Cost-effectiveness of intensification with SGLT2 inhibitors for type 2 diabetes.

OBJECTIVES: Using a US payer perspective, this study aimed to compare the lifetime cost-effectiveness of adding sodium-glucose cotransporter 2 (SGLT2) inhibitors vs switching to glucagon-like peptide 1 receptor agonists (GLP-1 RAs) among patients with type 2 diabetes who were not at glycated hemoglobin A1c target after dual therapy with metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors. STUDY DESIGN: The cost-effectiveness analysis was performed with the validated IQVIA Core Diabetes Model. Treatment effects were obtained from randomized clinical trials with economic data based on published literature. METHODS: Risk of treatment-emergent adverse events and complications were simulated using submodels informed by published risk equations adjusted for patient characteristics, physiological parameters, and history of complications. Outcomes included cumulative incidence of micro- and macrovascular complications, life-years (LYs), quality-adjusted life-years (QALYs), and total costs. Scenario analyses were performed to assess robustness of results to variations in clinical and cost inputs and assumptions. RESULTS: Over a lifetime time horizon, adding an SGLT2 inhibitor dominated the strategy of switching to a GLP-1 RA, improving survival by 0.049 LYs and 0.026 QALYs, and was associated with cost savings of $9511. The majority of the scenario analyses confirmed dominance of the DPP-4 inhibitor + SGLT2 inhibitor pathway vs the GLP-1 RA pathway. The probabilistic sensitivity analysis reinforced the base-case finding of cost savings while gaining QALYs. CONCLUSIONS: Intensification with an SGLT2 inhibitor on top of a DPP-4 inhibitor demonstrated slightly better efficacy and cost savings compared with switching to a GLP-1 RA in patients not at glycemic goal with metformin and a DPP-4 inhibitor.

Budget Impact of Oral Semaglutide Intensification versus Sitagliptin among US Patients with Type 2 Diabetes Mellitus Uncontrolled with Metformin.

BACKGROUND: Oral semaglutide was approved in 2019 for blood glucose control in patients with type 2 diabetes mellitus (T2DM) and was the first oral glucagon-like peptide 1 receptor agonist (GLP-1 RA). T2DM is associated with substantial healthcare expenditures in the US, so the cost of a new intervention should be weighed against clinical benefits. OBJECTIVE: This study evaluated the budget impact of a treatment pathway with oral semaglutide 14 mg daily versus oral sitagliptin 100 mg daily among patients not achieving target glycated hemoglobin (HbA1c) level despite treatment with metformin. METHODS: This study used the validated IQVIA™ CORE Diabetes Model to simulate the treatment impact of oral semaglutide 14 mg and sitagliptin 100 mg over a 5-year time horizon from a US healthcare sector (payer) perspective. Trial data (PIONEER 3) informed cohort characteristics and treatment effects, and literature sources informed event costs. Population and market share data were from the literature and data on file. The analysis evaluated the estimated budget impact of oral semaglutide 14 mg use for patients currently using sitagliptin 100 mg considering both direct medical and treatment costs to understand the impact on total cost of care, given underlying treatment performance and impact on avoidable events. RESULTS: In a hypothetical plan of 1 million lives, an estimated 1993 patients were treated with sitagliptin 100 mg in the target population. Following these patients over 5 years, the incremental direct medical and treatment costs of a patient using oral semaglutide 14 mg versus sitagliptin 100 mg was $US16,562, a 70.7% increase (year 2019 values). A hypothetical payer would spend an additional $US3,300,143 (7.1%) over 5 years for every 10% of market share that oral semaglutide 14 mg takes away from sitagliptin 100 mg. Univariate and scenario analyses with alternate inputs and assumptions demonstrated consistent results. CONCLUSIONS: Use of oral semaglutide 14 mg in patients currently receiving sitagliptin 100 mg substantially increases the budget impact for patients with T2DM whose blood glucose level is not controlled with metformin over a 5-year time horizon for US healthcare payers.

Patients with type 2 diabetes mellitus (T2DM) have many treatment options. Choices depend on factors such as cost, preference, and patient characteristics. Oral semaglutide was recently approved for the treatment of T2DM as the first oral therapy of its class. This study estimated the cost for patients treated with sitagliptin 100 mg, a commonly used T2DM treatment, versus oral semaglutide 14 mg for patients whose disease is not well controlled with metformin. Costs and effects were estimated over 5 years for each treatment strategy using predictive model equations and clinical trial data for the two treatments. These costs were considered for both a hypothetical healthcare plan of 1 million lives and the full US population. A patient treated with oral semaglutide 14 mg would expect to see 70.7% higher costs than a patient treated with sitagliptin 100 mg over 5 years. For every 10% of patients who would switch from sitagliptin 100 mg to oral semaglutide 14 mg, costs would increase by 7.1%. Changing the cost of oral semaglutide 14 mg had the greatest impact on model results. The findings from the analysis were consistent across a range of alternate model inputs. Oral semaglutide 14 mg is more costly than sitagliptin 100 mg over 5 years.

