BACKGROUND:

Although the efficacy of ezetimibe/simvastatin and atorvastatin on traditional lipid parameters has been studied extensively, the apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio, which has a better predictive value for cardiovascular events, has not previously been used as a primary endpoint in these two treatment groups.

OBJECTIVE:

Our objective was to compare the efficacy and safety of ezetimibe/simvastatin 10/20 mg versus atorvastatin 20 mg once daily in Korean patients with type 2 diabetes mellitus.

STUDY DESIGN:

This study was an open-label, randomized, controlled study. Type 2 diabetes patients with high levels of low-density lipoprotein (LDL) cholesterol (>100 mg/dL) were randomized to receive ezetimibe/simvastatin or atorvastatin.

MAIN OUTCOME MEASURE:

The primary endpoint was the difference in the percent change of ApoB/ApoA1 at 12 weeks, and secondary endpoints were changes in lipid profiles, glycosylated hemoglobin (HbA1c), homeostatic model assessment (HOMA) index, and C-reactive protein.

RESULTS:

In total, 132 patients (66 for each group) were enrolled and randomized. After 12 weeks of treatment, the ApoB/ApoA1 ratio was significantly reduced in both groups; however, the difference of changes between the two groups was not statistically significant (ezetimibe/simvastatin -38.6 ± 18.0 % vs. atorvastatin -34.4 ± 15.5 %; p = 0.059). There were no significant differences in changes to total cholesterol, LDL cholesterol, high-density lipoprotein cholesterol, triglycerides, ApoB, and ApoB48 between the two groups. However, the increments of ApoA1 were significantly greater in the ezetimibe/simvastatin group than in the atorvastatin group (2.8 ± 10.0 vs. -1.8 ± 9.8 %; p = 0.002). In the per-protocol analysis, improvement in ApoB/ApoA1 was significantly greater in the ezetimibe/simvastatin group (-42.8 ± 11.8 vs. -36.7 ± 13.2 %; p = 0.019). The changes in HbA1c, HOMA index, and C-reactive protein were comparable between the two groups. The adverse reaction rate was similar between the two groups (24.2 vs. 34.9 %; p = 0.180).

CONCLUSION:

Ezetimibe/simvastatin 10/20 mg is comparable to atorvastatin 20 mg for the management of dyslipidemia, and may have more favorable effects on apolipoprotein profiles than atorvastatin 20 mg in Korean patients with type 2 diabetes mellitus.

BACKGROUND:

Acute coronary syndrome (ACS) guidelines recommend early dual anti-platelet therapy (thienopyridines + acetylsalicylic acid [aspirin]). However, triple therapy (thienopyridines + aspirin + glycoprotein IIb/IIIa receptor inhibitors [GRIs]) has shown benefit in clinical trials.

OBJECTIVE:

This study assessed real-world ACS treatment patterns and outcomes in the acute care setting.

STUDY DESIGN:

A retrospective analysis of patients admitted to hospital with ACS (index event) from January 2007 to December 2009 was conducted (Thomson's MarketScan Hospital Drug Database).

PATIENTS:

Eligible patients were ≥18 years of age, of either sex, and had primary admission and discharge diagnoses of ACS.

OUTCOME MEASURES:

Cohorts were defined by anti-platelet treatment and then by the timing of treatment initiation (early initiation: within ≤2 days of admission; late initiation: ≥2 days post-admission). Patient characteristics, clinical outcomes, resource utilization, and costs were assessed using descriptive statistics.

RESULTS:

A total of 249,907 eligible patients were placed into four treatment cohorts (aspirin assumed for all patients): aspirin only; clopidogrel only (dual therapy); GRI only (dual therapy); and clopidogrel + GRI (triple therapy). Patients in the 'clopidogrel-only' cohort were more likely to be older, female, and have more co-morbidities than those in other cohorts; stroke (6.2 %) and re-hospitalization (15.4 %) rates were higher than in the 'GRI-only' and 'triple therapy' cohorts. The GRI-only cohort had higher major bleeding rates (3.3 %), mortality (7.6 %), and costs ($US21,975 [year 2010 values]) than the clopidogrel-only and triple-therapy cohorts. Late initiation cohorts were more likely to be older, female, and have more co-morbidities than early initiation cohorts. Major bleeding was more likely with GRI-only patients (regardless of initiation timing) than with other cohorts. Late-treated clopidogrel-only patients had higher rates of stroke (6.9 %), ACS-related re-admissions (6.1 %), and all-cause re-admissions (15.9 %) than other cohorts. Late treatment was associated with longer length of stay and significantly higher costs.

