Cost effectiveness of adding ezetimibe to atorvastatin therapy in patients not at cholesterol treatment goal in Canada.

INTRODUCTION: This analysis compared the cost effectiveness of adding ezetimibe to atorvastatin therapy versus atorvastatin titration or adding cholestyramine (a resin) for patients at high risk of a coronary artery disease (CAD) event who did not reach target cholesterol levels on their current atorvastatin dosage. The primary analysis focused on 65-year-old patients with low-density lipoprotein cholesterol (LDL-C) levels of 3.1 or 3.6 mmol/L with a treatment goal of <2.5 mmol/L, classified as very high risk according to the 2000 Canadian Guidelines for Management and Treatment of Hyperlipidaemia. METHODS: A previously developed Markov model was utilised to capture the cost and clinical consequences of lipid-lowering therapy in primary and secondary prevention of CAD. Comparisons between treatment strategies were made using ICERs (cost per QALY) from a Canadian Ministry of Health perspective. The effects of lipid-lowering therapies were based on clinical trial data. The risks of CAD events were estimated using Framingham Heart Study risk equations. Treatment costs and the costs of acute and long-term care for CAD events were included in the analysis. Costs (Canadian dollar, 2002 values) and outcomes were discounted at 5% per annum. RESULTS: Ezetimibe added to atorvastatin therapy compared with treatment with the most common fixed atorvastatin daily dosage (10 mg) or with common atorvastatin titration strategies (up to 20 mg daily; up to 40 mg daily) resulted in cost per QALY estimates ranging from 25,344 to 44,332 Canadian dollars. The addition of ezetimibe to atorvastatin therapy was less costly and more effective than the addition of cholestyramine (dominant). CONCLUSION: Our analysis suggests that adding ezetimibe to atorvastatin for patients not achieving treatment goals with their current atorvastatin dose produces greater clinical benefits than treatment with a fixed-dose atorvastatin or atorvastatin titration at an increased overall cost. The cost-effectiveness ratios provide strong evidence for the adoption of ezetimibe within the Canadian healthcare system.

The benefit of cholesterol-lowering medications after coronary revascularization: a population study.

BACKGROUND: In clinical trials, cholesterol-lowering medications have been proven to decrease mortality and morbidity and are strongly recommended as secondary prevention in patients with established coronary artery disease. In routine practice, the translation of these benefits to elderly patients with recent coronary revascularization is less well known. METHODS: Using the provincial computerized administrative databases of the Régie de l'Assurance Maladie du Québec, we identified all elderly patients (>65 years old) in Quebec, Canada, discharged alive after a coronary revascularization procedure (percutaneous coronary intervention or coronary artery bypass graft) between April 1, 1995, and December 31, 1997, and determined the percentage fulfilling prescriptions for cholesterol-lowering drug therapy. Time-dependent multivariable models examined the clinical end points of total mortality, acute myocardial infarctions, and repeat coronary revascularizations as a function of cholesterol-lowering drug exposure. Patients were followed up until death or December 31, 1999. RESULTS: We identified 11958 elderly patients who had a coronary revascularization between April 1, 1995, and December 31, 1997. During an average 3-year follow-up, users of cholesterol-lowering medications had a decreased risk of death [hazard ratio (HR) 0.66, 95% CI 0.45-0.96] or myocardial infarction (HR 0.77, 95% CI 0.54-1.11) but no reduction in repeat revascularizations (HR 1.06, 95% CI 0.88-1.28). CONCLUSIONS: In this population-based study of recently revascularized elderly patients, we observed health benefits associated with the use of cholesterol-lowering medications of similar size to those seen in randomized clinical trials. The translation of these benefits from clinical trials to a nonselected population of revascularized patients emphasizes the importance of this aspect of secondary prevention in clinical practice.

The use of cholesterol-lowering medications after coronary revascularization.

