In a patient without documented atherosclerotic cardiovascular disease (primary‑prevention setting), can statin therapy be discontinued?

Can Statins Be Discontinued in Primary Prevention Patients?

No, statins should generally not be discontinued in patients receiving them for primary prevention unless specific clinical circumstances warrant cessation—namely advanced age with frailty/limited life expectancy, severe intolerance, or a coronary artery calcium score of zero in selected low-to-intermediate risk individuals. 1

When Discontinuation IS Appropriate in Primary Prevention

Age-Related Considerations:

• In adults ≥75 years, discontinuation is reasonable when functional decline, multimorbidity, frailty, or life expectancy <3 years limits potential benefits, since the time-to-benefit for statins (typically 2-3 years) may exceed remaining lifespan 1
• For primary prevention in adults >85 years, discontinuation is reasonable in most cases, as evidence for benefit is extremely limited with only 8% of major trial participants being >75 years 1

Coronary Artery Calcium (CAC) Score Guidance:

• 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 statin therapy 1, 2
• Reassess CAC score in 5-10 years if therapy is withheld based on zero CAC 1
• However, even with CAC=0, current cigarette smoking (HR 2.12), diabetes (HR 1.68), and hypertension (HR 1.57) remain independently associated with incident ASCVD events over 16-year follow-up 2

Severe Intolerance:

• Discontinue immediately if severe muscle symptoms suggestive of rhabdomyolysis occur (unexplained intense muscle pain, weakness, or fatigue) 1, 3
• Discontinue if creatine kinase levels >10× upper limit of normal with muscle symptoms 1, 3

When Discontinuation is NOT Appropriate

Critical Contraindication to Stopping:

• Statins must NOT be discontinued in patients with established atherosclerotic cardiovascular disease (history of MI, stroke, TIA, coronary revascularization, or peripheral arterial disease), except for severe intolerance or end-of-life care 1
• Discontinuation in secondary prevention increases short-term mortality and major adverse cardiac events more than two-fold, stroke risk four-fold, and mortality nearly four-fold 1

Primary Prevention in Younger/Middle-Aged Adults:

• For adults aged 40-75 years without ASCVD but with elevated cardiovascular risk, statins should be continued as they provide proven mortality and morbidity benefit 4, 5
• In adults aged 65-75 years without established CVD, continue statins as evidence supports benefit in this age group 1

Alternative Strategies to Complete Discontinuation

Dose Modification Approach:

• Consider dose reduction if high-dose statins cause side effects rather than complete cessation, to maintain lipid control while minimizing adverse effects 1
• Trial alternative statins if myalgia or other side effects occur—different statins have varying myopathy risk profiles 1, 3
• Use alternate-day dosing with longer-acting statins (atorvastatin or rosuvastatin) when daily therapy is not tolerated 3, 6

Combination Therapy:

• Add ezetimibe if statins are poorly tolerated at high doses, allowing lower statin dosing while maintaining lipid control 1, 7
• Moderate-intensity statin with ezetimibe combination shows lower incidence of statin-associated muscle symptoms (0.7% vs 5.7%) compared to high-intensity statin monotherapy, with similar LDL-C reduction 7, 8

Management of Muscle Symptoms Without Discontinuation

Temporary Hold Protocol:

• Temporarily discontinue for 2 weeks to 2 months until symptoms resolve and CK normalizes 3, 6
• Evaluate for secondary contributors: hypothyroidism, vitamin D deficiency, impaired renal/hepatic function, rheumatologic disorders 3, 6
• If symptoms persist beyond 2 months after discontinuation, the muscle pain is likely NOT caused by the statin 6

Rechallenge Strategy:

• Restart the same statin at 50% of the previous dose to test causality 3, 6
• Switch to statins with lower myopathy risk (pitavastatin, fluvastatin, or pravastatin as alternatives) 3
• Consider non-statin options (ezetimibe, PCSK9 inhibitors, bempedoic acid) only after failure of at least 2-3 different statins 3

Common Pitfalls to Avoid

• Do not permanently discontinue without confirming causality through rechallenge; many reported adverse events are attributable to the nocebo effect 3
• Do not abruptly discontinue in patients with recent acute coronary syndrome or established cardiovascular disease unless a compelling medical reason exists 3
• Require failure of at least two to three different statins before labeling a patient as truly statin-intolerant 3
• The cardiovascular benefits of statins substantially outweigh the small risk of muscle symptoms in all but the lowest-risk individuals 6