Comparison of medical resources and costs among patients with coronary heart disease and impaired glucose tolerance in the Acarbose Cardiovascular Evaluation trial.

BACKGROUND: The Acarbose Cardiovascular Evaluation (ACE) trial (ISRCTN91899513) evaluated the alpha-glucosidase inhibitor acarbose, compared with placebo, in 6522 patients with coronary heart disease and impaired glucose tolerance in China and showed a reduced incidence of diabetes. We assessed the within-trial medical resource use and costs, and quality-adjusted life years (QALYs). METHODS: Resource use data were collected prospectively within the ACE trial. Hospitalizations, medications, and outpatient visits were valued using Chinese unit costs. Medication use was measured in drug days, with cardiovascular and diabetes drugs summed across the trial by participant. Health-related quality of life was captured using the EuroQol-5 Dimension-3 Level questionnaire. Regression analyses were used to compare resource use, costs, and QALYs, accounting for regional variation. Costs and QALYs were discounted at 3% yearly. RESULTS: Hospitalizations were 6% higher in the acarbose arm during the trial (rate ratio 1.06, p = .009), but there were no significant differences in total inpatient days (rate ratio 1.04, p = .30). Total costs per participant, including study drug, were significantly higher for acarbose (¥ [Yuan] 56 480, £6213), compared with placebo (¥48 079, £5289; mean ratio 1.18, p < 0.001). QALYs reported by participants in the acarbose arm (3.96 QALYs) were marginally higher than in the placebo arm (3.95 QALYs), but the difference was not statistically significant (0.01 QALYs; p = .58). CONCLUSIONS: Acarbose, compared with placebo, participants cost more due to study drug costs and reported no statistically significant difference in QALYs. These higher within-trial costs could potentially be offset in future by savings from the acarbose-related lower incidence of diabetes.

The Cost-Effectiveness of Rivaroxaban Plus Aspirin Compared with Aspirin Alone in the COMPASS Trial: A US Perspective.

BACKGROUND: Rivaroxaban 2.5 mg twice daily with aspirin 100 mg daily was shown to be better than aspirin 100 mg daily for preventing cardiovascular (CV) death, stroke or myocardial infarction in patients with either stable coronary artery disease (CAD) or peripheral artery disease (PAD). The cost-effectiveness of this regimen in this population is essential for decision-makers to know. METHODS: US direct healthcare system costs (in USD) were applied to hospitalized events, procedures and study drugs utilized by all patients. We determined the mean cost per participant for the full duration of the trial (mean follow-up of 23 months) plus quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) over a lifetime using a two-state Markov model with 1-year cycle length. Sensitivity analyses were performed on the price of rivaroxaban and the annual discontinuation rate. RESULTS: The costs of events and procedures were reduced for Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) patients who received rivaroxaban 2.5 mg orally (BID) plus acetylsalicylic acid (ASA) compared with ASA alone. Total costs were higher for the combination group ($7426 versus $4173) after considering acquisition costs of the study drug. Over a lifetime, patients receiving rivaroxaban plus ASA incurred $27,255 more and gained 1.17 QALYs compared with those receiving ASA alone resulting in an ICER of $23,295/QALY. ICERs for PAD only and polyvascular disease subgroups were lower. CONCLUSION: Rivaroxaban 2.5 mg BID plus ASA compared with ASA alone was cost-effective (high value) in the USA. COMPASS ClinicalTrials.gov identifier: NCT01776424.

The cost-effectiveness of rivaroxaban with or without aspirin in the COMPASS trial.

