When is it appropriate to discontinue statin (HMG-CoA reductase inhibitor) therapy?

When to Discontinue Statin Therapy

Statin discontinuation is appropriate in older adults (≥75 years) with functional decline, multimorbidity, frailty, or reduced life expectancy (<3 years), and in patients experiencing severe statin-associated adverse effects that cannot be managed with dose adjustment or alternative statins. 1, 2

Clinical Scenarios for Discontinuation

Older Adults and Limited Life Expectancy

• In adults ≥75 years of age, it may be reasonable to stop statin therapy when functional decline (physical or cognitive), multimorbidity, frailty, or reduced life-expectancy limits the potential benefits. 1

• Statins require years to accrue cardiovascular benefits while risks remain immediate, making discontinuation appropriate when life expectancy is <3 years. 2

• For primary prevention in adults >85 years, discontinuation is reasonable in most cases, as evidence for benefit is extremely limited with only 8% of trial participants being >75 years in major trials. 2

• The time-to-benefit for statins exceeds remaining lifespan in frail elderly patients, where quality of life takes priority over long-term cardiovascular risk reduction. 2

Severe Adverse Effects

• Discontinue immediately when patients experience severe muscle symptoms or fatigue, and evaluate for rhabdomyolysis by checking creatine kinase levels, kidney function, and urinalysis. 2

• For mild to moderate muscle symptoms, temporarily discontinue statin therapy until symptoms can be evaluated, then assess for other conditions including hypothyroidism, vitamin D deficiency, reduced kidney or liver function, and rheumatologic disorders. 2

• After symptom resolution (typically within 2 months), consider rechallenging with the original statin at a lower dose or switching to a different statin (pravastatin or rosuvastatin preferred) to establish causality. 2, 3

• If muscle symptoms persist beyond 2 months after discontinuation, the pain is likely NOT caused by the statin, and alternative diagnoses should be pursued. 3

When Discontinuation is NOT Recommended

Secondary Prevention (Established Cardiovascular Disease)

• In patients with established atherosclerotic cardiovascular disease (history of MI, stroke, TIA, coronary revascularization, or peripheral arterial disease), statins should NOT be discontinued except for severe intolerance or end-of-life care. 4, 5

• Discontinuation in secondary prevention patients increases short-term mortality and major adverse cardiac events, with more than two-fold increased cardiovascular events, four-fold increased stroke risk, and nearly four-fold increased mortality. 4

• Statin-adherent patients with coronary disease are half as likely to experience subsequent myocardial infarction compared to non-adherent patients. 4

• Discontinuation after acute coronary syndromes or stroke is particularly harmful and may cause atherosclerotic plaque destabilization. 5, 6

Primary Prevention in Younger Adults

• Do NOT discontinue statins due to concerns about diabetes risk, as cardiovascular and mortality benefits exceed the risk of diabetes. 1

• While statin use increases diabetes risk (hazard ratio 1.36), the cardiovascular benefits in appropriate risk groups far outweigh this concern. 1

Special Consideration: CAC Score of Zero

• In patients reluctant to continue statin therapy, measuring coronary artery calcium (CAC) may help guide decisions—a CAC score of zero in middle-aged adults (40-55 years) with borderline risk or older adults (55-80 years) with low risk burden may support withholding or discontinuing therapy. 1

• Reassess CAC score in 5-10 years if therapy is withheld based on zero CAC. 1

Critical Pitfalls to Avoid

• Never discontinue statins abruptly in high-risk secondary prevention patients, particularly those with recent acute coronary syndrome or stroke. 2

• Avoid continuing statins reflexively until death in end-of-life care—regular reassessment of indication is necessary to ensure cardiovascular prevention remains aligned with patient goals and prognosis. 2

• Do not attribute pre-existing muscle symptoms to statins without proper evaluation—obtain baseline history of muscle symptoms before starting therapy. 2

• Physician or patient preference accounts for 55% of discontinuation in clinical trials rather than true adverse effects, highlighting the importance of proper counseling about benefits versus risks. 4

Management Strategy Instead of Complete Discontinuation

• Consider dose reduction if high-dose statins cause side effects rather than complete cessation. 4

• Add ezetimibe if statins are poorly tolerated at high doses, allowing lower statin dosing while maintaining lipid control. 4

• Trial alternative statins if myalgia or other side effects occur—different statins have varying myopathy risk profiles. 4

• Schedule re-counseling sessions at 1 month and 6 months to prevent the most common discontinuation patterns and educate about residual cardiovascular risk. 4