What is the cause of intermittent claudication in the calf when walking in a diabetic patient on atorvastatin (atorvastatin calcium)?

From the Guidelines

Calf claudication with walking in a diabetic patient on atorvastatin is most likely due to peripheral artery disease (PAD), but statin-induced myopathy should also be considered. The patient's symptoms are consistent with PAD, which occurs when atherosclerotic plaque narrows arteries supplying the legs, causing pain during activity that resolves with rest 1. Diabetes accelerates atherosclerosis, significantly increasing PAD risk 1. While atorvastatin helps reduce cardiovascular risk, it can rarely cause muscle-related side effects ranging from mild myalgia to severe rhabdomyolysis. To differentiate between these causes, an ankle-brachial index (ABI) should be performed to assess for PAD. If PAD is confirmed, the following interventions should be considered:

• Continue atorvastatin as it's beneficial
• Add antiplatelet therapy (aspirin 75-100mg daily)
• Optimize diabetes control
• Recommend supervised exercise therapy (30-45 minutes of walking 3-5 times weekly) 1. If statin myopathy is suspected (pain persists at rest, elevated creatine kinase), consider reducing atorvastatin dose or switching to a different statin like rosuvastatin or pravastatin. Regardless of cause, smoking cessation, blood pressure control, and regular exercise are essential interventions for symptom improvement 1.

From the FDA Drug Label

Atorvastatin calcium may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Pain in extremity5.98.53.79.33.16.0 Musculoskeletal pain3.65.23.25.12.33.8 Muscle spasms3.04.64.85.12.43.6 Myalgia3.13.65.98.42.73.5

The cause of calf claudication with walking in a diabetic patient on atorvastatin may be related to myopathy or musculoskeletal pain, which are listed as potential adverse reactions to atorvastatin 2. However, it is essential to note that the FDA drug label does not directly address the specific condition of calf claudication.

• Myopathy and rhabdomyolysis are potential risks associated with atorvastatin, particularly in patients with risk factors such as age, uncontrolled hypothyroidism, renal impairment, and concomitant use with certain other drugs 2.
• Pain in extremity, musculoskeletal pain, muscle spasms, and myalgia are all reported adverse reactions to atorvastatin, which could potentially contribute to calf claudication 2.

From the Research

Calf Claudication in Diabetic Patients on Atorvastatin

• Calf claudication is a symptom of peripheral arterial disease (PAD), which is characterized by atherosclerosis leading to narrowing of the major arteries distal to the aortic arch 3.
• The most common presenting symptom of PAD is claudication, which is induced by walking or exercise and usually resolves with rest 4.
• Diabetes is a significant risk factor for PAD, and patients with diabetes are at increased risk of developing PAD and subsequent claudication 3, 4.
• Atorvastatin, a statin, is commonly used to manage hyperlipidemia in patients with diabetes, but its effect on claudication symptoms is not directly addressed in the provided studies.
• However, statin therapy is recommended as part of the management of claudication, along with exercise, smoking cessation, and antiplatelet therapy 3.

Pathophysiology and Risk Factors

• PAD is a chronic obstruction of the arteries supplying the lower extremities, leading to reduced blood flow and oxygen delivery to the muscles 4.
• Risk factors for PAD include smoking, diabetes, lipid abnormalities, hypertension, and hyperhomocystinemia 4.
• The ankle-brachial index (ABI) can be used to screen for and diagnose PAD, with an ABI of less than 0.9 indicating a two- to fourfold increase in relative risk for cardiovascular events and all-cause mortality 3.

Management and Treatment

• Management of claudication includes exercise, smoking cessation, statin therapy, and antiplatelet therapy with aspirin or clopidogrel 3.
• Cilostazol, a new antiplatelet agent, has been shown to reduce claudication symptoms 4.
• Surgical revascularization may be considered in patients with lifestyle-limiting claudication symptoms that do not respond to medical therapy 3.
• Antithrombotic treatment, including aspirin, clopidogrel, and rivaroxaban, may be used to reduce the risk of cardiovascular events in patients with PAD 5, 6.