AHA & TCT: Quality research and outstanding questions
“Nature never gives you anything for free.” Richard Smalley was talking about fullerenes, an all-carbon molecule that continued to entice and perplex him six years after he won the Nobel Prize in chemistry for its discovery. It has been a decade since he made that comment to me, and fullerenes still tease researchers with their promise and perverseness.
Those words came to mind during the AHA’s conference this week as Stuart J. Connolly, MD, chair of the PALLAS trial and director of the division of cardiology at McMaster University in Hamilton, Ontario, unveiled the study’s negative findings. Counter to a hypothesis based on the success of dronedarone (Multaq, Sanofi-Aventis) in patients with paroxysmal or persistent atrial fibrillation (AF), the researchers found the drug to be harmful for patients with permanent AF.
Negative findings were expected—PALLAS was terminated on July 5 for safety reasons—but the actual details released on Nov. 14 were nonetheless a surprise. Nearly twice as many patients in the dronedarone arm than in the control group died, had a stroke or had an unplanned cardiovascular hospitalization. The ATHENA trial, whose results informed the FDA’s approval of dronedarone for managing patients with intermittent AF, had shown significant benefits for that patient population
The PALLAS findings were disappointing, given the disease burden.
“This [permanent AF] is a patient population with high-burden vascular events and for whom there previously have been very few clinical trials and no very promising therapies,” Connolly said at a late-breaking clinical trials session.
But because PALLAS was well designed, it provided unambiguous results that leave physicians with a clear message: do not prescribe dronedarone to patients with permanent AF. Discussant N.A. Mark Estes III, MD, director of the New England Cardiac Arrhythmia Center at Tufts Medical Center in Boston, reiterated that the drug should continue to be used as indicated, but he recommended monitoring patients.
The panelists complimented the PALLAS research team and its sponsor, Sanofi-Aventis, for both quality and openness. The study was scientifically sound and advanced knowledge.
It was not the only standout at the AHA and TCT conferences. The ATLAS-ACS trial showed that the oral factor Xa inhibitor rivaroxaban (Xarelto, Bayer/Janssen) added to standard treatment lowered the risk of death, MIs and strokes compared to standard therapy and a placebo in patients with acute coronary syndromes (ACS). C. Michael Gibson, MD, chief of clinical research in the cardiology division at Beth Israel Deaconess Medical Center in Boston, presented the results Nov. 13 at AHA.11.
“The first question is does the drug work?” Gibson said in a video interview with Cardiovascular Business. “We found about a 16 percent relative risk reduction for everyone on rivaroxaban versus placebo.”
Both low and higher doses of the drug had similar effectiveness, he said, although the lower dose had a lower bleeding risk. “The lower dose hits the sweet spot of safety and effectiveness,” Gibson said.
Several analyses at the TCT conference added clarity to the issue of transcatheter aortic valve implantation (TAVI), a particularly timely topic, given the FDA’s approval of the Sapien transcatheter heart valve device (Edwards Lifesciences) on Nov. 2. Based on the PARTNER Cohort A data, Matthew R. Reynolds, MD, of Saint Luke’s Mid America Heart Institute in Kansas City, Mo., found the cost effectiveness of TAVI compared with surgical aortic valve replacement (SAVR) depended on whether TAVI is performed via the femoral artery or transapically.
The transfemoral TAVI approach resulted in a difference of $2,496 compared with SAVR but one-year follow-up costs were higher in the TAVI group for a $287 difference. The transapical TAVI approach had an increase cost of $11,008 compared with SAVR but the one-year follow-up was less in the TAVI group for a $1,412 difference, mainly due to the high SAVR rehabilitation costs.
“Results of this trial indicate that for patients with severe aortic stenosis and high surgical risk, TAVI is an economically attractive and possibly dominant strategy compared with surgical aortic valve replacement, provided that patients are suitable for the transfemoral approach,” Reynolds said during the Nov. 10 presentation.
Similarly, another study based on PARTNER A data concluded that TAVI potentially met the cost-effectiveness thresholds of the U.K. National Institute for Health and Clinical Excellence (NICE). James Eaton, MSc, of Oxford Outcomes, discussed the results Nov. 8.
Additionally, a quality-of-life (QOL) study based on PARTNER A found that patients who underwent TAVI fared better compared with those undergoing SAVR. In a presentation Nov. 10, David J. Cohen, MD, of Saint Luke’s Mid-American Heart Institute, said they observed “a very important and significant benefit in favor of TAVR over surgical AVR at one month.” At six months, the differences diminished and at 12 months were no longer significant, he said.
He reported no significant QOL differences at one month in transapical subgroup of patients, some difference at the six months and at 12 months, data were similar. “These findings demonstrate that in patients suitable for a transfemoral approach, transcatheter AVR provides important benefits over SAVR from the patient’s perspective,” he concluded.
Panelists at both conferences emphasized that such well-done trials contribute to evidence that guides practice, and whether findings prove negative or positive, much still can be learned from them. Nature does not reveal her secrets easily; that was Smalley’s message. But she sometimes whispers clues that can be perceived through hard work and good science.
Feel free to share your research experiences—past, present or anticipated—by emailing me at cstuart@CardiovascularBusiness.com.
Candace Stuart, Editor, Cardiovascular Business