The effect of fibrate-statin combination therapy on cardiovascular events: a retrospective cohort analysis

Objective: To investigate the long-term efficacy of fibrate-statin combination therapy on cardiovascular events as opposed to lipid levels. Research design and methods: A retrospective analysis was performed of patients attending metabolic clinics. Cardiovascular risk factor, baseline and final lipid data and details of concomitant drug therapies were gathered on all subjects. Outcome measure: The occurrence of major adverse cardiovascular events (MACE) was recorded and major prognostic factors associated with outcome determined. Results: A total of 318 patients with mixed dyslipidaemia were identified on fibrate-statin therapy. Follow-up comprised an average of 7.5 years totalling 2400 patient-years. Patients were 78% male aged 62 years and 68% had evidence of previous cardiovascular disease (CVD). Smoking was present in 17%, hypertension in 41% and 32% had established diabetes. Baseline lipid parameters were total cholesterol (TC) 6.84 mmol/L, triglycerides (TG) 6.09 mmol/L and HDL-C 1.09 mmol/L. Fibrate-statin combination reduced TC by 27% to 4.64 mmol/L, TG by a median 42% to 2.33 mmol/L and increased HDL-C by 21% to 1.22 mmol/L. Non-HDL-C was reduced by 35% and apolipoprotein B by 17%. MACE occurred in 25%. Logistic regression analysis showed that patients with MACE had higher initial TC (7.02 vs. 6.80 mmol/L; p = 0.002), established CVD (65 vs. 57%; p = 0.05) and a lesser atherogenic index response (31 vs. 38%; p = 0.008). Cox regression analysis showed that age (p 0.002), and previous CVD (p < 0.001) were determinants of outcome allied either to reduction in TG (p = 0.009), TC (p = 0.04) and increase in HDL-C (p = 0.05) or change in TG (p = 0.002) and non-HDL-C (p = 0.01). Conclusion: Fibrate-statin therapy in a population with mixed dyslipidaemia resulted in an improved lipid profile with few side-effects. Consistent with its effects, decreases in TG allied with modest decrease in cholesterol and an increase in HDL-C, were associated with better prognosis.