Use and impact of the prehospital 12-lead ECG in the primary PCI era (PHECG2): protocol for a mixed-method study.

Introduction: Use of the prehospital 12-lead ECG (PHECG) is recommended in patients presenting to emergency medical services (EMS) with suspected acute coronary syndrome (ACS). Prior research found that although PHECG use was associated with improved 30-day survival, a third of patients (typically women, the elderly and those with comorbidities) under EMS care did not receive a PHECG.The overall aim of the PHECG2 study is to update evidence on care and outcomes for patients eligible for PHECG, specifically addressing the following research questions: (1) Is there a difference in 30-day mortality, and in reperfusion rate, between those who do and those who do not receive PHECG? (2) Has the proportion of eligible patients who receive PHECG changed since the introduction of primary percutaneous coronary intervention networks? (3) Are patients that receive PHECG different from those that do not in terms of social and demographic factors, or prehospital clinical presentation? (4) What factors influence EMS clinicians' decisions to perform PHECG? Methods and analysis: This is an explanatory, mixed-method study comprising four work packages (WPs). WP1 is a population-based, linked-data analysis of a national ACS registry (Myocardial Ischaemia National Audit Project). WP2 is a retrospective chart review of patient records from three large regional EMS. WP3 comprises focus groups of EMS personnel. WP4 will synthesise findings from WP1-3 to inform the development of an intervention to increase PHECG uptake. Ethics and dissemination: The study has been approved by the London-Hampstead Research Ethics Committee (ref: 18LO1679). Findings will be disseminated through feedback to participating EMS, conference presentations and publication in peer-reviewed journals. Trial registration number: NCT03699137.

Cost-effectiveness of DPP-4 inhibitor and SGLT2 inhibitor combination therapy for type 2 diabetes.

OBJECTIVES: Maintaining glycemic control limits costly health risks in patients with type 2 diabetes (T2D), but accomplishing this may require individualized strategies. Generic medications (eg, sulfonylureas [SU], insulin) are common in T2D management due to their efficacy and costs; however, relatively new drug classes (eg, dipeptidyl peptidase 4 [DPP-4] inhibitors, sodium-glucose cotransporter 2 [SGLT2] inhibitors) have demonstrated clinical benefits in combination therapy. The objective of this study was to evaluate the long-term cost-effectiveness of a strategy involving branded combination therapy with DPP-4 inhibitors and SGLT2 inhibitors (pathway 1) compared with a generic alternative with SU and insulin (pathway 2) on a background of metformin. STUDY DESIGN: Cost-effectiveness analysis using the validated IQVIA CORE Diabetes Model from the US payer perspective. METHODS: Cost-effectiveness analysis. Lifetime clinical and economic outcomes (discounted 3%/year) were modeled for a T2D cohort failing to achieve glycemic goal on metformin monotherapy. Patient baseline data and treatment effects reflect results of clinical trials. Direct medical cost inputs are from multiple published sources. Scenario analyses on key intervention effects and assumptions tested robustness of results. RESULTS: Pathway 1 had higher direct medical costs compared with pathway 2, yet also increased total quality-adjusted life-years (QALYs) by 0.24. Increased costs were partially offset by a reduction in diabetes-related complications and delayed insulin initiation. The incremental cost-effectiveness ratio (ICER) for pathway 1 is favorable at $64,784/QALY. Scenario analyses showed limited impact; nearly all ICERs were less than $100,000/QALY. CONCLUSIONS: In the United States, sequential addition of SGLT2 inhibitors to DPP-4 inhibitors may be considered cost-effective compared with traditional treatment with generic medications for patients who fail to achieve glycemic goal on metformin.

Ertugliflozin Compared to Other Anti-hyperglycemic Agents as Monotherapy and Add-on Therapy in Type 2 Diabetes: A Systematic Literature Review and Network Meta-Analysis.

