Cardiovascular-related Hospitalizations Research Articles

Multicenter Cluster-Randomized Trial of a Multifactorial Intervention to Improve Antihypertensive Medication Adherence and Blood Pressure Control Among Patients at High Cardiovascular Risk (The COM99 Study)

Medication nonadherence is common and results in preventable disease complications. This study assessed the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events. In this multicenter, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥ 50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients' pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end point of all-cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62, 95% confidence interval 0.50 to 0.78) and were more likely to be adherent (odds ratio 1.91, 95% confidence interval 1.19 to 3.05) than control group patients at 6 months. After 5 years, 16% of the patients in the intervention group and 19% in the control group met the composite end point (hazard ratio 0.97, 95% confidence interval 0.67 to 1.39). A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events.

Dronedarone: A New Antiarrhythmic Agent

Dronedarone is an antiarrhythmic agent recently approved by the United States Food and Drug Administration for the reduction of cardiovascular-related hospitalizations in patients with paroxysmal or persistent atrial fibrillation or atrial flutter. The drug is a derivative of amiodarone and has been modified to reduce the organ toxicities frequently encountered with amiodarone. Dronedarone exerts its antiarrhythmic effects through multichannel blockade of the sodium, potassium, and calcium channels and also possesses antiadrenergic activity, thereby exhibiting pharmacologic effects of all four Vaughan Williams classes of antiarrhythmics. The efficacy of dronedarone for the maintenance of sinus rhythm, ventricular rate control, and reduction in cardiovascular-related hospitalizations has been demonstrated in several randomized, placebo-controlled trials. Although a high rate of gastrointestinal events (e.g., nausea, vomiting, and diarrhea) has been associated with dronedarone, more serious adverse events such as thyroid, liver, or pulmonary toxicities have not been observed. Because of a possible increase in mortality, dronedarone should be avoided in patients with New York Heart Association class IV or II-III heart failure with a recent decompensation. Given the efficacy and safety data currently available, dronedarone represents a reasonable alternative for maintenance of sinus rhythm in appropriately selected patients.

Integrating Clinical Trial Findings into Practice through Risk Stratification: The Case of Heart Failure Management

Heart failure case management programs have been shown in clinical trials to be highly effective at preventing future hospitalizations. But the absolute benefits of these programs depend on the baseline risk of outcome in the treated population. Because baseline risks of hospitalization in trials are often higher than community-based samples, translating trial results to the community setting may be misleading. One solution is to identify subgroups for intervention that have sufficiently high baseline risk. Using estimates of hospitalizations averted from a previously published systematic review of heart failure management, we estimated a program's efficiency based on level of predicted risk. Medical history and demographic data on heart failure patients from a large integrated US health plan were used to build a logistic regression-based prognostic risk score for cardiovascular-related hospitalization over 1 year. We calculated the crude rate of hospitalizations for comparison with trial data. We also calculated the program's potential dollar savings from averting hospitalizations. The average risk of hospitalization in the systematic review's trials was 45%; our population's average observed risk was 18% and the risk among the highest risk patients was 33%. After accounting for the assumed annual intervention cost of $700, the base-case analysis (at $6000 per hospitalization) shows a savings of $122/patient at highest risk; failing to intervene according to predicted risk (no targeting) would actually cost $211/patient. Our findings illustrate how clinical trial findings can be efficiently integrated into community settings by using a prognostic risk score to focus attention on high-risk subgroups.

Serum Alkaline Phosphatase and Phosphate and Risk of Mortality and Hospitalization

