EDITORIAL COMMENT
Prevention and TreatmentA Tale of Two Strategies*
George A. Diamond, MD, FACC* and
Sanjay Kaul, MD, FACC
Division of Cardiology, Cedars-Sinai Medical Center and David Geffen School of Medicine, University of California, Los Angeles, California.
* Reprint requests and correspondence: Dr. George A. Diamond, 2408 Wild Oak Drive, Los Angeles, California 90068. (Email: gadiamond{at}pol.net).
It was the best of times, it was the worst of times,
it was the age of wisdom, it was the age of foolishness,
it was the epoch of belief, it was the epoch of incredulity,
it was the season of Light, it was the season of Darkness ...
Charles Dickens (1)
A Dickensian duo of contrasting imperatives underlies the current management of atherosclerotic heart disease: to treat the anatomic stenosis causing myocardial ischemia and to prevent the plaque disruption causing myocardial infarction. The former leads us to do stress tests and angiograms to identify flow-limiting lesions and then to crush them by direct surgical intervention, while the latter leads us to identify risk factors, such as cholesterol, and prescribe drugs, such as statins, to mitigate those risks.
A host of clinical trials support each approach. In general, treatment is better suited to unstable coronary syndromes, and prevention is better suited to stable coronary disease. The recent COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, for example, showed that percutaneous coronary intervention (PCI) did not improve outcomes when added to optimal medical therapy in patients with stable disease (2). It is uncertain, however, if these findings are applicable to older subjects, given their under-representation in the pivotal trials upon which current guidelines are based.
In this issue of the Journal, Afilalo et al. (3) shed new light on the effectiveness of statins in "elderly" patients with known coronary disease. In their meta-analysis of 9 trials enrolling patients between 65 and 82 years of age, statins reduced all-cause mortality by 22% over 5 years of follow-up. Rates of nonfatal infarction, stroke, and revascularization were reduced even more. Importantly, the magnitude of benefit was substantially larger than previously reported and increased with age, a 50% mortality reduction being observed in those over 80 years of age. Although the authors were unable to perform a formal assessment of safety, a recent review concluded that statins are "remarkably safe," even in the elderly (4).
A limitation of this meta-analysis is the unavailability of patient-level data, which would have permitted an assessment according to pertinent clinical and demographic subgroups. Such details can be important, because patients in clinical trials differ from those in routine clinical practice. In addition, the time to onset of benefit and the effect of low-density lipoprotein (LDL) cholesterol (at baseline and on treatment) were not evaluated.
Nonetheless, using a previously published empirical survival model (5), the study has substantial practical relevance (Table 1). As suggested by Afilalo et al. (3), an 85-year-old man with known disease has a greater baseline risk (18.8% vs. 1.3%), and therefore obtains a greater benefit (8.9% vs. 0.4%) from statin treatment compared with an otherwise similar 55-year-old man. Thus, although the absolute gain in survival is lower in the 85-year-old (2.1 vs. 4.3 years), it is proportionately greater (75% vs. 23%) relative to baseline expectations of survival (2.8 vs. 18.8 years). All things being equal, then, the older we become, the more value we should ascribe to each additional year of life (and to the treatment that provides it).
Two practical problems, however, continue to plague the effectiveness of statin therapy in clinical practice. First, long-term adherence to therapy remains poor, averaging only 62% over 2 years (6–10). Second, the so-called "treatment gap" (the proportion of statin candidates not receiving statin treatment) remains large, especially among the elderly. In one study, only 57% of "high-risk" patients attained LDL <100 mg/dl, and 18% attained LDL <70 mg/dl (11). Preferred drug lists and tiered formularies further compound this misutilization (12).
Meanwhile, the use of PCI continues to increase despite the lack of equivalent evidence of outcomes benefit. Current reimbursement policy actually encourages such misuse. Once drugs and devices are approved for marketing, physicians often use them in unapproved ways, and payers reimburse such "off-label" use to the same degree as "on-label" use.
Fine-tuning these financial incentives might help to close the treatment gap and increase adherence to statin therapy (13). Suppose the Center for Medicare and Medicaid Services (CMS) discounted a drug’s price, not by some fixed amount as it does now, but in direct proportion to its proven therapeutic benefit, so that one with more benefit is awarded a higher discount than another with less benefit. For example, imagine that one statin costing $2 per day (call it Positor) has a discount of 90% because it is proven to improve survival, whereas a competitive statin also costing $2 per day (call it Negator) has a discount of 10% because it only improves some surrogate marker. As a result, patients pay $6/month for Positor versus $54/month for Negator. Which of the two would you and your patient prefer?
Because the total price of the prescription does not change (with CMS picking up the difference), a high discount will not erode the manufacturer’s profits. In fact, profits are more likely to soar as a result of facilitated access to the less-costly drug and favorable shifts in market share. The CMS might even exploit this windfall to negotiate volume discounts with the manufacturer, thereby offsetting some of the cost of the plan. Although such negotiations are currently prohibited by existing law, the issue is under Congressional review. Thus, as a result of these incentives, the manufacturer is rewarded with competitive advantages for documenting the benefits of its drugs, and the patient is rewarded with better access to these benefits at more affordable prices.
Critics might argue that this plan requires a huge new bureaucracy. On the contrary, the needed infrastructure is largely in place. The Food and Drug Administration already calls on advisory panels to help decide if a drug meets standards of efficacy and safety. All it need do is empower these panels with the additional authority to set the discount for the drug based on the scientific evidence they are already reviewing. As new data become available, manufacturers could request a new review, just as they now petition for labeling changes.
