Effects of High Density Lipoprotein Raising Therapies on Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus, with or without Renal Impairment: The Action to Control Cardiovascular Risk in Diabetes Study.

BACKGROUND: The role of high density lipoprotein-raising interventions in addition to statin therapy in patients with diabetes remains controversial. Chronic kidney disease (CKD) is a strong modifier of cardiovascular (CV) outcomes. We therefore investigated the impact of CKD status at baseline on outcomes in patients with diabetes randomized to standard statin or statin plus fenofibrate treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial. METHODS: Among 5,464 participants in the ACCORD lipid trial, 3,554 (65%) were free of CKD at baseline, while 1,910 (35%) had mild to moderate CKD. Differences in CV outcomes during follow-up between CKD and non-CKD subgroups were examined. In addition, the effect of fenofibrate as compared to placebo on CV outcomes was examined for both subgroups. RESULTS: All CV outcomes were 1.4-3 times higher among patients with CKD as compared to non-CKD patients. In patients with CKD, the addition of fenofibrate had no effect on any of the primary or secondary outcomes. In patients without CKD, however, the addition of fenofibrate was associated with a significant 36% reduction of CV mortality (hazards ratio [HR] 0.64; 95% CI 0.42-0.97; p value for treatment interaction <0.05) and 44% lower rate of fatal or non-fatal congestive heart failure (CHF; HR 0.56; 95% CI 0.37-0.84; p value treatment interaction <0.03). CONCLUSIONS: For patients with type 2 diabetes at high CV risk but no CKD, fenofibrate therapy added to statin reduced the CV mortality and the rate of fatal and non-fatal CHF.

Cardiovascular Outcomes in Action to Control Cardiovascular Risk in Diabetes: Impact of Blood Pressure Level and Presence of Kidney Disease.

BACKGROUND: Persons with chronic kidney disease (CKD) represent a population prone to cardiovascular disease (CVD) but vulnerable to adverse medication effects. We assessed the impact of intensive antihypertensive therapy on the cerebrovascular and other CVD outcomes in high-risk patients with type 2 diabetes and baseline CKD. METHODS: Using current guideline criteria, 1,726 (36.9%) of 4,678 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) arm had mild to moderate CKD (CKD1-3B) at baseline. Participants of this study were randomized to intensive (systolic <120 mm Hg) or standard (systolic <140 mm Hg) BP goals. Fatal and non-fatal stroke were pre-specified secondary outcomes of the ACCORD study. RESULTS: Total cerebrovascular events were significantly higher in participants with baseline CKD (0.66%/year) compared with participants free of CKD (0.28%/year). A significantly higher rate of events was observed in CKD participants. Intensive antihypertensive therapy in participants without CKD at baseline resulted in a 55% significant reduction of any stroke (hazard ratio 0.447; 95% CI 0.227-0.880) and a 50% reduction of non-fatal stroke (hazard ratio 0.498; 95% CI 0.250-0.993). In participants with CKD at baseline, the occurrence of any stroke was reduced by 38% (hazard ratio 0.623; 95% CI 0.361-1.074) and non-fatal stroke by 36% (hazard ratio 0.642; 95% CI 0.361-1.142). Test for interaction was NS between the 2 groups. Changes in other CVD outcomes did not reach statistical significance. CONCLUSIONS: These findings suggest that intensive antihypertensive therapy offers significant cerebrovascular protection in diabetic participants without CKD at baseline, but significant benefit to patients with CKD cannot be excluded.