Elevated alkaline phosphatase (AlkPhos) and phosphate levels are associated with cardiovascular morbidity and mortality in patients receiving dialysis. A retrospective cohort study was conducted to test these associations in outpatients with an estimated GFR > or =60 ml/min/1.73 m(2). Patients with serum AlkPhos and phosphate levels measured between 2000 and 2002 (n = 10,743) at Montefiore Medical Center (MMC) clinics were followed through September 11, 2008 (median 6.8 years). Mortality data were obtained via Social Security Administration records (n = 949 deaths). Hospitalization data were obtained from MMC records. The mean age was 51 years, 64% were women, 22% were white, 26% were non-Hispanic black, 16% were Hispanic, 13% had a diagnosis of hypertension, 9% had diabetes mellitus, and 8% had cardiovascular disease at baseline. AlkPhos and phosphate were independently associated with mortality and cardiovascular-related hospitalization after multivariable adjustment. Comparing patients in the highest (> or =104 U/L) versus lowest quartile of AlkPhos (< or =66 U/L), the adjusted hazard ratio (HR) for mortality was 1.65 (P trend across quartiles <0.001). For the highest compared with the lowest quartile of serum phosphate (> or =3.8 mg/dl versus < or =3.0 mg/dl), the adjusted HR for mortality was 1.29 (P trend across quartiles = 0.008). High AlkPhos but not phosphate levels were also associated with all-cause, infection-related, and fracture-related hospitalization. Higher levels of serum AlkPhos and phosphate were associated with increased mortality and cardiovascular-related hospitalization in an inner-city clinic population. Further studies are needed to elucidate mechanisms underlying these associations.

Improving Adherence to Treatment Guidelines

Patients with chronic diseases often require complex medication regimens to meet evidence-based treatment guidelines. However, translating evidence-based recommendations into clinical care has proven to be difficult. Several factors-patient adherence, disease complexity, competing medical issues, guideline dissemination, and clinical inertia-are thought to contribute to this problem. In this manuscript, we describe a multidisciplinary ambulatory approach to improve the care of patients with chronic conditions. Our goal was to design an intervention that focused on improving the prescription rates of medications known to reduce cardiovascular-related events and hospital admissions for patients with diabetes mellitus, coronary artery disease, heart failure, chronic kidney disease, or stroke. We also describe the critical lessons we have learned in implementing our intervention, including the successes and barriers we encountered during the project.

Cardiovascular and Economic Outcomes After Initiation of Lipid-Lowering Therapy With Atorvastatin vs Simvastatin in an Employed Population

To compare the risk of cardiovascular-related hospitalization, statin adherence, and direct (medical and drug) and indirect (disability and medically related absenteeism) costs in US employees in whom atorvastatin or simvastatin was newly prescribed. Active employees aged 18 to 64 years with a new atorvastatin or simvastatin prescription were identified from a deidentified claims database for 23 privately insured US companies from January 1, 1999, through December 31, 2006. Employees given atorvastatin were matched to those given simvastatin according to propensity scores based on patient characteristics, index statin dose, preindex cardiovascular events, and wage. Outcomes were compared between matched cohorts during the 2-year postindex period, including the risk of cardiovascular-related hospitalization, adherence to the index statin, use of other lipid-lowering drugs, direct medical costs for third-party payers, and indirect costs to employers. Indirect costs were computed as follows: Disability Payments + Daily Wage x Days of Medically Related Absenteeism. Atorvastatin and simvastatin drug costs were imputed using recent pricing to account for the availability of lower-cost generic simvastatin after the study period. Among 13,584 matched pairs, treatment with atorvastatin vs simvastatin was associated with a reduced risk of cardiovascular-related hospitalization, higher adherence, and less use of other lipid-lowering drugs. The increase in statin costs associated with atorvastatin vs simvastatin therapy was almost completely offset by reductions in medical service and indirect costs. In this study, treatment with atorvastatin compared with simvastatin was associated with a reduced risk of cardiovascular events, reduced indirect costs, and a minimal difference in total costs to employers.

Survival and hospitalization among patients using nocturnal and short daily compared to conventional hemodialysis: a USRDS study

We estimated the survival and hospitalization among frequent hemodialysis users in comparison to those patients undergoing thrice-weekly conventional hemodialysis. All patients had similar characteristics and medical histories. In this cohort study of frequent hemodialysis users and propensity score-matched controls, the collaborating clinicians identified 94 patients who used nocturnal hermodialysis (NHD) and 43 patients who used short-duration daily hemodialysis (SDHD) for a minimum of 60 days. Ten propensity score-matched control patients for each NHD and SDHD patient were identified from the United States Renal Data System database. Primary outcomes were risk for all-cause mortality and risk for the composite outcome of mortality or major morbid event (acute myocardial infarction or stroke) estimated using Cox proportional hazards models. Risks for all-cause, cardiovascular-related, infection-related, and vascular access-related hospital admissions were also studied. Nocturnal hemodialysis was associated with significant reductions in mortality risk and risk for mortality or major morbid event when compared to conventional hemodialysis. There was a reduced but non-significant risk of death for patients using SDHD compared to controls. All-cause and specific hospitalizations did not differ significantly between NHD and SDHD patients and their matched control cohorts. Our study suggests that NHD may improve patient survival.