INTRODUCTION: Ertugliflozin is a new sodium-glucose co-transporter-2 inhibitor (SGLT2i) for the treatment of type 2 diabetes mellitus. As there are no head-to-head trials comparing the efficacy of SGLT2is, the primary objective of this analysis was to indirectly compare ertugliflozin to other SGLT2i in patient populations with inadequately controlled glycated hemoglobin (HbA1c > 7.0%) and previously treated with either diet/exercise, metformin alone or metformin plus a dipeptidyl peptidase-4 inhibitor (DPP4i). METHODS: A systematic literature review (SLR) identified randomized controlled trials (RCTs) reporting outcomes at 24-26 weeks of treatment. Comparators to ertugliflozin were the SGLT2is canagliflozin, dapagliflozin and empagliflozin, with non-SGLT2i comparators also evaluated third-line [insulin and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)]. Outcomes were change from baseline in HbA1c, weight and systolic blood pressure (SBP) as well as HbA1c < 7% and key safety events. Bayesian network meta-analysis was used to synthesize evidence. Results are presented as the median of the mean difference (MD) or as odds ratios with 95% credible intervals (CrI). RESULTS: In patients uncontrolled on diet/exercise, the efficacy of ertugliflozin 5 mg monotherapy was not significantly different from that of other low-dose SGLT2is in terms of HbA1c reduction, while ertugliflozin 15 mg was more effective than dapagliflozin 10 mg (MD - 0.36%, CrI - 0.65, - 0.08) and empagliflozin 25 mg (MD - 0.31%, CrI - 0.58, - 0.04). As add-on therapy to metformin, ertugliflozin 5 mg was more effective in lowering HbA1c than dapagliflozin 5 mg (MD - 0.22%, CrI - 0.42, - 0.02), and ertugliflozin 15 mg was more effective than dapagliflozin 10 mg (MD - 0.26%, CrI - 0.46, - 0.06) and empagliflozin 25 mg (MD - 0.23%, CrI - 0.44, - 0.03). Among patients uncontrolled on combination therapy metformin plus a DPP4i, no relevant RCTs with insulin were identified from the SLR. One study with a GLP-1 RA was included in a sensitivity analysis due to limited data. There were no differences between ertugliflozin 5 or 15 mg and other SGLT2is, with the exception of dapagliflozin 10 mg, which was significantly less effective when added to sitagliptin and metformin. Overall, there were no other significant differences for remaining efficacy and safety outcomes except for a lower SBP for canagliflozin 300 mg compared to ertugliflozin 15 mg in the diet/exercise population. CONCLUSIONS: Indirect comparisons for HbA1c reduction found that ertugliflozin 5 mg was more effective than dapagliflozin 5 mg when added to metformin monotherapy, whereas ertugliflozin 15 mg was more effective than dapagliflozin 10 mg and empagliflozin 25 mg when added to diet/exercise and to metformin monotherapy. The HbA1c reduction associated with ertugliflozin was no different than that associated with canagliflozin across all populations. FUNDING: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Pfizer Inc., New York, NY, USA.

Ezetimibe in high-risk, previously treated statin patients: a systematic review and network meta-analysis of lipid efficacy.

PURPOSE: While statins are used as first-line treatments for high-risk patients with hypercholesterolemia, statin monotherapy is often insufficient to achieve target low-density lipoprotein cholesterol (LDL-C) levels. Second-line treatment options include up-titration of statin dose, switching to a more potent statin, or combination therapy, e.g., with ezetimibe. The aim of this study was to evaluate the efficacy of adding ezetimibe to simvastatin, atorvastatin, or rosuvastatin monotherapy versus doubling the dosage or switching to a higher-potency statin in a population of patients with hypocholesterolemia at high risk of cardiovascular disease (CVD) and who had been previously treated with a statin. METHODS: A systematic literature search was performed and evidence bases were established for populations of atorvastatin-, simvastatin-, and rosuvastatin-experienced patients using eligible randomized controlled trials (RCTs). Based on the available data, we constructed networks of evidence and conducted a Bayesian network meta-analysis (NMA) within each statin population. The primary outcome of interest was percent change from baseline in LDL-C. Changes in total cholesterol were explored as a secondary outcome. FINDINGS: Across all patient populations, 35 RCTs were identified and included in the evidence base. Among patients on simvastatin therapy, the addition of ezetimibe resulted in a mean difference (MD) in LDL-C of - 13.62% (95% CrI - 19.99, - 6.91; see table below) compared to doubling the starting dose of simvastatin. In the population of patients on atorvastatin therapy, the addition of ezetimibe resulted in an MD in LDL-C of - 14.71% (95% CrI - 16.46, - 12.95) compared to doubling the starting dose of atorvastatin. The addition of ezetimibe to rosuvastatin resulted in an MD in LDL-C of - 14.96% (95% CrI - 17.79, - 12.11), compared to doubling the starting rosuvastatin dose. Similar trends were observed for changes in total cholesterol. IMPLICATIONS: Given the available data, the addition of ezetimibe to ongoing simvastatin, atorvastatin, or rosuvastatin monotherapy offers greater reduction in LDL-C among patients at high risk of CVD compared to doubling the initial statin dose.

Cost-effectiveness of intensification with sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes on metformin and sitagliptin vs direct intensification with insulin in the United Kingdom.

AIM: To evaluate the long-term cost-effectiveness of an intensification strategy with sodium-glucose co-transporter-2 (SGLT2) inhibitors (pathway 1) compared with NPH insulin (pathway 2) in patients with type 2 diabetes (T2D) in the United Kingdom who were not at goal on metformin and sitagliptin. METHODS: Cost-effectiveness analysis was performed using the well-established, validated IQVIA CORE Diabetes Model from the payer perspective over a patient's lifetime. Randomized clinical trials informed treatment effect measures, while public or published sources informed economic inputs. Scenario analyses of glycated haemoglobin (HbA1c), hypoglycaemia rate, body mass index effects, SGLT2 inhibitor cardiovascular protective effects, and population characteristics were conducted to assess the robustness of results. RESULTS: Pathway 1 increased life-years and quality-adjusted life-years (QALYs) compared with pathway 2 (13.49 vs. 13.37, and 9.40 vs. 9.22, respectively). Additional drug costs in pathway 1 were offset by diabetes-related complication decreases, leading to slightly lower direct medical costs for pathway 1 (£25747 vs £26095). Pathway 1 was therefore cost-neutral (no interpretable incremental cost-effectiveness ratio), while improving clinical outcomes. Scenario analyses consistently showed cost-neutrality or cost-effectiveness of pathway 1. The highest result remained less than £3000/QALY, reflecting older patients (≥65 years) with lower baseline HbA1c (7%). CONCLUSIONS: For UK patients with T2D not at goal on metformin and sitagliptin therapy, treatment intensification with SGLT2 inhibitors prior to NPH insulin is cost-neutral or cost-effective compared with immediate NPH insulin intensification.

