Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: A meta-analysis

David Preiss, Sreenivasa Rao Kondapally Seshasai, Paul Welsh, Sabina A. Murphy, Jennifer E. Ho, David D. Waters, David A. DeMicco, Philip Barter, Christopher P. Cannon, Marc S. Sabatine, Eugene Braunwald, John J P Kastelein, James A de Lemos, Michael A. Blazing, Terje R. Pedersen, Matti J. Tikkanen, Naveed Sattar, Kausik K. Ray

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Abstract

Context: A recent meta-analysis demonstrated that statin therapy is associated with excess risk of developing diabetes mellitus. Objective: To investigate whether intensive-dose statin therapy is associated with increased risk of new-onset diabetes compared with moderate-dose statin therapy. Data Sources: We identified relevant trials in a literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (January 1, 1996, through March 31, 2011). Unpublished data were obtained from investigators. Study Selection: We included randomized controlled end-point trials that compared intensive-dose statin therapy with moderate-dose statin therapy and included more than 1000 participants who were followed up for more than 1 year. Data Extraction: Tabular data provided for each trial described baseline characteristics and numbers of participants developing diabetes and experiencing major cardiovascular events (cardiovascular death, nonfatal myocardial infarction or stroke, coronary revascularization). We calculated trial-specific odds ratios (ORs) for new-onset diabetes and major cardiovascular events and combined these using random-effects model meta-analysis. Between-study heterogeneity was assessed using the I2 statistic. Results: In 5 statin trials with 32 752 participants without diabetes at baseline, 2749 developed diabetes (1449 assigned intensive-dose therapy, 1300 assigned moderate-dose therapy, representing 2.0 additional cases in the intensive-dose group per 1000 patient-years) and 6684 experienced cardiovascular events (3134 and 3550, respectively, representing 6.5 fewer cases in the intensive-dose group per 1000 patient-years) over a weighted mean (SD) follow-up of 4.9 (1.9) years. Odds ratios were 1.12 (95% confidence interval [CI], 1.04-1.22; I2 = 0%) for new-onset diabetes and 0.84 (95% CI, 0.75-0.94; I2 = 74%) for cardiovascular events for participants receiving intensive therapy compared with moderate-dose therapy. As compared with moderate-dose statin therapy, the number needed to harm per year for intensive-dose statin therapy was 498 for new-onset diabetes while the number neededto treat per year for intensive-dose statin therapy was 155 for cardiovascular events. Conclusion: In a pooled analysis of data from 5 statin trials, intensive-dose statin therapy was associated with an increased risk of new-onset diabetes compared with moderate-dose statin therapy.

Original languageEnglish (US)
Pages (from-to)2556-2564
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume305
Issue number24
DOIs
StatePublished - Jun 22 2011

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Meta-Analysis
Therapeutics
Odds Ratio
Confidence Intervals
Information Storage and Retrieval
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Preiss, D., Seshasai, S. R. K., Welsh, P., Murphy, S. A., Ho, J. E., Waters, D. D., ... Ray, K. K. (2011). Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: A meta-analysis. JAMA - Journal of the American Medical Association, 305(24), 2556-2564. https://doi.org/10.1001/jama.2011.860

Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy : A meta-analysis. / Preiss, David; Seshasai, Sreenivasa Rao Kondapally; Welsh, Paul; Murphy, Sabina A.; Ho, Jennifer E.; Waters, David D.; DeMicco, David A.; Barter, Philip; Cannon, Christopher P.; Sabatine, Marc S.; Braunwald, Eugene; Kastelein, John J P; de Lemos, James A; Blazing, Michael A.; Pedersen, Terje R.; Tikkanen, Matti J.; Sattar, Naveed; Ray, Kausik K.

In: JAMA - Journal of the American Medical Association, Vol. 305, No. 24, 22.06.2011, p. 2556-2564.

