12 May 2008 - Lowering levels of low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) to targets below those currently recommended reduces early signs of cardiovascular disease in patients with Type 2 diabetes, scientists report. However, these benefits did not translate into a reduction in clinical events in the study, and the authors emphasize that longer-term follow-up is needed to assess the benefits and risks of more aggressive treatment.

Barbara Howard, MD (MedStar Research Institute, Hyattsville, Maryland, USA) and colleagues compared standard and aggressive lipid- and BP-lowering treatment in 500 American-Indian patients with Type 2 diabetes. Patients in the standard therapy group were treated to reach the current goal levels for LDL-C of 100 mg/dl or lower and systolic (S)BP of 130 mmHg or lower, while those in the aggressive therapy group were treated to reach goals of 70 mg/dl or lower LDL-C and 115 mmHg or lower SBP.

The authors report in the Journal of the American Medical Association that mean target LDL-C and SBP levels for both groups were reached and maintained over the 3-year study period.

Mean LDL-C levels in the last 12 months of the study were 72 mg/dl and 104 mg/dl in the aggressive versus standard group, respectively, and mean SBP levels were 117 mmHg and 129 mmHg. At 3 years, carotid IMT had regressed from baseline by 0.012 mm in the aggressive therapy group but progressed by 0.038 mm in the standard therapy group (p<0.001). Furthermore, left ventricular (LV) mass index decreased further during the study with aggressive treatment, by 2.4 g/m2.7 compared with 1.2 g/m2.7 (p=0.03) with standard treatment.

However, there was no difference in the rate of cardiovascular events at 1.6/100 and 1.5/100 person-years in the aggressive- and standard-therapy groups, respectively. And adverse events and serious adverse events related to BP medication occurred more frequently in the aggressive therapy group than the standard therapy group, at 38.5% versus 26.7% (p=0.005) and four versus one events (p=nonsignificant), respectively.

Commenting on the lack of benefit on hard outcomes, Barbara Howard told: "I think there was no difference in clinical events because the event rates were low in the standard group - about half the rates we seen in our surveillance of this population."

Howard explained that this is probably because patients were treated to current diabetes goals. "That does not happen in the majority of people with diabetes," she said, noting that previous studies have shown less than half of diabetic patients are at LDL-C or BP targets, and too many smoke.

Noting that the team plans continued follow-up of the study population, she continued: "We know that IMT and LV mass predict future clinical events, so the improvements should ultimately lead to a difference in events. But, if events remain low in the standard group, the aggressive therapy may not have a sufficient benefit to risk ratio."

Eric Peterson, MD and Tracy Wang, MD (Duke University Medical Center, North Carolina, Durham, USA) commented in a related editorial that, while awaiting long-term data, "a practical middle-of-the-road approach might be to support intensive lipid-lowering with statin therapy in patients with diabetes, because this is supported by prior, large, randomized, clinical, end point-driven trials, and has relatively few adverse effects or patient risks."

They added: "For intensive BP management, however, more data are needed because the benefits are not assured and there are modest, but measurement-negative effects on patients' finances and well-being."

JAMA 2008; 299:1678-1689/1718-1720