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Colchicine for prevention of cardiovascular events.

ABSTRACT: BACKGROUND:Colchicine is an anti-inflammatory drug that is used for a wide range of inflammatory diseases. Cardiovascular disease also has an inflammatory component but the effects of colchicine on cardiovascular outcomes remain unclear. Previous safety analyses were restricted to specific patient populations. OBJECTIVES:To evaluate potential cardiovascular benefits and harms of a continuous long-term treatment with colchicine in any population, and specifically in people with high cardiovascular risk. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ClinicalTrials.gov, WHO International Clinical Trials Registry, citations of key papers, and study references in January 2015. We also contacted investigators to gain unpublished data. SELECTION CRITERIA:Randomised controlled trials (parallel-group or cluster design or first phases of cross-over studies) comparing colchicine over at least six months versus any control in any adult population. DATA COLLECTION AND ANALYSIS:Primary outcomes were all-cause mortality, myocardial infarction, and adverse events. Secondary outcomes were cardiovascular mortality, stroke, heart failure, non-scheduled hospitalisations, and non-scheduled cardiovascular interventions. We conducted predefined subgroup analyses, in particular for participants with high cardiovascular risk. . MAIN RESULTS:We included 39 randomised parallel-group trials with 4992 participants. Colchicine had no effect on all-cause mortality (RR 0.94, 95% CI 0.82 to 1.09; participants = 4174; studies = 30; I² = 27%; moderate quality of evidence). There is uncertainty surrounding the effect of colchicine in reducing cardiovascular mortality (RR 0.34, 95% CI 0.09 to 1.21, I² = 9%; participants = 1132; studies = 7; moderate quality of evidence). Colchicine reduced the risk for total myocardial infarction (RR 0.20, 95% CI 0.07 to 0.57; participants = 652; studies = 2; moderate quality of evidence). There was no effect on total adverse events (RR 1.52, 95% CI 0.93 to 2.46; participants = 1313; studies = 11; I² = 45%; very low quality of evidence) but gastrointestinal intolerance was increased (RR 1.83, 95% CI 1.03 to 3.26; participants = 1258; studies = 11; I² = 74%; low quality of evidence). Colchicine showed no effect on heart failure (RR 0.62, 95% CI 0.10 to 3.88; participants = 462; studies = 3; I² = 45%; low quality of evidence) and no effect on stroke (RR 0.38, 95% CI 0.09 to 1.70; participants = 874; studies = 3; I² = 45%; low quality of evidence). Reporting of serious adverse events was inconsistent; no event occurred over 824 patient-years (4 trials). Effects on other outcomes were very uncertain. Summary effects of RCTs specifically focusing on participants with high cardiovascular risk were similar (4 trials; 1230 participants). AUTHORS' CONCLUSIONS:There is much uncertainty surrounding the benefits and harms of colchicine treatment. Colchicine may have substantial benefits in reducing myocardial infarction in selected high-risk populations but uncertainty about the size of the effect on survival and other cardiovascular outcomes is high, especially in the general population from which most of the studies in our review were drawn. Colchicine is associated with gastrointestinal side effects based on low-quality evidence. More evidence from large-scale randomised trials is needed.

SUBMITTER: Hemkens LG

PROVIDER: S-EPMC6956668 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Colchicine for prevention of cardiovascular events.

Hemkens Lars G LG Ewald Hannah H Gloy Viktoria L VL Arpagaus Armon A Olu Kelechi K KK Nidorf Mark M Glinz Dominik D Nordmann Alain J AJ Briel Matthias M

The Cochrane database of systematic reviews 20160127 1

<h4>Background</h4>Colchicine is an anti-inflammatory drug that is used for a wide range of inflammatory diseases. Cardiovascular disease also has an inflammatory component but the effects of colchicine on cardiovascular outcomes remain unclear. Previous safety analyses were restricted to specific patient populations.<h4>Objectives</h4>To evaluate potential cardiovascular benefits and harms of a continuous long-term treatment with colchicine in any population, and specifically in people with hig ...[more]