Research output: Contribution to journalArticle

Preiss, D, Seshasai, SRK, Welsh, P, Murphy, SA, Ho, JE, Waters, DD, DeMicco, DA, Barter, P, Cannon, CP, Sabatine, MS, Braunwald, E, Kastelein, JJP, de Lemos, JA, Blazing, MA, Pedersen, TR, Tikkanen, MJ, Sattar, N & Ray, KK 2011, 'Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: A meta-analysis', JAMA - Journal of the American Medical Association, vol. 305, no. 24, pp. 2556-2564. https://doi.org/10.1001/jama.2011.860
Preiss, David ; Seshasai, Sreenivasa Rao Kondapally ; Welsh, Paul ; Murphy, Sabina A. ; Ho, Jennifer E. ; Waters, David D. ; DeMicco, David A. ; Barter, Philip ; Cannon, Christopher P. ; Sabatine, Marc S. ; Braunwald, Eugene ; Kastelein, John J P ; de Lemos, James A ; Blazing, Michael A. ; Pedersen, Terje R. ; Tikkanen, Matti J. ; Sattar, Naveed ; Ray, Kausik K. / Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy : A meta-analysis. In: JAMA - Journal of the American Medical Association. 2011 ; Vol. 305, No. 24. pp. 2556-2564.
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abstract = "Context: A recent meta-analysis demonstrated that statin therapy is associated with excess risk of developing diabetes mellitus. Objective: To investigate whether intensive-dose statin therapy is associated with increased risk of new-onset diabetes compared with moderate-dose statin therapy. Data Sources: We identified relevant trials in a literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (January 1, 1996, through March 31, 2011). Unpublished data were obtained from investigators. Study Selection: We included randomized controlled end-point trials that compared intensive-dose statin therapy with moderate-dose statin therapy and included more than 1000 participants who were followed up for more than 1 year. Data Extraction: Tabular data provided for each trial described baseline characteristics and numbers of participants developing diabetes and experiencing major cardiovascular events (cardiovascular death, nonfatal myocardial infarction or stroke, coronary revascularization). We calculated trial-specific odds ratios (ORs) for new-onset diabetes and major cardiovascular events and combined these using random-effects model meta-analysis. Between-study heterogeneity was assessed using the I2 statistic. Results: In 5 statin trials with 32 752 participants without diabetes at baseline, 2749 developed diabetes (1449 assigned intensive-dose therapy, 1300 assigned moderate-dose therapy, representing 2.0 additional cases in the intensive-dose group per 1000 patient-years) and 6684 experienced cardiovascular events (3134 and 3550, respectively, representing 6.5 fewer cases in the intensive-dose group per 1000 patient-years) over a weighted mean (SD) follow-up of 4.9 (1.9) years. Odds ratios were 1.12 (95{\%} confidence interval [CI], 1.04-1.22; I2 = 0{\%}) for new-onset diabetes and 0.84 (95{\%} CI, 0.75-0.94; I2 = 74{\%}) for cardiovascular events for participants receiving intensive therapy compared with moderate-dose therapy. As compared with moderate-dose statin therapy, the number needed to harm per year for intensive-dose statin therapy was 498 for new-onset diabetes while the number neededto treat per year for intensive-dose statin therapy was 155 for cardiovascular events. Conclusion: In a pooled analysis of data from 5 statin trials, intensive-dose statin therapy was associated with an increased risk of new-onset diabetes compared with moderate-dose statin therapy.",
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T1 - Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy

T2 - A meta-analysis

AU - Preiss, David

AU - Seshasai, Sreenivasa Rao Kondapally

AU - Welsh, Paul

AU - Murphy, Sabina A.

AU - Ho, Jennifer E.

AU - Waters, David D.

AU - DeMicco, David A.

AU - Barter, Philip

AU - Cannon, Christopher P.

AU - Sabatine, Marc S.

AU - Braunwald, Eugene

AU - Kastelein, John J P

AU - de Lemos, James A

AU - Blazing, Michael A.

AU - Pedersen, Terje R.

AU - Tikkanen, Matti J.

AU - Sattar, Naveed

AU - Ray, Kausik K.

