Assessment of the Risk of Rhabdomyolysis and Myopathy During Concomitant Treatment with Ticagrelor and Statins

Abstract

The introduction of ticagrelor, one of the first directly-acting oral antiplatelet drugs, provided new possibilities in the prevention of thrombotic events in patients with acute coronary syndromes (ACS). Current guidelines recommend ticagrelor in dual antiplatelet therapy with aspirin over clopidogrel for prevention of stent thrombosis in patients with ACS. Moreover, in the management of ACS, lipid-lowering treatment with high-intensity statin therapy is advised for secondary prevention of cardiovascular events over the long term. Despite the apparent advantages of combined antiplatelet and lipid-lowering treatments, a possible interaction between statins and ticagrelor may lead to myopathy and rhabdomyolysis. In this review, relevant information was gathered on the ticagrelor-statin interaction that might lead to this life-threatening condition. This review focuses on the most widely used statins—simvastatin, atorvastatin, and rosuvastatin. Possible mechanisms of this interaction are discussed, including CYP3A4 isoenzymes, organic anion transporter polypeptide (OATPs), P-glycoprotein and glucuronidation. PubMed database was searched for relevant case reports and all data gathered from the introduction of ticagrelor to March 2018 are presented and discussed. In summary, co-administration of statins and ticagrelor was found to be relatively safe in routinely prescribed doses. However, caution should be exercised, especially in elder populations.

Montelukast modifies simvastatin‐induced myopathy and hepatotoxicity

“…MNK treatment (10 mg/kg) for 7 days led to significant antioxidant, anti-inflammatory and reduction in AST and ALT in a rat model for lipopolysaccharide-induced toxicity (Mohamadin et al, 2011). The Statins can cause different degrees of muscle injury and inflammation which may result in renal injury (Danielak et al, 2018). The results of the present study showed that MNK and SMV treatments increased myoglobin and creatinine levels significantly compared to control group.…”

“…Statins can cause different degrees of muscle injury and inflammation which may result in renal injury (Danielak et al, ). The results of the present study showed that MNK and SMV treatments increased myoglobin and creatinine levels significantly compared to control group.…”

“…Rhabdomyolysis occurs in 0.1% of patients receiving statins, namely SMV and atorvastatin. Rhabdomyolysis could lead to renal impairment (Danielak, Karaźniewicz‐Łada, & Główka, ). Such adverse effects can be monitored by measuring plasma creatine kinase (CK) (Taylor et al, ).…”

Commentary to: Ticagrelor Use in Indian Patients Undergoing Neuroendovascular Procedures: A Single-Center Experience

“…6 The authors have mentioned that in cases where Ticagrelor was used they monitored the creatinine. Recently there has been a spate of cases 7,8 where ticagrelor has caused rhabdomyolysis when used in conjunction with statins. Thus, it is pertinent that we are aware of this devastating complication while using this particular drug.…”

“…Thus, for the authors and any such cases, an alternative of Fluvastatin, which is metabolized by P450 CYP2C9, is suggested. While it is routinely safe to use the 2 drugs together, caution may be advisable, especially in elderly cases, 8 as most of the ages reported were above 60 years, and the author population reported the age range was wide (20-75 years). Also, it might be advisable to monitor cases with creatinine kinase and myoglobin values rather than creatinine alone, as they might be more specific.…”