What is the risk of statin (HMG-CoA reductase inhibitor)-induced tendon rupture?

From the Guidelines

The risk of statin-induced tendon rupture is unfounded, according to the 2019 American College of Cardiology/American Heart Association guideline on the management of blood cholesterol 1. This guideline provides a comprehensive overview of statin-associated side effects, including muscle symptoms, liver enzyme elevation, and new-onset diabetes mellitus. However, it does not support a definitive association between statin use and tendon rupture. Some key points to consider when evaluating the risk of tendon rupture in patients taking statins include:

• The guideline emphasizes the importance of assessing musculoskeletal symptoms before initiating statin therapy, as these symptoms are common in the general adult population 1.
• Predisposing factors for statin-associated muscle symptoms, such as age, female sex, and comorbidities, should be identified before starting therapy 1.
• While the guideline does not support a link between statin use and tendon rupture, it is essential to monitor patients for any adverse effects and adjust treatment accordingly.
• The benefits of statin therapy in reducing cardiovascular risk typically outweigh the potential risks for most patients, and alternative cholesterol-lowering strategies should be considered on a case-by-case basis 1.

From the FDA Drug Label

Injury: tendon rupture The risk of statin-induced tendon rupture is not quantified in the provided drug labels.

• Tendon rupture is listed as a potential adverse reaction in the postmarketing experience section of the labels 2 and 2.
• However, the frequency of this adverse reaction is not specified, and it is not possible to establish a causal relationship to drug exposure due to the voluntary reporting of reactions from a population of uncertain size.

From the Research

Statin-Induced Tendon Rupture Risk

• The risk of statin-induced tendon rupture is a topic of ongoing research, with some studies suggesting a possible association between statin therapy and tendon rupture 3, 4.
• However, other studies have found no significant association between statin use and tendon rupture, including a systematic review that found no positive association between statin therapy and tendon rupture for the total study population 5.
• A propensity score-matched sequential cohort study found that statin use does not increase the risk of tendon rupture, irrespective of gender, age, statin dose, or treatment duration 6.
• A case-control study found no overall association between statin use and tendon rupture, but suggested that women with tendon rupture were more likely to be on statins 7.
• Certain systemic conditions, such as diabetes, gout, rheumatoid arthritis, and chronic kidney disease, may increase the risk of tendon rupture, and patients with these conditions who are taking statins should be educated about this risk 4.
• The use of certain drugs, such as corticosteroids and fluoroquinolones, in combination with statins may also increase the risk of tendon rupture 4.

Tendon Rupture Risk Factors

• Diabetes
• Gout
• Rheumatoid arthritis
• Chronic kidney disease
• Use of corticosteroids and fluoroquinolones
• Female sex (in some studies) 7

Statin Therapy and Tendinopathy

• Simvastatin may reduce the risk of tendinopathy 5.
• Statins may deleteriously affect tendon extracellular matrix by inhibiting synthesis of matrix metalloproteinases and cell cycle regulatory proteins 3.