Innovative strategies such as this are already being piloted in the private sector. Over the past decade, health plans have sought to save money by charging higher patient copayments for brand-name drugs to encourage the use of lower-cost generics. Now they are lowering copayments for drugs with proven preventive benefit (14). If patients no longer have to pay the cost of a statin, so goes the reasoning, they will more likely adhere to treatment, thereby forestalling higher-cost eventualities (stroke, reinfarction, revascularization). Aetna will conduct a formal evaluation of this new strategy later this year, by waiving copayments for statins (along with a few other agents) in post-infarction patients and tracking subsequent outcome and cost. From the patients’ perspective, this might be the closest thing there is to getting something for nothing.
The CMS could attach similar financial incentives to the performance of PCI by reimbursing approved "on-label" use at a higher level than for unapproved "off-label" use. Simply put, if payment drives utilization, and utilization drives outcome, payment can drive outcome. Unlike "pay-for-performance," for which there is little proof of effectiveness (15), evidence-based reimbursement would: 1) target the expectation of benefit rather than actual outcome; 2) rely on empirical data rather than consensus opinion; 3) apply to individuals rather than groups; and 4) be large in size and immediate in impact.
If we are to pay for preventive care in proportion to its clinical value, consumers will need to be informed about these values. Currently, manufacturers are faced with substantial regulatory hurdles in attempting to provide truthful information to physicians and patients about the use of their products. Insurers, patient advocacy groups, and the Surgeon General’s office are not so constrained, and are free to inform the public truthfully about the value even of "off-label" uses. They should be encouraged to do so.
Although these are revolutionary proposals, so too was the original Medicare law. Its passage instantly assured the elderly of unfettered access to health care, but it also engendered a deep disconnect between what the providers of that care should do (according to the evidence), and what they are paid to do (according to reimbursement policies). The statin treatment gap is but one example.
This situation will not change unless and until we realign the financial and scientific incentives and begin rewarding caregivers, not for the prodigal provision of products and services, but for the enlightened provision of therapeutic benefit. Evidence-based reimbursement can be the bridge to this "far, far better thing" (1).
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Footnotes
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* Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. 
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References
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1. Dickens C. A Tale of Two Cities. 1859(reprinted by Penguin Classics: London, 2000).2. Boden WE, O’Rourke RA, Teo KK, et al. COURAGE Trial Research Group Optimal medical therapy with or without PCI for stable coronary disease N Engl J Med 2007;356:1572-1574.[Free Full Text] 3. Afilalo J, Duque G, Steele R, Jukema JW, de Craen AJM, Eisenberg MJ. Statins for secondary prevention in elderly patients: a hierarchical Bayesian meta-analysis J Am Coll Cardiol 2008;51:37-45.[Abstract/Free Full Text] 4. Armitage J. The safety of statins in clinical practice Lancet 2007June 6;[E-pub ahead of print]. 5. Diamond GA, Staniloff HM, Forrester JS, Pollock BH, Swan HJC. Computer-assisted diagnosis in the noninvasive evaluation of patients with suspected coronary artery disease J Am Coll Cardiol 1983;1:444-455.[Abstract] 6. Kopjar B, Sales AE, Pineros SL, Sun H, Li YF, Hedeen AN. Adherence with statin therapy in secondary prevention of coronary heart disease in Veterans Administration male population Am J Cardiol 2003;92:1106-1108.[CrossRef][Web of Science][Medline] 7. Mantel-Teeuwisse AK, Goettsch WG, Klungel OH, de Boer A, Herings RMC. Long term persistence with statin treatment in daily medical practice Heart 2004;90:1065-1066.[Free Full Text] 8. Caspard H, Chan AK, Walker AM. Compliance with a statin treatment in a usual-care setting: retrospective database analysis over 3 years after treatment initiation in health maintenance organization enrollees with dyslipidemia Clin Ther 2005;27:1639-1646.[CrossRef][Web of Science][Medline] 9. Campione JR, Sleath B, Biddle AK, Weinberger M. The influence of physicians’ guideline compliance on patients’ statin adherence: a retrospective cohort study Am J Geriatr Pharmacother 2005;3:229-239.[CrossRef][Medline] 10. Perreault S, Blais L, Dragomir A, Bouchard MH, Lalonde L, Laurier C, Collin J. Persistence and determinants of statin therapy among middle-aged patients free of cardiovascular disease Eur J Clin Pharmacol 2005;61:667-674.[CrossRef][Web of Science][Medline] 11. Davidson MH, Maki KC, Pearson TA, et al. Results of the National Cholesterol Education (NCEP) Program Evaluation Project Utilizing Novel e-Technology (NEPTUNE) II survey and implications for treatment under the recent NCEP Writing Group recommendations Am J Cardiol 2005;96:556-563.[CrossRef][Web of Science][Medline] 12. Ridley DB, Axelsen KJ. Impact of Medicaid preferred drug lists on therapeutic adherence Pharmacoeconomics 2006;24(Suppl 3):65-78.[Web of Science][Medline] 13. Diamond GA, Denton TA, Matloff JM. Fee-for-benefitA strategy to improve the quality of health care and control costs through reimbursement incentives. J Am Coll Cardiol 1993;22:343-352.[Abstract] 14. Fuhrmans V. New tack on copays: cutting them. Employers, insurers bet that covering more of the cost of drugs can save money over the long term for chronic conditions Wall Street Journal. 2007May 8:D1. 15. Glickman SW, Ou FS, DeLong ER, et al. Pay for performance, quality of care, and outcomes in acute myocardial infarction JAMA 2007;297:2373-2380.[Abstract/Free Full Text]
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