Edwards' PARTNER Results Published, FDA Approves PARTNER II

September 22, 2010—Edwards Lifesciences (Irvine, CA) announced that The New England Journal of Medicine published (online ahead of print) results from Cohort B of the PARTNER trial by Martin B. Leon, MD, et al, which studied the Edwards Sapien transcatheter heart valve for the treatment of severe aortic stenosis. The results of the trial successfully met the primary endpoints of all-cause mortality and mortality plus repeat hospitalization. The results were also presented on September 23 at the Transcatheter Cardiovascular Therapies scientific symposium in Washington, DC.

The study investigators concluded, “in patients with severe aortic stenosis who were not suitable candidates for surgery, TAVI [transcatheter aortic valve implantation], as compared with standard therapy, significantly reduced the rates of death from any cause, the composite endpoint of death from any cause or repeat hospitalization, and cardiac symptoms, despite the higher incidence of major strokes and major vascular events.”

The article further states, “on the basis of a rate of death from any cause at 1 year that was 20 percentage points lower with TAVI than with standard therapy, balloon-expandable TAVI should be the new standard of care for patients with aortic stenosis who are not suitable candidates for surgery.”

The company noted that according to the study investigators, “aortic stenosis is an insidious disease with a long latency period followed by rapid progression after the appearance of symptoms, resulting in a high rate of death” and concluded that “standard medical therapy...did not alter the natural history of severe aortic stenosis.”

According to Edwards, PARTNER studied 358 patients with severe, symptomatic aortic stenosis deemed inoperable for traditional open heart surgery. Patients were evenly randomized to receive either the Edwards Sapien valve or standard therapy. In the United States, the Edwards Sapien transcatheter valve is an investigational device and not yet commercially available.

As detailed in The New England Journal of Medicine, at 1 year, the rate of death from any cause (Kaplan–Meier analysis) was 30.7% with TAVI, as compared to 50.7% with standard therapy (hazard ratio with TAVI, 0.55; 95% confidence interval [CI], 0.40–0.74; P < .001). The rate of the composite endpoint of death from any cause or repeat hospitalization was 42.5% with TAVI compared to 71.6% with standard therapy (hazard ratio, 0.46; 95% CI, 0.35–0.59; P < .001). Among survivors at 1 year, the rate of cardiac symptoms (New York Heart Association class III or IV) was lower among patients who had undergone TAVI than among those who had received standard therapy (25.2% vs 58%, P < .001). At 30 days, TAVI, as compared to standard therapy, was associated with a higher incidence of major strokes (5% vs 1.1%, P = .06) and major vascular complications (16.2% vs 1.1%, P < .001). In the year after TAVI, there was no deterioration in the functioning of the bioprosthetic valve, as assessed by evidence of stenosis or regurgitation on an echocardiogram, the investigators reported in The New England Journal of Medicine.

On September 23, Edwards announced that the US Food and Drug Administration conditionally approved the first of two planned cohorts of the PARTNER II randomized controlled trial. The first cohort of PARTNER II will study the next-generation Edwards Sapien XT transcatheter heart valve. This trial includes the low-profile NovaFlex transfemoral delivery system, which broadens the number of eligible patients.

This cohort will study up to 450 patients with severe, symptomatic aortic stenosis using a 2:1 randomization of the Edwards SAPIEN XT valve delivered transfemorally versus standard therapy. The primary endpoint of the trial is a composite of death, major stroke, and repeat hospitalization, with secondary endpoints that include valve performance and quality-of-life indicators.

Edwards anticipates a second patient cohort for the trial to compare open heart surgery with the Edwards Sapien XT valve delivered either transfemorally or transapically. The Edwards Sapien XT valve received CE Mark approval in March 2010 and is commercially available in Europe. In the United States, the Sapien XT is an investigational device and not commercially available, the company advised.