Should statin therapy be resumed in a patient with Chronic Kidney Disease (CKD) stage four and impaired renal function?

From the Guidelines

Resuming statin therapy in patients with chronic kidney disease (CKD) stage four is generally recommended, particularly for those with established atherosclerotic cardiovascular disease or high cardiovascular risk. According to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, statin therapy is recommended for all CKD patients who have had a stroke event 1. The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol also supports the use of statins in patients with CKD, as they are at high risk for atherosclerotic cardiovascular disease (ASCVD) 1.

The choice of statin and dose should be individualized, but moderate-intensity statins such as atorvastatin 20 mg daily or rosuvastatin 10 mg daily are typically appropriate choices. No dose adjustments are usually needed specifically for CKD stage four, though starting at a lower dose and titrating up may be prudent to monitor for side effects. Regular monitoring should include lipid panels every 3-6 months initially, liver function tests at baseline and as clinically indicated, and creatine kinase if muscle symptoms develop.

Patients should be educated about potential side effects including muscle pain, which occurs in approximately 5-10% of patients. Statins are beneficial in CKD because these patients have accelerated atherosclerosis and higher cardiovascular risk compared to the general population. While statins may not significantly slow CKD progression, their cardiovascular protective effects outweigh potential risks in most CKD stage four patients, making continuation of therapy appropriate unless specific contraindications exist, as supported by the KDIGO guidelines 1 and the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline 1.

Key points to consider when resuming statin therapy in CKD stage four patients include:

• The patient's overall cardiovascular risk profile
• The presence of established atherosclerotic cardiovascular disease
• The potential benefits and risks of statin therapy
• The need for regular monitoring of lipid panels, liver function tests, and creatine kinase
• The importance of patient education on potential side effects and the benefits of statin therapy.

In patients with CKD who are currently taking a statin, it may be reasonable to continue the statin, as supported by the SHARP trial (Study of Heart and Renal Protection) 1. However, the decision to resume statin therapy should be individualized and based on the patient's specific clinical circumstances.

From the FDA Drug Label

Patients with Severe Renal Impairment (not on hemodialysis):Initiate at 5 mg once daily; do not exceed 10 mg once daily.

Resuming statin therapy in the setting of CKD stage four:

• The FDA drug label recommends initiating rosuvastatin at 5 mg once daily and not exceeding 10 mg once daily in patients with severe renal impairment (not on hemodialysis) 2.
• It is essential to weigh the benefits and risks of statin therapy in patients with CKD stage four, considering the potential increased risk of myopathy and rhabdomyolysis.
• Key considerations:
  • Monitor renal function and adjust the dosage as needed.
  • Inform patients of the risk of myopathy and rhabdomyolysis and instruct them to promptly report any unexplained muscle pain, tenderness, or weakness.
  • Discontinue rosuvastatin if markedly elevated CK levels occur or if myopathy is diagnosed or suspected.

From the Research

Resuming Statin Therapy in CKD Stage Four

• The decision to resume statin therapy in patients with CKD stage four should be based on individual patient risk factors and the potential benefits of statin therapy 3, 4, 5, 6.
• Statins have been shown to exert beneficial effects on kidney function, including reducing 24-hour urinary protein excretion and increasing glomerular filtration rate (GFR) 3.
• The use of statins in patients with CKD stage four is controversial, as these patients are underrepresented in clinical trials 3, 5.
• However, some studies suggest that statins may be effective and safe for secondary prevention of cardiovascular events in patients with mild to moderate CKD, including those with stage four disease 3, 4, 6.
• The choice of statin and dose should be individualized based on patient factors, such as kidney function, cardiovascular risk, and potential drug interactions 4, 6.
• Other lipid-lowering therapies, such as ezetimibe and PCSK9 inhibitors, may also be considered in patients with CKD stage four who are at high risk of cardiovascular events 4, 6.
• The benefits and risks of statin therapy should be carefully weighed in patients with CKD stage four, and the decision to resume therapy should be made on a case-by-case basis 3, 5, 6.
• Some studies have shown that rosuvastatin and atorvastatin may be more effective than other statins in reducing the risk of major adverse cardiovascular events (MACE) and improving kidney function in patients with CKD 6.
• The anti-inflammatory effects of statins, as well as their ability to increase high-density lipoprotein cholesterol (HDL-C) levels, may also be beneficial in patients with CKD stage four 7.