Impact of Ezetimibe on the Rate of Cardiovascular-Related Hospitalizations and Associated Costs Among Patients With a Recent Acute Coronary Syndrome: Results From the IMPROVE-IT Trial (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).

BACKGROUND: Ezetimibe, when added to simvastatin therapy, reduces cardiovascular events after recent acute coronary syndrome. However, the impact of ezetimibe on cardiovascular-related hospitalizations and associated costs is unknown. METHODS AND RESULTS: We used patient-level data from the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) to examine the impact of simvastatin-ezetimibe versus simvastatin-placebo on cardiovascular-related hospitalizations and related costs (excluding drug costs) over 7 years follow-up. Medicare Severity-Diagnosis Related Groups were assigned to all cardiovascular hospitalizations. Hospital costs were estimated using Medicare reimbursement rates for 2013. Associated physician costs were estimated as a percentage of hospital costs. The impact of treatment assignment on hospitalization rates and costs was estimated using Poisson and linear regression, respectively. There was a significantly lower cardiovascular hospitalization rate with ezetimibe compared with placebo (risk ratio, 0.95; 95% confidence interval, 0.90-0.99; P=0.031), mainly attributable to fewer hospitalizations for percutaneous coronary intervention, angina, and stroke. Consequently, cardiovascular-related hospitalization costs over 7 years were $453 per patient lower with ezetimibe (95% confidence interval, -$38 to -$869; P=0.030). Although all prespecified subgroups had lower cost with ezetimibe therapy, patients with diabetes mellitus, patients aged ≥75 years, and patients at higher predicted risk for recurrent ischemic events had even greater cost offsets. CONCLUSIONS: Addition of ezetimibe to statin therapy in patients with a recent acute coronary syndrome leads to reductions in cardiovascular-related hospitalizations and associated costs, with the greatest cost offsets in high-risk patients. These cost reductions may completely offset the cost of the drug once ezetimibe becomes generic, and may lead to cost savings from the perspective of the healthcare system, if treatment with ezetimibe is targeted to high-risk patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique Identifier: NCT00202878.

Economic evaluation of ezetimibe treatment in combination with statin therapy in the United States.

AIMS: This study assessed the cost-effectiveness of ezetimibe with statin therapy vs statin monotherapy from a US payer perspective, assuming the impending patent expiration of ezetimibe. METHODS: A Markov-like economic model consisting of 28 distinct health states was used. Model population data were obtained from US linked claims and electronic medical records, with inclusion criteria based on diagnostic guidelines. Inputs came from recent clinical trials, meta-analyses, and cost-effectiveness analyses. The base-case scenario was used to evaluate the cost-effectiveness of adding ezetimibe 10 mg to statin in patients aged 35-74 years with a history of coronary heart disease (CHD) and/or stroke, and with low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL over a lifetime horizon, assuming a 90% price reduction of ezetimibe after 1 year to take into account the impending patent expiration in the second quarter of 2017. Sub-group analyses included patients with LDL-C levels ≥100 mg/dL and patients with diabetes with LDL-C levels ≥70 mg/dL. RESULTS: The lifetime discounted incremental cost-effectiveness ratio (ICER) for ezetimibe added to statin was $9,149 per quality-adjusted life year (QALY) for the base-case scenario. For patients with LDL-C levels ≥100 mg/dL, the ICER was $839/QALY; for those with diabetes and LDL-C levels ≥70 mg/dL, it was $560/QALY. One-way sensitivity analyses showed that the model was sensitive to changes in cost of ezetimibe, rate reduction of non-fatal CHD, and utility weight for non-fatal CHD in the base-case and sub-group analyses. LIMITATIONS: Indirect costs or treatment discontinuation estimation were not included. CONCLUSIONS: Compared with statin monotherapy, ezetimibe with statin therapy was cost-effective for secondary prevention of CHD and stroke and for primary prevention of these conditions in patients whose LDL-C levels are ≥100 mg/dL and in patients with diabetes, taking into account a 90% cost reduction for ezetimibe.

State transition model: vorapaxar added to standard antiplatelet therapy to prevent thrombosis post myocardial infarction or peripheral artery disease.

