Comparing the effectiveness of rosuvastatin and atorvastatin in preventing cardiovascular outcomes: estimates using the Archimedes model.

OBJECTIVE: This study used simulation to compare the effectiveness of rosuvastatin 20 mg vs atorvastatin 40 mg, and rosuvastatin 40 mg vs atorvastatin 80 mg in preventing MACE in a range of patient populations with varying baseline cardiovascular risk. RESEARCH DESIGN AND METHODS: The Archimedes Model was used to simulate head-to-head clinical trials in nine patient populations: Framingham Risk Score (FRS)≥5%, 5-10%, 10-20%, >20%, EURO-SCORE≥5% and >10%, diagnosed diabetes, secondary prevention (history of myocardial infarction or stroke, CVD), and acute coronary syndrome (ACS). Simulated patients, aged 45-70 at trial start, were based on the NHANES 1999-2006. Treatments were modeled using results from the STELLAR, JUPITER, CARDS, ASCOT-LLA, and TNT trials. Treatment models were confirmed using trial validations. RESULTS: Comparing rosuvastatin 20 mg vs atorvastatin 40 mg, the 5-year numbers needed to treat to prevent one MACE event (NNT) were 525, 70, and 55 for the FRS≥5%, CVD, and ACS groups, respectively. Comparing rosuvastatin 40 mg vs atorvastatin 80 mg the corresponding NNT values were 468, 63, and 51. The 20-year relative risks of MACE in the FRS≥5% population were 0.907 (0.901-0.913) for rosuvastatin 20 mg vs atorvastatin 40 mg and 0.892 (0.884-0.901) for rosuvastatin 40 mg vs atorvastatin 80 mg. The relative risks were similar for the remaining populations. CONCLUSIONS: This study found that rosuvastatin 20 mg and 40 mg lowers the risk of MACE more than atorvastatin 40 mg and atorvastatin 80 mg. While simulation models cannot replace real-world clinical trials, this study bridges gaps in the evidence, and identifies high risk cohorts that would likely see additional benefit from treatment with rosuvastatin rather than atorvastatin.

Health and economic outcomes for exenatide once weekly, insulin, and pioglitazone therapies in the treatment of type 2 diabetes: a simulation analysis.

BACKGROUND: Patients with type 2 diabetes (T2DM) are at risk of long-term vascular complications. In trials, exenatide once weekly (ExQW), a GLP-1R agonist, improved glycemia, weight, blood pressure (BP), and lipids in patients with T2DM. We simulated potential effects of ExQW on vascular complications, survival, and medical costs over 20 years versus standard therapies. PATIENTS AND METHODS: The Archimedes model was used to assess outcomes for ~25,000 virtual patients with T2DM (NHANES 1999-2006 [metformin ± sulfonylureas, age 57 years, body mass index 33 kg/m(2), weight 94 kg, duration T2DM 9 years, hemoglobin A1c [A1C] 8.1%]). The effects of three treatment strategies were modeled and compared to moderate-adherence insulin therapy: advancement to high-adherence insulin at A1C ≥ 8% (treat to target A1C < 7%) and addition of pioglitazone (PIO) or ExQW from simulation start. ExQW effects on A1C, weight, BP, and lipids were modeled from clinical trial data. Costs, inflated to represent 2010 $US, were derived from Medicare data, Drugstore.com, and publications. As ExQW was investigational, we omitted ExQW, PIO, and insulin pharmacy costs. RESULTS: By year 1, ExQW treatment decreased A1C (~1.5%), weight (~2 kg), and systolic BP (~5 mmHg). PIO and high-adherence insulin decreased A1C by ~1%, increased weight, and did not affect systolic BP. After 20 years, A1C was ~7% with all strategies. ExQW decreased rates of cardiovascular and microvascular complications more than PIO or high-adherence insulin versus moderate-adherence insulin. Over 20 years, ExQW treatment resulted in increased quality-adjusted life-years (QALYs) of ~0.3 years/person and cost savings of $469/life-year versus moderate adherence insulin. For PIO or high-adherence insulin, QALYs were virtually unchanged, and costs/life-year versus moderate-adherence insulin increased by $69 and $87, respectively. CONCLUSIONS: This long-term simulation demonstrated that ExQW treatment may decrease rates of cardiovascular and some microvascular complications of T2DM. Increased QALYs, and decreased costs were also projected.

Physicians' actions and influence, such as aggressive blood pressure control, greatly improve the health of diabetes patients.

Managing diabetes and preventing its associated morbidities require active partnerships between physicians and patients. Studies to date lack the level of detail to quantify the degree to which interventions that are more controlled by physicians influence outcomes versus those that are more controlled by patients. Using the Archimedes model, we simulated a thirty-year clinical trial and compared the effects of three sets of interventions over which physicians have progressively less control: compliance with process-of-care standards, such as conducting foot and retinal exams and screening for signs of early kidney disease; control of biomarkers, such as hemoglobin A1c and blood pressure; and lifestyle modifications, such as patients' switching to healthier diets and losing weight. We found that if all US adults diagnosed with type 2 diabetes met quality targets in all of these areas, they would experience a nearly 16 percent increase in quality-adjusted life-years and a nearly 23 percent reduction in fifteen-year mortality over the thirty-year simulation period. Meeting aggressive biomarker targets yielded the most benefit. Meeting conservative biomarker targets came next, followed closely by meeting process-of-care standards. The incremental benefits of complying fully with diet and smoking cessation yielded the least benefit. Thus, through measures more readily within their control, and through collaboration with their patients, physicians have a substantial opportunity to improve outcomes. These findings can inform policy makers' rational resource allocation decisions and the design of programs to improve diabetes care.