Dronedarone approved for atrial arrhythmias

FDA on July 2 announced the approval of the oral antiarrhythmia drug dronedarone for the maintenance of normal heartbeat in certain patients with a history of paroxysmal or persistent atrial fibrillation or atrial flutter. Dronedarone is made by Sanofi-Aventis under the brand name Multaq and will be available in the United States this summer, the company said. Dronedarone is indicated to reduce the risk of cardiovascular-related hospitalization in patients with a recent episode of atrial fibrillation or flutter whose heart rhythm has returned to normal or will be corrected through cardioversion, according to the product’s labeling. Only patients whose condition is characterized by “associated cardiovascular risk factors,” such as age greater than 70 years, hypertension, diabetes, previous cerebrovascular accident, left atrium diameter of 50 mm or greater, or left ventricular ejection fraction less than 40%, should be treated with dronedarone, the labeling states. The labeling includes a boxed warning stating that dronedarone increases the risk of death and is contraindicated in patients with New York Hospital Association (NYHA) class IV heart failure as well as certain patients with NYHA class II or III heart failure.

Predictors of Recurrent Cardiovascular Hospitalizations in Patients with Diastolic Heart Failure

Introduction: The prevalence of diastolic heart failure (DHF) ranges from 13 to 74% depending on the population studied. Despite the high prevalence, morbidity and mortality associated with DHF, very few trials have examined treatment options for these patients. This analysis examined factors predicting recurrent cardiovascular related hospitalizations, number of cardiovascular hospitalizations and number of hospital days at each admission in patients with DHF. Methods: A retrospective case review was performed including patients with DHF from the tele health program.

Adherence to K/DOQI Bone Metabolism Guidelines

Guidelines for the treatment of patients with chronic kidney disease recommend laboratory testing of markers of bone metabolism, including intact parathyroid hormone, calcium, and phosphorus. The authors sought to evaluate the concordance of contemporary clinical practice with treatment recommendations. Trends were evaluated (2002 to 2005) in testing for bone metabolism in patients with chronic kidney disease, and the relation between bone metabolism markers, severity of chronic kidney disease, and cardiovascular hospitalizations were examined. Retrospective cohort. Large United States health-maintenance organization. Chronic kidney disease. Little variation was found in testing rates over time. Testing frequency was positively correlated with severity of kidney disease, referral to nephrology, and test type (annual testing was most likely for intact parathyroid hormone, and least likely for calcium). Patients with higher intact parathyroid hormone values had a greater risk of cardiovascular-related hospitalization; after adjusting for potential confounders, those with an intact parathyroid hormone value of 200 and greater had a relative risk of 2.16 (95% confidence interval, 1.09 to 4.29). This study supports the hypothesized association between disorders of bone metabolism and cardiovascular disease, but it does not address whether increased testing for disorders of bone metabolism will improve outcomes for patients with chronic kidney disease. Nor does our analysis imply that controlling parathyroid hormone will prevent cardiovascular hospitalizations. Future studies should more fully explore those critical clinical questions.