CONCLUSIONS:

Real-world anti-platelet treatment patterns are consistent with ACS guidelines recommending early initiation and selective GRI use. In contrast to recommendations, some outcomes were improved with triple therapy compared with dual therapy.

Lomitapide (Juxtapid(TM)), an orally administered inhibitor of the microsomal triglyceride transfer protein, inhibits the synthesis of chylomicrons and very low-density lipoprotein, thereby reducing plasma levels of low-density lipoprotein cholesterol (LDL-C). Lomitapide is used to lower lipid levels in adults with homozygous familial hypercholesterolemia, a rare, potentially life-threatening genetic disease that is commonly caused by mutations in the LDL receptor gene or other genes that affect the function of the LDL receptor. In a multinational single-arm, open-label, 78-week, phase III trial, lomitapide reduced mean plasma LDL-C levels by 50 % from baseline in 23 evaluable adults with homozygous familial hypercholesterolemia over a 26 week treatment period. Reductions from baseline in LDL-C levels were sustained for up to 78 weeks with continued lomitapide treatment. In this study, the initial dosage of lomitapide was 5 mg once daily for two weeks, with upward titration thereafter to 10, 20, 40, and 60 mg at weeks 2, 6, 10, and 14, respectively, or until an individually assessed maximum dosage was achieved. Prior to the start of treatment with lomitapide, other lipid-lowering therapy (including LDL apheresis) was stabilized over a 6-week period, and then continued throughout the lomitapide treatment phase. Lomitapide was generally well tolerated; the most common adverse events in the phase III trial were gastrointestinal events.

PURPOSE:

To measure the adherence and persistence of patients with acute coronary syndrome (ACS) initiating prasugrel after percutaneous coronary intervention (PCI).

METHODS:

Using the Thomson Reuters MarketScan Commercial and Medicare Supplemental database, a retrospective cohort study identified patients initiating prasugrel following ACS-PCI hospitalization in 2009-2011. Prasugrel adherence over 12 months was measured using the medication possession ratio (MPR); predictors of adherence were identified using a logistic regression model. Persistence was defined as time on continuous therapy; a Cox model identified predictors of prasugrel discontinuation.

RESULTS:

Among 1,340 patients, the mean age was 57 years; 79.5 % were male. Median prasugrel MPR was 93.2 %; 69.0 % of patients had an MPR ≥80 %. Predictors of adherence <80 % included prior PCI [odds ratio (OR) 0.60; 95 % confidence interval (CI) 0.40-0.90], prior depression (OR 0.37; 95 % CI 0.16-0.84), prior bleeding (OR 0.41; 95 % CI 0.19-0.86), and baseline anticoagulant use (OR 0.13; 95 % CI 0.03-0.55). Baseline statin use predicted higher adherence (OR 1.56; 95 % CI 1.21-2.02). The median duration of prasugrel therapy was 259 days. Predictors of discontinuation included prior anemia [hazard ratio (HR) 1.63; 95 % CI 1.21-2.21], prior cardiomyopathy (HR 2.72; 95 % CI 1.44-5.13), and prior ischemic heart disease (HR 1.15; 95 % CI 1.00-1.32); baseline statin use predicted reduced risk of discontinuation (HR 0.85; 95 % CI 0.75-0.97).

CONCLUSIONS:

Although adherence to prasugrel was generally high, the duration of therapy was frequently below recommendations. An awareness of risk factors for low adherence or early discontinuation can point to appropriate targets for intervention.

Benzocaine is a widely used topical oropharyngeal anesthetic and has been reported to cause methemoglobinemia. We discuss benzocaine-induced methemoglobinemia and review the causes, presentation, and management of this serious complication. Treatment with methylene blue will result in reversal of methemoglobinemia and clinical recovery in most cases but needs to be used at appropriate doses in carefully selected individuals. Physicians who perform procedures involving the application of benzocaine for topical anesthesia need to rapidly identify and treat methemoglobinemia to avoid significant associated morbidity and mortality.

