CRP Testing+Statin Therapy Cost Effective To Prevent Heart Disease/death
"JUPITER study........treating intermediate-risk patients with normal LDL-cholesterol levels but elevated CRP levels.......with rosuvastatin 20 mg significantly reduced the primary end point.......-a composite of nonfatal MI, nonfatal stroke, hospitalization for unstable angina, revascularization, and confirmed death from cardiovascular causes-by 44% .......the proportion of patients who had an MI, stroke, revascularization, or hospitalization for unstable angina or died from cardiovascular causes was 1.6% in the rosuvastatin arm and 2.8% in the placebo arm, an absolute risk reduction of 1.2%"|
In The Lancet: JUPITER Study Reports Reducing hsCRP & LDL to Low Levels with ...
Mar 29, 2009 ... The study population was derived from JUPITER-a randomised, double-blind, placebo-controlled trial that was designed to investigate whether ...www.natap.org/2009/HIV/033109_03.htm
CRP testing plus statin therapy cost-effective in primary-prevention patients: JUPITER
February 8, 2011, Michael O'Riordan
Boston, MA - Treating intermediate-risk patients with low levels of LDL cholesterol but elevated C-reactive protein (CRP) levels with rosuvastatin (Crestor, AstraZeneca) for the primary prevention of vascular events is cost-effective, according to a new economic analysis, with the treatment strategy comparing favorably with the cost-effectiveness of fully implementing the National Cholesterol Education Program (NCEP) lipid-lowering guidelines .
Using data from Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER), the investigators, led by Dr Niteesh Choudhry (Brigham and Women's Hospital, Boston, MA), report that treating JUPITER-eligible patients with rosuvastatin had an incremental cost-effectiveness of $25 198 per quality-adjusted life-year (QALY) gained when compared with usual care. The benefit of CRP testing and rosuvastatin treatment is most cost-effective in patients with a Framingham risk score >10% and would become more cost-effective as the price of the drug is lowered.
"I think that for the higher-risk patients, those with a Framingham risk higher than 10%, it seems like this would be a highly cost-effective strategy," Choudhry told heartwire. "This kind of analysis and other analyses like this one give us evidence for basing our resource-allocation decisions. These are not numbers that individual doctors should use, but numbers that healthcare systems and large payers should be looking at. Based on this, relative to most of the other stuff that we do in healthcare, however, this strategy looks to be cost-effective."
The results of the study are published in the February 15, 2011 issue of the Journal of the American College of Cardiology.
The implications of the JUPITER study
Previously reported by heartwire, the JUPITER study was a landmark primary-prevention trial led by Dr Paul Ridker (Brigham and Women's Hospital) testing the hypothesis that a strategy of treating intermediate-risk patients with normal LDL-cholesterol levels but elevated CRP levels would significantly reduce the risk of cardiovascular events.
Treatment with rosuvastatin 20 mg significantly reduced the primary end point-a composite of nonfatal MI, nonfatal stroke, hospitalization for unstable angina, revascularization, and confirmed death from cardiovascular causes-by 44% compared with individuals treated with placebo. In terms of absolute benefits, the proportion of patients who had an MI, stroke, revascularization, or hospitalization for unstable angina or died from cardiovascular causes was 1.6% in the rosuvastatin arm and 2.8% in the placebo arm, an absolute risk reduction of 1.2%.
"Our purpose was to address the difficulty that healthcare systems have in taking the results of a provocative trial like JUPITER and putting them into the real world," said Choudhry. "There are a lot of nagging questions that a trial result like this leaves, and our intent was to weigh the benefits seen in JUPITER with their costs and evaluate that strategy over the long term."
In the new analysis, the group constructed a cost-effectiveness model using the JUPITER criteria, comparing the cost-effectiveness of CRP testing followed by rosuvastatin treatment in patients with CRP levels >2.0 mg/L vs usual care (no testing and no treatment). The cost of rosuvastatin was assumed to be $3.63 per day, based on the quoted price from a major pharmacy, until approximately 2018, when it was assumed to cost $1/day as a generic drug, while the cost of CRP testing was based on the current Medicare payment rate for the test.
Patients treated with usual care were estimated to have an average quality-adjusted life expectancy of 10.29 QALYs, with associated costs of $19 717. CRP testing followed by rosuvastatin treatment, on the other hand, resulted in a quality-adjusted life expectancy of 10.61 QALYs and costs of $27 616. This translated into an incremental cost-effectiveness of $25 198 per QALY gained when compared with usual care.
