Published online before print April 23, 2007, doi: 10.1161/CIRCULATIONAHA.106.667683
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(Circulation. 2007;115:2398-2409.)
© 2007 American Heart Association, Inc.
Health Services and Outcomes Research |
Incremental Benefit and Cost-Effectiveness of High-Dose Statin Therapy in High-Risk Patients With Coronary Artery Disease
From the University of Michigan Department of Internal Medicine (P.S.C., B.K.N., H.S.G., R.A.H., S.V.), and Veterans Affairs Ann Arbor Health Services Research & Development Center of Excellence (P.S.C., B.K.N., R.A.H., S.V.), Ann Arbor, Mich.
Reprint requests to Paul Chan, MD, MSc, Veterans Affairs Ann Arbor Health Services Research & Development Center for Excellence, Cardiology (111-A), 2215 Fuller Rd, Ann Arbor, MI 48105. E-mail paulchan{at}umich.edu
Received October 2, 2006; accepted March 15, 2007.
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Abstract |
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Background— Recent clinical trials found that high-dose statin therapy, compared with conventional-dose statin therapy, reduces the risk of cardiovascular events in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD). However, the actual benefit and cost-effectiveness of high-dose statin therapy are unknown.
Methods and Results— We designed a Markov model to compare daily high-dose with conventional-dose statin therapy for hypothetical 60-year-old cohorts with ACS and stable CAD over patient lifetime. Pooled estimates for major clinical end points (all-cause mortality, myocardial infarction, stroke, rehospitalization, and revascularization) from relevant clinical trials were incorporated. Incremental benefit was quantified as quality-adjusted life-years (QALYs). Threshold analyses determined at what price difference high-dose statins would yield incremental cost-effective ratios below $50 000, $100 000, and $150 000 per QALY gained. In ACS patients, a high-dose versus conventional-dose statin strategy resulted in a gain of 0.35 QALYs. In threshold analyses, a high-dose statin strategy consistently yielded incremental cost-effective ratios below $30 000 per QALY even under conservative model assumptions. In stable CAD patients, a high-dose statin strategy yielded a gain of only 0.10 QALYs and was sensitive to model assumptions about statin efficacy. The daily cost difference between a high- and conventional-dose statin would need to be <$1.70, $2.65, and $3.55 to yield incremental cost-effective ratios below $50 000, $100 000, and $150 000 per QALY.
Conclusions— High-dose statin therapy is potentially highly effective and cost-effective in patients with ACS. In patients with stable CAD, however, the cost-effectiveness of high-dose statin therapy is highly sensitive to model assumptions about statin efficacy and cost. Use of high-dose statins can be supported on health economic grounds in patients with ACS, but the case is less clear for patients with stable CAD.
Key Words: cholesterol • coronary disease • cost-benefit analysis • drugs • statins
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Introduction |
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Recent clinical trials have demonstrated that high-dose statin therapy provides cardiovascular benefits beyond conventional (low- to moderate-dose) statin therapy among patients with acute coronary syndrome (ACS) and stable coronary artery disease (CAD).1–4 In response, the National Cholesterol Education Program has proposed the use of high-dose statin therapy in populations at an increased risk for CAD-related events with an optional therapeutic low-density lipoprotein (LDL) target level of
70 mg/dL. Despite this enthusiasm, no studies to date have directly quantified the incremental benefit and costs of high-dose versus conventional-dose statin therapy. It is common practice for clinical trials (such as the statin trials comparing high- versus conventional-dose statins) to use composite primary end points to ensure adequate power in evaluating a new treatment.5,6 However, individual component end points are often clinically dissimilar (eg, death and rehospitalization for unstable angina), and trials run the risk that a significant result may be driven by "soft" end points that are of less clinical importance than harder end points such as mortality.5,7 The ability to weight the clinical impact of such diverse end points would provide greater insight into the actual benefits achieved with a particular intervention. Moreover, although prior studies have shown that conventional-dose statin therapy is cost-effective for high-risk patients compared with placebo,8–12 it remains unclear whether high-dose statin therapy provides incremental clinical benefit that is cost-effective beyond conventional-dose statin therapy. Issues of cost are particularly relevant at this time given the patent expiration and subsequent price reduction of simvastatin and pravastatin.