The Darkening Cloud of Diabetes

OBJECTIVE—We aimed to evaluate the changes in cardiovascular-related health care utilization (drug therapies, hospitalizations) and mortality for the diabetic population during a 9-year period in Saskatchewan, Canada.RESEARCH DESIGN AND METHODS—We identified annual diabetes prevalence rates for people aged ≥30 years between 1993 and 2001 from the administrative databases of Saskatchewan Health. Annual rates of evidence-based drug therapies (antihypertensives, ACE inhibitors, β-blockers, calcium channel blockers, 3-hydroxy-3-metaglutaryl coenzyme A reductase inhibitors [statins]), hospitalizations for cerebrovascular and cardiac events, and all-cause mortality were estimated. Rates were direct age and sex standardized using the 2001 Canadian population, and trends over time were assessed using Joinpoint regression.RESULTS—From 1993 to 2001, diabetes prevalence increased 34% (4.7–6.5%, P < 0.001) with the highest rates in men and those aged ≥65 years. The rate of increase in diabetes prevalence appeared to slow in those aged <65 years (P < 0.01 for trend). Significant increased use of evidence-based drug therapies was observed (41% increase in antihypertensive agents, 97% increase in ACE inhibitors, 223% increase in statin therapies; all P < 0.05 for trend). During this period, both cerebrovascular and cardiac-related hospitalizations declined by 36% (9.5 vs. 6.1 per 1,000) and 19% (38.0 vs. 30.6 per 1,000) (P < 0.05 for trends), respectively, with similar reductions regardless of sex. No change in all-cause mortality was observed (17.7 vs. 17.8 deaths per 1,000; P > 0.05).CONCLUSIONS—During our period of study, there was an increase in the utilization of evidenced-based drug therapies in people with diabetes and reductions in cardiovascular-related hospitalizations. Despite this, we observed no change in all-cause mortality.

Cost-effectiveness analysis of aldosterone blockade with eplerenone in patients with heart failure after acute myocardial infarction in the French context: The EPHESUS study

The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) randomized clinical trial demonstrated the efficacy of eplerenone, a new aldosterone antagonist diuretic, with standard treatment versus standard treatment alone in the reduction of cardiovascular mortality and cardiovascular-related hospital readmissions for patients with heart failure after an acute myocardial infarction. We assessed the incremental cost per life-year saved of eplerenone in the French context versus standard treatment. A within-trial study was designed. A piecewise regression model yielded death rates and survival gains adjusted for patients' characteristics, based on the extraction of comparable patients from the Saskatchewan Health database. Resource use was collected alongside the clinical trial data. Only direct medical costs were considered. All costs were in 2003 euros. Costs and outcomes were discounted at 5%. The overall mortality rate was 14.4% in the treatment group versus 16.7% in the placebo group (p=0.008). Combined cardiovascular deaths and hospitalization rates were 26.7% in the treatment group versus 30.3% in the placebo group (p=0.002). The discounted survival gain was 3.2 weeks. The incremental cost per life-year saved was euro15,382 (95% confidence interval 8274-42,723). Seventy-four per cent of the values of the incremental cost-effectiveness ratio fell under a euro15,000 per life-year saved threshold. The cost of eplerenone leads to an acceptable level of incremental cost per life-year saved when compared with existing treatments in the cardiovascular domain for the prevention of cardiovascular death and morbidity in patients with heart failure after an acute myocardial infarction.

Reduction in cardiovascular related hospitalization with nocturnal home hemodialysis

Cardiovascular disease remains the leading cause of death among patients with end-stage renal disease (ESRD). Nocturnal home hemodialysis (NHD) (5 - 6 sessions per week; 6 - 8 hours per session) is a novel form of home-based renal replacement therapy, which has been shown to improve several cardiovascular risk factors. The impact of NHD on hospitalization rate has remained unclear. We hypothesized that augmentation of small and middle molecular clearance by NHD would result in a reduction of dialysis related or cardiovascular specific hospitalizations. In this controlled cohort study, we studied 32 NHD patients (age: 43 +/- 2 [mean +/- SEM]) 1 year before and 2 years after conversion to NHD and 42 CHD patients (mean age: 44 +/- 2) (matched for age, dialysis vintage and controlled for comorbidities) during the same time period. The primary outcome was the change in a composite of dialysis or cardiovascular related admissions rate before and after conversion to NHD. Secondary outcomes included changes in all cause hospitalization rate, visits to emergency, reasons and duration of hospitalization and dialysis-related biochemical parameters. During the study period, dialysis or cardiovascular-related admission rate was stable for the CHD control cohort (from 0.48 +/- 0.14 [baseline] to 0.40 +/- 0.12 [end of study] admission per patient year, p = NS). In contrast, conversion to NHD is associated with a decrease in our composite endpoint (from 0.50 +/- 0.15 to 0.17 +/- 0.06 admission per patient year, p = 0.04). Cardiovascular disease (37%) was the principal cause for hospitalization in the control population. In comparison, vascular access related admission was the primary cause of admission for the NHD cohort (56%), p = 0.001. Of the biochemical parameters, NHD is associated with a decrease in plasma phosphate (from 1.7 +/- 0.1 to 1.3 +/- 0.1 mM, p = 0.01) and an improved control of anemia (from 114 +/- 2 to 122 +/- 3 g/l, p = 0.02). Conversion to NHD is associated with a decrease in dialysis and cardiovascular-related hospital admission. The clinical and mechanistic relevance in uremic patients of improved phosphate and anemia management requires further examination.

