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.
Doppler indices do reflect the increased RVR in patients with ADPKD and they correlate with renal function disturbance, with the development of systemic arterial hypertension, and with ultrasonographic abnormality of the kidney in these subjects.
Background
Cardiovascular disease (CVD) is the end result of vascular aging and atherosclerosis, having its origins in childhood. The aim of our study was to compare arterial stiffness (AS) and intima-media thickness (IMT) as markers of an early vascular damage between obese adolescents, adolescents with diabetes type 1 (T1D) and lean control subjects.
Methods
We analyzed AS and IMT in 68 obese adolescents (13.27±2.31 years), 42 adolescents with T1D (14.95±2.35 years) lasting over 5 years and 38 controls (15.02±1.94 years). AS (measured by pulse wave velocity [PWV], arterial compliance [AC] and β-stiffness) and IMT were assessed using an e-tracking ultrasound method.
Results
A significant difference between the groups was found for AC (p=0.022) and PWV (p=0.010), with the lowest compliance and higher velocities in T1D patients. When corrected for age, the difference in AC among the groups did not reach a statistical difference (p=0.059). Correlation analysis in the obese adolescents showed lower AC in females (p=0.041), with higher systolic blood pressure (SBP) (p=0.032). In T1D adolescents, disease duration was the strongest determinant of AS (AC p=0.028, β p=0.029 and PWV p=0.003), followed by body mass index (BMI; PWV p=0.008; β p=0.033), SBP (AC p<0.001; PWV p=0.023), diastolic BP (AC p=0.049; PWV p=0.048) and HbA1c (PWV p=0.048). No significant correlations were found for AS measures or IMT with sex, age, BMI, Tanner stage or BP levels in controls.
Conclusions
Early vascular damage is more pronounced in T1D adolescents than in obese or lean adolescents, which may emphasize the impact of hyperglycemia as a major threat for cardiovascular health.
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