Document Detail

Moving beyond JUPITER: will inhibiting inflammation reduce vascular event rates?
MedLine Citation:
PMID:  23225175     Owner:  NLM     Status:  MEDLINE    
The recent JUPITER trial demonstrated that potent statin therapy reduces by 50 % the risk of heart attack and stroke among men and women with low levels of low-density lipoprotein (LDL)-cholesterol who are at increased vascular risk due to elevated levels of C-reactive protein (CRP), a biomarker of low-grade systemic inflammation. In JUPITER, both absolute risk and the absolute risk reduction with statin therapy were related to the level of CRP, whereas no such relationship was observed for LDL-C. Further, on-treatment levels of CRP and LDL-C were independently associated with residual risk, and the genetic determinants of statin-induced CRP reduction differed from the genetic determinants of statin-induced LDL reduction. Despite these data, it is impossible in any statin trial to establish whether the clinical benefits of treatment are due to LDL-reduction alone, to inflammation inhibition, or to a combination of both processes. To address the hypothesis that lowering inflammation will lower vascular event rates, two large-scale placebo controlled trials using targeted anti-inflammatory agents for the secondary prevention of myocardial infarction have been initiated. The first trial, the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS), is evaluating whether interleukin-1β (IL-1β) inhibition as compared to placebo can reduce rates of recurrent myocardial infarction, stroke, and cardiovascular death among stable coronary artery disease patients who remain at high vascular risk due to persistent elevations of hsCRP (≥ 2 mg/L), despite contemporary secondary prevention strategies. The second trial, the Cardiovascular Inflammation Reduction Trial (CIRT) has been funded by the National Heart, Lung, and Blood Institute (NHLBI) and will evaluate whether low dose methotrexate (target dose 20 mg/week) as compared to placebo will reduce major vascular events among a group of post-myocardial infarction patients with either diabetes or metabolic syndrome, groups known to have high risk on the basis of a persistent pro-inflammatory response. Together, CANTOS and CIRT represent a core test of the inflammation hypothesis of atherothrombosis and the exploration of a potential new phase for cardiovascular therapeutics.
Paul M Ridker
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current atherosclerosis reports     Volume:  15     ISSN:  1534-6242     ISO Abbreviation:  Curr Atheroscler Rep     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-05-21     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  100897685     Medline TA:  Curr Atheroscler Rep     Country:  United States    
Other Details:
Languages:  eng     Pagination:  295     Citation Subset:  IM    
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MeSH Terms
Cardiovascular Diseases* / blood,  epidemiology,  prevention & control
Cholesterol, LDL / blood*,  drug effects
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Inflammation / blood,  drug therapy*
Morbidity / trends
Randomized Controlled Trials as Topic*
Risk Factors
World Health
Grant Support
Reg. No./Substance:
0/Cholesterol, LDL; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors

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