Long-Term Cost-Effectiveness Analysis of Nebivolol Compared with Standard Care in Elderly Patients with Heart Failure

The SENIORS trial demonstrated that nebivolol is effective in the treatment of heart failure in elderly patients (e.g. > or = 70 years). This analysis evaluates the cost effectiveness of nebivolol compared with standard treatment. An individual patient-simulation model based on a Markov modelling framework was developed to compare costs and outcomes for nebivolol and standard care in patients with heart failure starting treatment at the age of 70 years. Health states were defined by New York Heart Association (NYHA) class and death. At a given NYHA class and a given cycle, patients could die, be hospitalized for cardiovascular disease or remain stable. Risks for these events were derived from individual patient data from the SENIORS trial. The risk of each event in a given cycle was based on the subject's baseline characteristics and time in the current health state. The economic analysis was conducted from the UK NHS perspective with a lifetime horizon. The costs (euro; year 2006 values) considered were drug costs for nebivolol and other cardiac drugs, costs of GP visits, outpatient specialist visits and cardiovascular-related hospitalizations. Univariate and probabilistic sensitivity analysis was conducted. In the baseline analysis, the total cost per patient was euro6740 and euro9288, and QALYs were 5.194 and 5.843 for patients aged 70 years at the start of treatment for the standard treatment and nebivolol groups, respectively. The probabilistic sensitivity analysis provided an incremental cost-effectiveness ratio of euro3926 (95% CI 3731, 4159) per QALY. This analysis indicates that nebivolol appears to be a cost-effective treatment for elderly patients with heart failure compared with standard care.

Comment on: Evans JM, Ogston SA, Emslie-Smith A, Morris A (2006) Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia 49:930–936

To the Editor: The recent paper by Evans et al. [1] on the risk of adverse cardiovascular outcomes in patients with type 2 diabetes treated with sulfonylureas or metformin is of great interest to us. The authors cited a study by our group [2], as having ‘re-ignited’ this long-standing debate. We found the similarity in risk estimates between the two studies striking, with both reporting a 40% lower mortality for metformin users compared to sulfonylurea users. This was particularly reassuring for us, as we did not have access to clinical data in the administrative databases we used [2]. Though Evans et al. did not include it in their cited literature, we also reported a follow-up analysis that evaluated non-fatal events defined by cardiovascular-related hospitalisations [3]. Interestingly, the results from Evans et al. were again very similar to ours, despite the lack of clinical data, with the risk of cardiovascular hospitalisation not increased for sulfonylurea users, suggesting similar baseline risk. An increased risk of hospitalisation was observed by Evans et al. for their Combination 2 (sulfonylurea first, metformin added) cohort, although, to our reading, it appears that their monotherapy and combination therapy cohorts were not entirely mutually exclusive (i.e. subjects in the Combination 1 and 2 cohorts also contributed time to the respective monotherapy cohorts), confounding their analyses with respect to duration and severity of diabetes. Evans et al. suggest that these results support the hypothesis that metformin is cardioprotective, as did Sasali and Leahy [4] in an editorial accompanying our original paper. We question this conclusion, as it remains difficult to fully discern the causal relationship from this series of observational studies. We do recognise that an accumulation of evidence from observational studies can support inferences of causality. To that end, we recently conducted a dose–response relationship analysis within our study cohorts, and observed that increased exposure to sulfonylureas (based on either dosing or adherence) was associated with increased overall and cardiovascular-related mortality [5]. The relationship was particularly evident for the firstgeneration sulfonylureas, chlorpropamide and tolbutamide, but also apparent for glyburide. In contrast, we observed no difference in mortality associated with higher or lower doses of metformin. These results, along with a potential pathophysiological mechanism of impaired myocardial ischaemic preconditioning, prompted D. S. Bell in an accompanying editorial [6] to suggest that it is indeed sulfonylureas that are cardiotoxic. Regardless of the pathophysiological explanation, we believe that the totality of available evidence, from trials [7] and observational studies [1–3, 5], strongly supports the use of metformin as first-line therapy in type 2 diabetes. In the absence of randomised trial evidence of clinical benefit, J. A. Johnson (*) :D. T. Eurich : S. R. Majumdar Faculty of Medicine and Dentistry, University of Alberta, 1200-10405 Jasper Avenue, Edmonton, AB T5J 3N4, Canada e-mail: jeff.johnson@ualberta.ca

Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with Type 2 diabetes

Metformin therapy reduces microvascular complications in Type 2 diabetes; questions remain, however, regarding its impact on macrovascular events. This study examined metformin use in relation to risk of cardiovascular-related hospitalization and mortality. We conducted a retrospective cohort analysis, using Saskatchewan Health administrative databases to identify new users of oral antidiabetic drugs. Subject groups were defined by medication use during 1991-1999: sulphonylurea monotherapy, metformin monotherapy, or combination therapy. Deaths and non-fatal hospitalizations recorded during the study period were identified as cardiovascular-related from ICD-9 codes. The main outcome was a composite of first non-fatal hospitalization or death. Standard multivariate techniques, including propensity scores, were used to adjust for potential confounding. Multivariate Cox proportional hazard models were used to examine the relationship between metformin use and the composite endpoint. Metformin monotherapy was associated with a lower risk of the composite endpoint (adjusted hazard ratio 0.81; 95% confidence interval 0.68, 0.97) compared with sulphonylurea monotherapy. Combination therapy with meformin and a sulphonylurea was associated with lower mortality, but had similar hospitalization rates, to sulphonylurea monotherapy. Metformin monotherapy was associated with a lower risk of cardiovascular-related morbidity and mortality, and combination metformin and sulphonylurea therapy was associated with a reduced risk of fatal cardiovascular events, when compared with sulphonylurea monotherapy.

A multicenter disease management program for hospitalized patients with heart failure

Background Despite the availability of proven therapies, outcomes in patients with heart failure (HF) remain poor. In this 2-stage, multicenter trial, we evaluated the effect of a disease management program on clinical and economic outcomes in patients with HF. Methods and results In Stage 1, a pharmacist or nurse assessed each patient and made recommendations to the physician to add or adjust angiotensin-converting enzyme (ACE) inhibitors and other HF medications. Before discharge (Stage 2), patients were randomized to a patient support program (PSP) (education about HF, self-monitoring, adherence aids, newsletters, telephone hotline, and follow-up at 2 weeks, then monthly for 6 months after discharge) or usual care. In Stage 1 (766 patients) ACE inhibitor use increased from 58% on admission to 83% at discharge ( P < .0001), and the daily dose (in enalapril equivalents) increased from 11.3±8.8 mg to 14.5±8.8 mg ( P < .0001). In Stage 2 (276 patients) there was no difference in ACE inhibitor adherence, but a reduction in cardiovascular-related emergency room visits (49 versus 20, P = .030), hospitalization days (812 versus 341, P = .003), and cost of care ($CDN 2,531 less per patient) in favor of the PSP. Conclusion Simple interventions can improve ACE inhibitor use and patient outcomes.

Association between adherence to diuretic therapy and health care utilization in patients with heart failure.

