Letter by Vos et al 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”

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HomeCirculationVol. 122, No. 23Letter by Vos et al 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” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Vos et al 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” Eddie Vos Colin P. Rose Pierre Biron Eddie VosEddie Vos Sutton, Quebec, Canada (Vos) Search for more papers by this author Colin P. RoseColin P. Rose Department of Medicine McGill University Montréal, Quebec, Canada (Rose) Search for more papers by this author Pierre BironPierre Biron Department of Pharmacology (Retired) Faculty of Medicine Université de Montréal Montréal, Quebec, Canada (Biron) Search for more papers by this author Originally published7 Dec 2010https://doi.org/10.1161/CIRCULATIONAHA.110.954016Circulation. 2010;122:e576To The Editor:We read with interest the article by Mora and colleagues,1 who are well supported when stating that “statins had not been found to reduce total or coronary mortality in women, men, or combined for primary prevention” but suggest that their Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study indicates differently. We respectfully disagree.The article gives no data about cardiovascular mortality, which for men and women combined differed by only 8 (author's response to Ridker and Glynn2; corresponding P=0.37). In women specifically, calculating from combined data in Table 3 in the article by Mora et al,1 there would have been 10 cardiovascular deaths on rosuvastatin versus 13 on placebo, which would generate a P value of 0.51. The infarct and stroke findings were also not different in women after ≈6500 on-statin years.The only significant benefit in women in any of the 5 primary end point components was the 73% reduction in revascularizations. These are not disease end points per se but medical decisions based on hospital presentations and catheterization laboratory availability. To illustrate the softness of this end point and for perspective, we note that other research found revascularizations reduced by 90%, both for coronary artery bypass grafting and percutaneous coronary intervention, by the subject first presenting to a closer non–catheterization laboratory hospital when experiencing an acute coronary event,3 and, in these circumstances, deaths in the non–catheterization laboratory cohort were significantly fewer after 6 months.Interestingly, the reduction in revascularizations by rosuvastatin may be related to the well-known angina-reducing, nitroglycerin-mimicking (nitric oxide/endothelial nitric oxide synthase–promoting) pathway of statins,4,5 an effect that could reduce the number of hospital presentations and thus interventions. It is unknown whether such beneficial nitric oxide/endothelial nitric oxide synthase effect is attenuated by tolerance over subsequent years or decades, as happens with nitroglycerin, because JUPITER was halted at a mean follow-up of 1.9 years.In cost-benefit terms, the 21 fewer revascularizations in JUPITER after 6500 female on-statin years would represent an outlay of $625 000 per procedure avoided at an April 2010 US pharmacy chain retail price. Put another way, 303 women would have to take rosuvastatin for 1 year at >$2000 each to avoid 1 revascularization.With regard to total mortality in women, the authors suggest benefit and, in Figure 2A, introduce the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) using PRAVASTATIN study. However, as in JUPITER, the mortality benefit of MEGA was not from fewer cardiovascular deaths, which were identical in the statin and nonstatin groups, but also from the anomaly of fewer deaths from cancer.Therefore, physicians and women patients should be informed that rosuvastatin has thus far not been shown to reduce the risk of cardiovascular death, myocardial infarction, or stroke in high-risk primary prevention patients, as in the case of JUPITER, in which virtually all subjects had some form of metabolic syndrome.The authors report risks for combined nonequipoise end points and P values for differences and heterogeneity with men that are of limited value to prescribers and patients. An alternative and more patient-centered approach would be to avoid ambiguity by reporting numbers needed to treat per year (annualized numbers needed to treat) with confidence intervals starting at year 1 for the 5 primary end point components.We respectfully ask the authors to publish a simple table with these yearly numbers, separately for men and for women. This would be a vital clarification of JUPITER, a study likely to affect statin-prescribing decisions for years to come.Eddie Vos, MEng Sutton, Quebec, CanadaColin P. Rose, MD, PhD Department of Medicine McGill University Montréal, Quebec, CanadaPierre Biron, MD Department of Pharmacology (Retired) Faculty of Medicine Université de Montréal Montréal, Quebec, CanadaDisclosuresNone.