Key result
Fenofibrate fails to reduce coronary events versus placebo in patients with type 2 diabetes.
Why the study?
Patients with type 2 diabetes mellitus are at increased cardiovascular risk partly due to dyslipidaemia, and the effect of fenofibrate on cardiovascular events needed assessment.
Does fenofibrate 200 mg daily reduce coronary events in patients with type 2 diabetes mellitus not taking baseline statin therapy?
RCT (n=9,795)
Yes
Does fenofibrate 200 mg daily reduce coronary events in patients with type 2 diabetes mellitus not taking baseline statin therapy?
Hazard Ratio: 0.89 (95% CI 0.75–1.05)
Absolute Event Rate: 5.2% vs 5.9%
p-value: p=0.16
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“This 27% relative reduction in total CVD events with fenofibrate in type 2 diabetes patients with marked atherogenic dyslipidemia is of a similar order to that observed with statin treatment. Physicians can prevent one fatal or non-fatal cardiovascular event by treating only 23 of these patients over 5 years with fenofibrate.”
“The evidence base for fibrate use is much less certain, with conflicting results in the FIELD study, which was negative, and the diabetes subgroup of the VA-HIT study which was positive.”
“These findings on macrovascular disease build on earlier results of the FIELD trial showing clear benefits for patients with microvascular complications. Fenofibrate reduces the need for laser treatment in patients with diabetic disease in the small vessels of the eyes. It also reduces the risk of amputations resulting from disease in the small vessels of the limbs.”
In patients with type 2 diabetes, fenofibrate did not significantly reduce the primary composite of coronary events, although it did reduce total cardiovascular events and microvascular complications like retinopathy and albuminuria.
BACKGROUND: Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease, partly owing to dyslipidaemia, which can be amenable to fibrate therapy. We designed the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study to assess the effect of fenofibrate on cardiovascular disease events in these patients. METHODS: We did a multinational, randomised controlled trial with 9795 participants aged 50-75 years, with type 2 diabetes mellitus, and not taking statin therapy at study entry. After a placebo and a fenofibrate run-in phase, we randomly assigned patients (2131 with previous cardiovascular disease and 7664 without) with a total-cholesterol concentration of 3.0-6.5 mmol/L and a total-cholesterol/HDL-cholesterol ratio of 4.0 or more or plasma triglyceride of 1.0-5.0 mmol/L to micronised fenofibrate 200 mg daily (n=4895) or matching placebo (n=4900). Our primary outcome was coronary events (coronary heart disease death or non-fatal myocardial infarction); the outcome for prespecified subgroup analyses was total cardiovascular events (the composite of cardiovascular death, myocardial infarction, stroke, and coronary and carotid revascularisation). Analysis was by intention to treat. The study was prospectively registered (number ISRCTN 64783481). FINDINGS: Vital status was confirmed on all but 22 patients. Averaged over the 5 years' study duration, similar proportions in each group discontinued study medication (10% placebo vs 11% fenofibrate) and more patients allocated placebo (17%) than fenofibrate (8%; p<0.0001) commenced other lipid treatments, predominantly statins. 5.9% (n=288) of patients on placebo and 5.2% (n=256) of those on fenofibrate had a coronary event (relative reduction of 11%; hazard ratio [HR] 0.89, 95% CI 0.75-1.05; p=0.16). This finding corresponds to a significant 24% reduction in non-fatal myocardial infarction (0.76, 0.62-0.94; p=0.010) and a non-significant increase in coronary heart disease mortality (1.19, 0.90-1.57; p=0.22). Total cardiovascular disease events were significantly reduced from 13.9% to 12.5% (0.89, 0.80-0.99; p=0.035). This finding included a 21% reduction in coronary revascularisation (0.79, 0.68-0.93; p=0.003). Total mortality was 6.6% in the placebo group and 7.3% in the fenofibrate group (p=0.18). Fenofibrate was associated with less albuminuria progression (p=0.002), and less retinopathy needing laser treatment (5.2%vs 3.6%, p=0.0003). There was a slight increase in pancreatitis (0.5%vs 0.8%, p=0.031) and pulmonary embolism (0.7%vs 1.1%, p=0.022), but no other significant adverse effects. INTERPRETATION: Fenofibrate did not significantly reduce the risk of the primary outcome of coronary events. It did reduce total cardiovascular events, mainly due to fewer non-fatal myocardial infarctions and revascularisations. The higher rate of starting statin therapy in patients allocated placebo might have masked a moderately larger treatment benefit.
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A Keech (2005) conducted an RCT in type 2 diabetes mellitus (n=9,795). micronised fenofibrate vs. matching placebo was evaluated on coronary events (coronary heart disease death or non-fatal myocardial infarction) (HR 0.89, 95% CI 0.75-1.05, p=0.16). Fenofibrate did not significantly reduce the risk of coronary events compared to placebo in patients with type 2 diabetes (5.2% vs 5.9%; HR 0.89; 95% CI 0.75-1.05; p=0.16).
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