When should statin (HMG-CoA reductase inhibitor) therapy be stopped in patients with a history of cardiovascular disease or those at high risk of developing cardiovascular disease, particularly in the elderly or those with significant comorbidities?

When to Stop Statins

In adults 75 years or older, it is reasonable to stop statin therapy when functional decline (physical or cognitive), multimorbidity, frailty, or reduced life expectancy limits the potential benefits of statin therapy. 1

Primary Considerations for Statin Discontinuation

Age-Based Decision Framework

For patients ≤75 years with established ASCVD (history of MI, stroke, revascularization, or peripheral arterial disease):

• Continue statin therapy indefinitely unless contraindications develop or intolerable side effects occur 1
• High-intensity statin therapy should be maintained in this population as the benefits clearly outweigh risks 1
• Discontinuation after acute vascular events is associated with worse cardiovascular outcomes and mortality compared to patients never prescribed statins 2, 3

For patients >75 years with established ASCVD:

• Continue moderate- or high-intensity statin therapy if the patient is tolerating it well 1, 4
• Evaluate potential for ASCVD risk reduction, adverse effects, drug-drug interactions, frailty status, and patient preferences before making discontinuation decisions 1
• If already tolerating high-intensity therapy, it is reasonable to continue unless contraindications develop 1, 4

Specific Clinical Scenarios Warranting Discontinuation

The following conditions in adults ≥75 years support stopping statins: 1, 5, 4

• Functional decline: Progressive physical disability limiting activities of daily living or significant cognitive impairment (e.g., moderate-to-severe dementia)
• Multimorbidity with limited life expectancy: Multiple serious comorbidities suggesting survival <1-2 years (e.g., metastatic cancer, end-stage organ failure)
• Frailty syndrome: Meeting clinical frailty criteria including unintentional weight loss, exhaustion, weakness, slow gait speed, and low physical activity
• Severe polypharmacy concerns: When drug-drug interactions pose significant safety risks that cannot be mitigated

Primary Prevention Context (No Established ASCVD)

For adults ≥75 years without established cardiovascular disease:

• The benefit-risk ratio becomes less favorable with advancing age 5, 4
• Do not initiate statins in patients with only mildly elevated LDL-C (e.g., 103 mg/dL) without other compelling indications 5
• If already on statin therapy and tolerating well, continuation may be reasonable after shared decision-making 4
• Consider CAC scoring in adults 76-80 years; a CAC score of zero supports avoiding statin therapy 1

Critical Caveats About Discontinuation

When NOT to Stop Statins

Never discontinue statins in the following scenarios without compelling contraindications: 2, 6, 3

• Immediately after acute vascular events (acute MI, stroke, TIA, or acute limb ischemia) - discontinuation is associated with a harmful rebound phenomenon and worse outcomes than never being prescribed statins
• In patients <75 years with established ASCVD who are tolerating therapy - the mortality and morbidity benefits are substantial and well-established
• During elective procedures unless absolutely necessary - even brief discontinuation may be harmful

The Rebound Phenomenon

• Statin discontinuation, particularly after acute events, triggers biological rebound with increased inflammatory markers and plaque destabilization 2, 3
• Patients who stop statins after acute events have worse cardiovascular outcomes than statin-naive patients, suggesting harm beyond loss of benefit 2
• This effect appears within days to weeks of discontinuation 6, 3

Practical Algorithm for Decision-Making

Step 1: Determine if patient has established ASCVD

• If YES and age ≤75: Continue statin indefinitely 1
• If YES and age >75: Proceed to Step 2
• If NO and age >75: Proceed to Step 3

Step 2: For patients >75 with established ASCVD

• Assess for functional decline, frailty, multimorbidity, or life expectancy <1-2 years 1
• If NONE of these present: Continue statin therapy (moderate- or high-intensity based on tolerance) 1, 4
• If ANY present: Discontinuation is reasonable after shared decision-making 1

Step 3: For patients >75 without established ASCVD

• If LDL-C 70-189 mg/dL and already on statin: Consider discontinuation, especially if functional decline or frailty present 1
• If not yet on statin: Do not initiate unless very high risk with multiple risk factors 5, 4

Safety Considerations

• The risk of serious statin-related adverse events is extremely low: rhabdomyolysis <0.1%, serious hepatotoxicity ≈0.001%, new-onset diabetes ≈0.2% per year 7
• Most muscle symptoms reported in clinical practice (≈10% discontinuation rate) are not pharmacologically caused by statins, as placebo-controlled trials show <1% difference in muscle symptoms between statin and placebo groups 7
• In patients for whom statin treatment is guideline-recommended, benefits greatly outweigh risks across all age groups where initiation is recommended 7