CardioExchange Archive

The ACC started the day with the release of 3 highly-anticipated clinical trials.

ACCORD (Action to Control Cardiovascular Risk in Diabetes Study) tested two separate therapeutic approaches in type 2 diabetics. In one arm, 5,518 patients already taking simvastatin were randomized to fenofibrate or placebo. After 4.7 years of followup, the annual rate of nonfatal MI, nonfatal stroke, or CV death was 2.2% in the fenofibrate group versus 2.4% in the placebo group (HR 0.92, CI 0.79-1.08, p=0.32). The investigators reported a possible benefit in the subgroup of patients who had both elevated triglycerides at baseline and low HDL cholesterol.

The second arm of the study tested a strategy of aggressive blood pressure control versus standard control in 4,733 subjects to intensive-therapy, where the systolic blood pressure target was 120 mm Hg or lower, or standard therapy, where the goal was 140 mm Hg. The annual rate of nonfatal MI, nonfatal stroke, or CV death was 1.87% in the intensive therapy group versus 2.09% in the standard-therapy group, a nonsignificant difference. There were fewer strokes in the intensive therapy group but the more intense drug therapy resulted in more serious adverse events caused by drug therapy.

In an companying editorial, Peter Nilsson writes that “we learn from the completed ACCORD study that flexible goals should probably be applied to the control of hyperglycemia, blood pressure, and dyslipidemia in patients with type 2 diabetes, taking into account individual clinical factors of importance.”

NAVIGATOR (Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research) randomized, in a 2 x 2 factorial design, 9306 patients with impaired glucose tolerance to valsartan or placebo and nateglinide (a short-acting insulin secretagogue) or placebo. In the valsartan arm of the trial, valsartan therapy resulted in a significant reduction in the incidence of diabetes from 33.1% in the valsartan group versus 36.8% in the placebo group (HR 0.86; CI .80=.92, p<0.001). Unfortunately, this difference did not translate into clinical benefit, as there were no significant differences in any of the clinical endpoints.
In the nateglinide arm of the trial, there were no significant differences in clinical outcomes between patients who received nateglinide and patients who received placebo.
In an accompanying editorial, David Nathan writes that “the prevention of diabetes remains a critical public health priority, but for now we should steer away from these two drugs and use effective lifestyle interventions and, in selected persons, metformin to combat the epidemic.”

EVEREST II (Endovascular Valve Edge-to-Edge Repair Study ) is the first large trial of catheter-based mitral valve repair in which 279 patients with significant mitral regurgitation (MR) and suitable anatomy were randomized on a 2:1 basis to the MitraClip (184) or surgery (95). At 30 days the new device was much safer than surgery: 1 MitraClip patient had a GI complication requiring surgery and 12 required significant transfusions. By contrast, in the surgery group there were 2 deaths, 2 major strokes, 1 patient who underwent reoperation, 4 patients who had urgent CV surgery, 4 patients who required ventilation for more than 48 hours, and 42  patients who required significant transfusions.
At one year, clinical efficacy was similar between the two groups. The clinical success rate, defined as freedom from the combined outcome of death, MV surgery or re-operation for MV dysfunctions, or an MR score >2 at 1 year, was 72.4% in the MitraClip group versus 87.8% in the control group.
Presenting the results of the pivotal trial, Ted Feldman concluded that “the MitraClip procedure is an important therapeutic option for selected patients with significant mitral regurgitation given the demonstrated safety, effectiveness and clinical benefit.”