Studies find greater risk reduction following treatment of patients with dyslipidemia.
Patients who have type 2 diabetes are at high risk for cardiovascular disease. Although medications such as statins can help reduce this cardiovascular complication, it is still important to consider other treatment options that can further reduce this risk. One such class of medication is fibrates, which helps reduce plasma triglycerides and also helps increase HDL cholesterol. The American Diabetes Association guideline recommends statin and fibrate combination therapy in type 2 diabetes patients with triglycerides > 2.3 mmol/L and HDL less than 0.9 mmol/L. The goal of this study was to estimate the individual treatment effect of fenofibrate on major cardiovascular events in patients with type 2 diabetes. They analyzed the results from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD), the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trials, and the Second Manifestations of ARTerial disease (SMART) study.
In FIELD study, the effect of fenofibrate was evaluated in a total of 9,795 patients with type 2 diabetes who were not taking the statin therapy. The primary outcome for this study was coronary events, including myocardial infarction, and results showed that this occurred in 544 patients. FIELD also showed 11% reduction in coronary events in patients who were using fenofibrate compared to placebo. The ACCORD trial enrolled 5,518 patients with type 2 diabetes and studied the effect of combination therapy of fenofibrate with atorvastatin. According to the results, there was a 8% reduction in major cardiovascular events, including stroke, cardiovascular death, and myocardial infarction when patients used combination therapy. In the SMART study, a total of 1,829 patients with type 2 diabetes were studied and major cardiovascular events were observed in 334 patients.
The mean age for all three trials was 62.2 years and 66% of the enrolled participants were men. A total of 22%, 37%, and 66% of participants had a cardiovascular history in the FIELD, ACCORD, and SMART trials, respectively. The five-year major cardiovascular events risk for all three trials was 9.4% and 6.7% in patients with (N=, 3,918) and without dyslipidemia (N=13,224) , respectively. The median absolute risk reduction was 2.15% in patients with dyslipidemia and 0.22% in patients without dyslipidemia. Overall, it was found that more than half the patients with dyslipidemia had a substantial treatment effect.
Since patients with 2 diabetes have high risk of cardiovascular disease, it is important to place them on necessary treatment options even if it means having to take multiple medications.
Overtreatment is not desirable due to both side effects and cost. However, it is important that health care professionals understand that some patients might benefit from multi-drug therapy, and that benefits outweigh the harms, such as cost and side effects. Results found that patients with dyslipidemia had more treatment effects of fenofibrate than patients without dyslipidemia. It is important to consider though that patients with dyslipidemia had higher triglyceride levels and therefore increased cardiovascular disease risk. Few patients without dyslipidemia had good effects from fenofibrate therapy. Because of these results, it can be concluded that fenofibrate should be used as individualized treatment and based on clinical decision .
This study had few limitations, including the fact that the results of this study cannot be generalized to the entire population because patients in clinical trial setting have larger treatment benefit due to better adherence. Another limitation of this study was that the cutoffs of both triglycerides and HDL to define dyslipidemia were not established. The differences in this definition might not lead to generalizable results among the broad population.
- Because patients with type 2 diabetes have a high risk of cardiovascular disease, it is necessary to consider placing some patients on multiple medications, such as both statins and fibrates.
- The overall effect of fenofibrate treatment was observed largely in patients with dyslipidemia.
- The median major cardiovascular event risk was 6.7% in patients without dyslipidemia and 9.4% in patients with dyslipidemia with fenofibrate treatment.
Koopal C, Visseren F, Westerink J et al. Predicting the Effect of Fenofibrate on Cardiovascular Risk for Individual Patients With Type 2 Diabetes Mellitus. Diabetes Care 2018 Feb.
Vidhi Patel, Pharm. D. Candidate 2018, LECOM School of Pharmacy