Year in Review: Physicians Pick the Biggest News of 2016, in Interventional Cardiology and Beyond
TCTMD journalists asked a range of experts about what developments moved the needle this past year—either forwards or back.
As the days ticked down on 2016, the TCTMD news team reached out to a range of cardiologists internationally to ask what they saw as the biggest advances in the year gone by. Many pointed to TAVR’s march into lower and lower risk patients. Several noted twists and turns in the treatment of coronary artery disease, particularly the EXCEL and NOBLE trials of unprotected left main disease, pharmacotherapy in atrial fibrillation patients undergoing PCI, and the advances and setbacks seen in the world of bioresorbable scaffolds.
Beyond the cath lab, physicians highlighted a number of US Food and Drug Administration (FDA) decisions in the diabetes, cholesterol-lowering and endovascular spheres as well as CT angiography, remote heart rhythm monitoring, A-fib ablation, and more.
Coronary Artery Disease
Asked to name the most significant advance in the treatment of CAD, several experts pointed to the EXCEL and NOBLE trials comparing surgery and drug-eluting stents for the treatment of unprotected left main disease.
Azeem Latib, MD (San Raffaele Scientific Institute, Milan, Italy), noted that left-main stenting is growing in Europe. “So to have the data from EXCEL—a well-conducted, adequately powered study using second-generation drug-eluting stents, as well as the right endpoints (taking revascularization out of the endpoint)—reinforces what we have been doing,” he said.
For Harold Dauerman, MD (University of Vermont, Burlington), however, EXCEL was only half the story because of the “conflicting results” with NOBLE. “While it wasn’t the overwhelmingly positive results that many interventional cardiologists would have hoped for, this is going to impact the ability of guidelines to change and clinical practice to change in any clear direction with respect to choosing drug-eluting stenting versus bypass surgery,” he commented. “The ongoing inconsistency of the results is going to dampen growth of left main stenting.”
Likewise, James de Lemos, MD (University of Texas Southwestern Medical Center, Dallas), called out EXCEL and NOBEL as noteworthy. “It’s going to take longer follow-up to get at the issue a little bit better,” he said. “Certainly, though, it’s big news, and many patients may—even if the short-term risks of nonprocedural MI are higher with PCI—choose PCI.”
On the stenting front, de Lemos also pointed to the NORSTENT study, presented at ESC 2016, which showed that bare-metal stents perform much better than physicians would have thought.
“While [NORSTENT] probably has modest impact in the US, in a cost-constrained environment the results really support bare-metal stents, like the very good ones used in NORSTENT, as suitable options that don’t put patients at prohibitive risk for complications,” de Lemos told TCTMD.
Dauerman and Latib both also made mention of the ABSORB II results. Latib said that he and colleagues have been using the Absorb bioresorbable scaffold (Abbott Vascular) for 2 years and so far have been very happy with the technology.
“It’s very attractive to be able to put something in the artery that goes away, but we have been waiting for longer-term data to really understand the true advantage of the technology compared with second-generation drug-eluting stents,” he said. “When the ABSORB II 3-year data became available, along with ABSORB China, I think it gave us a reason to take a moment to pause and reevaluate.”
Dauerman, meanwhile, called the 3-year ABSORB II results “sobering.”
“The increased risk of thrombotic events is very concerning but in addition, the absence of any distinction in vasomotion between the Xience group and the Absorb group gives some pause to the entire hypothesis that a dissolving stent somehow improves the physiology of the coronary artery long-term,” Dauerman said. “Whether this is specific to the Absorb platform or a general concern for all bioresorbable vascular scaffolds is not known, but it definitely calls into question the entire hypothesis that you’re getting less inflammation and better endothelial function with the resorbable scaffold.”
Changing gears, and on a more positive note, Dauerman also listed as one of the year’s highlights the PIONEER AF-PCI trial, which studied the best anticoagulation/antiplatelet regimen for A-fib patients undergoing PCI. The trial “lends weight to the already growing practice of dropping aspirin in favor of single antiplatelet therapy plus oral anticoagulation after PCI,” Dauerman said. “Consistent with the WOEST trial, triple therapy increases bleeding. I don’t think this [trial] can absolutely exclude the possibility of increased risk of thrombotic events with a tailored approach, but the consistent benefit in terms of bleeding by dropping the aspirin for A-fib patients is probably real enough to change clinical practice.”