Clinical Perspective p 2409
With these issues in mind, our objectives were 2-fold. We first evaluated the actual benefits achieved with high-dose statin therapy using a decision-analysis model. This approach allows us to convert (and therefore quantify) the clinical benefit achieved with high-dose statin therapy into a familiar and standardized measure: quality-adjusted life-years (QALYs). Second, because costs for statins are presently evolving, we also conducted threshold analyses to evaluate at what cost difference high-dose statin therapy compared with conventional-dose statin therapy would remain cost-effective.
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Methods |
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Model Design
A Markov decision-analysis model for ACS and stable CAD (see below) was developed to compare high-dose with conventional-dose statin therapy in a hypothetical 60-year-old cohort (mean age of subjects in the trials) (Figure 1).13 We assumed that patients with ACS do not remain at high risk for life, and we therefore modeled ACS patients to transition into a stable CAD state after 2 years (ie, after the mean follow-up of ACS trials). For our model estimates, we included only those trials (n=4) that directly compared a high-dose with a conventional-dose statin strategy.1–4 Patients in our model were at risk for death, myocardial infarction, stroke, rehospitalization, and revascularization annually, were followed up until death, and were eligible for repeat events. We adhered to recommendations for the conduct of cost-effectiveness analyses by using a societal perspective on health utilities and costs and applying a 3% annual discount rate.13 TreeAge Pro (Williamstown, Mass) was used for model design and all analyses.
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Incremental Clinical Benefits With High-Dose Statin Therapy
To quantify the incremental clinical benefit of high-dose statin therapy into QALYs, we first performed a pooled analysis of clinical end points from the 4 clinical trials that directly compared high-dose with conventional-dose statin therapy.1–4 Because of significant differences in study populations (ie, baseline event risks) and trial follow-up, the 4 trials were divided into 2 categories: ACS trials (the Pravastatin or Atorvastatin Evaluation and Infection Therapy [PROVE-IT] and the Aggrastat to Zocor [A to Z] trials)1,2 and stable CAD trials (Treating to New Targets [TNT] and the Incremental Decrease in End Points Through Aggressive Lipid Lowering [IDEAL] trials).3,4 Within the 2 categories, we pooled outcomes separately for all-cause mortality, stroke, nonfatal myocardial infarction, rehospitalization for ACS and/or unstable angina, and revascularization. Stroke event rates for the stable CAD trials were reported as combined fatal and nonfatal strokes, and we assumed that the vast majority of these were nonfatal. These end points were chosen because they were components of the composite end point in at least 1 of the 4 trials, and we took the published trial estimates at "face value," recognizing that there were potential differences and limitations in the designs across studies. Crude event data were abstracted by 2 of the authors (P.S.C., B.K.N.) from the trial publications. When data were unreported in the publication, we contacted the trial investigators for additional information. Summary risk ratios (RRs) and corresponding 95% CIs for each of the outcomes were estimated with the use of random-effects models (Table 1
and Table 2).14 Because TNT did not collect data on rehospitalization or revascularization, summary RRs for these outcomes in the stable CAD patients were obtained from IDEAL only.
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Additional Clinical Inputs for the Model
Base-case values, estimate ranges, and literature sources for additional model inputs are shown in Table 1
.10,15–23 Of note, patients suffering a stroke were modeled for potential disability (none, mild, moderate to severe),16,17 and it was assumed that 20% of myocardial infarctions would be complicated.18 For patients undergoing revascularization, percutaneous coronary intervention accounted for 70% of the procedures.10
To estimate mortality, we used actual mortality data derived from the trials themselves for the initial period (ACS: first 2 years; stable CAD: first 5 years). Patients with ACS transitioned into the stable CAD state after 2 years and assumed stable CAD trial rates thereafter. Long-term survival after 5 years (mean duration of stable CAD trials) was modeled with a proportional hazards model to avoid misspecification bias.24 Age-specific survival curves were generated by incorporating all-cause mortality data from standard US life tables19 and developing a mortality RR of 1.16 for patients in the model compared with the general US population. Next, outcomes beyond 5 years in the model were simulated in 3 different ways: (1) sustained risk reduction as during trial follow-up (base-case); (2) decrement in risk reduction benefit by 50%; and (3) no further risk reduction (RR=1).
Utilities
Incremental clinical benefit achieved with high-dose statin therapy was modeled with the use of health state utilities, which allows for estimation of QALYs gained.13 Quality-of-life adjustments for utility estimates were derived from the medical literature. A baseline utility of 0.974 was used in patients without recurrent events.10 Patients suffering a disabling stroke or myocardial infarction had long-term modifications of their health state utility (Table 1),10,18,25–28 whereas patients with hospitalizations for revascularization or ACS/unstable angina had a short-term disutility of 0.5 applied (ACS/unstable angina and angioplasty, 1 week; coronary artery bypass surgery, 4 weeks).
