Risky Business
What LDL-C goal does AACE recommend for a patient at Extreme Risk?
"In adults undergoing pharmacotherapy for dyslipidemia who have ASCVD or are at increased risk for ASCVD, AACE suggests for treatment to an LDL-C target of <70 mg/dL."
What is the mechanism of statin-induced myopathy and which genetic variant may predispose patients to this adverse effect?
Inhibition of coenzyme Q10 synthesis; SLCO1B1 polymorphism associated with increased risk.
What are the LDL-lowering percentages of ezetimibe, bempedoic acid, and PCSK9 inhibitors?
Ezetimibe ~15–20%, bempedoic acid ~20%, PCSK9i ~50–60%.
What triglyceride level increases pancreatitis risk and how should it be managed acutely?
TG >1000 mg/dL; manage with IV insulin, dietary fat restriction, possibly fibrates
What framework did AACE 2025 use to grade evidence and strength of recommendations?
GRADE (Grading of Recommendations Assessment, Development, and Evaluation).
A patient with controlled LDL-C on moderate-intensity statin has ApoB of 102 mg/dL.
What is the next step and rationale?
Intensify therapy. ApoB >90 mg/dL in high-risk patients signals residual risk despite LDL control.
Which statin is preferred in a patient on protease inhibitors and why?
Pravastatin; minimal CYP3A4 metabolism avoids drug-drug interactions.
How does bempedoic acid differ mechanistically from statins and what patient population is it ideal for?
Inhibits ATP citrate lyase (upstream of HMG-CoA reductase); used in statin-intolerant patients.
Describe the findings and population studied in REDUCE-IT and how they inform use of icosapent ethyl.
Patients with ASCVD or DM + 1 risk factor, on statin, TG 135–499, LDL 40–100. EPA reduced events by 25%.
What is the AACE stance on using ApoB vs. non-HDL-C for residual risk assessment?
ApoB is preferred due to better correlation with atherogenic particle burden.
Compare the LDL-C targets between AACE and ACC/AHA for a patient with recent NSTEMI and CKD stage 3.
AACE: LDL <55 mg/dL (Extreme Risk);
ACC/AHA: High-intensity statin without numeric LDL target, focus on >50% reduction.
A patient has SAMS symptoms on atorvastatin 80 mg but needs continued therapy. What’s the next evidence-based step?
Switch to low-dose rosuvastatin with alternate-day dosing; consider CK, TSH, and vitamin D evaluation.
A patient with statin intolerance and HeFH is on ezetimibe. LDL-C remains >130. Next step?
Add PCSK9 inhibitor. In HeFH, early and aggressive LDL-C lowering is critical.
How does EPA differ from EPA+DHA in lipid effects?
EPA lowers TG without raising LDL; DHA may increase LDL slightly.
What is the role of advanced lipid testing (e.g., particle size, sdLDL) per AACE 2025?
Not routinely recommended; ApoB and LP(a) are the key actionable tests.
What lipid targets should be prioritized in a 36-year-old woman with SLE, persistent inflammation, and LP(a) of 92 mg/dL?
LDL <55 mg/dL; also consider using ApoB <80 mg/dL as target.
LP(a) adds risk even if LDL appears controlled.
Describe the typical clinical and laboratory features distinguishing SAMS from polymyositis.
SAMS: normal to mildly elevated CK, resolves on dechallenge. Polymyositis: proximal weakness, CK >1000, EMG/biopsy abnormalities.
Inclisiran and PCSK9 mAbs differ in what key clinical aspects?
Inclisiran = siRNA with dosing every 6 months; outcome data still emerging.
PCSK9 mAbs = every 2–4 weeks, robust outcome data.
A patient with T2DM and TG 380 mg/dL is on atorvastatin 40 mg. LDL = 68. What are next steps?
Add EPA (icosapent ethyl) for ASCVD risk reduction; do not use niacin or DHA-containing omega-3s.
How are LP(a) levels interpreted and what is the threshold for elevated risk?
LP(a) >50 mg/dL (~125 nmol/L) associated with increased ASCVD risk; no target treatment yet, but more aggressive LDL lowering is advised.
Which patients should be considered for lipoprotein(a) testing and how does it influence management per AACE 2025?
Patients with premature ASCVD, FH, or a family history of early MI; elevated LP(a) justifies more aggressive LDL lowering and PCSK9i use.
What is the evidence for using statins in elderly patients ≥75 years with no ASCVD?
Unclear benefit in primary prevention; use clinical judgment and shared decision-making per AACE and ACC/AHA.
Which non-statin agent is contraindicated in patients with gout and why?
Niacin; increases uric acid levels, may precipitate flares.
What is the mechanism of fibrates and their place in AACE 2025 lipid therapy?
Activate PPAR-α, reduce VLDL synthesis; not routinely recommended unless TG >500 or severe risk of pancreatitis.
In what patient scenarios should PCSK9 inhibitors be considered even before adding ezetimibe?
FH or extreme risk patients with very high LDL-C where rapid/intensive LDL lowering is needed.