Primary Prevention With Statin Therapy in the Elderly
2017; Lippincott Williams & Wilkins; Volume: 135; Issue: 20 Linguagem: Inglês
10.1161/circulationaha.117.028271
ISSN1524-4539
AutoresPaul M. Ridker, Eva Lonn, Nina P. Paynter, Robert J. Glynn, Salim Yusuf,
Tópico(s)Pharmaceutical Practices and Patient Outcomes
ResumoHomeCirculationVol. 135, No. 20Primary Prevention With Statin Therapy in the Elderly Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBPrimary Prevention With Statin Therapy in the ElderlyNew Meta-Analyses From the Contemporary JUPITER and HOPE-3 Randomized Trials Paul M Ridker, MD, Eva Lonn, MD, Nina P. Paynter, PhD, Robert Glynn, ScD and Salim Yusuf, MD Paul M RidkerPaul M Ridker From Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (P.M.R., N.P.P., R.G.); and the Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (E.L., S.Y.). Search for more papers by this author , Eva LonnEva Lonn From Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (P.M.R., N.P.P., R.G.); and the Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (E.L., S.Y.). Search for more papers by this author , Nina P. PaynterNina P. Paynter From Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (P.M.R., N.P.P., R.G.); and the Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (E.L., S.Y.). Search for more papers by this author , Robert GlynnRobert Glynn From Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (P.M.R., N.P.P., R.G.); and the Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (E.L., S.Y.). Search for more papers by this author and Salim YusufSalim Yusuf From Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (P.M.R., N.P.P., R.G.); and the Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (E.L., S.Y.). Search for more papers by this author Originally published6 Apr 2017https://doi.org/10.1161/CIRCULATIONAHA.117.028271Circulation. 2017;135:1979–1981Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2017: Previous Version 1 The use of statin therapy for secondary prevention is established in all age groups.1 However, in primary prevention, current cardiovascular guidelines in the United States and Canada describe the role for statin therapy in the elderly as uncertain.To examine this question, we performed a meta-analysis of age-specific outcome data from 2 recent primary prevention statin trials, JUPITER (Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin)2 and HOPE-3 (Heart Outcomes Prevention Evaluation).3 We combined new subgroup data from these contemporary trials using a fixed-effect meta-analysis with inverse variance weighting of the log hazard ratios by age group (<65, 65–<70, and ≥70 years) using the meta package in R (R version 3.2.3). The pooled treatment effect within each subgroup was estimated, as was the between-subgroup heterogeneity statistic, Q.The JUPITER trial, published in 2008, evaluated rosuvastatin 20 mg daily among 17 802 men and women free of cardiovascular disease with low-density lipoprotein cholesterol levels 2 mg/L.2 For the end point of hard atherosclerotic cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), the JUPITER trial overall reported a 47% reduction in risk (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.40–0.69; P<0.0001), as well as a 20% reduction in all-cause mortality (HR, 0.80; 95% CI, 0.67–0.97; P=0.02). As shown in the Figure (top), for the 5695 JUPITER participants ≥70 years of age, a comparable 39% reduction in risk was found for this combined cardiovascular end point (HR, 0.61; 95% CI, 0.43–0.86; P=0.004); a nonsignificant 20% reduction in all-cause mortality in this age strata (HR, 0.80; 95% CI, 0.62–1.0; P=0.09) was previously reported.4 These elderly participants, representing 32% of the total JUPITER population, suffered 55% of all the hard atherosclerotic cardiovascular events occurring in the trial. In JUPITER, effects were consistent across age groups, and a formal test for heterogeneity was nonsignificant. Rates of drug withdrawal in the rosuvastatin groups were 14.3%, 17.0%, and 21.6% among those <65, 65 to <70, and ≥70 years of age, respectively.Download figureDownload PowerPointFigure. Rosuvastatin in the JUPITER (Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) and HOPE-3 (Heart Outcomes Prevention Evaluation) primary prevention trials. A, Numbers of individuals at risk, incidence rates, and hazard ratios for nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death in the JUPITER2 and HOPE-33 primary prevention trials, stratified by age. B, Meta-analysis within age subgroups of the JUPITER2 and HOPE-33 primary prevention trials evaluating the