PMID: 26816301

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Project description:ImportanceIn the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial, the anti-inflammatory monoclonal antibody canakinumab significantly reduced the risk of recurrent cardiovascular events in patients with previous myocardial infarction (MI) and high-sensitivity C-reactive protein (hs-CRP) levels of 2 mg/L or greater.ObjectiveTo estimate the cost-effectiveness of adding canakinumab to standard of care for the secondary prevention of major cardiovascular events over a range of potential prices.Design, setting, and participantsA state-transition Markov model was constructed to estimate costs and outcomes over a lifetime horizon by projecting rates of recurrent MI, coronary revascularization, infection, and lung cancer with and without canakinumab treatment. We used a US health care sector perspective, and the base case used the current US market price of canakinumab of $73 000 per year. A hypothetical cohort of patients after MI aged 61 years with an hs-CRP level of 2 mg/L or greater was constructed.InterventionsCanakinumab, 150 mg, administered every 3 months plus standard of care compared with standard of care alone.Main outcomes and measuresLifetime costs and quality-adjusted life-years (QALYs), discounted at 3% annually.ResultsAdding canakinumab to standard of care increased life expectancy from 11.31 to 11.36 years, QALYs from 9.37 to 9.50, and costs from $242 000 to $1 074 000, yielding an incremental cost-effectiveness ratio of $6.4 million per QALY gained. The price would have to be reduced by more than 98% (to $1150 per year or less) to meet the $100 000 per QALY willingness-to-pay threshold. These results were generally robust across alternative assumptions, eg, substantially lower health-related quality of life after recurrent cardiovascular events, lower infection rates while receiving canakinumab, and reduced all-cause mortality while receiving canakinumab. Including a potential beneficial effect of canakinumab on lung cancer incidence improved the incremental cost-effectiveness ratio to $3.5 million per QALY gained. A strategy of continuing canakinumab selectively in patients with reduction in hs-CRP levels to less than 2 mg/L would have a cost-effectiveness ratio of $819 000 per QALY gained.Conclusions and relevanceCanakinumab is not cost-effective at current US prices for prevention of recurrent cardiovascular events in patients with a prior MI. Substantial price reductions would be needed for canakinumab to be considered cost-effective.

Project description:BackgroundInfluenza is a common respiratory infection that may cause complications, including cardiovascular events. Influenza illness has been shown to double the risk of myocardial infarction, with the highest risk among patients with established cardiovascular disease. Vaccination against influenza has been associated with reductions in myocardial infarction, cerebrovascular disease, and death.ObjectiveTo evaluate the evidence for influenza vaccination as a strategy to reduce cardiovascular events specifically in patients with established cardiovascular disease.Data sources and study selectionMEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched with the terms "influenza vaccine" and "cardiovascular disease". Included in this review were randomized controlled trials (RCTs), nonrandomized studies, and meta-analyses that compared influenza vaccination against control in patients with established cardiovascular disease and that reported clinically meaningful cardiovascular outcomes (defined as cardiovascular death, myocardial infarction, and stroke).Data extraction and synthesisThe search yielded 10 studies (3 nonrandomized studies, 5 RCTs, and 2 meta-analyses). The nonrandomized studies and the RCTs had inconsistent results with respect to cardiovascular death and adverse cardiovascular events. The 2 meta-analyses, which included the same 4 RCTs involving patients with established cardiovascular disease, showed that the influenza vaccine reduced cardiovascular death by about 50% relative to control. Vaccination also reduced major cardiovascular events by about 43%; the reduction was greater (54%) in the subgroup of patients with recent (≤ 1 year) acute coronary syndrome. However, these data are potentially confounded by small sample sizes, low event rates, and variable outcome reporting. There was also high clinical heterogeneity among the studies, which may not reflect contemporary practice.ConclusionsGiven the limitations of these data, it is unclear whether the cardiovascular benefit with influenza vaccination in patients with cardiovascular disease is a true effect. Nevertheless, because of the potential benefit and the low risk of adverse events, the annual influenza vaccine should be recommended for all patients with established cardiovascular disease.

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Project description:BackgroundThe role of aspirin in reducing lipoprotein(a)-mediated atherothrombotic events in primary prevention is not established.ObjectivesThis study sought to assess whether low-dose aspirin benefits individuals with elevated plasma lipoprotein(a)-associated genotypes in the setting of primary prevention.MethodsThe study analyzed 12,815 genotyped individuals ≥70 years of age of European ancestry and without prior cardiovascular disease events enrolled in the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial of 100 mg/d aspirin. We defined lipoprotein(a)-associated genotypes using rs3798220-C carrier status and quintiles of a lipoprotein(a) genomic risk score (LPA-GRS). We tested for interaction between genotypes and aspirin allocation in Cox proportional hazards models for incidence of major adverse cardiovascular events (MACE) and clinically significant bleeding. We also examined associations in the aspirin and placebo arms of the trial separately.ResultsDuring a median 4.7 years (IQR: 3.6-5.7 years) of follow-up, 435 MACE occurred, with an interaction observed between rs3798220-C and aspirin allocation (P = 0.049). rs3798220-C carrier status was associated with increased MACE risk in the placebo group (HR: 1.90; 95% CI: 1.11-3.24) but not in the aspirin group (HR: 0.54; 95% CI: 0.17-1.70). High LPA-GRS (vs low) was associated with increased MACE risk in the placebo group (HR: 1.70; 95% CI: 1.14-2.55), with risk attenuated in the aspirin group (HR: 1.41; 95% CI: 0.90-2.23), but the interaction was not statistically significant. In all participants, aspirin reduced MACE by 1.7 events per 1,000 person-years and increased clinically significant bleeding by 1.7 events per 1,000 person-years. However, in the rs3798220-C and high LPA-GRS subgroups, aspirin reduced MACE by 11.4 and 3.3 events per 1,000 person-years respectively, without significantly increased bleeding risk.ConclusionsAspirin may benefit older individuals with elevated lipoprotein(a) genotypes in primary prevention.

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Colchicine for prevention of cardiovascular events.

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Colchicine for prevention of cardiovascular events.

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