Striving to LDL-c <70 mg/dL beneficial for high-risk diabetic retinopathy patients with too high cholesterol

ESC 2017 Japanese EMPATHY study shows less cerebral and possibly cardiac events with more intensive statin treatment in high-risk diabetics with retinopathy.

Japanese study questions benefit of treat-to-target statin therapy in diabetic retinopathy(EMPATHY)

Presented at the ESC congress 2017 by: Hiroshi Itoh (Tokyo, Japan)

Background

There is limited evidence about the optimal treatment regime with statins in patients with diabetes. Prior studies included only a few diabetic patients or were compared with placebo (CARDS). Diabetics with retinopathy have a higher risk on cardiovascular events compared to diabetics without retinopathy.

Therefore, the Japanese EMPATHY trial investigated a treat-to-target protocol with statins including intensive treatment in 5.042 diabetic patients with hypercholesterolemia and retinopathy. Based on different treatment protocols between Japan, Europe and the US, an LDL-c treatment target of <70 mg/dL (ADA/ACC 2008, intensive arm) and 100-120 mg/dL (JAS 2007, standard arm) were chosen. Median follow-up was 37 months.

Main results

• There was no difference between both treatment arms of the primary endpoint (cardiovascular events or death: HR 0.84, 95% CI 0.67-1.07, P=0.15).
• However, there were more cerebral events with the standard protocol (secondary endpoint): HR 0.52, 95% CI 0.31-0.88, P=0.01). There was no difference in number of other secondary cardiac, renal or vascular events.
• Kaplan-meier analyses showed an increase in stroke events (cerebral infarction, cerebral hemmoraghe, subarchnoid hemmoragh) with the standard protocol (HR 0.64, 95% CI 0.40-1.01, P=0.05) as well as cerebral infarction (HR 0.54, 95% CI 0.32-0.90, P=0.02).
• The frequency adverse events was increased using the intensive protocol, but most were mild (10.1% vs 6.7%, P<0.001).
• As LDL-c-lowering in the cohort was lower than expected, a post-hoc analysis was performed including only patients that reached their LDL-c target on average, or at their last visit. This analysis did show a difference of the primary endpoint between both treatment arms, in favor of intensive treated patients (last visit LDL-c target reached HR 0.43, 95% CI 0.27-0.68, P<0.001). The low effectivity may thus explain the absence of difference in primary endpoints between both arms in the total cohort.

Conclusion

Striving to an LDL-c <70 mg/dL in high-risk diabetic patients with hypercholesterolemia and retinopathy seems to result in a clinical benefit for these patients. This needs further investigation.

During the discussion at the press conference, Itoh mentioned that about halve of patients did not reach their LDL-c target in the study. This is a result of the insurance system in Japan, leading to high costs for patients in the intensive treatment arm. Patients in the standard arm were possible not treated long enough. In addition, he stated in a press release that the number of cardiac events were low in the study. There were more cerebral than cardiac events, something that is typical for Asian populations.

- Our reporting is based on the information provided at the ESC congress -