Threshold Analyses for Cost-Effectiveness
Costs
To perform threshold analyses for cost-effectiveness, our model assessed direct costs of inpatient and outpatient medical care (Table 1).10,13,16,25,28–38 To estimate costs, we used (1) Medicare reimbursement rates, (2) inflation-adjusted values from published data, and (3) wholesale drug costs derived from the Red Book.13,31 All patients had annual costs of $1700 related to their nonstatin medical therapy.10 Average single-event costs derived from Medicare diagnosis related group codes for myocardial infarction, stroke, revascularization, and rehospitalization were $5650, $9000, $16 450, and $2800, respectively. Patients suffering disability from a stroke had additional annual long-term costs.16,32–34
Because the actual costs of statins are in flux, we conducted threshold analyses on this variable. Instead of modeling separate costs for high- and conventional-dose statins, we modeled the price difference between a high- and conventional-dose statin at which a high-dose statin strategy would remain under a $50 000, $100 000, and $150 000 per QALY threshold. By taking this approach, our cost-effectiveness analyses reflect the impact of price differentials between high- and conventional-dose statins rather than a specific fixed price for statins that may be subject to change over time.
For all cost data, the upper and lower bounds of the estimate ranges were calculated as 25% above and below the base-case value, unless otherwise specified in Table 1. All cost estimates were standardized to 2005 US dollars by using the healthcare component of the Consumer Price Index.38
Sensitivity Analyses
To account for model assumptions and uncertainties, sensitivity analyses were performed for each variable over their range of estimates. To perform this, we modeled high-dose and conventional-dose statin therapies as daily treatment with atorvastatin 80 mg and simvastatin 20 mg (year 2005 annual costs of $1380 and $870, respectively31). We chose atorvastatin 80 mg daily to represent high-dose statin therapy primarily because it was the regimen studied in 3 of the 4 trials. We chose simvastatin 20 mg daily to represent conventional-dose statin therapy because this dosing or its equivalent was used in the trials and because it is the cheapest of the conventional-dose statins. Incremental cost-effectiveness was highly sensitive to (1) the modeled efficacy of high-dose statin therapy beyond clinical trial duration and (2) the difference in cost between high- and conventional-dose statin treatment, and therefore these variables were explored further in 2-way sensitivity analyses to assess the range of potential effects. Finally, we performed 10 000 independent Monte Carlo simulations with multivariable probabilistic sensitivity analysis, in which every variable in each simulation was randomly sampled across their range of estimates, to better assess the precision of our cost-effectiveness estimates.13
The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.
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Results |
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Pooled Analysis
Events for each trial used in the pooled analysis are summarized in Table I in the online-only Data Supplement. Mean durations of follow-up in the ACS and stable CAD trials were 2 and 5 years, respectively.
In the ACS trials, baseline annual incidence rates for conventional statin therapy were 2.32% for all-cause mortality, 3.55% for myocardial infarction, 0.63% for stroke, 2.40% for rehospitalization, and 5.82% for revascularization (Table 1). A high-dose statin strategy, compared with a conventional-dose statin strategy, was associated with significant reductions in all-cause mortality (RR=0.76; 95% CI, 0.62 to 0.94; P=0.01) and revascularization (RR=0.88; 95% CI, 0.79 to 0.99; P=0.04) but not with myocardial infarction (RR=0.92; 95% CI, 0.78 to 1.07; P=0.27), stroke (RR=0.89; 95% CI, 0.61 to 1.31; P=0.57), or rehospitalization (RR=0.84; 95% CI, 0.61 to 1.18; P=0.32) (Table 2).
In the stable CAD trials, baseline annual incidence rates for conventional statin therapy were 1.39% for all-cause mortality, 1.33% for myocardial infarction, 0.70% for stroke, 1.06% for rehospitalization, and 3.34% for revascularization (Table 1). A high-dose statin strategy, compared with a conventional-dose statin strategy, was associated with significant reductions in myocardial infarction (RR=0.81; 95% CI, 0.73 to 0.91; P<0.001), stroke (RR=0.82; 95% CI, 0.70 to 0.96; P=0.01), and revascularization (RR=0.77; 95% CI, 0.69 to 0.86; P<0.001) but not with all-cause mortality (RR=0.99; 95% CI, 0.89 to 1.10; P=0.89) or rehospitalization (RR=0.83; 95% CI, 0.69 to 1.01; P=0.06) (Table 2).