AIMS: The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial demonstrated that rivaroxaban 2.5 mg BID with aspirin 100 mg was more effective than aspirin 100 mg daily alone for the prevention of cardiovascular (CV) death, stroke, or myocardial infarction in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). We aimed to examine the cost-effectiveness of rivaroxaban using patient-level data from the COMPASS trial. METHODS AND RESULTS: We performed an in-trial analysis and extrapolated our results for 33 years using a two-state Markov model with a 1-year cycle length. Hospitalization events, procedures, and study drugs were documented for patients. We applied country-specific (Canada, France, and Germany) direct healthcare system costs (in USD) to healthcare resources consumed by patients. Average cost per patient during the trial (mean follow-up of 23 months), quality-adjusted life years (QALYs), and lifetime cost-effectiveness were calculated. Costs of events and procedures were reduced with rivaroxaban 2.5 mg BID with aspirin. The addition of rivaroxaban 2.5 mg BID increased total costs for the combination group. Over a lifetime horizon (in trial +33 years), rivaroxaban plus aspirin was associated with 1.17 QALYs gained, yielding an incremental cost-effectiveness ratio (ICER) of $3946/QALY, $9962/QALY, and $10 264/QALY in Canada, France, and Germany, respectively. PAD and polyvascular disease subgroups had lower ICERs. CONCLUSION: Rivaroxaban 2.5 mg twice daily plus aspirin compared with aspirin alone reduces direct healthcare costs. After acquisition costs of rivaroxaban, the lifetime cost-effectiveness of 2.5 mg twice daily plus aspirin is highly cost-effective in Canada, France, and Germany.(COMPASS ClinicalTrials.gov identifier: NCT01776424).

Screening for Glucose Perturbations and Risk Factor Management in Dysglycemic Patients With Coronary Artery Disease-A Persistent Challenge in Need of Substantial Improvement: A Report From ESC EORP EUROASPIRE V.

OBJECTIVE: Dysglycemia, in this survey defined as impaired glucose tolerance (IGT) or type 2 diabetes, is common in patients with coronary artery disease (CAD) and associated with an unfavorable prognosis. This European survey investigated dysglycemia screening and risk factor management of patients with CAD in relation to standards of European guidelines for cardiovascular subjects. RESEARCH DESIGN AND METHODS: The European Society of Cardiology's European Observational Research Programme (ESC EORP) European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V (2016-2017) included 8,261 CAD patients, aged 18-80 years, from 27 countries. If the glycemic state was unknown, patients underwent an oral glucose tolerance test (OGTT) and measurement of glycated hemoglobin A1c. Lifestyle, risk factors, and pharmacological management were investigated. RESULTS: A total of 2,452 patients (29.7%) had known diabetes. OGTT was performed in 4,440 patients with unknown glycemic state, of whom 41.1% were dysglycemic. Without the OGTT, 30% of patients with type 2 diabetes and 70% of those with IGT would not have been detected. The presence of dysglycemia almost doubled from that self-reported to the true proportion after screening. Only approximately one-third of all coronary patients had completely normal glucose metabolism. Of patients with known diabetes, 31% had been advised to attend a diabetes clinic, and only 24% attended. Only 58% of dysglycemic patients were prescribed all cardioprotective drugs, and use of sodium-glucose cotransporter 2 inhibitors (3%) or glucagon-like peptide 1 receptor agonists (1%) was small. CONCLUSIONS: Urgent action is required for both screening and management of patients with CAD and dysglycemia, in the expectation of a substantial reduction in risk of further cardiovascular events and in complications of diabetes, as well as longer life expectancy.

Diabetes as a cardiovascular risk factor: An overview of global trends of macro and micro vascular complications.

The global prevalence of diabetes is predicted to increase dramatically in the coming decades as the population grows and ages, in parallel with the rising burden of overweight and obesity, in both developed and developing countries. Cardiovascular disease represents the principal cause of death and morbidity among people with diabetes, especially in those with type 2 diabetes mellitus. Adults with diabetes have 2-4 times increased cardiovascular risk compared with adults without diabetes, and the risk rises with worsening glycaemic control. Diabetes has been associated with 75% increase in mortality rate in adults, and cardiovascular disease accounts for a large part of the excess mortality. Diabetes-related macrovascular and microvascular complications, including coronary heart disease, cerebrovascular disease, heart failure, peripheral vascular disease, chronic renal disease, diabetic retinopathy and cardiovascular autonomic neuropathy are responsible for the impaired quality of life, disability and premature death associated with diabetes. Given the substantial clinical impact of diabetes as a cardiovascular risk factor, there has been a growing focus on diabetes-related complications. While some population-based studies suggest that the epidemiology of such complications is changing and that rates of all-cause and cardiovascular mortality among individuals with diabetes are decreasing in high-income countries, the economic and social burden of diabetes is expected to rise due to changing demographics and lifestyle especially in middle- and low-income countries. In this review we outline data from population-based studies on recent and long-term trends in diabetes-related complications.