OBJECTIVE: To evaluate long-term health benefits and risks of adding vorapaxar (VOR) to the standard care antiplatelet therapy (SC) of aspirin and/or clopidogrel, among a population with a recent myocardial infarction (MI) and/or peripheral artery disease (PAD). RESEARCH DESIGN AND METHODS: In a state-transition model, patients transition between health states (event-free, recurrent MI, stroke, death), while at risk of experiencing non-transition-related revascularization and non-fatal bleeding events. Risk equations developed from the TRA 2°P-TIMI 50 trial's patient-level data were used to predict cardiovascular (CV) outcomes over longer time horizons. Additional sources, including trials and US-based observational studies, informed the inputs for short-term CV risk, non-CV death, and health-related quality of life. Survival and quality-adjusted life-years (QALYs) were estimated over a lifetime horizon, discounted at 3% per year. RESULTS: Within a cohort of 7361 patients with recent MI and/or PAD, VOR + SC relative to SC alone yielded 176 fewer CV events (MIs, strokes, or CV deaths), but 27 more major bleeding events. VOR + SC was associated with increased life expectancy and health benefits (19.93 undiscounted life-years [LYs], 9.57 discounted QALYs vs. 19.61 undiscounted LYs, 9.41 discounted QALYs). The results were most sensitive to scenarios varying time of vorapaxar initiation, and the assumptions in the 90 day period post-MI. Additional analyses showed that add-on vorapaxar provides consistent incremental benefits in high-risk subgroups. CONCLUSION: This study contributes to the growing literature on secondary prevention add-on therapy, as results from these modeling analyses suggest that adding vorapaxar to SC for patients at high atherothrombotic risk can provide long-term health benefits.

A State Transition Model for Health Outcomes Associated with Vorapaxar Treatment as an Add-on to Standard Care Antiplatelet Therapy in the Prevention of Thrombotic Events for Patients with a Recent Myocardial Infarction.

BACKGROUND: The TRA 2°P-TIMI 50 trial showed the addition of vorapaxar to standard care (SC) antiplatelet therapy reduced the combined risk of death, myocardial infarction (MI), and stroke, while exhibiting an increase in moderate, but not other bleeding events. OBJECTIVE: Our objective was to estimate the long-term health benefits and risks of vorapaxar as an add-on to SC treatment (lifetime aspirin and up to 12 months of clopidogrel) for patients with a prior MI and without a history of cerebrovascular disease. METHODS: In the state transition model we developed, the patients transition between states due to recurrent MI, stroke, or death, and are at risk of non-fatal bleeding. Risk equations were developed from individual patient-level data from the TRA 2°P-TIMI 50 trial to predict long-term cardiovascular (CV) outcomes. Additional sources informed inputs for case fatality, bleeding rates on SC, risk of non-CV death, and utilities. RESULTS: Over a lifetime horizon, fewer CV events and more bleeding events occurred in the vorapaxar (VOR) + SC arm, relative to the SC-only arm. These results were ultimately accompanied by an increase in life expectancy and health benefits associated with add-on vorapaxar treatment, as the VOR + SC arm yielded an average of 8.27 discounted quality-adjusted life-years (QALYs) compared with an average of 7.96 discounted QALYs in the SC-only arm. CONCLUSION: This model framework leveraged novel risk equations to make long-term projections of CV events in a population at high risk of recurrence. Model results suggest vorapaxar is most effective as add-on therapy to SC antiplatelet treatment when initiated upon hospital discharge post-MI.

Cost-effectiveness of adding ezetimibe to atorvastatin vs switching to rosuvastatin therapy in Portugal.

BACKGROUND: Statin monotherapy is the mainstay of low-density lipoprotein cholesterol (LDL-C) management for high cardiovascular risk patients in Portugal; however, several therapeutic options are available and predicted to have different clinical and economic impacts. The aim of this study was to evaluate the cost-effectiveness of adding ezetimibe 10 mg (EZ10) to atorvastatin 10 or 20 mg (A10/20) vs switching to rosuvastatin 10 or 20 mg (R10/20) in Portuguese patients with coronary heart disease (CHD) and/or diabetes who are currently above the LDL-C goal. METHODS: A Markov model was used to describe CHD disease progression and the lifetime costs and utilities associated with each disease state were used to estimate the gains in life-years and quality-adjusted life-years (QALYs), as well as the incremental cost-effectiveness ratio (ICER), of the two treatment regimens. Model inputs, such as age, gender, and prevalence of cardiovascular risk factors of the dyslipidemic Portuguese patients were obtained from the Portuguese cohort of the Dyslipidemia International Study (DYSIS). The efficacy of each treatment regimen, the cost of drugs and of treating CHD events, and the utilities for each disease state were derived from published sources. RESULTS: The estimated lifetime discounted number of QALYs gained by patients treated with A10/20 was 8.70, while in those switching to R10/20 it was 8.81 and in those adding EZ10 it was 8.93. Discounted total health costs were estimated to be €11,131 for A10/20, but €14,511 and €16,571 for R10/20 and A10/20 + EZ10, respectively. The ICER of adding ezetimibe vs switching to rosuvastatin was €16,465/QALY. Based on the Portuguese cost-effectiveness willingness-to-pay threshold of €30,000/QALY, adding ezetimibe vs switching to rosuvastatin would be a cost-effective use of resources in Portugal. Sensitivity analyses in patients with differing clinical histories (CHD or diabetes or both) yielded similar values, with no ICER over €30,000/QALY. CONCLUSIONS: From the perspective of the National Health Service, prescribing ezetimibe to high cardiovascular risk patients being treated with atorvastatin vs switching them to rosuvastatin is projected to be a cost-effective use of resources in Portugal.

