By Mark McCarty, Regulatory Editor

Five-year data for novel cardiology devices are often unavailable before that iteration of the device has become obsolete, but those data are nonetheless important. Hans Gustav Thyregod of Copenhagen University Hospital reported five-year data for the first two generations of the Medtronic Corevalve device, stating that five-year mortality for lower-risk patients, those with STS scores of less than four percent, were equal for the Corevalve and surgical aortic valve replacement.

Thyregod unveiled the new data set for the first two Corevalve iterations at this year’s meeting of the American College of Cardiology, and he noted that the combined endpoint of all-cause mortality, stroke or myocardial infarction for those with STS scores of less than four percent was slightly higher than 35 percent for patients with a surgically implanted valve. Patients with TAVR devices came in at 31.5 percent, but the p score was only 0.51, making this measure a statistical deadlock.

The Nordic Aortic Valve Intervention (Notion) trial is a study of all valve patients of at least 70 years of age at three institutions in Denmark, using the mortality/stroke/MI composite as the primary endpoint. Secondary outcomes were echocardiography-determined safety and efficacy measures, and enrollment ran from December 2009 to April 2013. The principle inclusion criteria consisted in part of severe aortic stenosis and life expectancy of greater than a year, while patients with severe coronary artery or other valve disease were excluded. The 280 enrollees were nearly equally randomized to surgical and transcatheter valve placement, and crossover was a net three patients from TAVR to SAVR. Five-year follow-up consisted of 102 TAVR and 94 SAVR patients.

Patients were largely indistinguishable for age and sex, and overall average Society for Thoracic Surgery (STS) scores were 2.9 for TAVR and 3.1 for SAVR. Four in five in the surgical arm scored below four percent on the STS measure, while 83.4 percent in the transcatheter were in that lower risk category. There was a numerical difference in New York Heart Association class III or IV patients, but the higher rate of these sicker patients in TAVR did not reach statistical significance.

All-cause mortality for all enrollees, regardless of risk score, was even at 27.7 percent, although the numbers converged and diverged several times over the course of the study. Stroke was more common in the TAVR arm (10.5 percent compared to 8.2 percent for surgical), while myocardial infarction was nearly numerically equivalent. As is often seen in these studies, the need for pacing exposes TAVR patients to a greater risk of death, with 38.2 percent of TAVR patients with pacing expiring by year five compared to only 21.7 percent without pacing.

Thyrogod told BioWorld Medtech that there was no meaningful difference in class III versus class IV heart failure between the two study arms, although the enrollees in this study “were less symptomatic compared to other randomized trials.” He said this was due in part to enrollment of asymptomatic patients who suffered from complications related to the stenosis, such as left ventricular hypertrophy and new-onset atrial fibrillation, an artifact of the all-comers nature of the study.

Thyrogod said embolic protection devices became available during the course of the study, but “we never used them during the trial” due to the obvious impact on the statistical plan. “They were not that developed and there was no indication for their use” in TAVR, either, he said.

Bicuspid valves slip past echo

At five years, 77 percent of SAVR patients had no or only trace regurgitation versus only about 39 percent for the Corevalve, and Thyrogod said the study ended up with a few patients with bicuspid valve despite that it was known at the time that both asymmetric calcification and bicuspid valve drive regurgitation. This was due to the use of transthoracic and transesophageal echocardiography rather than CT imaging, which he said is now routine practice in Denmark.

At five years, effective orifice area was 1.66 square centimeters for TAVR and 1.23 for SAVR, while the mean pressure gradient at five years again favored the Corevalve (13.71 millimeters of mercury compared to 8.22 for SAVR). Both measures favored TAVR for nearly the entirety of the five years, but the differences also grew over time for the most part. Still, Thyrogod said the observed differences in valve performance “didn’t translate into differences in functional class at five years.”

Thyrogod said TAVR patients were more likely to report dyspnea at two years, “but that difference had leveled out at five years.” Differences in orifice area, pressure gradient and regurgitation all seemed to have no effect on functional class after five years, but he said New York Heart Association function class is a crude measure. Still, he said, “we haven’t done all our quality-of-life data” analysis, which might drive the numbers toward one approach.

As is often the case, permanent pacemaker implantation rates hit TAVR harder than SAVR, and Thyrogod said this study entailed predilatation for all patients, but not post-dilatation. He said valve placement, one of the long-standing sources of pacemaker implantation, was also a factor, but he said the standard practice for pacemaker implantation at the time may have driven overutilization. “There are other studies suggest that just putting in a pacemaker immediately after the procedure can sometimes be avoided,” he said.

Thyrogod said he could not be certain whether the rate of pacemaker improved as the study advanced, but stated, “they probably did because we got the second generation of the valve and put more emphasis on higher valve position. My gut feeling is that it would be a lower rate in the last part of the study, but I don’t have the data to prove that.”