Strategies for Primary Prevention of Coronary Heart Disease Based on Risk Stratification by the ACC/AHA Lipid Guidelines, ATP III Guidelines, Coronary Calcium Scoring...

Background: Several approaches have been proposed for risk-stratification and primary prevention of coronary heart disease (CHD), but their comparative and cost-effectiveness is unknown. Methods: We constructed a state-transition microsimulation model to compare multiple approaches to the primary prevention of CHD in a simulated cohort of men aged 45–75 and women 55–75. Risk-stratification strategies included the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on the treatment of blood cholesterol, the Adult Treatment Panel (ATP) III guidelines, and approaches based on coronary artery calcium (CAC) scoring and C-reactive protein (CRP). Additionally we assessed a treat-all strategy in which all individuals were prescribed either moderate-dose or high-dose statins and all males received low-dose aspirin. Outcome measures included CHD events, costs, medication-related side effects, radiation-attributable cancers, and quality-adjusted-life-years (QALYs) over a 30-year timeframe. Results: Treat-all with high-dose statins dominated all other strategies for both men and women, gaining 15.7 million QALYs, preventing 7.3 million myocardial infarctions, and saving over $238 billion, compared to the status quo, far outweighing its associated adverse events including bleeding, hepatitis, myopathy, and new-onset diabetes. ACC/AHA guidelines were more cost-effective than ATP III guidelines for both men and women despite placing 8.7 million more people on statins. For women at low CHD risk, treat-all with high-dose statins was more likely to cause a statin-related adverse event than to prevent a CHD event. Conclusions: Despite leading to a greater proportion of the population placed on statin therapy, the ACC/AHA guidelines are more cost-effective than ATP III. Even so, at generic prices, treating all men and women with statins and all men with low-dose aspirin appears to be more cost-effective than all risk-stratification approaches for the primary prevention of CHD. Especially for low-CHD risk women, decisions on the appropriate primary prevention strategy should be based on shared decision making between patients and healthcare providers

Strategies for Primary Prevention of Coronary Heart Disease Based on Risk Stratification by the ACC/AHA Lipid Guidelines, ATP III Guidelines, Coronary Calcium Scoring, and C-Reactive Protein, and a Global Treat-All Strategy: A Comparative--Effectiveness Modeling Study

<div><p>Background</p><p>Several approaches have been proposed for risk-stratification and primary prevention of coronary heart disease (CHD), but their comparative and cost-effectiveness is unknown.</p><p>Methods</p><p>We constructed a state-transition microsimulation model to compare multiple approaches to the primary prevention of CHD in a simulated cohort of men aged 45–75 and women 55–75. Risk-stratification strategies included the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on the treatment of blood cholesterol, the Adult Treatment Panel (ATP) III guidelines, and approaches based on coronary artery calcium (CAC) scoring and C-reactive protein (CRP). Additionally we assessed a treat-all strategy in which all individuals were prescribed either moderate-dose or high-dose statins and all males received low-dose aspirin. Outcome measures included CHD events, costs, medication-related side effects, radiation-attributable cancers, and quality-adjusted-life-years (QALYs) over a 30-year timeframe.</p><p>Results</p><p>Treat-all with high-dose statins dominated all other strategies for both men and women, gaining 15.7 million QALYs, preventing 7.3 million myocardial infarctions, and saving over $238 billion, compared to the status quo, far outweighing its associated adverse events including bleeding, hepatitis, myopathy, and new-onset diabetes. ACC/AHA guidelines were more cost-effective than ATP III guidelines for both men and women despite placing 8.7 million more people on statins. For women at low CHD risk, treat-all with high-dose statins was more likely to cause a statin-related adverse event than to prevent a CHD event.</p><p>Conclusions</p><p>Despite leading to a greater proportion of the population placed on statin therapy, the ACC/AHA guidelines are more cost-effective than ATP III. Even so, at generic prices, treating all men and women with statins and all men with low-dose aspirin appears to be more cost-effective than all risk-stratification approaches for the primary prevention of CHD. Especially for low-CHD risk women, decisions on the appropriate primary prevention strategy should be based on shared decision making between patients and healthcare providers.</p></div

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.

<p>*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.</p

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).

<p>*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.</p

Acceptability curves for basecase simulations. 4a: Men only. 4b: Women only.

<p>Abbreviations same as in prior figures.</p

Results of basecase simulations. 3A: Men only. 3B: Women only.

<p>*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.</p

Inclusion and Exclusion Criteria as Well as Overview of each Approach to Primary Prevention Strategies Evaluated in the Model.

<p>* 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.</p><p>^# Stress test deemed positive if >10% of myocardium demonstrates reversible ischemia. Positive stress test would lead to coronary angiography and if indicated coronary revascularization.</p><p>JUPITER = Justification for the Use of Statins in Primary Prevention</p><p>ATP III = Adult Treatment Panel III</p><p>SHAPE = Screening for Heart Attack Prevention and Education</p><p>YO = Years-Old</p><p>LDL-C = Low-density lipoprotein</p><p>CRP = C-Reactive Protein</p><p>FRS = Framingham Risk Score</p><p>CAC = Coronary Artery Calcium</p><p>PCE = pooled cohort risk equation</p><p>Inclusion and Exclusion Criteria as Well as Overview of each Approach to Primary Prevention Strategies Evaluated in the Model.</p

Selected Inputs to the State-Transition Model.

<p>*beta distribution for probabilistic sensitivity analysis</p><p>^†log-normal distribution for probabilistic sensitivity analysis</p><p>^#The status quo simulation represents outcomes based on current statin and aspirin use in the US primary prevention population</p><p>^{^}Includes costs of adverse events</p><p>CABG = coronary artery bypass graft surgery</p><p>CAC = coronary artery calcium</p><p>CHD = coronary heart disease</p><p>CI = confidence interval</p><p>CRP = C-reactive protein</p><p>FRS = Framingham Risk Score</p><p>JUPITER = Justification for the Use of Statins in Primary Prevention study</p><p>LDL-C = low-density lipoprotein in milligrams per deciliter</p><p>mSv = milisieverts</p><p>MI = myocardial infarction</p><p>PCI = percutaneous coronary intervention</p><p>QALYs = quality adjusted life years</p><p>RR = relative risk</p><p>Selected Inputs to the State-Transition Model.</p