Systematic review and meta-analysis of the efficacy of cardioversion by vernakalant and comparators in patients with atrial fibrillation.

PURPOSE: Rate and rhythm control are two well established treatment objectives for atrial fibrillation (AF) patients. While symptom reduction is a primary treatment goal, therapeutic practice related to cardioversion varies by region and patient, with several precautions associated with the use of current therapies. No comprehensive literature review on the relative efficacy of existing cardioversion approaches compared to newly available therapies has been conducted. METHODS AND RESULTS: A systematic literature review and meta-analysis were undertaken to evaluate the efficacy of pharmacologic therapies in eliciting cardioversion within 2 and 8-24 h among patients with recent-onset, short duration AF. Eligible studies included randomized controlled trials in which cardioversion rates were evaluated in at least 2 treatment groups. Bayesian mixed-treatment comparisons estimated odds ratios (95% credible intervals) for successful cardioversion. Results within 2 h showed vernakalant IV, propafenone IV and flecainide (IV and oral) were more efficacious in pair-wise comparisons to placebo. Results were mixed in analyses comparing efficacy rates between 8 and 24 h. Few adverse events were reported, with the most common being bradycardia and hypotension. CONCLUSIONS: In pair-wise comparisons of active treatment arms to one another, results suggest vernakalant IV, propafenone IV and flecainide appear to be effective in achieving rapid cardioversion in patients with short duration AF compared to other agents. Application of these findings to clinical practice need to account for the variable comorbidity profiles of patients, important determinants in the selection of appropriate therapy for individual patients. Though best practice methods were used, further research comparing treatments through direct head-to-head comparisons may be warranted to confirm these findings and further inform clinical practice.

Cost-effectiveness of extended-release niacin/laropiprant added to a stable simvastatin dose in secondary prevention patients not at cholesterol goal in Germany.

Coronary heart disease (CHD) remains the leading cause of death in Germany despite statin use to reduce low-density lipoprotein cholesterol (LDL-C) levels; improving lipids beyond LDL-C may further reduce cardiovascular risk. A fixed-dose combination of extended-release niacin (ERN) with laropiprant (LRPT) provides comprehensive lipid management. We adapted a decision-analytic model to evaluate the economic value (incremental cost-effectiveness ratio [ICER] in terms of costs per life-years gained [LYG]) of ERN/LRPT 2 g over a lifetime in secondary prevention patients in a German setting. Two scenarios were modelled: (1) ERN/LRPT 2 g added to simvastatin 40 mg in patients not at LDL-C goal with simvastatin 40 mg; (2) adding ERN/LRPT 2 g compared with titration to simvastatin 40 mg in patients not at LDL-C goal with simvastatin 20 mg. In both scenarios, adding ERN/LRPT was cost-effective relative to simvastatin monotherapy at a commonly accepted threshold of €30,000 per LYG; ICERs for ERN/LRPT were €13,331 per LYG in scenario 1 and €17,684 per LYG in scenario 2. Subgroup analyses showed that ERN/LRPT was cost-effective in patients with or without diabetes, patients aged ≤ 65 or >65 years and patients with low baseline high-density lipoprotein cholesterol levels; ICERs ranged from €10,342 to €15,579 in scenario 1, and from €14,081 to €20,462 in scenario 2. In conclusion, comprehensive lipid management with ERN/LRPT 2 g is cost-effective in secondary prevention patients in Germany who have not achieved LDL-C goal with simvastatin monotherapy.

Comparative efficacy of the addition of ezetimibe to statin vs statin titration in patients with hypercholesterolaemia: systematic review and meta-analysis.

