Ticagrelor and Statin Interaction Induces Rhabdomyolysis and Acute Renal Failure: Case reports and Scoping Review

Pramod Theetha Kariyanna¹, Syed Haseeb¹, Yuvraj Singh Chowdhury¹, Apoorva Jayarangaiah², Andrii Maryniak¹, George Mo¹, Sudhanva Hegde¹, Jonathan D. Marmur¹ and Isabel. M. McFarlane^1,

¹Division of Cardiovascular Disease and Department of Internal Medicine, State University of New York: Downstate Medical Center, Brooklyn, New York, United States-11203.

²Department of Internal Medicine, NYC Health and Hospitals/Jacobi Medical Center, Bronx, N.Y., U.S.A-10461

Cite this paper:
Pramod Theetha Kariyanna, Syed Haseeb, Yuvraj Singh Chowdhury, Apoorva Jayarangaiah, Andrii Maryniak, George Mo, Sudhanva Hegde, Jonathan D. Marmur and Isabel. M. McFarlane. Ticagrelor and Statin Interaction Induces Rhabdomyolysis and Acute Renal Failure: Case reports and Scoping Review. American Journal of Medical Case Reports. 2019; 7(12):337-341. doi: 10.12691/ajmcr-7-12-9

Abstract

Ever since evidence about the increased risk of stent thrombosis with drug eluting stents (DES) surfaced in 2005, the Food and Drug Administration (FDA) has recommended the use of dual antiplatelet therapy (aspirin with P2Y12 inhibitor) following DES placement. The PLATO trial demonstrated lower mortality rates with the use of Ticagrelor when compared to clopidogrel (9.8% vs. 11.7%, p<0.001) when treating patients with acute coronary syndrome. Given their pleiotropic benefits, statins are today the second most prescribed drug in the United States and often co-prescribed with Ticagrelor. FDA’s post market surveillance of Ticagrelor use along with statins in post-myocardial infarction care is now revealing novel and serious adverse events. We present two cases of rhabdomyolysis and acute renal failure (ARF) which develop while the patients were on statins and Ticagrelor. Case 1: A 66-year-old female presented with bilateral thigh pain for 3 days. One month prior to presentation, she was managed for non-ST segment elevation myocardial infarction (NSTEMI) and had been started on aspirin, ticagrelor and simvastatin. Laboratory values revealed creatinine kinase (CK) level at 40,000 U/L and creatinine 3.2 mg/dL suggesting rhabdomyolysis and ARF. Case 2: A 63-year-old male presented with generalized body aches and fatigue for 4 days. He had sustained STEMI two months before and received two drug eluting stents (DES) and aspirin, ticagrelor and rosuvastatin had been initiated. CK was 380,000 U/L and creatinine 7.94 mg/dL suggesting rhabdomyolysis and ARF. Both patients presented with rhabdomyolysis and acute renal failure within weeks after ticagrelor and statin were commenced. A review of the literature indicated that 11 similar cases of ticagrelor-induced ARF and rhabdomyolysis had been reported. Ticagrelor competes with statins when metabolized by cytochrome P450 (CYP) 3A4 leading to statin retention, leading to major adverse effects like rhabdomyolysis and acute renal failure. Our review is intended to alert clinicians about this important drug interaction.

Keywords:
ticagrelor statins rhabdomyolysis acute renal failure drug interaction cytochrome P450 (CYP) 3A4 adenosine diphosphate (ADP) receptor P2Y12

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