Simon de Denus

Statins and liver toxicity: a meta-analysis.

Study Objective. To assess the risk of liver function test (LFT) abnormalities with the use of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (statins) for the treatment of hyperlipidemia.

Decreased Argatroban Clearance Unaffected by Hemodialysis in Anasarca

OBJECTIVE: To report the case of a patient with acute renal failure and anasarca undergoing hemodialysis who demonstrated a prolonged effect of argatroban despite having no hepatic dysfunction. CASE SUMMARY: A 54-year-old white woman with a past medical history of St. Judes prosthetic mitral valve placement was admitted for anasarca secondary to acute renal failure of unknown origin. In order to prevent valve thrombosis and stroke, argatroban was initiated. Despite having no hepatic dysfunction, the patient demonstrated an elevated activated partial thromboplastin time (aPTT) for a prolonged period of time, requiring a significant dose reduction. This suggested reduced clearance of argatroban. Furthermore, this prolonged effect persisted despite hemodialysis. DISCUSSION: Patients with severe renal dysfunction eliminate argatroban at a rate similar to that in healthy volunteers, while those with hepatic disease have a marked decrease in argatroban elimination. Our patient apparently had a reduction in argatroban elimination similar to that in patients with hepatic dysfunction. The few published reports regarding the use of argatroban in patients undergoing hemodialysis generally lack any information regarding variations in plasma concentrations of argatroban, the aPTT, or the type of dialyzer used. The available data, as well as our report, suggest that dosing adjustment during hemodialysis may not be necessary in patients without associated hepatic dysfunction. CONCLUSIONS: This report suggests that in patients who are fluid-overloaded, the anticoagulant effects of argatroban may be prolonged to a degree similar to that observed in patients with hepatic disease. Our report supports the previously published data that hemodialysis has little, if any, role in increasing argatroban elimination.

Removal of lepirudin, a recombinant hirudin, by hemodialysis, hemofiltration, or plasmapheresis

Lepirudin (recombinant hirudin), a direct thrombin inhibitor, is an effective alternative method of anticoagulation in patients with heparin‐induced thrombocytopenia. However, because it is eliminated by the kidneys, the half‐life of lepirudin may be substantially prolonged in patients with renal failure. Patients undergoing hemodialysis must be closely monitored, and therapy must be individualized based on each patients ability to clear the drug. Current literature on the removal of lepirudin by dialysis or plasmapheresis is limited, but available data suggest that lepirudin can be removed with these methods. The ability of filtration systems to remove lepirudin from the blood is highly dependent on the membrane material used in the system. Understanding the effects of hemodialysis, hemofiltration, and plasmapheresis on lepirudin levels is important, especially since no antidote is available to treat elevated serum lepirudin concentrations.

Dyslipidemias and HMG-CoA Reductase Inhibitor Prescription in Heart Transplant Recipients

BACKGROUND: The treatment of dyslipidemias in orthotopic heart transplant (OHT) recipients is not highlighted in the National Cholesterol Education Program Adult Treatment Panel guidelines. Emerging data suggest that hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) safely reduce the risk of transplant rejection and coronary artery vasculopathy in OHT patients. OBJECTIVE: To assess the proportion of patients from our institution reaching the low-density lipoprotein cholesterol (LDL-C) target of <100 mg/dL, evaluate the impact of statins in reaching this goal, and evaluate the prescribing practice for statins in US OHT centers. METHODS: The management of dyslipidemia of OHT recipients followed at our institution was retrospectively evaluated. In addition, the use of statins in adult OHT centers in the US that performed ≥1 5 OHTs per year was assessed through a survey. RESULTS: Of the 328 patients from our institution, 58.5% achieved an LDL-C <100 mg/dL. Patients prescribed statins were more likely to reach this goal (p < 0.01). A total of 85.0% of centers responding to the survey use statins as a part of their post-OHT protocol, primarily to reduce coronary artery vasculopathy (70.6%). CONCLUSIONS: Due to the potential for improved outcomes, a large proportion of patients are prescribed a statin. Our results support previous findings that statins are safe and effective in reducing LDL-C in the management of dyslipidemias in OHT recipients. Nonetheless, dyslipidemias are suboptimally managed in many post-OHT patients.

