Direct and indirect costs of management of long-term warfarin therapy in Canada.

BACKGROUND: Comparisons of overall costs and resource utilization associated with anticoagulation management are important as new alternatives to warfarin are introduced. The aim of the present study was to assess total costs of warfarin-based anticoagulation in different health care models. METHODS: Physician- or pharmacist-managed hospital- or community-based anticoagulation clinics in five Canadian provinces were asked to provide itemized information on costs for staff, laboratory, hardware and overheads associated with warfarin management. At each site, cohorts of patients were provided with diaries and participants prospectively entered all costs for warfarin medication and associated health professional contacts, travel to the laboratory, required assistance and time lost from work by patient or caregiver over 3months. All costs were calculated for a 3-month period. RESULTS: Data from 429 patients at 15 sites were evaluated. The cost from the Ministry of Health perspective ranged from $108 to $199 per 3months in the different settings, the patient costs were $40-$80 and the total societal costs ranged from $188-$244. Sensitivity analyses with typical blood test intervals, the most prescribed strength of warfarin and dispensing fee from another province increased these estimates to $230-$302. When reimbursement for unemployed caregivers was also entered the total cost was $308-$503 per 3months. CONCLUSIONS: The total cost for warfarin-based anticoagulation amounted to at least 10 times the lowest cost for the drug. The costs provided should be useful for comparisons with newer drugs without requirement for routine laboratory monitoring and dose adjustments.

Underutilisation of ACE inhibitors in patients with congestive heart failure.

Congestive heart failure (CHF) is associated with substantial morbidity and mortality, and is the only major cardiovascular disease increasing in prevalence. Despite abundant evidence to support their efficacy and cost-effectiveness, angiotensin-converting enzyme (ACE) inhibitors are sub-optimally used in patients with CHF. This paper reviews the evidence for the sub-optimal use of ACE inhibitors in patients with CHF, the factors contributing to this, and its implications for health systems. A systematic review of all articles assessing practice patterns (specifically the use of ACE inhibitors in CHF) identified by MEDLINE, search of bibliographies, and contact with content experts was undertaken. 37 studies have documented the use of ACE inhibitors in patients with CHF. Studies assessing use among all patients with CHF document 33% to 67% (median 51%) of all patients discharged from hospital and 10% to 36% (median 26%) of community dwelling patients were prescribed ACE inhibitors. Rates of ACE inhibitor use range from 43% to 90% (median of 71%) amongst those discharged from hospital having known systolic dysfunction, and from 67% to 95% (median of 86%) for those monitored in specialty clinics. Moreover, the dosages used in the 'real world' are substantially lower than those proven efficacious in randomised, controlled trials, with evaluations reporting only a minority of patients achieving target doses and/or an overall mean dose achieved to be less than one-half of the target dose. Factors predicting the use and optimal dose administration of ACE inhibitors are identified, and include variables relating to the setting (previous hospitalisation, specialty clinic follow-up), the physician (cardiology specialty versus family practitioner or general internist, board certification), the patient (increased severity of symptoms, male, younger), and the drug (lower frequency of administration). In light of the substantial evidence for reductions in morbidity and mortality, clearly, the prescription of ACE inhibitors is sub-optimal. Wide variability in ACE inhibitor use is noted, with higher rates consistently reported among patients having systolic dysfunction confirmed by an objective assessment--an apparent minority of the those having CHF. Optimisation of the prescription of proven efficacious therapies has the potential to confer a substantial reduction in the total cost of care for patients with CHF by reducing hospitalisations and lengths of hospital stays. It is likely that only multifaceted programs targeted toward the population at large will yield benefits to the healthcare system, given the widespread nature of the sub-optimal prescription of therapies proven effective in the management of patients with CHF.

Cholesterol risk management: a systematic examination of the gap from evidence to practice.

Hypercholesterolemia is a major risk factor for coronary heart disease, and data indicate that aggressive cholesterol reduction decreases mortality and morbidity associated with this disease. Many patients with hypercholesterolemia, however, are not screened, prescribed appropriate lipid-lowering therapy, or treated to target cholesterol levels. Practice patterns are particularly inadequate for those patients at highest risk for having a cardiac event. We performed a literature search to identify studies of practice patterns in the management of patients with hypercholesterolemia with regard to screening, implementing lipid-lowering therapy, and treating to lipid goals. The findings highlight the potential for substantial opportunities to improve patient outcomes. Future studies should evaluate reasons for suboptimal cholesterol management as well as provide steps to improve management.

Poor adherence with hypolipidemic drugs: a lost opportunity.

All articles assessing adherence to hypolipidemic drugs were reviewed and categorized by patient population (clinical trial, unselected) and reported as rates of nonadherence and discontinuation. Overall, levels of discontinuation reported in clinical trials (6-31%) and lipid clinics (2-38%) are similar, with unselected populations consistently reporting higher rates (15-78%). Rates of nonadherence in clinical trials and lipid clinics also are comparable, with unselected populations having the highest rates. Across all settings, rates of discontinuation and nonadherence are consistently reported to be poorer with resins and niacin than with hydroxy-6-methylglutamate coenzyme A reductase inhibitors. Adherence to hypolipidemic agents appears to decrease in parallel with level of follow-up. Data evaluating mechanisms of poor adherence are limited. While the search for new, efficacious therapies must continue, efforts focused on improving adherence to proven therapy may have a greater overall impact on health than any single new agent.