Attitudes and lifestyle factors in relation to oral health and dental care in Sweden: a cross-sectional study.

OBJECTIVE: The aim of the present study was to investigate attitudes to and perceptions of dental treatment and costs, self-assessed personal oral health status and dental self-care in an adult Swedish population, with special reference to potential associations between these factors and periodontal status. MATERIAL AND METHODS: The study population comprised 1577 subjects who had undergone radiographic dental examination. The subjects were grouped by severity of periodontitis, based on extent of bone loss, as none, mild/moderate or severe. Subjects answered a questionnaire about socioeconomic factors, oral care habits and attitudes to dental treatment. Other questions covered medical history, smoking and other life style factors. Associations were tested using the Chi-squared test and a logistic regression model. RESULTS: Compared to subjects with no periodontitis, those with mild/moderate or severe periodontitis were less likely to afford (p < .001), more often refrained from treatment due to costs (p < .001) and in the past year had experienced dental problems for which they had not sought treatment (p < .001). They also reported more anxiety in relation to dental appointments (p = .001). Regarding caries prevention, the severe periodontitis group used least fluoride products (p = .002). CONCLUSIONS: Swedish adults regard their oral health as important, those with periodontitis have a more negative perception of their oral health and are less prone to seek help. These discouraging findings suggest the need for targeted measures, which focus on improving the care of this group of patients.

Effectiveness of different outreach strategies to identify individuals at high risk of diabetes in a heterogeneous population: a study in the Swedish municipality of Södertälje.

BACKGROUND: Identifying type 2 diabetes mellitus (T2DM) is a prerequisite for the institution of preventive measures to reduce future micro and macrovascular complications. Approximately 50% of people with T2DM are undiagnosed, challenging the assumption that a traditional primary healthcare setting is the most efficient way to reach people at risk of T2DM. A setting of this kind may be even more suboptimal when it comes to reaching immigrants, who often appear to have inferior access to healthcare and/or are less likely to attend routine health checks at primary healthcare centres. OBJECTIVES: The objective of this study was to identify the best strategy to reach individuals at high risk of T2DM and thereby cardiovascular disease in a heterogeneous population. METHODS: All 18-65-year-old inhabitants in the Swedish municipality of Södertälje ( n∼51,000) without known T2DM and cardiovascular disease were encouraged to complete the Finnish Diabetes Risk Score (FINDRISC: score > 15 indicating a high and > 20 a very high risk of future T2DM and cardiovascular disease) through the following communication channels: primary care centres, workplaces, Syrian orthodox churches, pharmacies, crowded public places, mass media, social media and mail. Data collection lasted for six weeks. RESULTS: The highest response rate was obtained through workplaces (27%) and the largest proportion of respondents at high/very high risk through the Syrian orthodox churches (18%). The proportion reached through primary care centres was 4%, of whom 5% were at elevated risk. The cost of identifying a person at elevated risk through the Syrian orthodox church was €104 compared with €8 through workplaces and €112 through primary care centres. CONCLUSIONS: The choice of communication channels was important to reach high/very high-risk individuals for T2DM and for screening costs. In this immigrant-dense community, primary care centres were inferior to strategies using workplaces and churches in terms of both the proportion of identified at-risk individuals and costs.

Cost-effectiveness of optimized adherence to prevention guidelines in European patients with coronary heart disease: Results from the EUROASPIRE IV survey.

