- Select the muscle symptom / CK category that best describes the patient's presentation.
- Indicate whether secondary causes (hypothyroidism, vitamin D deficiency, drug–drug interactions, strenuous exercise, recent illness) have been evaluated and addressed.
- Select the number of different statins the patient has already tried at the lowest tolerated dose.
- Select whether the patient's LDL-C is currently above goal for their ASCVD risk category.
- A color-coded recommendation appears as soon as all four fields are filled. No data are stored or transmitted.
For educational and clinical decision-support use by licensed clinicians only. Always confirm against current guideline updates and individualize to the patient.
When to Use
Use this tool when a patient on statin therapy reports new muscle symptoms (myalgia, weakness, cramps) or when a CK elevation is discovered. It guides the initial triage and management decision along the ACC 2022 / NLA pathway — from confirming whether the presentation represents simple myalgia, statin myopathy, or the rare emergency of rhabdomyolysis, through to the choice of non-statin add-on therapy for confirmed statin intolerance.
Appropriate population
Adults on statin therapy who present with new or worsening muscle symptoms, or an unexplained CK elevation. Also useful when planning a rechallenge strategy after a prior statin was stopped for muscle adverse effects.
When NOT to rely on it alone
This tool does not substitute for direct clinical assessment, a thorough drug history, or laboratory evaluation. Rhabdomyolysis features require immediate physician evaluation and possibly emergency department management. The tool does not score SAMS causality (use the SAMS-CI scale for that) and does not account for individual ASCVD risk stratification — LDL goal-setting must be done independently using the patient's 10-year risk and comorbidities.
Pearls & Pitfalls
True complete statin intolerance is uncommon
Randomized crossover studies (including the SAMSON trial) show that a large proportion of patients who report statin-related muscle symptoms on open-label therapy tolerate the same statin when blinded. Most patients can be successfully rechallenged with a different statin or an intermittent dosing regimen. Premature abandonment of statin therapy increases ASCVD risk.
Prefer hydrophilic statins for rechallenge
Rosuvastatin and pravastatin are hydrophilic and have lower rates of muscle adverse effects compared with lipophilic statins (simvastatin, atorvastatin, lovastatin). For rechallenge, start at the lowest available dose. Intermittent dosing (e.g., rosuvastatin 5–10 mg two to three times per week) exploits rosuvastatin's long half-life and is an evidence-supported option for SAMS.
Pitfalls
- Do not use CK alone to define intolerance — most patients with true SAMS have a normal or only mildly elevated CK (myalgia category).
- CK >10× ULN without AKI/myoglobinuria is statin myopathy, not rhabdomyolysis — management differs.
- CYP3A4 inhibitors (azole antifungals, certain macrolides, HIV PIs) and fibrates (gemfibrozil > fenofibrate) potentiate statin myopathy risk; always review the full drug list before rechallenge.
- Hypothyroidism and vitamin D deficiency independently cause myalgia; correct these before attributing symptoms to the statin.
Why Use This Aid
Statins are the most widely prescribed lipid-lowering agents and the cornerstone of ASCVD risk reduction. Muscle adverse effects are the most common reason for statin discontinuation and are often cited in patients who are, in fact, experiencing nocebo effects rather than true pharmacological harm. A systematic, pathway-based approach — distinguishing severity, ruling out secondary causes, counting prior rechallenge attempts, and assessing residual LDL-C risk — reduces both under-treatment (abandoning effective therapy) and over-treatment (prolonging an agent that is causing genuine harm). This tool structures that pathway at the point of care, consistent with the ACC 2022 Expert Consensus Decision Pathway and the 2022 NLA scientific statement.
Statin Intolerance & SAMS Decision Aid
Complete all four fields to receive a color-coded management recommendation based on the ACC 2022 / NLA pathway.
⚕ Decision logic based on: Lloyd-Jones DM et al. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies (JACC 2022;80:1366–1418) and Cheeley MK et al. NLA Scientific Statement on Statin Intolerance (J Clin Lipidol 2022;16:361–375). True complete statin intolerance is uncommon — most patients tolerate rechallenge with a different statin. Requires physician confirmation.
Next Steps
Use the recommendation to support — not replace — individualized clinical judgment.
- For rhabdomyolysis or severe myopathy: admit, check BMP/CK/urine myoglobin, and initiate aggressive IV hydration. Involve nephrology if AKI develops.
- Before any rechallenge: confirm secondary causes (TSH, 25-OH vitamin D, full medication reconciliation including OTCs and supplements).
- For rechallenge: restart at the lowest available dose, preferably with rosuvastatin or pravastatin. Consider alternate-day or twice-weekly dosing.
- For confirmed intolerance with LDL above goal: add ezetimibe first (low cost, well tolerated). If LDL remains above goal in a very-high-risk or high-risk patient, add a PCSK9 inhibitor (evolocumab or alirocumab) or bempedoic acid.
- Document the indication for non-statin add-on therapy and ensure prior authorization if required for PCSK9 inhibitors.
- Refer to a lipidologist or cardiologist if the LDL goal cannot be reached with available non-statin options alone.
Evidence & References
Decision Logic Summary
| Severity / CK Category | Secondary Causes? | Statins Tried | LDL Status | Recommendation |
|---|---|---|---|---|
| Rhabdomyolysis (CK >10× + AKI/myoglobinuria) | Any | Any | Any | STOP — emergency management; IV fluids; nephrology/ED |
| CK >10× ULN (myopathy) | Any | Any | Any | HOLD statin; recheck CK; rechallenge only after full resolution |
| CK 4–10× ULN + symptoms | Any | Any | Any | HOLD; normalize CK; exclude secondary causes; cautious rechallenge |
| Myalgia, CK <4× ULN | Not addressed | Any | Any | Address secondary causes first; then rechallenge |
| Myalgia, CK <4× ULN | Addressed | 0 or 1 | Any | Washout 2–4 wk; rechallenge with different (hydrophilic) statin or intermittent dosing |
| Myalgia, CK <4× ULN | Addressed | ≥2 | Above goal | Maximally tolerated statin + ezetimibe ± PCSK9i or bempedoic acid; consider lipid referral |
| Myalgia, CK <4× ULN | Addressed | ≥2 | At goal | Maintain maximally tolerated regimen; monitor LDL-C |
References
- Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-C Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk. J Am Coll Cardiol. 2022;80(14):1366–1418.
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/Multisociety Guideline on the Management of Blood Cholesterol. Circulation. 2019;139(25):e1082–e1143.
- Cheeley MK, Saseen JJ, Agarwala A, et al. NLA Scientific Statement on Statin Intolerance: a new definition and key considerations for ASCVD risk reduction in the statin-intolerant patient. J Clin Lipidol. 2022;16(4):361–375.
- Newman CB, Preiss D, Tobert JA, et al. Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. 2019;39(2):e38–e81.