PY - 2011/6/22

Y1 - 2011/6/22

N2 - Context: A recent meta-analysis demonstrated that statin therapy is associated with excess risk of developing diabetes mellitus. Objective: To investigate whether intensive-dose statin therapy is associated with increased risk of new-onset diabetes compared with moderate-dose statin therapy. Data Sources: We identified relevant trials in a literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (January 1, 1996, through March 31, 2011). Unpublished data were obtained from investigators. Study Selection: We included randomized controlled end-point trials that compared intensive-dose statin therapy with moderate-dose statin therapy and included more than 1000 participants who were followed up for more than 1 year. Data Extraction: Tabular data provided for each trial described baseline characteristics and numbers of participants developing diabetes and experiencing major cardiovascular events (cardiovascular death, nonfatal myocardial infarction or stroke, coronary revascularization). We calculated trial-specific odds ratios (ORs) for new-onset diabetes and major cardiovascular events and combined these using random-effects model meta-analysis. Between-study heterogeneity was assessed using the I2 statistic. Results: In 5 statin trials with 32 752 participants without diabetes at baseline, 2749 developed diabetes (1449 assigned intensive-dose therapy, 1300 assigned moderate-dose therapy, representing 2.0 additional cases in the intensive-dose group per 1000 patient-years) and 6684 experienced cardiovascular events (3134 and 3550, respectively, representing 6.5 fewer cases in the intensive-dose group per 1000 patient-years) over a weighted mean (SD) follow-up of 4.9 (1.9) years. Odds ratios were 1.12 (95% confidence interval [CI], 1.04-1.22; I2 = 0%) for new-onset diabetes and 0.84 (95% CI, 0.75-0.94; I2 = 74%) for cardiovascular events for participants receiving intensive therapy compared with moderate-dose therapy. As compared with moderate-dose statin therapy, the number needed to harm per year for intensive-dose statin therapy was 498 for new-onset diabetes while the number neededto treat per year for intensive-dose statin therapy was 155 for cardiovascular events. Conclusion: In a pooled analysis of data from 5 statin trials, intensive-dose statin therapy was associated with an increased risk of new-onset diabetes compared with moderate-dose statin therapy.

AB - Context: A recent meta-analysis demonstrated that statin therapy is associated with excess risk of developing diabetes mellitus. Objective: To investigate whether intensive-dose statin therapy is associated with increased risk of new-onset diabetes compared with moderate-dose statin therapy. Data Sources: We identified relevant trials in a literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (January 1, 1996, through March 31, 2011). Unpublished data were obtained from investigators. Study Selection: We included randomized controlled end-point trials that compared intensive-dose statin therapy with moderate-dose statin therapy and included more than 1000 participants who were followed up for more than 1 year. Data Extraction: Tabular data provided for each trial described baseline characteristics and numbers of participants developing diabetes and experiencing major cardiovascular events (cardiovascular death, nonfatal myocardial infarction or stroke, coronary revascularization). We calculated trial-specific odds ratios (ORs) for new-onset diabetes and major cardiovascular events and combined these using random-effects model meta-analysis. Between-study heterogeneity was assessed using the I2 statistic. Results: In 5 statin trials with 32 752 participants without diabetes at baseline, 2749 developed diabetes (1449 assigned intensive-dose therapy, 1300 assigned moderate-dose therapy, representing 2.0 additional cases in the intensive-dose group per 1000 patient-years) and 6684 experienced cardiovascular events (3134 and 3550, respectively, representing 6.5 fewer cases in the intensive-dose group per 1000 patient-years) over a weighted mean (SD) follow-up of 4.9 (1.9) years. Odds ratios were 1.12 (95% confidence interval [CI], 1.04-1.22; I2 = 0%) for new-onset diabetes and 0.84 (95% CI, 0.75-0.94; I2 = 74%) for cardiovascular events for participants receiving intensive therapy compared with moderate-dose therapy. As compared with moderate-dose statin therapy, the number needed to harm per year for intensive-dose statin therapy was 498 for new-onset diabetes while the number neededto treat per year for intensive-dose statin therapy was 155 for cardiovascular events. Conclusion: In a pooled analysis of data from 5 statin trials, intensive-dose statin therapy was associated with an increased risk of new-onset diabetes compared with moderate-dose statin therapy.

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