- Todd Neale and Michael O’Riordan
Structural Heart Disease
Several clinicians and researchers contacted by TCTMD pointed to expanded indications for different TAVR devices in Europe and the USA, permitting the treatment of intermediate-risk patients with aortic stenosis. Dauerman went so far as to say this shift “is going to change cath labs to the point where they’re doing more TAVR than they are doing STEMI PCI,” something that will have a profound impact on interventional cardiology training.
Likewise, Samir Kapadia, MD (Cleveland Clinic, OH), who also selected intermediate-risk TAVR as a highlight this year, pointed out that TAVR outcomes have been steadily improving as the procedure moves into lower-risk patients and said stroke rates have also decreased over the course of the trials.
But stroke in TAVR remained a focus in 2016. Citing promising but inconclusive data from the SENTINEL trial, for which he served as co-principal investigator, Kapadia said “neuroprotection is a major thing: whether we’re going to use it in patients, whether it will be approved in the United States, which patients to use [it in]—all these things remain unanswered but of major importance.”
Anita W. Asgar, MD (Montreal Heart Institute, Montreal, Canada), also picked the SENTINEL results as one of the most important studies in the TAVR space this year. “It’s always been a nagging issue for me: should we be using cerebral protection in our TAVR patients? Are we not treating our patients well because we don’t? And the SENTINEL trial . . . made me feel very comfortable in the fact that we don’t use it.”
She added that she hadn’t been expecting “a win” for cerebral protection, because the risk of stroke with TAVR has fallen so low. “You would have to enroll thousands of thousands of patients to see a clinical benefit. The imaging results were a bit more surprising, she said. “I expected to see a benefit in terms of MRI lesions, but we didn’t.”
Like Dauerman and Kapadia, Asgar also picked intermediate-risk TAVR as her choice for the number-one newsmaker in structural heart disease, but she had a slightly different take.
Citing the PARTNER 2A and SAPIEN 3 trials, “I now feel very justified, and very comfortable, sending the patient with aortic stenosis at intermediate risk for TAVR. But the other thing that I think is interesting was that in patients who couldn’t have transfemoral, if they had transapical or transthoracic, the results were not as good, and for me that was also practice changing,” she stressed. This finding was supported by quality-of-life data in intermediate-risk patients from PARTNER 2A presented at TCT 2016. “If we look at the other kinds of access that we tend to use—transthoracic, transaortic, or transapical—they don’t do as well in terms of overall endpoints for stroke and mortality compared to surgery, and they certainly don’t have a benefit in terms of quality of life. . . . The patient may as well just have surgery.”
“In sad news, the Direct Flow valve died” in 2016, Kapadia noted, but the Lotus valve (Boston Scientific) may well garner FDA approval this spring, he predicted.
Beyond aortic stenosis, none of the advances made in mitral and tricuspid valve interventions made Asgar’s top story lists. “We saw a lot of technology coming out for the mitral, but it’s really early days,” she said, adding, “We need more data.”
- Caitlin E. Cox and Shelley Wood
Clinical Cardiology and Prevention
Even though the latest drugs for the treatment of elevated LDL cholesterol were approved last year, the PCSK9 inhibitors alirocumab (Praluent, Sanofi-Regeneron) and evolocumab (Repatha, Amgen) continue to have a large impact on clinical practice and in the prevention of recurrent cardiovascular events, Michael Blaha, MD (Johns Hopkins Medical Institute, Baltimore, MD), told TCTMD. “The approvals were in 2015, but what 2016 brings is the GLAGOV study—the IVUS plaque regression study—and more and more evidence that lower LDL cholesterol is better and that lower is safe,” he said.
Supporting the “lower is better” hypothesis, Blaha pointed to a 2016 meta-analysis in JAMA by Michael Silverman, MD (Brigham and Women’s Hospital, Boston, MA) showing that therapies, including statins and nonstatins, that act on LDL receptor expression achieve similar reductions in the risk of vascular events with similar reductions in LDL cholesterol levels. As a result of these and other data, Blaha is optimistic the large cardiovascular outcomes studies with evolocumab and alirocumab—FOURIER and ODYSSEY Outcomes, respectively—will be positive.
“It’s an emerging and powerful story that we think shows all the ducks lining up in a row, that 2017 will bring a positive year in terms of positive outcomes studies,” said Blaha. “So, for 2016, the PCSK9 inhibitor story has not been derailed in any way. It’s really right on course. “
For hypertension, SPRINT, which included high-risk patients, continued to be debated, but Blaha noted that the HOPE-3 trial failed to show an incremental benefit in lower-to-intermediate risk patients. “I think the emerging story is that we’re moving toward a risk-based approach to blood pressure, just like we do with cholesterol,” he said. In doing so, physicians will likely start assessing patient risk and selecting “personalized therapy” to manage patients.
