Which patients can be discontinued from statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor) therapy?

Statin Discontinuation: Clinical Scenarios and Recommendations

Statins should be discontinued in older adults (≥75 years) with functional decline, multimorbidity, frailty, or limited life expectancy (<3 years), but should NOT be discontinued in patients with established atherosclerotic cardiovascular disease except for severe intolerance or end-of-life care. 1

When Discontinuation IS Appropriate

Older Adults with Limited Benefit Potential

• Discontinue statins in adults ≥75 years with functional decline, multimorbidity, frailty, or reduced life expectancy (<3 years), as the time-to-benefit for statins exceeds remaining lifespan. 1, 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. 1, 2
• Three major guidelines support discontinuation in patients with poor health status, including those with short life expectancy, as statins should only be considered in primary prevention for patients with at least 3 years of life expectancy. 3, 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. 1, 2
• All 18 reviewed guidelines recommend statin discontinuation related to intolerance issues, including muscle symptoms, elevation of transaminase levels, and contraindications. 2
• For mild to moderate muscle symptoms, temporarily discontinue until symptoms can be evaluated, then assess for other conditions that might increase risk, such as hypothyroidism, reduced kidney or liver function, rheumatologic disorders, or vitamin D deficiency. 2, 4

Specific Clinical Scenarios with No Benefit

• The ACC/AHA guidelines make no recommendations regarding the initiation or discontinuation of statins in patients with NYHA class II-IV ischemic systolic heart failure or in patients on maintenance hemodialysis, reflecting lack of evidence for benefit in these populations. 3

When Discontinuation is NOT Recommended

Established Atherosclerotic Cardiovascular Disease

• Statins should NOT be discontinued in patients with established ASCVD (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 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. 1
• Recent studies support an association between statin discontinuation and increased risk of myocardial infarction and cardiovascular death, with adjusted hazard ratios of 1.33 for any cardiovascular event and 1.46 for coronary events. 5, 6

Diabetes Risk Concerns

• Discontinuation of statins is NOT recommended due to concerns about diabetes risk, as cardiovascular and mortality benefits exceed the risk of diabetes. 3
• In trials of primary and secondary prevention, cardiovascular and mortality benefits of statin therapy exceed the risk of diabetes, suggesting a favorable benefit-to-harm balance. 3
• In people at high risk of developing diabetes, glucose status should be monitored regularly and diabetes prevention approaches reinforced, but statins should not be discontinued for this adverse effect. 3

Alternative Strategies Before Complete Discontinuation

Dose Reduction and Alternative Statins

• Consider dose reduction if high-dose statins cause side effects rather than complete cessation, to maintain lipid control while minimizing side effects. 1
• Trial alternative statins if myalgia or other side effects occur—different statins have varying myopathy risk profiles (pravastatin has lower risk of drug interactions due to its hydrophilic nature; simvastatin has higher risk of myopathy, especially at maximum doses). 4
• After symptom resolution, consider rechallenging with the original or lower dose of the same statin to establish causality between symptoms and therapy, if no contraindication exists. 2

Combination Therapy

• Add ezetimibe if statins are poorly tolerated at high doses, allowing lower statin dosing while maintaining lipid control, as an alternative strategy to complete discontinuation. 1
• For patients who cannot tolerate statins, consider combination therapy with ezetimibe and low-dose statin. 4

Special Considerations for Decision-Making

Coronary Artery Calcium Scoring

• 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

Risk Factors for Statin-Associated Adverse Effects

• Advanced age (especially >80 years), with women at higher risk than men, small body frame and frailty, multisystem disease (particularly chronic renal insufficiency due to diabetes), and polypharmacy all increase the risk of statin-associated muscle pain. 4
• Concomitant use of medications that interact with statins (cyclosporine, gemfibrozil, niacin, macrolide antibiotics, antifungal agents, cytochrome P-450 inhibitors) increases the risk of muscle symptoms. 4

Critical Pitfalls to Avoid

Discontinuation After Acute Events

• Discontinuing statins after acute events (e.g., acute myocardial infarction or stroke) has a harmful effect on cardiovascular outcomes and all-cause mortality; patients who discontinued their statin therapy had worse outcomes than those who were never prescribed statins, possibly due to a biological rebound phenomenon. 7
• Unless contraindicated, statins should not be discontinued, especially after an acute vascular event. 7

Misattributing Pre-existing Symptoms

• Obtain baseline history of muscle symptoms before starting statin therapy to avoid attributing pre-existing symptoms to statins, and evaluate patients for alternative causes of symptoms after discontinuation. 2, 4
• Do not dismiss fatigue in elderly patients as "just aging" or "not related to the statin"—the ACC/AHA guidelines explicitly recognize generalized fatigue as a symptom requiring evaluation during statin therapy. 4

Inappropriate Continuation in End-of-Life Care

• Avoid continuing statins reflexively until death, as medications are often continued inappropriately in end-of-life care. 2
• Failing to reassess indication is a common pitfall, and regular review is necessary to ensure that cardiovascular prevention remains aligned with the patient's goals and prognosis. 2