Can statins (3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors) cause disability due to side effects such as muscle pain or weakness?

From the Guidelines

Statins can cause disability due to side effects such as muscle pain or weakness in some patients, and it is recommended to identify potential predisposing factors for statin-associated side effects before initiation of treatment. According to the 2019 guideline on the management of blood cholesterol 1, statins can cause a spectrum of muscle-related adverse effects ranging from mild myalgia to severe myopathy and, in rare cases, rhabdomyolysis. These muscle symptoms can significantly impact mobility and daily functioning in affected individuals. The risk appears dose-dependent and varies between different statin medications.

Some key points to consider when evaluating the risk of statin-associated muscle symptoms include:

• Identifying potential predisposing factors for statin-associated side effects, such as new-onset diabetes mellitus and statin-associated muscle symptoms (SAMS), before initiation of treatment 1
• Reassessing and rechallenging patients with statin-associated side effects that are not severe to achieve maximal LDL-C lowering by modified dosing regimen, an alternate statin, or in combination with nonstatin therapy 1
• Measuring creatine kinase levels in individuals with severe statin-associated muscle symptoms, objective muscle weakness, and measuring liver transaminases and total bilirubin and alkaline phosphatase if there are symptoms suggesting hepatotoxicity 1

It is essential to note that while these side effects affect only a minority of patients, they can be severe enough in some cases to cause disability and necessitate medication discontinuation or adjustment. Patients experiencing significant muscle symptoms should contact their healthcare provider immediately rather than discontinuing medication without supervision. The underlying mechanism involves statins' interference with muscle cell metabolism and potential mitochondrial dysfunction. Risk factors include advanced age, female gender, small body frame, kidney or liver disease, hypothyroidism, and certain medications that interact with statins.

In terms of management, it is recommended to discontinue the statin until the symptoms can be evaluated, and then reassess and rechallenge to achieve maximal LDL-C lowering 1. If a causal relationship exists, discontinue the original statin, and once muscle symptoms resolve, use a low dose of a different statin. If persistent muscle symptoms are determined to arise from a condition unrelated to statin therapy, or if the predisposing condition has been treated, resume statin therapy at the original dose.

From the FDA Drug Label

Atorvastatin calcium may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including atorvastatin There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use, including reports of recurrence when the same or a different statin was administered

Statins, including atorvastatin, can cause disability due to side effects such as muscle pain or weakness, as they may lead to myopathy and rhabdomyolysis. Key points to consider:

• Myopathy and rhabdomyolysis are potential side effects of statin use, which can cause muscle pain, tenderness, or weakness.
• Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, and concomitant use with certain other drugs.
• Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, has been rarely reported with statin use. 2

From the Research

Statins and Disability

• Statins are effective cholesterol-lowering drugs that reduce the risk of cardiovascular disease events, but they can cause side effects such as muscle pain or weakness 3.
• The risk of myopathy, a condition characterized by muscle pain or weakness with elevated creatine kinase levels, is rare, typically occurring in fewer than one in 10,000 patients on standard statin doses 3.
• Rhabdomyolysis, a more severe form of myopathy, is even rarer and can lead to renal failure, but stopping statin use usually reverses these side effects, leading to a full recovery 3, 4.

Muscle Symptoms and Statins

• Statin therapy can cause a small excess of mostly mild muscle pain, but most reports of muscle symptoms by participants allocated statin therapy are not due to the statin 5.
• The risk of muscle symptoms varies between statins and increases with the use of higher doses and interacting drugs 3, 5.
• Some studies suggest that the benefits of statins outweigh the potential risks, including muscle pain, in the vast majority of cases 5, 6.

Management of Statin-Associated Muscle Symptoms

• The prevention of statin-related myopathy involves using the lowest statin dose required to achieve therapeutic goals and avoiding polytherapy with drugs known to increase systemic exposure and myopathy risk 4.
• Exchange of statin or reduction of dose may be beneficial in some patients, especially in primary prevention, although all statins have been associated with muscle pain 6.
• Careful clinical judgment is necessary to manage potential side effects on an individual basis, as the evidence in support of muscle pain caused by statins is not always strong 6, 7.