John Corbelli

Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia.

This multicenter, randomized, double-blind, placebo-controlled clinical study assessed the efficacy and safety of ezetimibe administered with lovastatin in primary hypercholesterolemia. After dietary stabilization, a 2- to 12-week washout period, and a 4-week single-blind placebo lead-in period, 548 patients with low-density lipoprotein (LDL) cholesterol > or =145 mg/dl (3.75 mmol/L) and < or =250 mg/dl (6.47 mmol/L) and triglycerides < or =350 mg/dl (3.99 mmol/L) were randomized to one of the following, administered daily for 12 weeks: ezetimibe 10 mg; lovastatin 10, 20, or 40 mg; ezetimibe 10 mg plus lovastatin 10, 20, or 40 mg; or placebo. The primary efficacy variable was percentage decrease in direct LDL cholesterol from baseline to end point for pooled ezetimibe plus lovastatin versus pooled lovastatin alone. Ezetimibe plus lovastatin significantly improved concentrations of LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides compared with lovastatin alone (p <0.01). The coadministration of ezetimibe provided an incremental 14% LDL cholesterol decrease, a 5% HDL cholesterol increase, and a 10% decrease in triglycerides compared with pooled lovastatin alone. Ezetimibe plus lovastatin provided mean LDL cholesterol decreases of 33% to 45%, median triglyceride decreases of 19% to 27%, and mean HDL cholesterol increases of 8% to 9%, depending on the statin dose. The coadministration of ezetimibe 10 mg plus the starting dose of lovastatin (10 mg) provided comparable efficacy to high-dose lovastatin (40 mg) across the lipid profile (LDL cholesterol, HDL cholesterol, and triglycerides). Ezetimibe plus lovastatin was well tolerated, with a safety profile similar to both lovastatin alone and placebo. The coadministration of ezetimibe and lovastatin may offer a new treatment option in lipid management of patients with hypercholesterolemia.

Economic consequences of ACS-related rehospitalizations in the US

Abstract Objective: To examine economic consequences related to rehospitalization following initial acute coronary syndrome (ACS) treatment in United States managed care settings. Study design: Retrospective observational studies. Research design and methods: Retrospective observational studies were conducted on two managed care populations to examine medical encounter insurance claims and charges for ACS-related rehospitalizations following an index hospitalization for new onset ACS (2002–2007). All charges were adjusted to year 2007 United States Dollars (USDs). Main outcome measures: The main outcomes for this study were the direct charges related to ACS rehospitalizations as captured in two separate medical encounter claims databases. Results: Of the 11,266 ACS patients identified for analysis in the health system plan, 3588 (32%) had at least one ACS rehospitalization. Of the 97,177 ACS patients enrolled in the nationally representative managed care database, 32,578 (34%) had at least one ACS-related rehospitalization. Multivariate analyses demonstrated that coronary artery bypass graft (CABG) was the strongest predictor of increased charges during the recurrence in both populations (p < 0.0001). When controlling for length of stay (LOS) in the model, CABG remained a significant predictor of increased charges, while percutaneous coronary intervention (PCI) and stent insertion became even stronger predictors of increased charges. Conclusions: The costs associated with ACS-related rehospitalizations in a real-world setting are high, even when controlling for known cost drivers such as length of stay.

Acute coronary syndrome emergency treatment strategies: Improved treatment and reduced mortality in patients with acute coronary syndrome using guideline-based critical care pathways.

BACKGROUND An acute coronary syndrome (ACS) emergency treatment strategies (ACSETS) critical care pathway (CCP), embedding guideline-based treatment, was evaluated in a 4-hospital system in Buffalo, NY, for its impact on ACS drug utilization, length of stay, and mortality. METHODS The study used an observational design comparing pre- (n = 1,240) and post- (n = 1,709) ACSETS implementation cohorts followed over 1 year. Both myocardial infarction (MI) (59%) and unstable angina (UA) (41%) patients were studied. Multivariate regression analysis was used to analyze possible differences in major end points. RESULTS Appropriate ACS medication use was significantly higher in the ACSETS group in the first 24 hours and at discharge. In a subgroup of managed care health insurance patients (n = 884 ), prescription refills for statins, beta-blockers, angiotensin-converting enzyme inhibitors, and clopidogrel were significantly greater in the ACSETS group up to and including 7 months after discharge, although at 7 months, actual refill rate was poor (30%-50%) for both groups. Length of stay was significantly reduced (HR 0.82 [0.72-0.90]). Inpatient mortality was not significantly reduced. One-year adjusted mortality was reduced significantly compared to non-ACSETS in the MI group (by 19%) (HR 0.81 [0.66-0.99]) but not in the UA group (HR 1.13 [0.71-1.79]). CONCLUSIONS ACSETS contributes to the proof of concept of critical care pathway (CCP) improvement of ACS care, as revealed by increased acute and chronic evidence-based use of medication, decreased length of stay, and, in the case of MI patients, decreased adjusted 1-year mortality. One-year mortality benefit was observed in MI but not UA patients.