Incremental Clinical Benefit With High-Dose Statin Therapy
Our model calibrated well to expected event rates for the duration of the trial period. A summary of individual end point event rates by 5-year intervals for ACS and stable CAD patients is given in Table II in the online-only Data Supplement.
ACS Patients
Table 3 shows model predictions for QALYs gained for the treatment strategies under the 3 scenarios modeled for statin efficacy beyond 5 years (first 2 years in ACS model; next 3 years in stable CAD model). When a constant risk reduction beyond 5 years (base-case) was assumed, a high-dose statin strategy was more effective (13.589 versus 13.237 QALYs, a gain of 0.352 QALYs), with the majority (86%) of the QALY gains achieved through a reduction in mortality risk (Figure 2). The average nondiscounted life expectancy in ACS patients treated with conventional-dose statins was 19.493 years, and the nondiscounted QALY gain achieved with high-dose statin treatment was 0.583 QALYs. Therefore, the marginal duration of treatment required with a high-dose statin strategy to gain 1 QALY was 33 patient-years.
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If the benefit of high-dose statin therapy tapered off (eg, a 50% decrement in risk reduction) after 5 years, a high-dose statin strategy in ACS patients would yield only a gain of 0.325 QALYs. This would diminish to 0.297 QALYs in the most conservative scenario, in which there would be no further clinical benefit with high-dose statin therapy beyond 5 years.
Stable CAD Trials
Similarly, for stable CAD patients, under base-case assumptions of constant risk reduction with high-dose statin therapy beyond the mean trial duration of 5 years, a high-dose statin strategy was more effective (13.770 versus 13.674 QALYs), with nearly half (49%) of the 0.096 QALY gain achieved through a reduction in stroke risk (Figure 2). The average nondiscounted life expectancy in stable CAD patients treated with conventional-dose statins was 19.974 years, and the nondiscounted QALY gain achieved with high-dose statin treatment was 0.157 QALYs. Therefore, the marginal duration of treatment required with a high-dose statin strategy to gain 1 QALY was 127 patient-years. This benefit with high-dose statin therapy would diminish even further to 0.066 QALYs and 0.037 QALYs under the other scenarios of a 50% decrement in risk reduction and no further benefit beyond 5 years, respectively.
Cost-Effectiveness
Base-Case Threshold Analysis
For ACS patients, when a sustained benefit of high-dose statins beyond 5 years is assumed, the incremental cost-effectiveness ratio (ICER) for a high-dose statin strategy would remain under $44 000 per QALY even when the net daily price difference between high- and conventional-dose statins was $3.50 (Figure 3). If instead one conservatively assumed a decrement in benefit to 50% and 0% beyond 5 years, a net daily cost difference between a high-dose and conventional-dose statin of $3.50 would yield ICERs of $52 600 and $63 300 per QALY, respectively.
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For stable CAD patients, under base-case assumptions of sustained statin efficacy beyond 5 years, the ICER for a high-dose statin strategy would remain below $50 000, $100 000, and $150 000 per QALY if the net daily cost difference between a high-dose and a conventional-dose statin remained below $1.70, $2.65, and $3.55, respectively. If one assumed a decrement in risk reduction benefit to 50% beyond 5 years with a high-dose statin strategy, the daily cost difference between statins would need to be below $1.20, $1.80, and $2.40, respectively, to remain under the same ICER thresholds.
Sensitivity Analyses
To conduct sensitivity analyses, we set our base-case analysis to compare atorvastatin 80 mg with simvastatin 20 mg therapy (daily cost difference of $1.40). In ACS patients, a high-dose statin strategy was more expensive ($70 581 versus $66 033) and more effective (0.352 QALYs gained), thereby yielding an ICER of $12 900 per QALY gained. A decrement in risk reduction benefit to 50% and 0% for all 5 outcomes beyond 5 years yielded larger ICERs of $19 400 and $27 100 per QALY. A high-dose statin strategy in ACS patients was modestly sensitive to the cost of statins and the relative risk reduction in all-cause mortality (Table 4). In each scenario, however, the ICER for a high-dose statin strategy remained under $26 000 per QALY. This upper threshold would increase to $49 500 per QALY if high-dose statin therapy was only 50% effective beyond 5 years (Table III in the online-only Data Supplement).
