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Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis |
Preiss D, Sashasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, Cannon CP, Sabatine MS, Braunwald E, Kastelein JJ, de Lemos JA, Blazing MA, Pedersen TR, Tikkanen MJ, Sattar N, Ray KK |
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CRD summary The review concluded that intensive-dose statin therapy was associated with an increased risk of new-onset diabetes compared with moderate-dose statin therapy. The authors' conclusions reflect the evidence presented and appear likely to be reliable. Authors' objectives To investigate whether intensive-dose statin therapy was associated with increased risk of new-onset diabetes compared with moderate-dose statin therapy. Searching MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from January 1996 to April 2011 for studies published in English; search terms were reported. Study selection Randomised controlled trials (RCTs) that compared intensive-dose with moderate-dose statin therapy were eligible for inclusion. Trials had to include more than 1,000 adult participants and have identical mean follow-up periods in each group of at least one year. Development of diabetes (the main outcome) was defined in three ways by the review authors. Further outcomes (mostly relating to cardiovascular disease) were also pre-specified.
In included trials, simvastatin and atorvastatin were studied using intensive and moderate regimens, and pravastatin was studied using a moderate regimen. The included populations had a previous myocardial infarction, recent acute coronary syndrome, or stable coronary heart disease. The mean age of participants ranged from 58 to 64 years; fasting plasma glucose levels ranging from 99 to 104mg/dL (where reported).
Two reviewers independently selected studies for inclusion, with disagreements resolved by a third reviewer. Assessment of study quality Two reviewers independently evaluated trial quality using the following characteristics: randomisation; concealment of allocation; baseline similarity of treatment groups; eligibility criteria; blinding of patients, care providers and outcome assessors; availability of point estimates; and use of an intention-to-treat analysis. Trials were assigned a Delphi score of up to 9 points. Disagreements between reviewers were resolved by consensus. Data extraction Data were obtained from investigators in order to calculate odds ratios (ORs) or hazard ratios with 95% confidence intervals (CIs). Methods of synthesis Meta-analyses were performed to calculate pooled odd ratios, using a random-effects model. Numbers needed to treat or harm were also calculated. Heterogeneity was assessed using χ2 and I2.
Subgroup analyses explored the effect of body mass index (BMI), high-density lipoprotein cholesterol, triglycerides, age, fasting plasma glucose, type of illness (acute coronary syndrome versus stable coronary heart disease), and type of statin. Sensitivity analyses explored the effect of using non-standard definitions of diabetes.
Funnel plots and Egger's test were used to assess for publication bias. Results of the review Five RCTs (n=32,752 participants without diabetes at baseline) were included in the review. The median Delphi score was 9 (range 6 to 9). The mean follow-up period was 4.9 years.
New-onset diabetes was significantly more frequent in patients receiving intensive statin treatment compared with those receiving moderate statin treatment (OR 1.12, 95% CI 1.04 to 1.22; I2 = 0%; five RCTs). The number needed to harm was 498 per year.
Intensive statin treatment was associated with fewer first major cardiovascular events (OR 0.84, 95% CI 0.75 to 0.94; I2=74%; five RCTs). The number needed to treat was 155 per year. Intensive treatment was not associated with lower all-cause mortality or lower rates of non-cardiovascular death.
Most subgroup and sensitivity analyses yielded similar results to the main analyses; the risk of developing diabetes was higher in patients with triglycerides below median levels compared with patients with higher levels.
Further results were reported.
There was no evidence of publication bias. Authors' conclusions Intensive-dose statin therapy was associated with an increased risk of new-onset diabetes compared with moderate-dose statin therapy. CRD commentary The review addressed a clear question and was supported by appropriate inclusion criteria. Attempts to identify relevant studies only published in English were undertaken solely by searching electronic databases, so the possibility of language and/or publication bias could not be ruled out; relevant studies may have been missed, but the authors found no evidence for publication bias. Suitable methods were employed to reduce the risks of reviewer error and bias throughout the review.
Trial quality was assessed and was used in interpreting the results of the review (although few details of the assessment results were provided). Sufficient trial details were provided. Appropriate methods were used to pool data and to assess and investigate heterogeneity.
The authors' conclusions reflect the evidence presented and appear likely to be reliable. Implications of the review for practice and research Practice: The authors stated that clinicians should be vigilant for the development of diabetes in patients receiving intensive statin therapy.
Research: The authors stated that there was a need to investigate the impact of intensive statin therapy on glycaemic control and treatment requirements in patients with established diabetes. Bibliographic details Preiss D, Sashasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, Cannon CP, Sabatine MS, Braunwald E, Kastelein JJ, de Lemos JA, Blazing MA, Pedersen TR, Tikkanen MJ, Sattar N, Ray KK. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 2011; 305(24): 2556-2564 Indexing Status Subject indexing assigned by NLM MeSH Cardiovascular Diseases /epidemiology /prevention & Diabetes Mellitus /epidemiology; Dose-Response Relationship, Drug; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors /administration & Odds Ratio; Randomized Controlled Trials as Topic; Risk; control; dosage /adverse effects AccessionNumber 12011003815 Date abstract record published 29/06/2011 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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