OBJECTIVE: To systematically review and analyse evidence for cholesterol-lowering efficacy of at least 4 weeks of add-on ezetimibe vs doubling statin dose, in adults with primary hypercholesterolaemia. RESEARCH DESIGN AND METHODS: MEDLINE, EMBASE and Cochrane databases were searched to identify randomised controlled trials of ezetimibe-statin combination vs statin titration (January 1993 - March 2010). Studies were selected using predefined criteria. Two reviewers conducted screening of articles, critical appraisal and data extraction; a third reviewer resolved disagreements. The difference between treatments was analysed for four co-primary outcomes: mean percentage change from baseline in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC); and proportion of patients achieving LDL-C treatment goal. Data were combined by two sets of direct comparison fixed and random effects meta-analysis: (1) compared data in the same treatment period between groups; (2) compared the incremental change in lipid levels of add-on ezetimibe vs doubling statin dose. Heterogeneity was assessed using the I(2) statistic. RESULTS: Thirteen studies including 5080 patients were included in the meta-analyses. Data on simvastatin, atorvastatin and rosuvastatin were analysed. Results for primary and secondary outcomes were in favour of the ezetimibe-statin combination. A significantly greater percentage reduction in LDL-C levels was achieved in patients treated with ezetimibe-statin vs statin monotherapy (weighted mean difference [WMD]: -14.1% [-16.1, -12.1], p < 0.001). Reduction in LDL-C levels attributed to add-on ezetimibe was significantly greater than that for statin dose doubling (WMD: -15.3% [-19.1, -11.4], p < 0.001). Achievement of LDL-C goal favoured add-on ezetimibe over statin titration and was statistically significant (odds ratio: LDL-C treatment goal 2.45 [1.95, 3.08], p = 0.007). CONCLUSIONS: Meta-analyses were restricted by the limited number of studies with similar trial design and method of statin titration. Results indicate that add-on ezetimibe is significantly more effective in reducing LDL-C levels than doubling statin dose, enabling more patients to achieve LDL-C goal.

Utilization patterns of extended-release niacin in Canada: analysis of an administrative claims database.

BACKGROUND AND OBJECTIVE: To evaluate utilization patterns with extended-release niacin (ERN) compared with those observed with other lipid-modifying drugs (LMDs). METHODS: A random sample of 17% of patients who had at least one LMD dispensation between January 2004 and February 2007 was obtained from the administrative databases of the Régie de l'assurance maladie du Quebec. Primary outcomes included drug adherence, persistence and discontinuation with ERN and other LMDs, and daily maintenance dose attainment (1500 mg and 2000 mg) with ERN at one-year follow-up. Adherence was defined as the sum of days of all dispensations divided by the total number of days of follow-up. Persistence was defined as renewal of prescription before the end of dispensation plus a grace period (50% prescription duration). RESULTS: Among 26,862 patients, the majority received statins (73.4%), whereas 867 (3.2%) received ERN. The mean age of ERN patients was 62 years and 75% were male. After one year, adherence with ERN was below that of statins (62.0% versus 74.9%), as was persistence (36.1% versus 46.7%), while discontinuation rates were higher (64.0% versus 53.3%). The median time until discontinuation for ERN was shorter than for statins (66 days versus 99 days). After one year, 5.8% of patients were taking 1500 mg or more and 3.2% were on 2000 mg. CONCLUSIONS: In the present cohort of patients from regular clinical practice in Quebec, ERN use was associated with low prescription rates, inferior adherence and persistence compared with other LMDs, high discontinuation rates, and very low 2000 mg dose attainment.

Projected cost-effectiveness of ezetimibe/simvastatin compared with doubling the statin dose in the United Kingdom: findings from the INFORCE study.

OBJECTIVE: To evaluate the incremental cost-effectiveness ratio (ICER) of switching to ezetimibe/simvastatin (Eze/Simva) compared with doubling the submaximal statin doses, in patients with acute coronary syndrome (ACS) events in the INFORCE study. METHODS: Lifetime treatment costs and benefits were computed using a Markov model. Model inputs included each patient's cardiovascular risk factor profile and actual lipid values at baseline and 12 weeks (endpoint). Cardiovascular event and drug costs were discounted at 3.5%. Age-specific utilities were based on UK literature values and non-coronary heart disease mortality rates on the Office of National Statistics data. In the INFORCE study, 384 patients taking statins at stable doses for ≥6 weeks before hospital admission were stratified by statin dose/potency (low, medium, and high) and then randomized to doubling the statin dose or switching to Eze/Simva 10/40mg for 12 weeks. RESULTS: The Eze/Simva group (n=195) had a higher mean baseline total cholesterol than the double-statin group (n=189). Analyses were adjusted for baseline characteristics. In the INFORCE study, Eze/Simva reduced low-density lipoprotein cholesterol (LDL-C) by ∼30% (vs. 4% with doubling statin doses) and significantly enhanced LDL-C goal attainment. In the cost-effectiveness analysis, Eze/Simva conferred 0.218 incremental discounted quality-adjusted life year (QALY) at a discounted incremental cost of £2524, for an ICER of £11,571/QALY (95% confidence interval=£8181-£18,600/QALY). The ICER was £13,552/QALY, £11,930/QALY, and £10,148/QALY in the low-, medium-, and high-potency strata, respectively. CONCLUSIONS: Switching to Eze/Simva 10/40 mg is projected to be a cost-effective treatment (vs. double-statin) in UK patients with ACS.

Population-based health-economic evaluation of the secondary prevention of coronary heart disease in Finland.

