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Revisiting JUPITER: When Is Statin Therapy Cost-Effective?

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Last November, results of the JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) trial showed that apparently healthy individuals with unremarkable levels of low-density lipoprotein cholesterol (LDL-C; average baseline levels, 104 mg/dL) but with elevated (≥2.0 mg/L) levels of high-sensitivity C-reactive protein (hs-CRP) had a dramatic reduction in cardiovascular risk with the use of rosuvastatin (Crestor) compared with placebo (see AHDB. 2008;1[9]:47-48). In March 2009, at a special session of the American College of Cardiology annual meeting, experts discussed the practical implications of the new analysis of JUPITER (Lancet. 2009;373:1175-1182) and the cost-effectiveness of extending statin therapy to populations with low LDL-C levels but with elevated hs-CRP levels.

Mark Hlatky, MD, professor of medicine and health research and policy at Stanford University, said that prescribing statin therapy to patients not previously considered candidates for such therapy could be cost-effective when using generic statins but not necessarily with brand-name statins.

The absolute benefits of statin therapy vary widely among individuals. “In particular, high-risk individuals have more to gain with statin treatment than low-risk individuals,” said Dr Hlatky. “In contrast, all patients have roughly the same chance of developing an adverse event to treatment.”

Paul Ridker, MD, lead investigator of JUPITER and Director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, said that “application of the strategy used in JUPITER over 5 years could prevent more than 250,000 events and cardiovascular deaths in the United States alone,” which may justify extending the population to be treated with statins. The 46% reduction in bypass surgery and angioplasty after a 2-year average follow-up time, said Dr Ridker, “has implications for healthcare cost-containment in terms of not only reducing the need for bypass surgery and stents but also the downstream agents that all the patients need when they get a stent.”

Dr Ridker noted that the beneficial effect of rosuvastatin occurred even in people at lowest risk: those with LDL-C <100 mg/dL who are thin and normotensive, and those with a Framingham risk of less than 10 (indicating a 10-year risk of a heart disease event of <10%). He said that JUPITER shows that the large benefit gained by statin therapy is not only LDL-C reduction but a “reduction in hs-CRP as well.”

The cost-effectiveness of using statins depends on the patient’s cardiovascular risk and the cost of the statin, says Dr Hlatky. “Cost-effectiveness is less favorable in low-risk individuals,” because less of the drug costs are offset by prevention of fewer cardiovascular events. The gradient cost-effectiveness of statin therapy is from $39,000 per quality-adjusted life-year (QALY) added in secondary prevention to $272,000 per QALY added in primary prevention. This model assumes that statins cost $3 to $4 per day. “When a statin costs less than $1 a day, therapy appears to be costeffective, even in lower-risk groups,” Dr Hlatky says. This could be achieved with generic statins, but it raises the question of cost-effectiveness with a more potent, branded statin.

Furthermore, the prospective analysis of JUPITER revealed that the patients randomized to rosuvastatin had a 43% reduction in venous thromboembolism compared with those randomized to placebo. Such a benefit decreases the number of patients that would need to be treated to avert 1 negative outcome, a number that was already low (22 over 5 years) when only cardiovascular events and deaths were considered.

Targeted use of hs-CRP testing to identify patients who might benefit from a statin may be more appropriate than broad screening, said Dr Hlatky. When statin therapy is a “close call,” defined as patients at intermediate risk of a heart attack or stroke, “hs-CRP testing may be helpful.”

Last modified: August 30, 2021