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In stable CAD patients, a high-dose statin strategy was likewise more expensive ($67 134 versus $63 920) and more effective (0.096 QALYs gained), giving an ICER of $33 400 per QALY gained. A decrement in risk reduction benefit to 50% and 0% for all 5 outcomes beyond 5 years yielded much smaller QALY gains and therefore larger ICERs of $68 200 and $158 600 per QALY. The effect of varying baseline event risks and the relative efficacy of high-dose statin treatment in reducing such events for each of the 5 outcomes are summarized in Table 4. A high-dose statin strategy was particularly sensitive to statin cost and its ability to reduce mortality and stroke. Otherwise, the upper ICER estimate ranges remained below $52 000 per QALY. This upper threshold in 1-way sensitivity analyses would increase to $106 000 per QALY if high-dose statin therapy was only 50% effective beyond 5 years (Table III in the online-only Data Supplement).
Finally, using multivariable sensitivity analysis, we determined that a high-dose statin strategy in ACS patients would yield ICERs below $31 000 per QALY 95% of the time and below $50 000 per QALY 99.8% of the time if statin efficacy was sustained beyond 5 years (Figure 4). This suggests high certainty that the ICER likely is below $31 000 per QALY. If instead statin efficacy was reduced to 50% beyond 5 years, 95% of all simulations would yield ICERs below $36 000 per QALY. In contrast, a high-dose statin strategy in stable CAD patients would yield ICERs below $50 000 per QALY 76% of the time and below $100 000 per QALY 95% of the time if statin efficacy was sustained beyond 5 years. The likelihood of generating ICERs below $50 000 and $100 000 per QALY would decrease even further (39% and 66%, respectively) if statin efficacy was reduced to 50% beyond 5 years.
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Discussion |
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Although recent trials have shown incremental cardiovascular benefit with high-dose statin therapy compared with conventional-dose statin treatment in high-risk populations, the cost-effectiveness of this strategy remains unclear. Our study found that a strategy of high-dose statin therapy in patients with ACS would be effective (net gain of 0.35 QALYs) and cost-effective, with effectiveness mediated primarily through reductions in all-cause mortality. Even under very conservative assumptions of attenuated statin benefit beyond 5 years or a large cost difference between high- and conventional-dose statins, a high-dose statin strategy in ACS patients remained cost-effective with ICERs consistently below $31 000 per QALY. In contrast, in patients with stable CAD, a high-dose statin strategy was only able to achieve a net gain of 0.10 QALYs, with half of the gains achieved through a reduction in stroke risk. This markedly smaller gain in effectiveness resulted in a base-case ICER of $33 400 per QALY in stable CAD patients that was highly sensitive to assumptions regarding statin efficacy over patient lifetime and statin cost, with ICER estimates exceeding $100 000 per QALY under more conservative model assumptions.
Our decision analysis highlights a current challenge in the design of clinical trials. As event rates for cardiovascular morbidity and mortality continue to decrease with ever-improving medical therapies, it is common practice for clinical trials to use composite primary end points to ensure adequate power in evaluating a new treatment.5 By modeling effectiveness for each major outcome of interest through health state utilities, decision analysis allowed us to better assess the impact of a high-dose statin strategy in ACS and stable CAD patients by "weighting" the relative gain in QALY for each outcome. Our findings suggest that the actual benefit achieved with high-dose statin therapy in ACS and stable CAD patients varies significantly in both absolute and relative terms. Although base-case ICERs yielded estimates below $50 000 per QALY in both cohorts, we demonstrated that a high-dose statin strategy in ACS patients yielded a 3.5-fold greater net gain in QALYs than in stable CAD patients. This is largely because the majority of the benefit achieved in ACS patients was through mortality risk reduction during the first 2 years of therapy. In contrast, the baseline event rates were markedly lower in stable CAD patients during these first 2 years, with half of the benefits of high-dose statin therapy achieved through stroke risk reduction (in which the relative gain in QALYs is smaller compared with death). This significantly smaller marginal QALY gain with high-dose statin therapy in stable CAD patients explains the extreme sensitivity of its ICER estimate to statin cost and model assumptions and therefore highlights the need to place into context an ICER estimate from a cost-effectiveness model. We therefore believe that routine use of decision analysis along with the reporting of clinical trials that use composite end points may provide an effective tool for interpreting the value of new treatments.
