| Abstract |
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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