Clinical Question:
In patients with type 2 diabetes, does fenofibrate prevent coronary events?
Bottom Line:
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.
Reference:
Keech A, Simes RJ, Barter P, et al, for the FIELD study investigators.
Effects of long-term fenofibrate therapy on cardiovascular events in 9795
people with type 2 diabetes mellitus (the FIELD study): randomised
controlled trial. Lancet 2005;366:1849-61.
Study Design:
Randomized controlled trial (double-blinded)
Synopsis:
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. They 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). 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. |