ACC.13 late-breakers: Mega-studies and potential game-changers

Many of the late-breaking clinical trials on tap at the American College of Cardiology’s (ACC) annual scientific session in San Francisco hold potential to change clinical practice, according to presenters at a Feb. 26 preview briefing.

“These are mega-studies,” said Patrick O’Gara, MD, director of clinical cardiology at Brigham and Women's Hospital in Boston and ACC vice president, referring to the large numbers of patients enrolled in the trials. “These are really robust and will lend themselves to valid outcomes, positive or negative.”

The ACC scheduled 22 late-breaking clinical trials for presentations on March 9-11 that range from stents to surgery to screening. The conference also offers numerous symposia, meet the expert talks, scientific sessions, oral abstracts, poster presentations, study opportunities, an expo and other events. The late-breaking clinical trials often draw the largest audiences.

Among the studies they highlighted as potential clinical game-changers were:

PREVAIL, a randomized controlled study that compares the Watchman Left Atrial Appendage Closure Device to long-term warfarin therapy in patients with atrial fibrillation who are at risk for stroke. “The number of patients suffering atrial fibrillation is huge in an age group where the risk of anticoagulation [such as warfarin] is becoming a real problem versus the benefit because of bleeding issues,” said Miguel Quiñones, MD, cardiology department chair and medical director at Methodist DeBakey Heart Center in Houston, noting the risks associated with anticoagulants such as warfarin. “If the trial does show positive results, the impact could be quite striking.”

PARTNER 2, Cohort B Outcomes: A randomized evaluation of the SAPIEN XT transcatheter valve system (Edwards Lifesciences) in patients with aortic stenosis who are not candidates for surgery. The study compares first-generation Sapien device with a newer device with a lower profile device for percutaneous transcatheter aortic valve replacement (TAVR). “The hope is that patients who are treated with a lower profile device will achieve at least the same type of efficacy outcome—that is, a reduction in their aortic stenosis—without creation of more aortic regurgitation at a lower cost related to vascular complications such as bleeding or stroke,” O'Gara said.

DIGOXIN STUDY : A study that evaluates if the use of digoxin reduces 30-day all-cause hospital admissions in ambulatory older patients with chronic heart failure and reduced ejection fraction.  “Digoxin is a very inexpensive drug,” Quiñones said, noting the associated cost burden of readmissions. “If it does have a major reduction of readmissions to the hospital, that could be significant.”

HPS2-THRIVE (Heart Protection Study 2—Treatment of HDL to Reduce the Incidence of Vascular Events), a randomized study that compares extended-release niacin/laropiprant 2g daily with a placebo in more than 25,000 patients who are at  high risk of occlusive vascular events. A recently published analysis of prespecified muscle and liver outcomes and participants’ reasons for stopping treatment found that one-quarter of participants stopped taking niacin/laropiprant after 3.9 years. Researches also reported a four-fold excess risk of myopathy in patients taking the therapy, with patients in China facing even higher risks.

“HPS2-THRIVE will impact how niacin is used in the United States,” said ACC.13 Co-Chair Christie Ballantyne, MD, chief of cardiology at Methodist DeBakey Heart Center in Houston.

Although initial findings have been negative, he noted that large number participants may allow for subgroup analyses on low-density lipoprotein cholesterol, triglicerides, high-density lipoprotein cholesterol and gender differences. “When you have large amounts of data, even when your primary endpoint is negative, it is useful to look at some of the subgroups, and they have a lot of power.”

PRAGUE-6 (Off-Pump Versus On-Pump CABG in High-risk Patients (Euroscore 6+): This study builds off previous studies comparing on- and off-pump bypass graft surgery that partially demonstrated benefits of the off-pump strategy. This study evaluates methods without extracorporeal circulation in patients with high operation risk, with EuroSCORE classification system of six points and more.

“It could push the envelope of off-pump CABG, both in academic centers and the community,” proposed Mark Davies, MB, BCh, PhD, of the Methodist Hospital Research Institute and ACC.13 co-chair.

In terms of the large numbers of patients in the trials, presenters called out several including:

CHAMPION PHOENIX with 11,000 patients: The main result will be presented on the trial, which compares the efficacy and safety of the intravenous P2Y12inhibitor cangrelor (The Medicines Company) with standard of care in PCI candidates.   

NEXT, with more than 3,000 patients from Japan. Presenters from the trial will release one-year outcomes from the trial, which compares biodegradable polymer and durable polymer stents.

REMINDER, with more than 1,000 patients. A randomized double-blind, placebo-controlled study evaluating early administration of eplerenone in patients with acute MI who do not have heart failure. 

ASTRONAUT, with more than 1,600 patients:  A multicenter, randomized double-blind study that evaluates early initiation of aliskiren compared to standard therapy in congestive heart failure patients. Outcomes include the reduction in cardiovascular death and heart failure re-hospitalization events.

DKCRUSH-III (Double-kissing of CRUSH III), with more than 400 patients in China with unprotected left main disease: The multicenter, randomized, prospective study compares two interventional strategies for managing lesions at the distal end of the left main.

For a complete list of late-breaking clinical trials, click here.