Fig 1.
State-transition diagram for Markov model.
CHD = coronary heart disease. MI = myocardial infarction.
Fig 2.
Flow-diagram of all strategies simulated.
*All persons with Framingham Risk Score >10% received aspirin 81mg daily, except for treat-all in which all men received aspirin 81mg. †SHAPE treats the following as risk factors: total cholesterol >200mg/dl, blood pressure >120/80, diabetes mellitus, smoking, family history of CHD, and metabolic syndrome. ‡SHAPE considers individuals without any of its specified risk factors to be “very low risk” and treats this as an “exit” from its screening algorithm, without calcium scoring being performed. We assumed such individuals not undergoing calcium scoring would then be treated to LDL-C goals in accordance with the approach of ATP III; in general such individuals have Framingham risk of <10%. §Per SHAPE, all persons with CAC >400 underwent nuclear stress testing followed by diagnostic coronary angiography and revascularization if indicated based on stress testing results in simulations. If nuclear stress testing is negative persons are treated to goal LDL-C of <70mg/dl. JUPITER = Justification for the Use of Statins in Primary Prevention. ATP III = Adult Treatment Panel III. SHAPE = Screening for Heart Attack Prevention and Education. YO = Years-Old. LDL-C = Low-density lipoprotein. CRP = C-Reactive Protein. FRS = Framingham Risk Score. CAC = Coronary Artery Calcium Score. PCE = pooled cohort risk equation. Other abbreviations same as in prior figure.
Table 1.
Inclusion and Exclusion Criteria as Well as Overview of each Approach to Primary Prevention Strategies Evaluated in the Model.
Table 2.
Selected Inputs to the State-Transition Model.
Fig 3.
Results of basecase simulations. 3A: Men only. 3B: Women only.
*Cost-effective as compared to less expensive AND less effective strategies with an incremental cost effectiveness ratio <$50,000/QALY gained for JUPITER compared to ACC/AHA and Texas compared to ATP III. #Cost-effective as compared to less expensive AND less effective strategies with an incremental cost effectiveness ratio <$50,000/QALY gained for treat-all with moderate-dose statins compared to ACC/AHA. ^Not cost-effective as compared to less expensive AND less effective strategies with an incremental cost effectiveness of ratio of > $50,000/QALY gained for both SHAPE and JUPITER compared to Texas. ICER = Incremental Cost Effectiveness Ratio. QALY = Quality-Adjusted Life Year. Other abbreviations same as in prior figures.
Table 3.
Outcomes for men and women based on microsimulations of one million patients for 2011–2040 ordered by increasing effectiveness (95% confidence interval). The cost effectiveness of each strategy is demonstrated as the cost per QALY gained as compared to the next less effective strategy.
Table 4.
Rates of strategy- and treatment-related complications based on microsimulations for 2011–2040 for men and women.
Fig 4.
Acceptability curves for basecase simulations. 4a: Men only. 4b: Women only.
Abbreviations same as in prior figures.
Fig 5.
Adherence Sensitivity analysis: Cost-effectiveness of strategies evaluated using an adherence rate of 19% for all non-CAC based strategies and a variable adherence rate for CAC based strategies in which the higher the CAC score the higher the adherence to therapy (women only simulation shown).
*Texas dominates treat-all with moderate-dose statins as well as all other risk-stratification strategies. #SHAPE is not cost-effective as compared to treat-all with moderate-dose statins as the ICER of SHAPE compared to treat-all with moderate-dose statins is $95,864 per QALY gained. Abbreviations same as in prior figures.
Fig 6.
Sensitivity Analysis: Costs per QALY of selected* strategies compared to treat-all with high-dose statins as a function of increasing statin disutility for men and women#. 6a: Men (cost-effectiveness threshold of $50,000 per QALY gained demonstrated by the dashed line). 6b: Women.
*Only strategies that were not dominated by treat-all with high-dose statins at 100-times basecase statin disutility are shown. #At 10-times the basecase statin disutility all strategies are more expensive and less costly than treat-all with high-dose statins, therefore they are dominated by treat-all high-dose statins and demonstrate a negative cost per QALY. At 100-times basecase statin disutility for men, status quo remains dominated by treat-all with high-dose statins and therefore retains a negative cost per QALY, while the other strategies shown are now more effective than treat-all with high-dose statins but more expensive, evidenced by a positive cost per QALY. Only JUPITER is cost-effective as compared to treat-all with high-dose statins as the cost per QALY gained via the JUPITER strategy is < $50,000 (noted by the dashed line) as compared to treat-all with high-dose statins. At 100-times basecase statin disutility for women and 1,000-times statin disutility for both men and women all strategies shown are more effective and more expensive than treat-all with high-dose statins but they are so much more effective than treat-all with high-dose statins that the cost per QALY gained is low and they are all more cost effective compared to treat-all with high-dose statins. Abbreviations same as in prior figures.
Table 5.
Age and Gender Sub-group Analysis: Outcomes for each strategy evaluated based on specific age and gender sub-group analyses—including number needed to treat9* and number needed to harm# for each strategy as compared to status quo and ATP III (strategies listed in order of increasing effectiveness).
Table 6.
Low-risk Subgroup Analysis: Outcomes for each strategy evaluated for men and women with a Framingham Risk Score (FRS) of less than 5%—including the number needed to treat and the number needed to harm for each strategy as compared to status quo and ATP III (strategies listed in order of increasing effectiveness)*, #.
Table 7.
Comparison of national implementation of the 2013 ACC/AHA guidelines and treating all persons with high-dose statins strategies with other population based strategies—Comparing CHD events prevented, costs saved, and QALYs gained for each strategy compared to status quo.