C. Raina Elley, MBChB, PhD; Vanessa Selak, MBChB, MPH
In patients with type 2 diabetes who are at high cardiovascular (CV) risk, does the combination of fenofibrate and simvastatin reduce major CV events more than simvastatin alone?
Randomized placebo-controlled trial (Action to Control Cardiovascular Risk in Diabetes lipid trial [ACCORD Lipid]). ClinicalTrials.gov NCT00000620.
Blinded (patients, clinicians, data collectors, and outcome adjudication committee).*
Mean 4.7 years.
77 centers in the USA and Canada.
5518 patients 40 to 79 years of age (mean age 62 y, 69% men) who had type 2 diabetes; glycated hemoglobin level ≥ 7.5%; CV disease or, if ≥ 55 years of age, risk factors for CV disease; low-density-lipoprotein (LDL) cholesterol level 1.55 to 4.65 mmol/L (60 to 180 mg/dL); high-density-lipoprotein (HDL) cholesterol level < 1.42 mmol/L (55 mg/dL) for women and African Americans or < 1.29 mmol/L (50 mg/dL) for other groups; and triglyceride level < 8.5 mmol/L (750 mg/dL) without lipid therapy or < 4.5 mmol/L (400 mg/dL) with lipid therapy.
Open-label simvastatin (dose according to current national lipid guidelines, mean 22 mg/d) for all patients, plus fenofibrate, 160 mg/d or dose adjusted according to estimated glomerular filtration rate (n = 2765), or placebo (n = 2753). All patients were also randomized to intensive or standard glycemic control in a 2 × 2 factorial manner.
Included a composite of major CV events (myocardial infarction, stroke, or CV death), composite of major coronary disease events (fatal coronary event, myocardial infarction, or unstable angina), death from any cause, and adverse events. The trial had 87% power to detect a 20% relative reduction in the primary outcome (α = 0.05).
99% (intention-to-treat analysis).
Groups did not differ for major CV events or death (Table). Fenofibrate reduced the composite of major CV events in men (11% vs 13%) but not in women (9.1% vs 6.6%) (P for interaction 0.01), and in the 17% of patients with triglyceride levels ≥ 204 mg/dL and HDL levels ≤ 34 mg/dL (12% vs 17%) but not in other patients (10% vs 10%) (P for interaction 0.06). Patients in the fenofibrate group were more likely than those in the placebo group to have elevated serum creatinine levels (34% vs 18%) but less likely to have microalbuminuria or macroalbuminuria. Groups did not differ for serious adverse events attributable to lipid medications, or for myopathy/myositis/rhabdomyolysis.
In patients with type 2 diabetes at high cardiovascular (CV) risk, the combination of fenofibrate and simvastatin did not reduce major CV events more than simvastatin alone.
Fenofibrate vs placebo in combination with simvastatin to prevent cardiovascular (CV) events in type 2 diabetes†
†NS = not significant; other abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from data in article.
‡Myocardial infarction, stroke, or CV death.
§Fatal coronary event, myocardial infarction, or unstable angina.
Elley CR, Selak V. Fenofibrate plus simvastatin did not prevent major CV events more than simvastatin alone in type 2 diabetes. Ann Intern Med. 2010;153:JC1–5. doi: 10.7326/0003-4819-153-2-201007200-02005
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Published: Ann Intern Med. 2010;153(2):JC1-5.
Cardiology, Coronary Risk Factors, Diabetes, Dyslipidemia, Endocrine and Metabolism.
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