Early Statin Therapy for Acute Coronary Syndromes

OBJECTIVE: To review the clinical benefit of statins in the early management of acute coronary syndromes (ACSs) and their possible mechanisms of benefit. DATA SOURCES: A MEDLINE search (1966–September 2001) was conducted using the following terms: pravastatin, lovastatin, simvastatin, atorvastatin, cerivastatin, fluvastatin, statins, hydroxymethylglutaryl coenzyme A reductase inhibitor, acute coronary syndromes, unstable angina, and myocardial infarction. Pertinent articles referenced in these publications were also reviewed. STUDY SELECTION AND DATA EXTRACTION: French- and English-language human and animal studies were selected and analyzed. DATA SYNTHESIS: In addition to their lipid-lowering properties, statins produce several nonlipid-related properties. These pleiotropic properties include improved endothelial function, reduction of inflammation at the site of the atherosclerotic plaque, inhibition of platelet aggregation, and anticoagulant effects, all of which may result in clinical benefit during ACSs. Preliminary studies and retrospective analyses of large clinical trials support the hypothesis that statins may be of benefit in ACSs. A recently published randomized, double-blind, multicenter trial evaluated the clinical impact of high-dose atorvastatin in patients with ACSs. Use of atorvastatin resulted in a decrease in a combined endpoint of cardiovascular events. Furthermore, initiation of statin therapy during hospitalization improves long-term compliance and may significantly improve clinical outcome. CONCLUSIONS: Early use of statins in ACSs appears to decrease cardiovascular events. We believe statin therapy should be initiated early (at the latest before hospital discharge) in all patients who have been hospitalized for ACSs. Ongoing studies will clarify the benefit of these agents in ACSs, the importance of their nonlipid-lowering properties, and the optimal cholesterol-target concentrations.

History of Depression as a Predictor of Adverse Outcomes in Patients Hospitalized for Decompensated Heart Failure

Study Objective. To evaluate the prevalence and impact of depression on the risk of in‐hospital death or need for cardiopulmonary resuscitation (CPR) in patients admitted for decompensated heart failure.

Plasma cholesterol concentrations, dietary fat intake, and cholesterol intake in pharmacy students.

OBJECTIVEnTo evaluate the impact of formal education on hyperlipidemia on pharmacy students dietary fat consumption and plasma cholesterol concentrations over a 3-month period.nnnDESIGNnProspective, open, nonrandomized, controlled trial.nnnSETTINGnCollege of pharmacy.nnnPARTICIPANTSnFirst professional-year (P1) and second professional-year (P2) pharmacy students.nnnINTERVENTIONnP2 students received 6 hours of formal education regarding cardiovascular risk factors and National Cholesterol Education Program guidelines for detection and treatment of hyperlipidemia.nnnMAIN OUTCOME MEASURESnPercentage of total caloric intake from fat and saturated fat and plasma cholesterol concentrations after 1 and 3 months.nnnRESULTSnSignificant differences were found between the percentage of total caloric intake from total and saturated fat for P1 and P2 students at all time points, with P1 > P2. A significant time effect was also found for percentage of total caloric intake from total and saturated fat as well as dietary cholesterol consumption for both groups, indicating no net effect of the formal educational intervention. No differences were found in average percentage of total caloric intakes from total and saturated fat between our student sample and that of a national sample of Americans of similar age from the National Health and Nutrition Examination Survey Series III (NHANES III). Female pharmacy students appeared to have lower plasma cholesterol concentrations than women of the same age group in the general American population.nnnCONCLUSIONnFormal education did not alter students percentage of total caloric intake from total and saturated fat or plasma cholesterol concentrations. Approximately 20% of pharmacy students may be eligible for more intensive diet and, perhaps, drug therapy for treatment of hypercholesterolemia.