The investigators also performed a number of sensitivity analyses, adjusting some of the assumptions made in the cost-effectiveness model. For example, if the effectiveness of rosuvastatin is reduced to the most unfavorable limit within the 95% confidence interval-such as reducing the rate of MI 30% instead of the 54% observed in JUPITER-the incremental cost-effectiveness ratio was $57 503 per QALY. If the effects of rosuvastatin persisted for just five years, the cost-effectiveness of CRP testing and statin therapy would be $62 146. In contrast, if the full effect of treatment lasted for 25 years and tapered off after 35 years, the cost-effectiveness ratio of the test-and-treat strategy would be $20 962 per QALY.
The investigators also looked at restricting CRP testing to patients with a Framingham risk score >10% for predicting MI and death from coronary disease. In these intermediate-risk patients, treatment leads to an incremental cost-effectiveness ratio of $14 205 per QALY, whereas restricting rosuvastatin to those with Framingham scores <10% results in a cost-effectiveness ratio of $54 961.
"The finding itself is not really all that surprising," said Choudhry. "Targeting the strategy to the higher-risk patients, who would otherwise qualify for it, leads to more cost-effective results."
To heartwire, Choudhry said that in North America, $50 000 to $100 000 per QALY is considered to be a cost-effective treatment. He said their approach in evaluating the cost-effectiveness of primary prevention based on JUPITER made a number of conservative assumptions, such as assuming that the treatment benefit of statins would last 15 years rather than assuming an indefinite benefit. As a whole, however, the vast majority of the sensitivity analyses yielded numbers that meet the criteria for cost-effectiveness, suggesting that results of their overall analysis are robust.
"Is this the best use of these healthcare dollars?"
In an editorial accompanying the published study , however, Dr Mark Hlatky (Stanford University School of Medicine, CA) writes that the results from the different sensitivity analyses show that "the cost-effectiveness ratio from JUPITER is highly leveraged on the assumption of sustained, deep risk reductions, an assumption for which we have little data."
He notes that the cost-effectiveness ratio tripled when investigators assumed the effects of statin therapy last only to five years and that JUPITER itself was stopped after an average follow-up of 1.9 years. The problem with cost-effectiveness analyses, writes Hlatky, is that they take a lifetime perspective, but few clinical trials follow patients for more than a couple of years, resulting in few long-term data on treatment efficacy.
In addition, he points out that the analysis was sensitive to changes in adverse effects. If just 2% of patients taking rosuvastatin experienced a decrease in their overall well-being, the cost-effectiveness ratio increased to $62 600 per QALY, reports Hlatky. Moreover, if the cost of the drug doesn't decrease to $1/day after eight years, again, the cost-effectiveness ratio would nearly double.
Finally, Hlatky writes that even cost-effective therapies cost money and that prevention rarely saves it, "despite the wishes of some that it did." Based on the investigators' finding that rosuvastatin treatment increases lifetime healthcare costs by $7900 per person, with between six and 12 million candidates for rosuvastatin based on JUPITER, "it implies it would cost between $50 billion and $95 billion to extend rosuvastatin therapy to JUPITER-eligible patients in the US," concludes Hlatky. "Are we convinced this is the best use of these healthcare dollars?
To heartwire, Choudhry, said that being cost-effective means that it's a good value for money, but it still means the healthcare system is spending money and that "one way or the other, the strategy adds cost." By his own back-of-the-envelope calculations, applying the test-and-treat strategy to patients with LDL cholesterol <130 mg/dL, CRP levels >2.0 mg/L, and a Framingham risk score >10% would cost a significant amount of money, so the decision should not be taken lightly. That said, in relative terms, applying treatment based on JUPITER is "not a bad deal," said Choudhry.
JUPITER was sponsored by AstraZeneca, but this analysis was not funded by an external source. No study author receives personal compensation from any pharmaceutical manufacturer. Hlatky reports no conflicts of interest.
1. Choudhry NK, Patrick AR, Glynn RJ, Avorn J. The cost-effectiveness of C-reactive protein testing and rosuvastatin treatment for patients with normal cholesterol levels. J Am Coll Cardiol 2011; 57: 784-791.
2. Hlatky M. The cost-effectiveness of rosuvastatin therapy. J Am Coll Cardiol 2011; 57: 792-793.
· Cochrane review stirs controversy over statins in primary prevention
[Lipid/Metabolic > Lipid/Metabolic; Jan 20, 2011]
· ASCOT analysis fuels debate over JUPITER-based CRP indication for statins
[Lipid/Metabolic > Lipid/Metabolic; Nov 18, 2010]
· JUPITER: Low LDL and low CRP best for reducing events in primary prevention
[Lipid/Metabolic > Lipid/Metabolic; Mar 29, 2009]
· JUPITER hits New Orleans: Landmark study shows statins benefit healthy individuals with high CRP levels
[Clinical cardiology > Clinical cardiology; Nov 09, 2008]