Which of the following statements regarding statin (HMG-CoA reductase inhibitor) therapy is false?

The FALSE Statement is D

Statement D is FALSE: If persistent muscle symptoms are determined to be unrelated to statin therapy, it is NOT recommended to avoid statin therapy—rather, statins should be continued or reinitiated since the symptoms are not caused by the statin. 1

Analysis of Each Statement

Statement A: TRUE - Statins and Pregnancy

• Statins are absolutely contraindicated in pregnancy due to teratogenic potential 2
• The FDA drug label explicitly lists pregnancy as an absolute contraindication 2
• Females of reproductive potential must use effective contraception during statin treatment 2

Statement B: Requires Clarification - Baseline ALT Measurement

While older guidelines (2002) recommended baseline ALT measurement 1, more recent evidence and practice patterns have evolved. The 2002 ACC/AHA/NHLBI advisory included liver enzyme monitoring in their recommendations 1. However, this statement is generally considered TRUE based on traditional practice, though contemporary guidelines have moved away from routine baseline and periodic monitoring in asymptomatic patients.

Statement C: TRUE - Management of Moderate Muscle Pain

• When patients develop moderate muscle pain on statin therapy, the correct approach is to discontinue the statin, evaluate for other causes, then consider reinitiating at a lower dose or the original dose 1
• The 2002 ACC/AHA guidelines recommend evaluating muscle symptoms initially, at 6-8 weeks after starting therapy, and at each follow-up visit 1
• If myopathy is diagnosed or suspected, statin therapy should be discontinued 2
• After resolution of symptoms, patients can usually be treated with a statin without harm, though with careful monitoring 1

Statement D: FALSE - The Correct Answer

This statement contradicts evidence-based management of statin-associated muscle symptoms:

• Large-scale randomized controlled trials demonstrate that only 1 in 15 muscle-related reports by participants allocated to statin therapy were actually due to the statin 3
• In randomized clinical trials, the difference in muscle symptoms between statin and placebo groups is <1%, compared to 10% discontinuation rates in clinical practice due to subjective complaints 4
• If persistent muscle symptoms are determined to be UNRELATED to statin therapy, the statin should be continued, especially in high-risk patients where cardiovascular event prevention is a priority 4
• The evidence shows that most (>90%) of all reports of muscle symptoms by participants allocated statin therapy were not due to the statin 3

Clinical Implications

The key distinction is:

• If symptoms are caused by the statin → discontinue, evaluate, consider rechallenge at lower dose 1
• If symptoms are unrelated to the statin → continue therapy, as the cardiovascular benefits greatly outweigh risks 4

This is particularly important because the small risks of muscle symptoms are much lower than the known cardiovascular benefits 3, and unnecessary discontinuation of statins in high-risk patients increases their risk of preventable cardiovascular events 4.