Can statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) cause damage in patients for whom they are indicated?

Statins Should Not Be Withheld When Indicated as Withholding May Cause Harm

Statins should be continued in patients for whom they are indicated, as withholding statin therapy can lead to increased cardiovascular morbidity and mortality. 1 The benefits of statins in reducing cardiovascular events substantially outweigh their potential risks in patients with appropriate indications.

Benefits of Statin Therapy When Indicated

• Statins reduce the probability of cardiovascular events (myocardial infarction or ischemic stroke) and mortality by at least a moderate amount in adults with cardiovascular risk factors and elevated risk scores. 1
• In patients with established atherosclerotic disease, statins reduce cardiovascular morbidity and mortality as well as the need for coronary artery interventions. 1
• Statins can halt progression or even contribute to regression of coronary atherosclerosis at doses that effectively reduce LDL cholesterol by 50%. 1
• For patients undergoing vascular surgery with or without clinical risk factors, statin use is reasonable and associated with reduced perioperative mortality. 1

Risks of Withholding Indicated Statin Therapy

• Discontinuation of statins in patients with acute coronary syndrome or those undergoing vascular interventions should be avoided as it may increase cardiovascular risk. 1
• For patients currently taking statins and scheduled for noncardiac surgery, statins should be continued to prevent adverse cardiovascular outcomes. 1
• In all patients with acute coronary syndrome, statin treatment in high doses should be initiated as early as possible while patients are in the hospital to reduce cardiovascular events. 1

Potential Adverse Effects of Statins

While statins are generally well-tolerated, some adverse effects may occur:

• Myopathy is the most frequent side effect, occurring in approximately 5-10% of patients receiving statins, but rhabdomyolysis is extremely rare. 1, 2
• The risk of myopathy increases with higher doses - approximately 0.03%, 0.08%, and 0.61% for simvastatin 20 mg, 40 mg, and 80 mg daily, respectively. 3
• Elevated liver enzymes may occur in some patients, with persistent increases to more than 3× ULN occurring in approximately 1% of patients. 3
• There is a small increased risk of developing diabetes mellitus with statin use, particularly with high-dose therapy. 1, 4
• Rare reports of cognitive impairment have been associated with statin use, generally nonserious and reversible upon discontinuation. 3

Risk Mitigation Strategies

To minimize adverse effects while maintaining cardiovascular benefits:

• Identify vulnerable patients for myopathy risk, including those with advanced age (>75 years), renal impairment, or those taking interacting medications. 1, 3
• Monitor liver enzymes initially, approximately 12 weeks after starting therapy, then annually or more frequently if indicated. 1
• Evaluate muscle symptoms and CK before starting therapy, then at 6-12 weeks and at follow-up visits. 1
• Avoid drug interactions that may increase statin-associated adverse effects, particularly with medications that inhibit CYP3A4. 1
• Consider dose adjustments in patients with severe renal impairment (CLcr 15-29 mL/min). 3

Special Considerations

• In patients >75 years of age with clinical ASCVD, it is reasonable to evaluate the potential for ASCVD risk-reduction benefits against adverse effects when initiating or continuing statin therapy. 1
• For patients with statin intolerance, consider alternative dosing strategies or lower-intensity statins before discontinuing therapy completely. 1
• Statins demonstrate rapid beneficial effects on coronary endothelial function within 24 hours, even before significant cholesterol reduction occurs, highlighting the importance of not interrupting therapy. 5

Conclusion

The evidence strongly supports that statins should not be withheld in patients for whom they are indicated. The cardiovascular benefits of statins substantially outweigh their potential risks in appropriate patients. Proper patient selection, monitoring, and management of adverse effects can further optimize the benefit-risk ratio of statin therapy.