Clinical impact of early clopidogrel discontinuation following acute myocardial infarction hospitalization or stent implantation: analysis in a nationally representative managed-care population

ABSTRACT Objectives: To evaluate the association between discontinuation of clopidogrel therapy and risk of acute myocardial infarction (AMI) hospitalization or cardiac revascularization in a nationally-representative patient population following hospitalization for an AMI or coronary stent insertion. Research design and methods: This observational cohort study was performed using data on patients from the PharMetrics Anonymous Patient-Centric Database who were hospitalized for an AMI or coronary stent insertion and subsequently treated with clopidogrel. Cox proportional hazard modeling was used to evaluate the association between clopidogrel discontinuation prior to 1 year post-initial AMI hospitalization and the primary endpoint of repeat AMI hospitalization or coronary intervention defined as percutaneous coronary intervention (PCI) with or without stent, or coronary artery bypass graft (CABG). Main outcome measures: The main outcome for this study was AMI hospitalization or coronary intervention defined as PCI with or without stent placement or CABG. Results: A total of 31 835 patients were included in the analyses. Patients were predominantly male and the average patient age was approximately 60 years. After controlling for baseline patient characteristics and follow-up time, discontinuation of clopidogrel was associated with a significantly higher rate of hospitalization for AMI or coronary intervention (HR 1.34, 95% CI 1.22–1.44). Conclusion: Within a population of ACS patients drawn from a database of 85 US health plans, clopidogrel discontinuation within 1 year following hospitalization for AMI or stent placement is associated with an increased risk of AMI hospitalization or coronary intervention. The results of this study should be interpreted within the context of observational research, which does not address cause and effect relationships.

Acute coronary syndrome emergency treatment strategies: a rationale and road map for critical pathway implementation.

Clinical guidelines have been established to improve the effectiveness of treatment of patients seeking treatment for acute coronary syndromes and to address the variability in physician approaches to these risks. In patients with established coronary heart disease, clinical trials have consistently demonstrated reduction in morbidity and mortality with secondary prevention therapies. Both ends of this spectrum of therapy can be underused in patients receiving conventional care. Because implementation of evidence-based guideline recommendations into clinical care is limited, presented here is a rationale and process that have been successful in guideline implementation for patients with acute coronary syndromes.

Economic consequences of severe bleeding in patients with acute coronary syndrome in the USA

IntroductionPrevious studies have demonstrated increased costs associated with bleeding in clinical trials, but none have yet examined the association of bleeding with costs/charges in a real-world setting. This study examines the association between health care charges and severe bleeding events among patients with acute coronary syndrome (ACS) in a real-world US setting.MethodsThis retrospective study of ACS patients enrolled in a regional, 570,000-member commercial health plan evaluated resource utilization for patients with and without severe bleeding using medical encounter data in health care administrative records. Inclusion criteria were continuous health plan enrollment in the 6 months before initial ACS-related hospitalization, age of at least 18 years, and an inpatient ACS claim between January 1995 and May 2007. Severe bleeding events were defined as having an in-hospital record for: (a) bleeding plus blood transfusion, (b) intracranial hemorrhage, or (c) blood transfusion followed by death. Hospitalizations in which the patient had a nonsevere bleeding event, defined as having an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for bleeding without transfusion or death, were removed from analysis. Resource utilization was assessed using hospital charges. Multiple linear regression analyses controlling for key covariates were used to assess the association of severe bleeding during initial hospitalization with an ACS diagnosis/procedure with charges and length of stay (LOS).ResultsThere were 11,266 ACS patients identified: 928 patients (8.2%) had severe bleeding during initial hospitalization. Severe bleeding events were associated with significantly higher hospital charges and increased LOS than hospitalizations without severe bleeding events. After adjusting for patient characteristics, in-hospital ACS-related procedures, and LOS, patients with severe bleeding incurred initial hospitalization charges that were

Clinical impact of early clopidogrel discontinuation following acute myocardial infarction hospitalization or stent implantation: analysis in a single integrated health network.

