Krešimir Putarek

Rosuvastatin-Induced Rhabdomyolysis - Possible Role of Ticagrelor and Patients’ Pharmacogenetic Profile

Up to the beginning of 2018, a total of eight cases describing rare but clinically important drug interactions between rosuvastatin and ticagrelor which resulted in rhabdomyolysis have been noted in the Global World Health Organization (WHO) adverse drug reaction (ADR) database (VigiBase) as well as in available literature. There are several possible factors which could contribute to the onset of rhabdomyolysis: old age, initially excessive rosuvastatin dose, drug–drug interactions (DDI) on metabolic enzymes (CYPs and UGTs) and drug transporter levels (ABCB1, ABCG2, OATP1B1) and pharmacogenetic predisposition. We reviewed all available cases plus the case of an 87‐year‐old female Croatian/Caucasian patient who developed rhabdomyolysis following concomitant treatment with rosuvastatin and ticagrelor. The results of the pharmacogenetic analysis indicated that the patient was a carrier of inactivating alleles CYP2C9*1/*3, CYP3A4*1/*22, CYP3A5*3/*3, CYP2D6*1/*4, UGT1A1*28/*28, UGT2B7 ‐161C/T, ABCB1 3435C/T and ABCB1 1237C/T which could have added to the interactions not only between ticagrelor and rosuvastatin but also other concomitantly prescribed medicines, such as amiodarone and proton pump inhibitors. In this case report, the possible multifactorial causes for rhabdomyolysis following concomitant use of rosuvastatin and ticagrelor such as old age, polypharmacy, renal impairment, along with pharmacogenetics will be discussed.

Ascending aorta and aortic arch pseudoanaeurysm — case report

Cardiologia CROATICA We present a 53-year-old patient who was admitted with high fever, cough and nasal discharge. She received her kidney transplant ten years ago with subsequent taking of common immunosupressive therapy with several past hospitalizations due to respiratory infections and respiratory failure. Twenty years ago, she underwent an urgent neurosurgical procedure due to subarachnoid bleeding with underlying ruptured intracranial anaeurysm. One month before actual hospitalization, the patient was complaining of chest pain. Diagnostic work-up of the infection included native computerised tomography (CT) of the thorax and abdomen with coincidental finding of the ascending aorta and aortic arch anaeurysm. Subsequent CT aortography with reconstructions was performed showing pseudoanaeurysm of the ascending aorta and aortic arch (6.2x2.7cm) anteriorly and laterally of the ascending aorta and arch until the origin of the left common carotid and left subclavian artery with wide communication of the aorta and pseudoanaeurysm. Anaeurysmatic dilatation of the splenic artery was diagnosed as well (2.6 cm). Cardiothoracic operation was planned and coronary angiography (transfemoral) was performed as well with the normal finding of the epicardial coronary arteries but with postprocedural haemorrhagic complication with large ipsilateral haematoma of the rectus abdominis and retroperitoneum requiring percutaneous occlusion with BeadBlock Terumo spheric particles of the inferior epigastric artery with an optimal result. Several heamodialysis procedures were undertaken after all contrast imaging procedures in order to protect the transplanted renal graft. Due to a blood loss, the patient was transfused with seven units of blood altogether. She was treated with meropenem and is afebrile with good general condition pending operation of the aorta.

Catheter directed thrombolysis for acute limb ischemia: eight cases in two years

Cardiologia CROATICA Introduction: Acute limb ischemia (ALI) is a challenging problem in angiology. It can be associated with significant morbidity or death even after successful limb revascularization. Management of ALI depends on the clinical status of the affected limb and patient comorbidities. We assessed the efficacy and complication of catheter directed thrombolysis for ALI in our institution during 2012 and 2013. Patients and Methods: During the period of 24 months, eight ALI patients were treated by catheter directed infusion with recombinant tissue plasminogen activator (r-tPA). Standard endovascular access and catheter techniques were involved starting with 5 mg bolus of r-TPA, followed by continuous infusion of 0.5-2 mg/h. Concomitant heparin at low dose was applied to prevent catheter-associated thrombus development. During r-TPA, infusion angiography was repeated to determine success of thrombus dissolution. Results: There were 5 males and 3 females, mean age of 74.8 years (range, 54-90 years). One patient had upper extremity ischemia, others had lower ALI. The average duration of symptoms was 3.6 days (1-10 days). Mean duration of r-TPA infusion was 24.2 hours (16 to 4 hours), with mean dosage of 36.6 mg (range 17 to 60 mg).Three patients (38%) had complete reestablishment of blood flow with catheter thrombolysis and mean ankle — brachial index (ABI) improved from 0.22 to 0.85. The other 4 patients (50%) had partial restoration of flow and needed additional endovascular or surgical intervention with final mean ABI improvement from 0.39 to 0.98. In one case catheter directed thrombolysis failed to reestablish blood flow and the patient underwent the bypass surgery. Only one patient had severe periprocedural complication (gastrointestinal bleeding) requiring a blood transfusion. Small access site hematoma was noticed in all of the treated patients. In the follow-up period (7 to 20 months) one patient had unfavorable course of affected limb which ended with an amputation 15 months after thrombolysis. The other seven patients were stabile, without significant impairment of the treated limb. Conclusion: Selective thrombolysis should be considered for ALI patients with the symptom onset less than 14 days and without motor deficit of the affected limb. It is a timeconsuming procedure with potential severe hemorrhagic complications. With the proper patient selection and coordinated multidisciplinary team, it could result in the reestablishment of flow and an acceptable bleeding complication rate.