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In addition to lowering blood lipids, clinical benefits of 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co-A; EC 1.1.1.34) reductase inhibitors may derive from altered vascular function favoring fibrinolysis over thrombosis. We examined effects of pitavastatin (NK-104), a relatively novel and long acting statin, on expression of tissue factor (TF) in human monocytes (U-937), plasminogen activator inhibitor-1 (PAI-1), and tissue-type plasminogen activator (t-PA) in human aortic smooth muscle cells (SMC) and human umbilical vein endothelial cells (HUVEC). In monocytes, pitavastatin reduced expression of TF protein induced by lipopolysaccharide (LPS) and oxidized low-density lipoprotein (OxLDL). Similarly, pitavastatin also reduced expression of TF mRNA induced by LPS. Pitavastatin reduced PAI-1 antigen released from HUVEC under basal, OxLDL-, or tumor necrosis factor-alpha (TNF-alpha)-stimulated conditions. Reductions of PAI-1 mRNA expression correlated with decreased PAI-1 antigen secretion and PAI-1 activity as assessed by fibrin-agarose zymography. In addition, pitavastatin decreased PAI-1 antigen released from OxLDL-treated and untreated SMC. Conversely, pitavastatin enhanced t-PA mRNA expression and t-PA antigen secretion in untreated OxLDL-, and TNF-alpha-treated HUVEC and untreated SMC. Finally, pitavastatin increased t-PA activity as assessed by fibrin-agarose zymography. Our findings demonstrate that pitavastatin may alter arterial homeostasis favoring fibrinolysis over thrombosis, thereby reducing risk for thrombi at sites of unstable plaques.

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Purpose To assess educational and professional outcomes of an accelerated combined bachelor of science–doctor of medicine (BS–MD) program using data collected from 1968 through 2018. Method Participants of this longitudinal study included 2,235 students who entered medical school between 1968 and 2014: 1,134 in the accelerated program and 1,101 in the regular curriculum (control group)—matched by year of entrance to medical school, gender, and Medical College Admission Test (MCAT) scores. Outcome measures included performance on medical licensing examinations, academic progress, satisfaction with medical school, educational debt, first-year residency program directors’ ratings on clinical competence, specialty choice, board certification, and faculty appointments. Results The authors found no practically important differences between students in the accelerated program and those in the control group on licensing examination performance, academic progress, specialty choice, board certification, and faculty appointments. Accelerated students had lower mean educational debt (P < .01, effect sizes = 0.81 and 0.45 for, respectively, their baccalaureate debt and medical school debt), lower satisfaction with their second year of medical school (P < .01, effect size = 0.21), and lower global satisfaction with their medical school education (P < .01, effect size = 0.35). Residency program directors’ ratings in 6 postgraduate competency areas showed no practically important differences between the students in the accelerated program and those in the control group. The proportion of Asian students was higher among program participants (P < .01, effect size = 0.43). Conclusions Students in the accelerated program earned BS and MD degrees at a faster pace and pursued careers that were comparable to students in a matched control who were in a regular MD program. Findings indicate that shortening the length of medical education does not compromise educational and professional outcomes.