Think "LOWER IS BETTER" for LDL in high CV risk patients

Continue to start a statin at target intensity, then recheck an LDL 4 to 12 weeks later and at least once a year....

Overview

As a cardiovascular pharmacist, there is an ongoing debate regarding the necessity of aiming for a specific LDL goal. For over a decade, the focus has been on using target DOSES of statins shown to reduce CV risk, rather than titrating to an LDL goal. But there’s been a shift toward a blended approach in recent years. Data comparing specific LDL targets are limited. But statins reduce CV risk even with a baseline LDL under 70 mg/dL. Plus adding ezetimibe or a PCSK9 inhibitor (Praluent, Repatha) for statin patients at very high CV risk, while lowering LDL to about 55 mg/dL or less, can further reduce CV risk.

NPS-adv

Management steps

Statin therapy and LDL monitoring

Continue to start a statin at target intensity, then recheck an LDL 4 to 12 weeks later and at least once a year.

Generally, think of the mantra “lower is better”, especially for patients at very high CV risk, such as with multiple CV events.
Consider the framework below, and use shared decision-making based on CV risk, patient preferences, etc.

Table (1). Shared decision-making based on CV risk, patient preferences
Cardiovascular Risk	Selected Examples	Target LDL Reduction
Very High	Multiple CV events OR Prior CV event + multiple risks (diabetes, smoking, etc)	≥ 50% AND < 55 mg/dL
High	Prior CV event, but not very high risk OR 10-year CV risk ≥ 20%	≥ 50% AND < 70 mg/dL
Intermediate	10-year CV risk 7.5% to < 20%	≥ 30% AND < 100 mg/dL

Evaluating adherence and treatment adjustments

If LDL stays above these targets, evaluate adherence to lifestyle changes and the statin, and address any statin concerns. Weigh adding a non-statin if that’s not enough, especially for patients at very high CV risk. But don’t add a non-statin in most lower-risk patients, those withOUT CV disease and 10-year CV risk less than 20%. Usually lean toward adding ezetimibe (Choletimb, etc) first. It reduces CV events in some high-risk patients also on a statin, lowers LDL another 20% or so when added to a statin.

Or consider adding an injectable PCSK9 inhibitor. These reduce CV events in high-risk patients on a statin, and lower LDL another 50% or so. But they cost about (15600 L.E/month ~ $550/month).
Avoid jumping to other non-statins (fibrates, etc), these aren’t shown to improve CV outcomes with an optimized statin.
Don’t worry about “too low” LDL. Long-term PCSK9 inhibitor data link LDL under 40 mg/dL with lower CV risk, without safety concerns.

NPS-adv

References

Writing Committee, Lloyd-Jones DM, Morris PB, et al. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022;80(14):1366-1418.
Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020 Jan 1;41(1):111-188.
Grundy SM, Stone NJ, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019 Jun 25;73(24):3168-3209.
Medication pricing by DrugEye Mobile app, accessed June 2023.