Results

1. Remain Well Well Event Survive Event History Primary CHD Event Event Death Event Death Well Stroke Survive Event History Primary Stroke Event Stroke Death Event Death Other Death Other Death Remain Event History Event History Event Survive Second Event History Secondary CHD Event Event History Event Death Event Death Atorvastatin 10 mg Stroke Survive Second Event History Secondary Stroke Event Stroke Death Event Death Other Death Other Death Remain SecondEvent History Second Event History CARDS Canadian cohort Second Event History Other Death Other Death Event Death Other Death Placebo Cost-effectiveness of atorvastatin 10 mg daily in the primary prevention of major cardiovascular events in patients with type 2 diabetes in Canada H. Khoury1, M. Wagner1, E. Merikle2, S.J. Johnson3, C. Roberts4 1BioMedCom Consultants inc, Montreal, QC, Canada; 2At the time of the study: Pfizer Canada Inc., Montreal, QC, Canada; Current affiliation: Center for Health Outcomes Research, United BioSource Corporation, Montreal, Canada; 3Analysis Group Inc., New York, NY; 4Global Outcomes Research, Pfizer Inc., New York, NY • Background • In Canada, the prevalence of cardiovascular disease (CVD) is five-fold higher in individuals with diabetes than those without.1 • To reduce the risk of cardiovascular (CV) events, the Canadian Diabetes Association recommends aggressive lipid management involving statin therapy for high-risk patients to reach and maintain low density lipoprotein cholesterol (LDL-C) level below 2.5 mmol/l, and total cholesterol to high density lipoprotein cholesterol ratio (TC:HDL-C) below 4.0.2 • The Collaborative Atorvastatin Diabetes Study (CARDS), a double-blind randomized controlled trial conducted in the UK and Ireland, explored primary prevention of CV events with atorvastatin 10 mg daily in 2,838 patients with type 2 diabetes and no previous history of coronary heart disease (CHD), with at least one other CVD risk factor, and baseline LDL-C levels ≤ 4.14 mmol/l.3 • Over a 3.9-year follow-up period, CARDS demonstrated that atorvastatin 10 mg daily achieved significant reduction of primary CV events (relative risk [RRR] vs placebo: 0.37; 95% CI: 0.52 to 0.17; P=.001), and also reduced all-cause mortality (RRR:0.27; 95% CI: 0.48–1.0; P=.059).3 • The CARDS Health Economic Model—a Markov-type decision analytic model of primary prevention designed to predict long-term outcomes—demonstrated that atorvastatin was cost-effective and improved clinical outcomes in US patients with type 2 diabetes and at least one other CVD risk factor.4 • Results • Over 10 yrs, patients treated with atorvastatin experienced fewer CV events, gained 0.07 QALYs/patient, and had 2% fewer deaths compared with placebo, at an additional cost of Can$922/patient. • Incremental costs decreased considerably over time despite the increase in drug costs, most likely as a result of decreased medical costs associated with fewer cardiac events. • The incremental cost-effectiveness of atorvastatin was Can$12,687/QALY [95% CI dominant–$66,048] at 10 yrs, Can$1,362 [dominant–$49,432] at 25 yrs (lifetime analysis), and Can$70,773/QALY [33,981–195,914] at 5 yrs. • The model was most sensitive to variations in age at baseline ($66,964 to -$1,896/QALY), followed by HRs for CHD and stroke • Systolic blood pressure, adherence rate, cholesterol levels, and cost of atorvastatin for subsequent years also had intermediate impact on incremental ratios. • The model was robust to variations in other risk factors such as gender, atrial fibrillation, and smoking status. • 95.7% and 98.3% of 1,000 simulations were below a Can$50,000/QALY in the 10-yr and 25-yr horizons, respectively, with almost half (46.3%) of the simulations indicating that atorvastatin is a dominant treatment strategy. Figure 1: Markov analytical model • Conclusions • Primary prevention of CV events with atorvastatin 10 mg/day resulted in incremental cost-effectiveness ratios well below many other commonly used healthcare interventions15 (10-yr: $12,687/QALY; 25-yr: $1,362/QALY). • Atorvastatin is cost-effective for the primary prevention of major CV events and associated death among Canadians with type 2 diabetes without established CVD. Univariate and multuivariate SA indicate that the results are robust to variations in input parameters. Objective To assess the clinical and economic benefits of atorvastatin 10 mg daily in Canadian patients with type 2 diabetes without established CHD and with at least one other CVD risk factor, from a Ministry of Health perspective, using the CARDS Health Economic Model. Table 1: Base-case input parameters Acknowledgements This study was funded by Pfizer Canada Inc. • Methods • The CARDS Health Economic Model predicts the incidence of CV events (CHD and stroke), total costs, survival and quality-adjusted life years (QALYs) (Figure1). • The model followed a hypothetical cohort of Canadians with type 2 diabetes and no documented history of CVD, with at least one other CVD risk factor, over 5, 10, and 25-year time horizons. • Annual transition probabilities for primary events were derived from the United Kingdom Prospective Diabetes Study (UKPDS) risk equations,5,6 and the CARDS trial.7 The risk of having a second event was increased to reflect the increased CVD risk for patients with diabetes with a prior myocardial infarction (MI).8 • Hazard ratios (HR) were taken from the CARDS trial.3 • Adherence rate: 100% for the 1st yr, adjusted to reflect decreasing rates from the CARDS trial3 during the first 4 yrs, and kept constant after 4 yrs. • Acute CVD-related mortality rates were based on the CARDS trial.3 Mortality due to causes other than CVD were taken from 2005 life tables for Canada.9 • Utility scores were obtained from a cross-sectional sample of the National Population Health Survey in Canada.10 • Resource utilization and costs: Canadian cost for atorvastatin was obtained from the Ontario Drug Benefit formulary (ODBF);11 drug cost was reduced by 50% after the 4th yr to account for genericization of atorvastatin.Acute care cost of stroke and aggregate acute care cost of CHD events (angina, MI, coronary artery bypass graft (CABG), percutaneous coronary interventions (PCI) with and without stent, and cardiac catheterization) were obtained from the Ontario Case Costing Initiative (OCCI) Acute Inpatient Cost 2003/04 database.12 Subsequent year costs for stroke and CHD (aggregate cost of MI and angina) were estimated based on O’Brien et al.13 • Costs and benefits were discounted by 5%.14 • One-way deterministic (tornado diagram) and probabilistic (acceptability curve) sensitivity analyses (SA) were conducted to assess model uncertainty. • References • 1 Mo F, Pogany LM, Li FC, Morrison H. 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