BACKGROUND: In clinical trials, cholesterol-lowering medications have been proven to decrease mortality and morbidity and are strongly recommended as secondary prevention for patients with established coronary artery disease. Whether physicians and patients follow this recommendation is unknown. Our objective was to determine the rate at which patients fill at least one prescription for cholesterol-lowering medications after coronary revascularization. METHODS: Using the computerized administrative databases of the Régie de l'assurance maladie du Québec, we identified all elderly patients (older than 65 years) who had a coronary revascularization procedure (percutaneous coronary intervention or coronary artery bypass graft) between Apr. 1, 1995, and Dec. 31, 1997, and who survived until hospital discharge. We also determined the percentage of these patients who filled one or more prescriptions for cholesterol-lowering drug therapy before Dec. 31, 1999, or death, whichever date came first. We used multivariate logistic regression models to examine the independent associations between filling a prescription for a cholesterol-lowering drug, patient characteristics and the type and year of coronary revascularization. RESULTS: We identified 11 958 elderly patients who had a coronary revascularization between Apr. 1, 1995, and Dec. 31, 1997. During a follow-up period that averaged 3 years, 4443 (37.2%) patients did not fill a prescription for a cholesterol-lowering medication. Patients who were male, of advanced age, who had diabetes or congestive heart failure were less likely to fill a prescription for a cholesterol-lowering medication. Patients whose initial revascularization procedure was coronary artery bypass grafting were also less likely than those who had angioplasty to start cholesterol-lowering medication (relative risk [RR] 0.77, 95% confidence interval [CI] 0.73 - 0.81). Use of cholesterol lowering medications before the revascularization procedure was very strongly associated with future drug use (RR 7.20, 95% CI 6.83-7.58). INTERPRETATION: In this population-based study of revascularized patients, we observed a substantial underutilization of cholesterol-lowering medications after revascularization. Our observations suggest an important role for continuity of care in the treatment of cardiovascular patients undergoing revascularization procedures.

Antibiotics in primary prevention of stroke in the elderly.

BACKGROUND AND PURPOSE: An increasing number of reports have linked infections to atherosclerosis and thrombosis. Thus, use of antibiotics may lower the risk of developing cerebrovascular disease. We investigated whether antibiotic use is associated with the risk of stroke in elderly individuals treated for hypertension. METHODS: A cohort of 29 937 elderly subjects initiating antihypertensive therapy between 1982 and 1995 was formed from the Quebec healthcare insurance database. A nested case-control design was used in which each subject hospitalized with a primary discharge diagnosis of stroke between 1987 and 1995 was matched on calendar time to 5 randomly selected controls from the cohort. Conditional logistic regression was used to estimate odds ratios of stroke after adjustment for predisposing factors. RESULTS: We identified 1888 cases and 9440 controls. The overall adjusted odds ratio for current antibiotic use was 0.80 (95% confidence interval, 0.63 to 1.01), and that for recent use was 0.81 (95% confidence interval, 0.70 to 0.94). Penicillin was the only individual antibiotic class that showed a protective association across different time windows. No significant association was found between stroke risk and the use of fluoroquinolones, macrolides, tetracyclines, or cephalosporins. CONCLUSIONS: Although no clear, consistent associations between overall antibiotic use and cerebrovascular disease could be found, an intriguing association between penicillin use and stroke should be explored further.

Antibiotics in primary prevention of myocardial infarction among elderly patients with hypertension.

BACKGROUND: Given the premise that certain bacteria (such as Chlamydia pneumoniae) may play a role in the etiology of atherosclerosis, subjects treated with antibiotics that have antibacterial activity against C pneumoniae may be at lower risk for the development of an acute myocardial infarction (MI) than untreated subjects. METHODS: A case-control design, nested within a cohort of 29,937 elderly subjects in whom antihypertensive therapy was initiated (1982-1995) was used, in which each subject who was hospitalized with a primary discharge diagnosis of MI between 1987 and 1995 (n = 1047) was matched on calendar time to 5 randomly selected control subjects for exposure contrasts. Conditional logistic regression analyses were conducted to adjust for predisposing factors for MI. RESULTS: Although no clear consistent effect of antibiotics use was found in relation to MI, a trend was observed for a decreased risk of acute MI in patients receiving a prescription for antichlamydial antibiotics in the preceding 3 months (odds ratio 0.68, 95% CI 0.46-1.00). Antibiotics without antichlamydial activity showed no benefit in MI risk. CONCLUSION: The beneficial effect of certain antichlamydial antibiotics in reducing the risk of MI cannot be excluded on the basis of this representative cohort of elderly patients in a routine clinical care setting. Larger prospective studies are required to confirm the usefulness of antibiotics in the primary prevention of MI.