48,114 higher than those of patients without bleeding (P<0.001).ConclusionIn a real-world setting, hospitalizations with both severe bleeding and an ACS diagnosis or procedure are associated with significantly higher hospitalization charges and resource use compared with ACS-related hospitalizations without bleeding events. However, due to the limitations of retrospective analyses, no causal relationship can be determined as patient comorbidities represent a possible source of confounding.

Prevalence of Stroke/Transient Ischemic Attack Among Patients with Acute Coronary Syndromes in a Real-World Setting

ABSTRACT Objective: To determine the association between the discontinuation of clopidogrel therapy prior to 1 year and the risk of acute myocardial infarction (AMI) hospitalization, coronary intervention or all-cause mortality in a cohort of managed-care patients following AMI hospitalization or stent insertion. Research design and methods: This observational cohort study included 1152 patients enrolled in the Health Alliance Plan who were hospitalized for AMI, or who underwent coronary stent placement. Clopidogrel use was assessed using pharmacy claims data. The association between discontinuation of clopidogrel prior to 1 year following the initial ACS event and the primary outcome of AMI hospitalization/procedure was assessed using Cox proportional hazards models. Additionally, an analysis was conducted to determine the association of discontinuation prior to 1 year with a secondary composite outcome of AMI hospitalization/coronary stent procedure or all-cause mortality. Main outcome measures: The primary outcome was AMI hospitalization or procedure. The secondary outcome was a composite of AMI hospitalization/ procedure, or all-cause mortality. Results: Discontinuation of clopidogrel in the total cohort of patients was associated with a significantly higher risk of the primary outcome of AMI hospitalization/ coronary intervention (HR 2.712, 95% CI 1.634–4.502). Consistent with this finding, discontinuation of clopidogrel was also associated with a significantly higher risk of the secondary composite endpoint (HR 1.844, 95% CI 1.281–2.653). Conclusions: In patients enrolled in an integrated health network, clopidogrel discontinuation prior to 1 year following AMI hospitalization or stent placement is associated with adverse outcomes including greater risk of death, AMI hospitalization or coronary intervention. These results should be interpreted within the context and limitations of observational research, which cannot attribute causality.

Fractional flow reserve guided percutaneous coronary intervention results in reduced ischemic myocardium and improved outcomes

Abstract Background: Atherothrombosis is a systemic disease that may manifest as acute ischemic events in multiple vascular beds. Patients who have experienced an atherothrombosis-related ischemic event in 1 vascular bed are at risk for developing ischemic events in other vascular beds. Antiplatelet therapy demands an understanding of the balance between arterial thrombosis benefit and adverse event risk. Clinical trials indicate that dual antiplatelet therapy with aspirin and the newer thienopyridines increases the risk of bleeding in patients with acute coronary syndromes (ACS) with prior cerebrovascular events. Informed clinical decision making requires a better understanding of the real-world prevalence of cerebrovascular events. Objective and Purpose: To estimate the prevalence of stroke and/or transient ischemic attack (TIA) among patients with ACS within US health plan populations. Methods: A retrospective, observational cohort study was conducted of patients with ACS in 5 health care claims databases. The index event was defined as the first documented inpatient health care claim for myocardial infarction or unstable angina. Patients with ≥ 12 months of pre-index medical care encounter information were included. Stroke/TIA was identified by the first health care claim for these conditions any time prior to or within 90 days following the index ACS event. Results: Across all databases, between 3.8% and 15.7% of patients with ACS had prior stroke/TIA and between 3.4% and 11.7% of patients with ACS with no history of cerebrovascular events had documented stroke/TIA following the index ACS hospitalization. Conclusion: Despite important differences between the various database populations, there is a high prevalence of documented stroke/TIA in patients with ACS both prior to and following the ACS event. These real-world findings, set within the context of the increased bleeding risk observed with the newer thienopyridines, are important considerations when selecting antiplatelet therapy for patients with ACS.

Valvuloarterial Impedance Predicts Heart Failure Readmissions in Patients Undergoing Transcatheter Aortic Valve Replacement

To determine if fractional flow reserve guided percutaneous coronary intervention (FFR‐guided PCI) is associated with reduced ischemic myocardium compared with angiography‐guided PCI.