BACKGROUND: This study aims to assess the cost-effectiveness of optimized guideline adherence in patients with a history of coronary heart disease. METHODS: An individual-based decision tree model was developed using the SMART risk score tool which estimates the 10-year risk for recurrent vascular events in patients with manifest cardiovascular disease (CVD). Analyses were based on the EUROASPIRE IV survey. Outcomes were expressed as an incremental cost-effectiveness ratio (ICER). RESULTS: Data from 4663 patients from 13 European countries were included in the analyses. The mean estimated 10-year risk for a recurrent vascular event decreased from 20.13% to 18.61% after optimized guideline adherence. Overall, an ICER of 52,968€/QALY was calculated. The ICER lowered to 29,093€/QALY when only considering high-risk patients (≥20%) with decreasing ICERs in higher risk patients. Also, a dose-response relationship was seen with lower ICERs in older patients and in those patients with higher risk reductions. A less stringent LDL target (<2.5 mmol/L vs. <1.8 mmol/L) lowered the ICER to 32,591€/QALY and intensifying cholesterol treatment in high-risk patients (≥20%) instead of high-cholesterol patients lowered the ICER to 28,064€/QALY. An alternative method, applying risk reductions to the CVD events instead of applying risk reductions to the risk factors lowered the ICER to 31,509€/QALY. CONCLUSION: Depending on the method used better or worse ICERs were found. In addition, optimized guidelines adherence is more cost-effective in higher risk patients, in patients with higher risk reductions and when using a less strict LDL-C target. Current analyses advice to maximize guidelines adherence in particular patient subgroups.

Homeostasis Model Assessment of Insulin Resistance and Survival in Patients With Diabetes and Acute Coronary Syndrome.

Objective: Insulin resistance has been linked to development and progression of atherosclerosis and is present in most patients with type 2 diabetes. Whether the degree of insulin resistance predicts adverse outcomes in patients with type 2 diabetes and acute coronary syndrome (ACS) is uncertain. Design: The Effect of Aleglitazar on Cardiovascular Outcomes after Acute Coronary Syndrome in Patients with Type 2 Diabetes Mellitus trial compared the peroxisome proliferator-activated receptor-α/γ agonist aleglitazar with placebo in patients with type 2 diabetes and recent ACS. In participants not treated with insulin, we determined whether baseline homeostasis model assessment of insulin resistance (HOMA-IR; n = 4303) or the change in HOMA-IR on assigned study treatment (n = 3568) was related to the risk of death or major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in unadjusted and adjusted models. Because an inverse association of HOMA-IR with N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been described, we specifically examined effects of adjustment for the latter. Results: In unadjusted analysis, twofold higher baseline HOMA-IR was associated with lower risk of death [hazard ratio (HR): 0.79, 95% CI: 0.68 to 0.91, P = 0.002]. Adjustment for 24 standard demographic and clinical variables had minimal effect on this association. However, after further adjustment for NT-proBNP, the association of HOMA-IR with death was no longer present (adjusted HR: 0.99, 95% CI: 0.83 to 1.19, P = 0.94). Baseline HOMA-IR was not associated with major adverse cardiovascular events, nor was the change in HOMA-IR on study treatment associated with death or major adverse cardiovascular events. Conclusions: After accounting for levels of NT-proBNP, insulin resistance assessed by HOMA-IR is not related to the risk of death or major adverse cardiovascular events in patients with type 2 diabetes and ACS.

Risk factors, treatment and prognosis in men and women with heart failure with and without diabetes.

OBJECTIVE: To test the hypothesis that risk factor pattern, treatment and prognosis differ between men and women with heart failure (HF) with and without diabetes in the Swedish Heart Failure Registry. METHODS: Patients with (n=8809) and without (n=27 465) type 2 diabetes (T2DM) included in the Swedish Heart Failure Registry (2003-2011) were followed for mortality during a median follow-up of 1.9 years (range 0-8.7 years). All-cause mortality, differences in background and HF characteristics were analysed in women and men with and without T2DM and with a special regard to different age groups. RESULTS: Of 36 274 patients, 24% had T2DM and 39% were women. In patients with T2DM, women were older than men (78 years vs 73 years), more frequently had hypertension, renal dysfunction and preserved ventricular function. Regardless of T2DM status, women with reduced ventricular function, compared with their male counterparts, were less frequently offered, for example, ACE inhibitors/angiotensin receptor II blockers (ARB). Absolute mortality was 48% in women with T2DM, 40% in women without; corresponding male mortality rates were 43% and 35%, respectively. Kaplan-Meier curves revealed shorter longevity in women with T2DM but female sex did not remain a significant mortality predictor following adjustment (OR 95% CI 0.90; 0.79 to 1.03). In those without T2DM, women compared with men lived longer; this pattern remained after adjustment (OR 0.72; 0.66 to 0.78). T2DM was a stronger predictor of mortality in women (OR 1.72; 1.53 to 1.94) than in men (OR 1.47; 1.34 to 1.61). CONCLUSIONS: T2DM is a strong mortality predictor in men and women with HF, somewhat stronger in women. The shorter survival time in women with T2DM and HF related to comorbidities rather than sex per se. Evidence-based management was less prevalent in women. Mechanisms behind these findings remain incompletely understood and need further attention.