To determine the relationship between adherence to diuretic therapy and health care utilization. Prospective, observational study. University-affiliated medical center. Forty-two patients with heart failure. Electronic monitoring of adherence to diuretic therapy (percentage of diuretic prescription container openings) and to scheduling (percentage of container openings within a specific time). All patients were prescribed a diuretic, most commonly furosemide (88%). Patients varied widely in adherence to therapy (mu = 72% +/- 30%) and to scheduling (mu = 43% +/- 30%). Education was a predictor of drug-taking adherence (p=0.0062) but not of scheduling adherence. Log-linear models revealed that poor scheduling adherence was associated with increased cardiovascular-related hospitalizations (chi2 11.63, p=0.0006) and predicted more heart failure-related hospitalizations (chi2 4.04, p=0.0444). In contrast, neither measure was significantly associated with cardiovascular- or heart failure-related emergency department visits. We found a moderate correlation between scheduling adherence and taking adherence (r = 0.6513). Patients taking a greater proportion of diuretic agents on schedule may decrease the risk of cardiovascular- and heart failure-related hospitalizations. If these findings are confirmed by a larger study, interventions to improve adherence and patient health outcomes should consider the timing of doses as well as the number of daily doses of a diuretic.

Effect of lovastatin on cardiovascular resource utilization and costs in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)

This cost-consequences analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study compares the costs of lovastatin treatment with the costs of cardiovascular hospitalizations and procedures. The cost of lovastatin treatment was defined as the average retail price and the cost of drug safety monitoring and adverse experiences. Costs were determined by actual rates of hospitalizations and procedures. Within a trial, lovastatin treatment cost approximately $4,654/patient. Lovastatin treatment significantly reduced the cumulative rate of cardiovascular hospitalizations and procedures (p = 0.002). Over the duration of the study, the cumulative number of cardiovascular hospitalizations and related therapeutic procedures was significantly reduced by 29%. The time to first cardiovascular-related hospitalization or procedure was significantly extended by lovastatin (p = 0.002). Lovastatin reduced the frequency of cardiovascular hospitalization (28%), and cardiovascular therapeutic (32%) and diagnostic procedures (23%). Among therapeutic procedures, treatment reduced coronary artery bypass graft surgery by 19% and percutaneous transluminal coronary angioplasty by 37%. Total cardiovascular-related hospital days were reduced by 26% (p = 0.025). The between-group offset in direct medical costs was $524, which resulted in a 11% cost offset of lovastatin therapy over the mean study duration of 5.2 years. Lovastatin provides meaningful reductions in cardiovascular-related resource utilization and reductions in direct cardiovascular-related costs associated with the onset of coronary disease.

Quantitative Zn speciation in smelter-contaminated soils by EXAFS spectroscopy

<h3>Objective</h3> A systematic review was undertaken to assess the effects of exercise-based cardiac rehabilitation (CR) for patients with stable angina. <h3>Methods</h3> Databases (Cochrane Central Register of Controlled Trials, MEDLINE, Embase and CINAHL) were searched up to October 2017, without language restriction. Randomised trials comparing CR programmes with no exercise control in adults with stable angina were included. Where possible, study outcomes were pooled using meta-analysis. Grading of Recommendations Assessment, Development and Evaluation was used to assess the quality of evidence. The protocol was published on the Cochrane Database of Systematic Reviews. <h3>Results</h3> Seven studies (581 patients), with a median of 12-month follow-up, were included. The effect of exercise-based CR on all-cause mortality (risk ratio (RR) 1.01, 95 % CI: 0.18 to 5.67), acute myocardial infarction (RR 0.33, 95% CI: 0.07 to 1.63) and cardiovascular-related hospital admissions (RR 0.14, 95% CI: 0.02 to 1.1) relative to control were uncertain. We found low-quality evidence that exercise-based CR results in a moderate improvement in exercise capacity (standard mean difference 0.45, 95% CI: 0.20 to 0.70). There was limited and very low-quality evidence for the effect of exercise-based CR on health-related quality of life (HRQoL), adverse events and costs. No data were identified on cost-effectiveness or return to work. <h3>Conclusions</h3> Exercise-based CR may improve the short-term exercise capacity of patients with stable angina pectoris. Well-designed randomised controlled trials are needed to definitely determine the impact of CR on outcomes including mortality, morbidity, HRQoL, and costs in the population of patients with stable angina receiving contemporary medical therapy.