Number Needed to Treat With Rosuvastatin to Prevent First Cardiovascular Events and Death Among Men and Women With Low Low-Density Lipoprotein Cholesterol and Elevated High-Sensitivity C-Reactive Protein

Abstract

for the JUPITER Study GroupBackground-As recently demonstrated, random allocation to rosuvastatin results in large relative risk reductions for first cardiovascular events among apparently healthy men and women with low levels of low-density lipoprotein cholesterol but elevated levels of high-sensitivity C-reactive protein. However, whether the absolute risk reduction among such individuals justifies wide application of statin therapy in primary prevention is a controversial issue with broad policy and public health implications. Methods and Results-Absolute risk reductions and consequent number needed to treat (NNT) values were calculated across a range of end points, timeframes, and subgroups using data from Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), a randomized evaluation of rosuvastatin 20 mg versus placebo conducted among 17 802 apparently healthy men and women with low-density lipoprotein cholesterol Ͻ130 mg/dL and high-sensitivity C-reactive protein Ն2 mg/L. Sensitivity analyses were also performed to address the potential impact that alternative statin regimens might have on a similar primary prevention population. For the end point of myocardial infarction, stroke, revascularization, or death, the 5-year NNT within JUPITER was 20 (95% CI, 14 to 34). All subgroups had 5-year NNT values for this end point below 50; as examples, 5-year NNT values were 17 for men and 31 for women, 21 for whites and 19 for nonwhites, 18 for those with body mass index Յ25 kg/m 2 and 21 for those with body mass index greater than 25 kg/m

Response to Letters Regarding Article, “Statins for the Primary Prevention of Cardiovascular Events in Women With Elevated High-Sensitivity C-Reactive Protein or Dyslipidemia: Results From the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and Meta-Analysis of Women from Primary Prevention Trials”

“…Finally, the requested data on numbers needed to treat have previously been published 4 and again indicate that the strategy of using statin therapy among individuals with elevated high-sensitivity C-reactive protein is at least as effective as the strategy of using statin therapy only among those with hyperlipidemia. …”

Development and Validation of a Model to Predict Absolute Vascular Risk Reduction by Moderate-Intensity Statin Therapy in Individual Patients With Type 2 Diabetes Mellitus

“…This seems a reasonable threshold when compared with the thresholds of 7.5% to 10% that are applied in current clinical guidelines for primary prevention 2,3,29 and even more when compared with the secondary prevention setting, in which NNTs are clearly lower with average 5-year NNTs ranging from 15 to 33, corresponding with 10-year NNTs of 8 to 17. 37 For preventive therapies that are associated with considerably higher NNTs, such as blood-pressure-lowering therapy (5-year NNTs between 80 and 160, 37 corresponding with 10-year NNTs between 40 and 80), previous studies have shown that applying a prediction model may similarly result in higher net benefit compared with a strategy in which all patients are treated. 38,39 Importantly, in patients at relatively high risk of cardiovascular events, the net benefit of a prediction-based treatment strategy will be comparable to a strategy in which all patients are treated because high-risk patients are likely to exceed the treatment threshold and therefore all will be treated in both scenarios.…”

Three Reasons to Abandon Low-Density Lipoprotein Targets

“…13,14 It should be noted that although C-reactive protein has been demonstrated to be an independent predictor of cardiovascular risk, it is not strongly related to the relative risk reduction of statins, although the evidence is not entirely consistent. 13,15,16 Thus, there is strong scientific evidence that LDL is not a very useful factor in determining who is at risk for cardiovascular disease or how much that risk will be reduced by a statin (Table).…”