Policymakers' perceptions of cardiovascular health in Europe.

BACKGROUND: Prevention of cardiovascular disease at population level has proven to be both possible and successful. The European Heart Health Charter (EHHC) outlines goals for successful cardiovascular (CV) prevention both in individuals and at a national level. The objective of this study was to explore key European health policymakers' perceptions of their country's proximity to the EHHC-targets and their views on obstacles to domestic CV health and on the actions needed to improve it. DESIGN: Questionnaire, descriptive. METHOD: The questionnaire was distributed to health policy leaders (n = 116) within the Ministries of Health, public health institutes, cardiac societies and heart foundations in 32 European countries, assessing previous knowledge, goal fulfilment of the EHHC, perceived obstacles to CV health, actions deemed to be important to improve the CV situation, and measures to promote CV health. RESULTS: The response rate was 68%. The general consensus was that the national CV situations were far from attaining the EHHC targets. How different health policy leaders rated the proximity to specific targets and measures did, however, not necessarily reflect the actual situation. There was a polarisation between the health policy leaders regarding obstacles to CV health and what actions are needed to improve it. There were small differences between the four professional groups and regions of the extent measures were believed to be used. CONCLUSION: Discrepant views on the CV situation and on the actions needed to improve it, underline the importance of information assessing the national situation and the necessity of a dialogue between organisations and policymakers responsible for CV disease throughout Europe.

Assessment of myocardium at risk with contrast enhanced steady-state free precession cine cardiovascular magnetic resonance compared to single-photon emission computed tomography.

BACKGROUND: Final infarct size following coronary occlusion is determined by the duration of ischemia, the size of myocardium at risk (MaR) and reperfusion injury. The reference method for determining MaR, single-photon emission computed tomography (SPECT) before reperfusion, is impractical in an acute setting. The aim of the present study was to evaluate whether MaR can be determined from the contrast enhanced myocardium using steady-state free precession (SSFP) cine cardiovascular magnetic resonance (CMR) performed one week after the acute event in ST-elevation myocardial infarction (STEMI) patients with total coronary occlusion. RESULTS: Sixteen patients with STEMI (age 64 +/- 8 years) received intravenous 99 m-Tc immediately before primary percutaneous coronary intervention. SPECT was performed within four hours. MaR was defined as the non-perfused myocardial volume derived with SPECT. CMR was performed 7.8 +/- 1.2 days after the myocardial infarction using a protocol in which the contrast agent was administered before acquisition of short-axis SSFP cines. MaR was evaluated as the contrast enhanced myocardial volume in the cines by two blinded observers. MaR determined from the enhanced region on cine CMR correlated significantly with that derived with SPECT (r2 = 0.78, p < 0.001). The difference in MaR determined by CMR and SPECT was 0.5 +/- 5.1% (mean +/- SD). The interobserver variability of contrast enhanced cine SSFP measurements was 1.6 +/- 3.7% (mean +/- SD) of the left ventricle wall volume. CONCLUSIONS: Contrast enhanced SSFP cine CMR performed one week after acute infarction accurately depicts MaR prior to reperfusion in STEMI patients with total occlusion undergoing primary PCI. This suggests that a single CMR examination might be performed for determination of MaR and infarct size.