Sunitinib (SUN) is a new tyrosine kinase inhibitor that possesses both anti-angiogenic and anti-tumor activities. Although SUN has improved survival rate in cancer patients, cardiotoxicity has been reported as a significant side effect. Several studies suggested a role for the aryl hydrocarbon receptor (AhR) and its regulated genes such as cytochrome P4501A1 (CYP1A1) in the pathogenesis of heart failure and cardiac hypertrophy. To test the hypothesis that SUN induces cardiac hypertrophy through the modulation of AhR, Wistar albino rats were treated for 15 and 30 days with increasing doses of SUN (25, 50, and 100 mg/kg), whereas at the in vitro level, rat cardiomyocyte H9c2 cells were incubated with SUN (1, 2.5, and 5 μM). Thereafter, cardiac hypertrophy parameters were determined at the biochemical, histopathology, and gene expression levels. SUN treatment causes increase in cardiac enzymes, changes in histopathology, and induction in several hypertrophic markers. This was associated with proportional increase in the CYP1A1 gene in a concentration- and time-dependent manner. The direct involvement of AhR in the SUN-induced cardiac hypertrophy in H9c2 cells was supported by the ability of resveratrol, an AhR antagonist, to block the SUN-induced hypertrophy and the ability of SB203580, a novel AhR agonist, to potentiate SUN-induced hypertrophic genes. This is the first demonstration that SUN induces hypertrophic genes in vivo and in vitro rat cardiomyocyte through AhR/CYP1A1-mediated mechanism.

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Purpose: Warfarin is an affordable drug used for numerous indications, and still a favorable choice for patients with a history of bleeding from direct oral anticoagulants or presence of valvular heart diseases. However, warfarin requires regular international normalized ratio (INR) monitoring for safety and efficacy. Warfarin's efficacy and safety is correlated with actual time spent within the therapeutic INR. Time in therapeutic range (TTR) is an estimate that measures the percentage of actual time spent within the therapeutic INR. Our aim was to investigate differences in anticoagulation control of warfarin using TTR between pharmacists and other health-care providers. Methods: This prospective observational study was conducted in an ambulatory-care setting of a tertiary hospital to compare anticoagulation management using TTR between clinics run by pharmacists versus other health-care providers. Results: A total of 62 patients were enrolled: 33 in the pharmacist-led clinic and 29 in the physician-led clinic. TTR levels were statistically higher among patients in the pharmacistled clinic than than the physician-led clinic (87.27%±3.82% and 52.48%±5.49%, respectively; p<0.001). For 27 patients followed retrospectively by physicians and prospectively by clinical pharmacists, TTR was statistically higher during clinical pharmacists' care (91.70% ±2.93% versus 61.39%±5.11%, respectively; p<0.001). During the study, approximately 82% of patients reached their target INR in the pharmacist-led clinic compared to 24% in the physician-led clinic. Conclusion: The findings of our study found that patients followed in the pharmacist-led clinic had higher TTR levels than those followed in the physician-led clinic.

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