OBJECTIVE: To evaluate the cost-effectiveness of generic atorvastatin 20 mg (A20), branded rosuvastatin 10 mg (R10), generic simvastatin 40 mg (S40) and the combination of generic S40 + branded ezetimibe 10 mg (S40 + EZ10) for the secondary prevention of coronary heart disease (CHD) in Finnish patients not meeting the target goal of low-density lipoprotein cholesterol (LDL-C) with S40. RESEARCH DESIGN AND METHODS: A probabilistic Markov model was employed to evaluate the costs and health outcomes of the different therapies based on the cardiovascular events avoided. The model included Framingham risk equations, Finnish population characteristics, event rates, quality of life estimates, resource use and unit costs. The LDL-C lowering efficacies were gathered from a systematic literature review, based on a search of Medline carried out in June 2008 (no time limit). MAIN OUTCOME MEASURES: Incremental cost per quality-adjusted life year (QALY) gained and incremental cost per life year gained (LYG). RESULTS: The efficacy (LDL-C decrease) gained from switching S40 to S40 + EZ10 was consistent in the literature review, whereas the LDL-C decrease gained from switching S40 to A20/R10 was uncertain. The incremental cost per QALY gained from switching generic S40 was lowest for S40 + EZ10 (22,841 euros [24,017 euros] and 26,595 euros [46,686 euros] for diabetic and non-diabetic men [women], respectively). The respective incremental cost per QALY gained for S40 + EZ10 vs. A20 were 19,738 euros (21,405 euros) and 23,596 euros (40,087 euros). A20 dominated R10. Based on the cost-effectiveness acceptability frontier with a willingness-to-pay value of 30,000 euros per QALY gained, the probability of cost-effectiveness for switching generic S40 to S40 + EZ10 was 100% for men and diabetic women. Sensitivity analyses showed that results were robust. CONCLUSIONS: In the Finnish secondary prevention population that is not at goal on S40, switching generic S40 to S40 + EZ10 is more cost-effective than switching S40 to generic A20 or R10.

[Cost effectiveness in the Danish health care of ezetemibe co-administration compared to simvastatin]. / Omkostningseffektivitet i det danske sundhedsvaesen ved ezetimibe-koadministration med simvastatin.

INTRODUCTION: The purpose of this analysis is to evaluate the cost effectiveness of ezetemibe coadministration compared to a shift to higher doses of simvastatin or to a more potent statin. MATERIALS AND METHODS: The calculations are based on a Markov model in which a patient who does not attain the desired cholesterol outcome with simvastatin treatment is treated either with ezetemibe coadministration, or with increased simvastatin doses, or with a more potent statin. Calculations are conducted for a total of 72 different patient types followed over the remainder of their lives. RESULTS: Ezetemibe coadministration evaluated over the entire lifetime will be somewhat more expensive than simvastatin titration but must, however, be seen in relation to improved survival and increased quality of life. For the typical patient, treatment will be associated with costs of between DKK 50,000 and 100,000 per gained year of life, which cannot be deemed too expensive in relation to other interventions provided by the Health Authorities. For some patient types who receive treatment with a potent statin (atorvastatin), savings will also be possible here as well as an increase in life expectancy and quality of life. CONCLUSION: The results of the study indicate that ezetemibe coadministration is cost effective. The results are sustainable even with quite significant changes of the estimates used and taking into account uncertainties in the material and methods.

Cholesterol reduction yields clinical benefits: meta-analysis including recent trials.

BACKGROUND: Previous meta-analyses reported by Gould et al found significant decreases of 15% in the risk for coronary heart disease (CHD)-related mortality and 11 % in risk for all-cause mortality per decrease of 10% in total cholesterol (TC) level. OBJECTIVE: To evaluate the effects of reducing cholesterol on clinical events after including data from recent clinical trials. METHODS: Using a literature search (MeSH key terms, including: bezafibrate, coronary disease, efficacy, gemfibrozil, hydroxymethylglutaryl-CoA reductase inhibitors, hypercholesterolemia, niacin [nicotinic acids], randomized controlled trials, and treatment outcome; years: 1999-2005), we identified trials published in English that assessed the effects of lipid-modifying therapies on CHD end points, including CHD-related death, myocardial infarction, and angina pectoris. We also included all studies from the previously published meta-analysis. Using the same analytic approach as previously, we determined the effects of net absolute reductions (1 mmol/L [38.7 mg/dL]) in TC and low-density lipoprotein cholesterol (LDL-C) on the relative risks (RRs) for all-cause mortality, CHD-related mortality, any CHD event (mortality or nonfatal myocardial infarction), and non-CHD-related mortality. RESULTS: We included 62 studies involving 216,616 patients, including 126,474 from 24 randomized controlled trials the findings of which were published since the previous meta-analysis (1998). Among all patients, for every 1-mmol/L decrease in TC, there was a 17.5 reduction in RR for all-cause mortality; 24.5 %, for CHD-related mortality; and 29.5% for any CHD event. Corresponding reductions for every 1-mmol/L decrease in LDL-C were 15.6%, 28.0%, and 26.6%, respectively. Similar relationships were observed in patients without CHD. No significant relationship was found between lipid reduction and non-CHD-related mortality risk. CONCLUSIONS: The results from the present analysis support conclusions from previous meta-analyses that cholesterol lowering is clinically beneficial in patients with CHD or at elevated CHD risk. These results also support the previous finding that non-CHD-related mortality is unrelated to lipid reductions.