Muscular and Renal Safety of Ticagrelor with High-Intensity Statins: Retrospective Cohort Findings

Abdullah S Alshammari,1 Amer A Shalwala,2 Mohammed A Alnuhait,1 Abdulfattah Y Alhazmi,1 Refal E Fagieha,3 Nura Bin Hallabi,1 Eyad A Alandijani,1 Mansour A Aloufi,1 Mudhhi S Alharbi,1 Reem S Alzahrani,4 Emad M Elkholy,3 Mahmoud E Elrggal,5 Abdulmalik S Alotaibi1 1Pharmaceutical Practices Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 2Pharmacy Department, King Abdulaziz Hospital, Makkah, Saudi Arabia; 3Pharmaceutical Services Department, King Abdullah Medical City, Makkah, Saudi Arabia; 4Pharmaceutical Company, Al nahdi Medical Company, Dammam, Saudi Arabia; 5Department of Pharmacology and Toxicology, Faculty of Medicine, Al-Qunfudah, Umm Al-Qura University, Makkah, Saudi ArabiaCorrespondence: Abdulmalik S Alotaibi, Email [email protected]: Ticagrelor is a widely used antiplatelet agent approved in over 70 countries, including the European Union and the United States, for reducing thrombotic events in patients with acute coronary syndromes (ACS). In clinical practice, combining ticagrelor with high-intensity statins is considered standard therapy for ACS. However, recent pharmacodynamic studies and case reports suggest potential drug-drug interactions that may increase the risk of adverse events, particularly muscular and renal complications. This study aimed to evaluate these risks in a real-world clinical setting in Saudi Arabia.Methods: This retrospective observational cohort study was conducted at the Makkah Cardiology Center, Saudi Arabia. The study included adult patients (n = 577) who were prescribed high-intensity statins, with or without concurrent ticagrelor. The primary outcomes were the incidence of statin-associated muscular complications—defined as myalgia, myopathy, myositis, or rhabdomyolysis—and acute kidney injury (AKI). Clinical data were extracted from the hospital information system, and statistical comparisons were conducted between patients receiving statin monotherapy and those receiving combination therapy.Results: The cohort consisted predominantly of male patients (74.5%). Muscle-related complications were significantly more common in the group receiving both ticagrelor and statins (20.2%) compared to the statin-only group (10.5%) (P = 0.001). Among comorbid conditions, hypertension was the only factor significantly associated with a higher incidence of muscle-related complications. Although a trend toward increased AKI incidence was observed in the combination therapy group, this difference did not reach statistical significance.Conclusion: This study highlights potential safety concerns related to the co-administration of ticagrelor and high-intensity statins, particularly the increased risk of muscle-related complications. While the findings on AKI were inconclusive, the results support the need for cautious use of this combination and call for larger prospective studies to further evaluate its safety profile and optimize treatment strategies.Keywords: ticagrelor, atorvastatin, rosuvastatin, statin-associated muscle symptoms, acute kidney injury