Stroke prophylaxis in nonvalvular atrial fibrillation.

Nonvalvular atrial fibrillation is the most prevalent dysrrhythmia, and carries with it an at least fivefold increased risk of ischaemic stroke. Currently, the implementation and optimization of prophylactic therapy (with warfarin or acetylsalicylic acid) is the most effective approach, at the population level, to optimize outcomes in patients with atrial fibrillation. Therefore, clinical trial evidence regarding warfarin and acetylsalicylic acid in stroke prophylaxis is highlighted. Recently, considerable data have emerged that indicate suboptimal use of warfarin in clinical practice (both in terms of the prescription and titration of therapy). Narrowing this gap between research evidence and clinical practice may be accomplished by identifying those patients who are eligible for prophylaxis, and then maintaining them at an adequate level of anticoagulation.

Adequacy of anticoagulation in patients with atrial fibrillation coming to a hospital.

STUDY OBJECTIVE: To evaluate the adequacy of anticoagulation in patients with atrial fibrillation (AF) coming to a hospital. DESIGN: Retrospective medical record review. SETTING: Tertiary care hospital. PATIENTS: Consecutive patients with a history of AF who had been prescribed warfarin and who had the international normalized ratio (INR) measured when they arrived at the hospital. Those who developed AF as a complication during hospitalization were excluded. MEASUREMENTS AND MAIN RESULTS: Of 1085 patients, 375 (mean age 73 yrs, 56.3% men) were eligible for further evaluation. Most had nonvalvular AF; in 44.5% the INR was subtherapeutic, in 36.5% it was therapeutic, and in 18.9% it was supratherapeutic. Patients admitted for any thromboembolic event and for ischemic stroke were significantly more likely to have subtherapeutic INRs. CONCLUSION: It is well documented in the literature that warfarin is underprescribed, but our results suggest that even in treated patients, about half are inadequately protected from thromboembolism.

Why do patients with atrial fibrillation not receive warfarin?

Atrial fibrillation (AF) is a growing public health problem associated with significant morbidity and mortality. Numerous randomized controlled trials of warfarin have conclusively demonstrated that long-term anticoagulation therapy can reduce the risk for stroke by approximately 68% per year in patients with nonvalvular AF, and even more in patients with valvular AF. However, available data show that of those patients with AF and no contraindication to warfarin therapy, only 15% to 44% are prescribed warfarin. Our literature review has identified patient-, physician-, and health care system-related barriers to warfarin prescription. However, the relative importance of these specific barriers remains unknown. Further work is needed to understand the discrepancy between the randomized controlled trial evidence and clinical practice patterns.

Prokinetic agents for the treatment of postoperative ileus in adults: a review of the literature.

Metoclopramide, cisapride, and erythromycin are commonly administered to reduce the duration of postoperative ileus (POI). As these agents are not without potential adverse effects, their efficacy in shortening the duration of POI should be evaluated. The etiology of POI is not well understood and therefore the precise treatment is unclear. Nasogastric suction is the mainstay of therapy, and management of fluid and electrolyte imbalances is crucial. The role of prokinetic agents is less understood. Available literature evaluating these drugs specifically for POI were reviewed, but results are confounded by issues such as sample size, variability in types of operations performed, and insensitive end points (flatus, bowel sounds). No literature supports reducing the duration of POI with metoclopramide, and limited data show benefit with cisapride. Data evaluating erythromycin are sparse, and the drug is believed to be ineffective. Domperidone, a prokinetic agent not available in the United States, has not been evaluated in POI. Due to these limitations, treatment remains largely supportive with a limited role for prokinetic agents.

An overview of commonly used antiplatelet agents.

Several agents inhibiting platelet function are commonly used in clinical practice, each having a unique mechanism of action. The complex cascade of events ultimately resulting in thrombus formation has several areas that pharmacologic agents can affect. The resultant effects range from being relatively non-specific with aspirin, ticlopidine, and clopidogrel to being specific with the glycoprotein IIb/IIIa receptor antagonists such that platelet aggregation will be inhibited irregardless of the metabolic pathway responsible for initiating aggregation. The clinical indications for these agents are vast, as platelet aggregation has been widely implicated in cardiovascular events. The degree of platelet inhibition is related to the frequency of bleeding. Aspirin is a relatively weak inhibitor of platelet function, ticlopidine has been said to have moderate activity, while the glycoprotein IIb/IIIa receptor antagonists are the most potent inhibitors of platelet aggregation. As our knowledge of the mechanisms of platelet aggregation expands, so will our treatment regimens. Clearly, we will await the results of future clinical trials to further define the role of antiplatelet agents.