BACKGROUND: A relationship between echolucency of carotid plaques and the consequent risk of ipsilateral ischemic stroke has been observed. An aggressive lipid-lowering therapy may increase the echogenicity of carotid plaque in patients with elevated low-density lipoprotein cholesterol levels. The aim of this study is to prospectively evaluate the long-term effect of high-dose atorvastatin on carotid plaque morphology in patients with first-ever transient ischemic attack or stroke.
METHODS: All patients with symptomatic first ischemic atherosclerotic cerebrovascular event occurred within the previous 10 days were enrolled. Carotid Doppler ultrasound of the neck vessels with 7-11 MHz probe for the definition of the atherosclerotic carotid framework was performed. The analysis of the gray-scale median (GSM) of each plate was carried out with image processing software.
RESULTS: A total of 240 symptomatic plaques were included and divided into 3 groups: 80 in group A (atorvastatin 80 mg), 80 in group B (atorvastatin 40 mg), and 80 to group C (no atorvastatin). GSM score increases significantly more extensive in group A than in group B (+48.65 vs. +39.46, P < .02) and group C (+48.65 vs. 19.3, P = .0002). An inverse association between reduction of low-density lipoprotein and the increase in the GSM score (r = -.456, P = .007) has been observed. Moreover, the reduction of high-sensitive C-reactive protein correlates inversely with the increase of the GSM (r = -.398, P = .021).
CONCLUSIONS: Dose-dependent effect of atorvastatin on symptomatic carotid plaque morphology may suggest a specific role of this drug in the atherosclerotic stroke prevention.

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High-density lipoprotein cholesterol (HDL-C) concentration is an independent risk factor for cardiovascular disease. Fibrates are widely used in the management of atherogenic dyslipidemia, principally for their triglyceride-lowering and HDL-C-raising effects. Fibrates may cause paradoxical reductions in HDL-C. These reductions are usually modest, but significant reductions have been observed. The molecular mechanism for these paradoxical reductions remains unexplained despite advances in our understanding of lipid metabolism. This review considers possible mechanisms for this effect, illustrated by a patient with an observed reduction in HDL-C of 88% after introduction of fenofibrate.

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Although organic anion transporting polypeptide (OATP)-mediated hepatic uptake is generally conserved between rodents and humans at a gross pharmacokinetic level, the presence of three major hepatic OATPs with broad overlap in substrate and inhibitor affinity, and absence of rodent-human orthologs preclude clinical translation of single-gene knockout/knockin findings. At present, changes in pharmacokinetics and tissue distribution of pravastatin, atorvastatin, simvastatin, and carboxydichlorofluorescein were studied in oatp1a/1b-knockout mice lacking the three major hepatic oatp isoforms, and in knockout mice with liver-specific knockin of human OATP1B1 or OATP1B3. Relative to wild-type controls, oatp1a/1b-knockout mice exhibited 1.6- to 19-fold increased intravenous and 2.1- to 115-fold increased oral drug exposure, due to 33%-75% decreased clearance, 14%-60% decreased volume of distribution, and ≤74-fold increased oral bioavailability, with the magnitude of change depending on the contribution of oatp1a/1b to pharmacokinetics. Hepatic drug distribution was 4.2- to 196-fold lower in oatp1a/1b-knockout mice; distributional attenuation was less notable in kidney, brain, cardiac, and skeletal muscle. Knockin of OATP1B1 or OATP1B3 partially restored control clearance, volume, and bioavailability values (24%-142% increase, ≤47% increase, and ≤77% decrease vs. knockout, respectively), such that knockin pharmacokinetic profiles were positioned between knockout and wild-type mice. Consistent with liver-specific humanization, only hepatic drug distribution was partially restored (1.3- to 6.5-fold increase vs. knockout). Exposure and liver distribution changes in OATP1B1-humanized versus knockout mice predicted the clinical impact of OATP1B1 on oral exposure and contribution to human hepatic uptake of statins within 1.7-fold, but only after correcting for human/humanized mouse liver relative protein expression factor (OATP1B1 = 2.2, OATP1B3 = 0.30).

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We report an unusual case of left main thrombosis with distal embolization in the left anterior descending coronary artery (LAD). Two filter wires were placed in both LAD and circumflex coronary arteries at the beginning of the procedure. Manual thrombectomy was performed but only a portion of the left main thrombosis was removed; residual debris was displaced into the distal LAD but captured by the filter. A loco-regional infusion of abciximab was finally administered by a microporous balloon in order to treat residual embolization in the distal LAD. This case shows that manual thrombectomy does not always allow for complete and safe removal of thrombotic material, especially when high-burden coronary thrombosis occurs in large, proximal vessels. A multi-device approach has proved useful in this patient, allowing to obtain complete resolution of luminal thrombosis.

It has often been suggested that Bayesian statistics is more congenial to the informational needs of policy makers than the standard frequentist methods. In order to illustrate this claim, we use both a Bayesian and a frequentist approach for revisiting a recommendation by the Dutch National Health Insurance Board that for all patients requiring lipid reduction, the cheapest alternative (Simvastatin) should be prescribed. We investigate whether Simvastatin and Atorvastatin, the most commonly used alternative, can be considered equivalent in terms of lipid control for patients with heterozygous familial hypercholesterolemia. Priors were elicited from GPs, cardiologists and internists. A systematic review for studies comparing Simvastatin and Atorvastatin was performed. The data from these studies were combined with the priors in a Bayesian meta-analysis. For comparability a frequentist meta-analysis was also performed. The two approaches lead to similar point estimates and 95% intervals. However, the Bayesian outcomes are easier to understand and interpret, and our Bayesian analysis leads to additional outcomes that would have more direct pertinence for policy makers, and which could help them to assess what the data have to say about the questions that are most relevant to the problems they face.