, PharmD, BCACP and Oluwaseun Awofisayo, PharmD Candidate 2023
Introduction
In October 2022, the American College of Cardiology released the “Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease” (2022 ECDP).(1) This report serves as an update to the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA “Guideline on the Management of Blood Cholesterol” given new trials and three new nonstatin therapies have been FDA approved for hypercholesterolemia since its release (Table 1).(2) The 2022 ECDP provides guidance towards their place in therapy and recommends a lower LDL goal for certain patients based upon nonstatin clinical trials until new formal guidelines are published.
Table 1: Nonstatin agents that may be used to manage LDL-related ASCVD Risk
ACS: acute coronary syndrome; LDL: low density lipoprotein; PCSK9i mAb: Proprotein convertase subtilisin/kexin type 9 inhibitors monoclonal antibodies; SUBQ: Subcutaneously; MACE: major adverse cardiovascular events; HR: Hazard ratio; CI: 95% confidence interval
Treatment Algorithm Updates
Secondary Prevention
The 2022 ECDP identifies subgroups of patients with clinical ASCVD summarized in Table 2. Very high-risk patients are defined the same as the 2018 guidelines: those with a history of multiple major ASCVD events or 1 major event and multiple high-risk conditions.
A New LDL Goal
The evidence from IMPROVE-IT, FOURIER, and ODYSSEY Outcomes trial showed that very high-risk patients demonstrate cardiovascular outcome benefits reaching lower LDLs with no adverse effect. Therefore, a new, lower goal of LDL <55 mg/dL is recommended for very high risk patients. High intensity statins are still first line with the addition of nonstatin therapies, namely ezetimibe or PCKS9i, to meet these goals. Previously, PCSK9is were not preferred due cost outweighing benefit, but since 2018, the cost has been reduced. PCSK9i are preferred for those requiring >25% LDL lowering. Bempedoic acid or inclisiran may be considered, but they are not as highly recommended due to pending cardiovascular morbidity and mortality data.
Table 2: Treatment for Secondary Prevention of ASCVD
ASCVD: atherosclerotic cardiovascular disease; LDL: low density lipoprotein; non-HDL: non-high density lipoproteins; PCSK9i: Proprotein convertase subtilisin/kexin type 9 inhibitors monoclonal antibodies
Primary Prevention
Treatment algorithms for the three primary prevention benefit groups are highlighted in Table 3. A major change in this population is the LDL goal of <70mg/dL for high risk patients with ASCVD risk >20% and consideration of ezetimibe adjunct therapy if needed. Otherwise, nonstatins are not generally recommended for primary prevention given limited evidence of benefit in this population. For patients with diabetes, high intensity statins are recommended for patients at a lower 10-year ASCVD risk of >7.5%. New LDL targets, rather than simply percentage reduction goals, were also recommended for patients in all 3 groups.
Table 3: Treatment for of Primary Prevention of ASCVD
ASCVD: atherosclerotic cardiovascular disease; LDL: low density lipoprotein; non-HDL: non-high density lipoproteins; PCSK9i: Proprotein convertase subtilisin/kexin type 9 inhibitors monoclonal antibodies; DM: diabetes mellitus
Patient/Provider Considerations
It is important to assess adherence, risk-enhancing factors and their level of control, current LDL-levels, cost, side effects, and polypharmacy. The guideline also addresses younger and older patients, familial hypercholesterolemia, pregnancy, and coronary artery calcification score use.
Conclusion
Overall, this 2022 ECDP provides answers to clinical questions regarding the use of new nonstatin therapy options and lower LDL goals for high and very high risk patients. Patients’ therapy should be reevaluated with these recommendations in mind.
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7. Ray KK, Wright RS, Kallend D, & ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020;382(16), 1507–1519. doi: 10.1056/NEJMoa1912387.
Kathryn Litten, PharmD, BCACP
Clinical Assistant Professor
The University of Texas at Austin College of Pharmacy
Oluwaseun Awofisayo
PharmD Candidate 2023
The University of Texas at Austin College of Pharmacy