Estimating health and economic benefits from using prescription omega-3 fatty acids in patients with severe hypertriglyceridemia.

Patients with increased triglyceride levels compared to those with normal levels are at higher risk for coronary heart disease. In patients with severe (≥500 mg/dl) hypertriglyceridemia (SHTG), clinical trials have demonstrated that prescription ω-3 fatty acids (P-OM3s) 4 g/day can decrease triglyceride levels by 45%. However, the precise health and economic benefits of decreasing SHTG with P-OM3 are unknown. We used the previously validated Archimedes model to simulate a 20-year trial involving subjects 45 to 75 years old with SHTG. The trial consisted of an intervention arm (P-OM3 4 g/day) and a control arm. Simulation results for the control arm indicated that subjects with SHTG are at about 2 times higher risk for myocardial infarction than those with normal triglyceride levels. Using estimates from previous epidemiologic studies and meta-analyses with OM3s, the model predicted 29% to 36% decreases in various measurements of adverse cardiac events for the intervention arm. The model also predicted a decrease in ischemic stroke of 24% (95% confidence interval 15 to 33). For the 20-year simulated trial, the cost per quality-adjusted life-year gained for the currently available P-OM3 approved by the Food and Drug Administration was $47,000. Results remained robust under different clinical assumptions. In our model P-OM3 was effective in decreasing triglyceride levels and cardiovascular disease risk in patients with SHTG. In conclusion, P-OM3 medication is cost effective in our simulated trial and comparable to other cost-effective cardiovascular interventions.

Effect of smoking cessation advice on cardiovascular disease.

Performance measures and guidelines encourage physicians to advise smokers to quit. The effect of these efforts on the morbidity, mortality, and cost of cardiovascular disease is not known. This article analyzes the effects of offering smoking cessation advice in the US population. The Archimedes model is used to simulate several clinical trials in which basic advice and medication advice are offered and to calculate the rates of myocardial infarctions, congestive heart disease deaths, strokes, life years, quality-adjusted life years (QALYs), costs, and cost/ QALY. The simulated population is a representative sample of the US population drawn from the Third National Health and Nutrition Survey conducted just before the performance measures and guidelines were introduced. The results show that offering basic advice and medication advice can prevent about 13% and 19% of myocardial infarctions and strokes, respectively. The 30-year cost/QALY is approximately $3000 less than the base-case assumptions and less than $10 000 under pessimistic assumptions.

Relationship of insulin resistance and related metabolic variables to coronary artery disease: a mathematical analysis.

OBJECTIVE: People with diabetes have an increased risk of coronary artery disease (CAD). An unanswered question is what portion of CAD can be attributed to insulin resistance, related metabolic variables, and other known CAD risk factors. RESEARCH DESIGN AND METHODS: The Archimedes model was used to estimate the proportion of myocardial infarctions that would be prevented by maintaining insulin resistance and other risk factors at healthy levels. Person-specific data from the National Health and Nutrition Examination Survey 1998-2004 were used to create a simulated population representative of young adults in the U.S. This population was then entered into a series of simulated clinical trials designed to explore the effects of each risk factor. Each trial had a control arm (all risk factors were allowed to progress without interventions) and a treatment arm (a risk factor was held to its value in young healthy adults). The trials continued for 60 years. The effects of these hypothetical "cures" of each risk factor provide estimates of their impact on CAD. RESULTS: In young adults, preventing insulin resistance would prevent approximately 42% of myocardial infarctions. The next most important determinant of CAD is systolic hypertension, prevention of which would reduce myocardial infarctions by approximately 36%. Following systolic blood pressure, the most important determinants are HDL cholesterol (31%), BMI (21%), LDL cholesterol (16%), triglycerides (10%), fasting plasma glucose and smoking (both approximately 9%), and family history (4%). CONCLUSIONS: Insulin resistance is likely the most important single cause of CAD. A better understanding of its pathogenesis and how it might be prevented or cured could have a profound effect on CAD.

The potential effects of HEDIS performance measures on the quality of care.

We analyzed the potential effects of different levels of performance on eight Health Care Employer Data and Information Set (HEDIS) measures for cardiovascular disease and diabetes during 1995-2005. The measures targeted 3.3 million (25 percent) heart attacks. Improvements in performance to those achieved by the median plan in 2005 imply prevention of 1.9 million myocardial infarctions (MIs, 15 percent), 0.8 million strokes (8 percent), and 0.1 million cases of end-stage renal disease (17 percent). If performance had been 100 percent, 1.4 million more MIs would have been prevented. Control of blood pressure has the largest potential effect on quality at the national level.