Can ticagrelor (P2Y12 inhibitor) and atorvastatin (HMG-CoA reductase inhibitor) cause acute kidney injury (AKI)?

Risk of Acute Kidney Injury with Ticagrelor and Atorvastatin Combination

The combination of ticagrelor and atorvastatin can lead to acute kidney injury through drug interactions and direct nephrotoxic effects, particularly in patients with pre-existing risk factors.

Mechanism of Kidney Injury

Ticagrelor and atorvastatin can contribute to acute kidney injury through several mechanisms:

1. Drug Interaction Pathway:

   • Ticagrelor can cause direct renal function deterioration, especially in patients over 75 years, those with pre-existing mild renal failure, or patients taking angiotensin receptor inhibitors 1
   • Ticagrelor is metabolized by CYP3A4, which can affect the metabolism of statins like atorvastatin 2
   • This interaction can increase statin exposure, leading to statin-induced myopathy and rhabdomyolysis 3, 1
   • Rhabdomyolysis can subsequently cause acute kidney injury due to myoglobinuria 4

2. Direct Nephrotoxic Effects:

   • Ticagrelor itself has been associated with renal function deterioration 1
   • Atorvastatin can cause rhabdomyolysis which may lead to acute kidney injury 4

Risk Factors

Patients at increased risk for this adverse effect include:

• Age ≥65 years 4
• Pre-existing renal impairment 5, 1
• Concomitant use of angiotensin receptor inhibitors 1
• Uncontrolled hypothyroidism 4
• Higher atorvastatin dosages 4
• Severe hypovolemia, sepsis, shock, or major surgery 4

Monitoring and Prevention

To reduce the risk of acute kidney injury with this combination:

1. Assess baseline renal function before initiating therapy 5
2. Monitor renal function one month after starting ticagrelor 1
3. Screen for drug interactions carefully before prescribing 1
4. Consider dose adjustment of atorvastatin in patients with kidney disease 3
5. Implement drug stewardship by identifying patients at risk of AKI and taking this into account when prescribing 5
6. Assess hydration status and ensure adequate hydration 5

Clinical Guidance

In patients with chronic kidney disease (CKD) receiving ticagrelor and atorvastatin:

• Monitor renal function more frequently 5
• Consider lower doses of atorvastatin in patients with CKD 3
• Be vigilant for symptoms of myopathy (muscle pain, tenderness, weakness) 4
• Check creatine kinase levels if symptoms of myopathy develop 4
• Temporarily discontinue atorvastatin in patients experiencing an acute condition with high risk of developing renal failure 4

Conclusion

While ticagrelor has shown benefits in patients with renal impairment in the PLATO trial 5, the combination with atorvastatin requires careful monitoring due to the potential for drug interactions and nephrotoxicity. The European Society of Cardiology and American College of Cardiology/American Heart Association guidelines recognize the need for caution with antithrombotic treatment in patients with CKD due to increased bleeding complications 5.

For patients requiring both medications, regular monitoring of renal function, appropriate dose adjustments, and vigilance for signs of myopathy are essential to prevent acute kidney injury.