effects of rosuvastatin on the composite end point of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death.The HOPE-3 trial, published in 2016, evaluated rosuvastatin 10 mg daily among 12 705 men and women free of cardiovascular disease who were at intermediate risk.3 For the identical end point of hard atherosclerotic cardiovascular events, the HOPE-3 trial overall reported a 24% reduction in risk (HR, 0.76; 95% CI, 0.64–0.91; P=0.002) and a 7% nonsignificant reduction in all-cause mortality (HR, 0.93; 95% CI, 0.80–1.08; P=0.32). As also shown in the Figure (top), for the 3086 HOPE-3 participants ≥70 years of age, a comparable nonsignificant 17% reduction in risk was found for the combined cardiovascular end point (HR, 0.83; 95% CI, 0.64–1.07; P=0.16), as well as a comparable nonsignificant 9% reduction in all-cause mortality (HR, 0.91; 95% CI, 0.73–1.13; P=0.38). In HOPE-3, those ≥70 years of age represented 24% of the total trial population yet suffered 43% of all the hard atherosclerotic cardiovascular events. As in JUPITER, observed effects in HOPE-3 were consistent across age groups, and a formal test for heterogeneity was nonsignificant. In HOPE-3, which had a longer average follow-up than JUPITER, rates of drug withdrawal in the rosuvastatin groups were 21.4%, 23.1%, and 29.1% among those <65, 65 to 70 years of age, respectively.In formal meta-analysis, a 26% relative risk reduction was observed for those >70 years for the end point of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death (HR, 0.74; 95% CI, 0.61–0.91; P=0.0048; Figure, bottom). For an expanded end point that also includes revascularization, effects were virtually identical in those >70 years of age (HR, 0.74; 95% CI, 0.61–0.89; P=0.0016). In neither of these analyses was evidence of heterogeneity by age observed (P=0.10 and 0.19, respectively).The much higher event rates in those ≥70 years of age, along with the comparable relative rate reductions, imply larger absolute rate reductions associated with statin treatment and hence smaller numbers needed to treat to prevent an event in older compared with younger people. These contemporary trials reinforce evidence from smaller numbers of elderly primary prevention patients enrolled in earlier statin trials.5Outcome data from JUPITER and HOPE-3 provide a starting point for discussions about statin use in primary prevention among the elderly. In our opinion, available data from existing trials support the use of statins in primary prevention among those ≥70 years of age. Our combined data do not, however, provide answers to all critical questions relevant for practice. Uncertainties remain with regard to hemorrhagic stroke, cognitive function, drug interactions, adherence, quality of life, and cost-effectiveness. Furthermore, despite the large sample sizes of JUPITER and HOPE-3, the number of individuals age ≥80 years is modest. Given the consistency of benefits for those >70 and <70 years of age, some benefit is likely even among those ≥80 years of age. This benefit, however, should be weighed against the potential for a modest impact on longevity and must take into account personal preferences with regard to the use of preventive measures.Paul M Ridker, MDEva Lonn, MDNina P. Paynter, PhDRobert Glynn, ScDSalim Yusuf, MDSources of FundingNo funding was used for this analysis. Both the JUPITER and HOPE-3 trials were originally supported by AstraZeneca.DisclosuresThe JUPITER trial was supported by in part by investigator-initiated research grants to Drs Ridker and Glynn from AstraZeneca. The HOPE-3 trial was supported in part by investigator-initiated research grants to Drs Yusuf and Lonn from AstraZeneca.FootnotesCirculation is available at http://circ.ahajournals.org.Correspondence to: Paul M Ridker, MD, Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital 900 Commonwealth Avenue, Boston, MA 02215. E-mail [email protected]References1. 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Vos E, Biron P and Rose C (2017) Letter by Vos et al Regarding Article, “Primary Prevention With Statin Therapy in the Elderly: New Meta-Analyses From the Contemporary JUPITER and HOPE-3 Randomized Trials”, Circulation, 10.1161/CIRCULATIONAHA.117.029008, 136:15, (1454-1455), Online publication date: 10-Oct-2017. May 16, 2017Vol 135, Issue 20 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.117.028271PMID: 28385949 Originally publishedApril 6, 2017 Keywordsanticholesteremic agentsclinical trial [publication type]agedPDF download Advertisement SubjectsPrimary Prevention
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