Combination a better bet than monotherapy in mixed dyslipidemia

The combination of pitavastatin and fenofibrate appears to have superior effect on non-high-density lipoprotein cholesterol (non–HDL-C), as well as other lipids, compared with a statin alone in high-risk patients with mixed dyslipidemia, according to a study.

“Moreover, the combination therapy was well tolerated, with a safety profile similar to that of monotherapy,” the investigators said.

In total, 343 Korean patients (average age, 62 years; average body mass index, 26 kg/m²) at high risk of cardiovascular disease were randomly assigned to receive pitavastatin 2 mg alone (n=171) or with fenofibrate 160 mg (n=172) after a run in period. All patients had a controlled low-density lipoprotein cholesterol (LDL-C; <100 mg/dL) and triglyceride (TG; 150–500 mg/dL) levels at baseline.

After 8 weeks of treatment, combination therapy led to a significantly greater reduction in the primary endpoint of non–HDL-C (–7.38 percent vs 5.07 percent with monotherapy; difference, −12.45 percent, 95 percent confidence interval, −17.18 to −7.72; p<0.001). [Clin Ther 2020;doi:10.1016/j.clinthera.2020.08.002]

The combination therapy also showed superior improvements in other lipids, such as HDL-C and apolipoproteins. While the LDL-C level was controlled similarly in the two groups, others that proved difficult to control on pitavastatin alone decreased significantly on the combination, as follows: total cholesterol (TC; –0.18 percent vs 3.60 percent), TG (–39.66 percent vs –2.09 percent), very–LDL-C (–39.66 percent vs 2.07 percent), and TC/HDL-C (–14.48 percent vs 3.55 percent).

Results for inflammatory markers such as fibrinogen (–10.23 percent vs 4.43 percent), high-sensitivity C-reactive protein (–16.67 percent vs 0 percent), and remnant cholesterol (–38.36 percent vs 1.22 percent), which is one of the parameters of atherogenic lipoprotein, likewise favoured the combination.

Finally, significantly more patients who received add-on fenofibrate than pitavastatin alone achieved the targets for non–HDL-C (88.30 percent vs 77.98 percent; p=0.0110) and apolipoprotein B (78.94 percent vs 68.45 percent; p=0.0021).

Adverse drug reactions occurred in 3.49 percent of patients (6/172) in the combination group and in 1.75 percent (3/171) in the monotherapy group.

“The current study did not report any adverse reactions additional to those already associated with fenofibrate therapy,” the investigators noted.

In patients with dyslipidaemia, statins are used as the standard for reducing CVD-related morbidity, including atherosclerosis. Pitavastatin is a moderate-intensity lipid-lowering medication with established efficacy and tolerability in Asian populations. On the other hand, fenofibrate is known to reduce the blood concentrations of TG and very–LDL-C, while increasing the HDL-C level. [Circulation 2019;139:e1046-e1081; Jpn Clin Med 2011;2:57-66; Am J Cardiol 2010;106:787-792]

“In patients with LDL-C controlled on pitavastatin, the addition of fenofibrate therapy further regulated the level of LDL-C and other blood lipids known to be CVD risk factors,” the investigators pointed out.

Therefore, pitavastatin–fenofibrate combination therapy represents an effective and well tolerated treatment in high-risk patients with mixed dyslipidaemia, they added.