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The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression |
Lavigne PM, Karas RH |
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CRD summary This review concluded that niacin reduced cardiovascular disease events, and this might not be mediated by changes in high-density lipoprotein cholesterol levels. The authors’ conclusions reflect the evidence presented, but limitations to the search, a lack of reporting of review methods, and variation between trials, mean that the reliability of their conclusions is uncertain. Authors' objectives To assess the effectiveness of niacin in reducing the number of cardiovascular disease events. Searching MEDLINE was searched for studies, published in English, between January 1966 and December 2011. Search terms were reported. Bibliographies of retrieved articles were scanned. Study selection Eligible were randomised controlled trials (RCTs) of niacin, either alone or combined with other lipid-altering therapy, compared with a control group. Trials had to report cardiovascular disease events and have a minimum of six months of follow-up. The included trials were published between 1975 and 2011. Niacin treatment ranged from 0.25g to 4.3g. Most trials included additional treatment. Control groups varied, including placebo, any statin, and conventional therapy. The mean age of participants ranged from 42 to 67.5 years. The percentage of men ranged from 43 to 100. The mean body mass index, where reported, ranged from 26.4 to 31.2 km/m². The proportions of participants with hypertension and diabetes, and the average low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels at the start of the trial, varied between trials. It appears that more than one reviewer independently selected studies for inclusion. Assessment of study quality Methodological quality was assessed, using the Jadad scale (maximum 5). The authors did not state how many reviewers assessed quality. Data extraction Data were extracted to calculate odds ratios, and 95% confidence intervals, for the composite end point of any cardiovascular disease event (cardiac death, nonfatal myocardial infarction, hospitalisation for acute coronary syndrome, stroke, or revascularisation). Data were also extracted for major coronary heart disease events and stroke (ischaemic or haemorrhagic). Where there were multiple active treatment arms, analyses were limited to the two groups from each trial that were least confounded for niacin use. The authors did not state how many reviewers extracted the data. Methods of synthesis Pooled odds ratios and 95% confidence intervals were calculated, using a DerSimonian and Laird, random-effects model. Heterogeneity was assessed using Ι². Subgroup analyses were conducted to evaluate the effects of niacin as an addition to statin therapy, and for trials where lipid-modifying interventions differed only with respect to niacin therapy. Sensitivity analyses were conducted excluding two of the largest trials. A meta-regression was conducted to assess the relationship between differences in on-treatment high-density lipoprotein cholesterol level, and the size of the effect of niacin on cardiovascular disease events. Results of the review Eleven RCTs were included in the review, with 9,959 participants. Sample size ranged from 76 to 3,908 participants. All the included trials scored 3 or more points for quality; eight were reported to be double-blind. Follow-up ranged from six months to 6.2 years. Niacin was associated with significantly fewer cardiovascular disease events (OR 0.66, 95% CI 0.49 to 0.89; 11 RCTs; Ι²=59%) and major coronary heart disease events (OR 0.75, 0.59 to 0.96; 10 RCTs; Ι²=31%). There was no significant association between niacin therapy and stroke incidence (OR 0.88, 95% CI 0.5 to 1.54; seven RCTs; Ι²=41%). The meta regression (nine RCTs) found no significant association between the magnitude of the on-treatment high-density lipoprotein cholesterol differences between treatment arms, and the magnitude of the effect of niacin on the outcomes. The results of sensitivity and subgroup analyses were reported. Authors' conclusions Niacin reduced cardiovascular disease events; this might not be mediated by changes in high-density lipoprotein cholesterol levels. CRD commentary The review question was clear, with defined inclusion criteria. Only one database was searched, and inclusion was restricted to trials in English, introducing potential for language and publication bias. Trial quality was assessed and an overall composite score was broadly reported. It appears that methods to reduce reviewer error and bias were used for selecting studies, but it was unclear if they were used for data extraction and quality assessment. The methods of analysis appear to have been appropriate. The authors highlighted some limitations in the evidence, including the variation in population characteristics, dosing, and comparators between trials. The authors’ conclusions reflect the evidence presented, but limitations to the search, a lack of reporting of review methods, and variation between trials, mean that the reliability of their conclusions is uncertain. Implications of the review for practice and research Practice: The authors did not state any implications for practice. Research: The authors stated that further research was needed to clearly define the role of niacin, in practice. They referred to an ongoing trial. Bibliographic details Lavigne PM, Karas RH. The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression. Journal of the American College of Cardiology 2013; 61(4): 440-446 Indexing Status Subject indexing assigned by NLM MeSH Cardiovascular Diseases /complications /epidemiology /metabolism /prevention & Cholesterol, HDL /blood; Humans; Hypolipidemic Agents /therapeutic use; Incidence; Niacin /therapeutic use; Randomized Controlled Trials as Topic; Regression Analysis; Risk Assessment; Stroke /epidemiology /etiology /prevention & Treatment Outcome; control; control AccessionNumber 12013011847 Date bibliographic record published 13/03/2013 Date abstract record published 08/08/2013 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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