We also assessed incremental cost-effectiveness of high-dose statin therapy in this study by performing threshold analyses of their price difference with conventional-dose statin therapy. Because generic statin prices are presently evolving, we believe that this study’s threshold analyses, by focusing on the difference in price between a high- and conventional-dose statin, will provide a framework for assessing the relative cost-effectiveness of high-dose statin therapy even while prices remain unfixed. The choice of conventional-dose statins against which high-dose statins should be measured for cost-effectiveness should now be the generic statins (simvastatin and pravastatin) because they are the cheapest conventional-dose statins available. For this reason and because of its representation as the conventional statin in 2 of the clinical trials themselves, simvastatin 20 mg daily was chosen for the base-case estimate for our sensitivity analysis. Moreover, high-dose pravastatin compared with conventional-dose statin therapy has not been studied previously in clinical trials, and high-dose simvastatin has only been studied in the A to Z trial in the ACS population, in which there were no statistically significant improvements in the primary cardiovascular outcome end point. This may reflect differences in the A to Z study trial design,39 heterogeneity in the composition of the primary end point,6 or the lack of a homogeneous class effect among all high-dose statin regimens. As a result, we chose atorvastatin 80 mg daily for the base-case estimate for high-dose statin therapy in our model on the basis of its representation in 3 of the 4 landmark trials used for our pooled analyses. Our findings demonstrate that a high-dose statin strategy will remain cost-effective in ACS patients regardless of conventional statin price as long as high-dose statin efficacy beyond 5 years remains modest (
50%) throughout a patient’s lifetime. In contrast, a high-dose statin strategy may not remain cost-effective in stable CAD patients as the price of conventional-dose statins decreases unless the price of high-dose nongeneric statins decreases accordingly (thereby keeping the price difference fixed) or the efficacy of high-dose generic statins (eg, pravastatin, simvastatin) is shown to be comparable to that of their high-dose nongeneric (eg, atorvastatin) counterparts.
We constructed our decision-analysis model to simulate the benefits of high-dose versus conventional-dose statin therapy rather than LDL titration goals. Because specific cohort data on LDL titration with conventional- and high-dose statin therapy are not presently available (eg, stroke risk reduction with the use of high-dose statins for specific patients who continue to have high LDL values despite conventional-dose statins), our model did not attempt to simulate LDL titration. Moreover, it remains unclear whether the use of nonstatin medications (such as ezetimide) to augment high- or conventional-dose statins has comparable cardioprotective effects for those unable to achieve LDL targets, thereby making a LDL titration model impossible to construct without making a number of questionable assumptions.
Limitations
The present study had several limitations. Decision-analysis models make simplifying assumptions, and these assumptions may have a large impact on underlying results. Our model inputs incorporated estimates for statins from relatively few trials comparing high- versus conventional-dose statin therapy and at face value. The true long-term clinical benefits with statin therapy also remain largely unknown. Given this, different scenarios were explored in sensitivity analyses. We assumed homogeneity of statin efficacy among statins of similar potencies. If significant heterogeneity in statin efficacy were to exist (ie, no class effect), inferences regarding the cost-effectiveness of individual statin drugs and dosing regimens would need to be trial specific. We modeled conventional statin therapy as simvastatin 20 mg in our sensitivity analyses. Use of higher simvastatin doses (eg, 40 mg) to represent conventional statin therapy would likely decrease the incremental gains in QALY and increase the ICER of a high-dose statin strategy, but outcome estimates with these doses remain unknown. We did not model potential statin benefit for other cardiovascular outcomes (such as congestive heart failure or peripheral vascular disease) because these were not components of the primary end point in any of the trials. Finally, our analyses were for a hypothetical 60-year-old cohort with ACS and stable CAD and would not apply to significantly older or younger patients if a significant treatment-by-age interaction exists.
Conclusions
Compared with conventional statin treatment, a high-dose statin strategy in patients presenting with ACS achieves significant gains in QALY and is cost-effective. In patients with stable CAD, the marginal gain in QALY is significantly smaller, and the cost-effectiveness of high-dose statin treatment is highly sensitive to model assumptions about statin efficacy over patient lifetime and statin cost.
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Acknowledgments |
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Sources of Funding
Dr Chan is supported by a National Institutes of Health Cardiovascular Multidisciplinary Research Training Grant and by the Ruth L. Kirchstein Research Service Award. None of the sponsors had any involvement in the design, collection, management, or analysis of the study or in manuscript preparation.
Disclosures
None.
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The online-only Data Supplement, consisting of tables, is available with this article at http://circ.ahajournals.org/cgi/content/full/CIRCULATIONAHA.106.667683/DC1.
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