Infective endocarditis (IE) occurs at a rate of approximately 0.9-6.2 per 100,000 people per year and is associated with a high morbidity and mortality despite advancements in antibiotic and surgical treatments. The general approach to the treatment of IE is initial clinical stabilization, early acquisition of blood cultures, and definitive medical and/or surgical treatment. Surgical consultation should be obtained early when indicated in order to determine the best treatment approach for each individual patient. Surgery is indicated in most cases of prosthetic valve endocarditis, Staphylococcus aureus endocarditis, fungal endocarditis, and endocarditis associated with large vegetations (≥10 mm). Initial antibiotic therapy for IE should be targeted to the culprit microorganism; however, in some cases, empiric therapy must be initiated prior to definitive culture diagnosis. Empiric antibiotics should be targeted toward the most likely pathogens, including staphylococci, streptococci, and enterococci species. Here we discuss the recommended antibiotic regimens for the most common causes of IE as indicated by the American Heart Association and European Society of Cardiology. In 2008, the ACC/AHA published guideline updates on the treatment of valvular heart disease, which included a focused update on endocarditis prophylaxis. According to the most recent guidelines, the number of patients who require antibiotic prophylaxis has decreased substantially. Treatment of IE should be targeted toward the causative microorganism and must be based on the type and location of valve involved (native, prosthetic, left or right sided), the clinical status of the patient, and the likelihood for clinical success. This requires a collaborative effort from multiple medical specialties including infectious disease specialists, cardiologists, and cardiothoracic surgeons.

Coronary atherothrombotic disease, including chronic stable angina and acute coronary syndromes (ACS), is associated with significant global burden. The acute clinical manifestations of atherothrombotic disease are mediated by occlusive arterial thrombi that impair tissue perfusion and are composed of a core of aggregated platelets, generated by platelet activation, and a superimposed fibrin mesh produced by the coagulation cascade. Long-term antithrombotic therapies, namely oral antiplatelet agents and anticoagulants, have demonstrated variable clinical effects. Aspirin and P2Y12 adenosine diphosphate (ADP) receptor antagonists have been shown to reduce the risk for thrombosis and ischaemic events by blocking the thromboxane (Tx) A2 and platelet P2Y12 activation pathways, respectively, whereas the benefits of oral anticoagulants have not been consistently documented. However, even in the presence of aspirin and a P2Y12 receptor antagonist, the risk for ischaemic events remains substantial because platelet activation continues via pathways independent of TxA2 and ADP, most notably the protease-activated receptor (PAR)-1 platelet activation pathway stimulated by thrombin. Emerging antithrombotic therapies include those targeting the platelet, such as the new P2Y12 antagonists and a novel class of oral PAR-1 antagonists, and those inhibiting the coagulation cascade, such as the new direct factor Xa antagonists, the direct thrombin inhibitors, and a novel class of factor IX inhibitors. The role of emerging antiplatelet agents and anticoagulants in the long-term management of patients with atherothrombotic disease will be determined by the balance of efficacy and safety in large ongoing clinical trials.

Elevated low-density lipoprotein cholesterol (LDL-C) is an established cause of cardiovascular disease and subsequent adverse events. The efficacy and safety of lowering plasma LDL-C to reduce the risk of coronary heart disease (CHD) and secondary event rates are now well established. What has not been established, however, is a plasma LDL-C lower threshold level of safety and efficacy. Here we review intensive plasma LDL-C-lowering with statins and argue that even further reductions of plasma LDL-C than current guideline targets is likely to safely reduce cardiovascular event rates. We discuss how to achieve very low levels of plasma LDL-C using both traditional and novel LDL-lowering therapies.

Several studies have reported a significant reduction in morbidity and mortality in patients with acute coronary syndrome (ACS) or in patients with stable ischemic heart disease with the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Based on these findings, current guidelines recommend the use of statin therapy before hospital discharge for all patients with ACS regardless of the baseline low-density lipoprotein level. Statins are also recommended to patients at high risk for cardiovascular disease. Statins have been introduced in the clinical arena to reduce the low-density lipoprotein (LDL) cholesterol level that is associated with coronary atherosclerosis; however, a growing body of evidence suggests that other mechanisms of action beyond the modification of the lipid profile may come into action. In particular, statins exert antiinflammatory effects, modulate endothelial function, and inhibit the thrombotic signaling cascade. All together the non-LDL cholesterol-lowering effects of statins are called pleiotropic effects. In this article we will review the evidence supporting the use of high-dose statins in patients undergoing percutaneous coronary intervention, and we will also attempt to highlight the possible mechanisms of action.