Finally, Blaha was also intrigued by ORION-1, a phase II study testing an investigational therapy targeting PCSK9 via RNA interference. “If these RNA interference drugs work, it’s going to open up so many therapeutic possibilities,” he said.
- Michael O’Riordan
The year 2016 wasn’t exactly a blockbuster year in cardiovascular imaging, according to James K. Min, MD (Weill Cornell Medical College, New York, NY). That said, he singled out the CONSERVE trial as important both from a clinical perspective as well as from a health policy and economic standpoint.
In CONSERVE, the 12-month MACE rate was similar in patients with suspected stable coronary artery disease who underwent direct versus selective catheterization guided by CT, but use of coronary angiography and revascularization was reduced, as was cost, with CT angiography. For Min, the $400 noninvasive test holds the potential to spare a lot of hospitals, insurers, and patients the $10,000 invasive catheterization procedure.
In other newsworthy findings, Min cited SCOT-HEART, a study showing advantages for coronary CT angiography over stress testing for diagnosing patients with chest pain. He also noted that the National Institutes for Health and Care Excellence (NICE) is now recommending CT angiography as the first-line investigation for patients with stable chest pain who have typical or atypical symptoms, as well as those with nonanginal chest pain and ECG changes suggestive of coronary artery disease.
NICE tends to be conservative, said Min, so the decision is big news in the CT field.
For intravascular imaging, TCTMD turned to Gary S. Mintz, MD (Cardiovascular Research Foundation, New York, NY), who listed the OPINION study presented at EuroPCR in May. The trial, according to Mintz, was the first ever randomized, head-to-head comparison of IVUS- and OCT-guided PCI. It resulted in comparable outcomes at 1 year in terms of both their effectiveness in optimizing stenting and optimizing patient outcomes. While the trial was small, Mintz pointed out that “right now there isn’t another one that will have [clinical outcomes] data available in the near future.”
- Michael O’Riordan and Yael L. Maxwell
On the carotid front, 2016 brought the first FDA approval of a carotid stent (ENROUTE Transcarotid NPS, Silk Road Medical), for use in transcarotid artery revascularization procedures, along with Centers for Medicare & Medicaid Services (CMS) coverage of the procedure in patients at high risk for endarterectomy, noted William Gray, MD (Main Line Health/Lankenau Heart Institute, Wynnewood, PA). “This provides direct carotid access for the first time,” he said.
Gray also pointed to 3-year data from IN.PACT SFA that were presented in September at VIVA 2016. The long-term results showed the durability of a drug-coated balloon (IN.PACT Admiral, Medtronic) over plain balloon angioplasty without attrition in outcomes. Additionally, the international, multicenter IMPERIAL trial was initiated and likely will be completed in the New Year. That trial of 435 patients is a head-to-head test of two drug-eluting stents for use in the SFA (Eluvia, Boston Scientific and Zilver, Cook Medical).
Gray, who is the international PI of IMPERIAL, said it is important because of the dearth of data on how these stents compare with each other. “This should give us 1-year data probably in early 2018,” he noted.
Another important data set that emerged this year, he added, was the 1-year results from the US-based, multicenter ILLUMENATE Pivotal IDE trial presented at TCT 2016. The trial showed good outcomes for treatment of superficial femoral and/or popliteal artery lesions in a varied patient population and could potentially become the third such device to be approved in the United States, he predicted. “Hopefully, we look forward to having those data presented at the FDA and another device available in the marketplace.”
- L. A. McKeown
The biggest news in heart failure actually took place in the endocrinology space, according to Javed Butler, MD, PhD (Stony Brook School of Medicine, Stony Brook, NY). This was the EMPA-REG trial of empagliflozin (Jardiance, Boehringer Ingelheim), which recently received an expanded indication from the FDA for reducing cardiovascular death in patients with type 2 diabetes.
The trial “showed remarkable reduction in diabetic patients in new-onset heart failure, as well as reduction in cardiovascular event rate and heart failure mortality in those people who had heart failure,” Butler said. “So I think prevention of heart failure in high-risk patients is pretty big news. These data are very exciting and I think on the basis of these data, not for prevention but actually for treatment of heart failure, there are three trials that will now start looking at this class of drugs.”
Butler was not the only one to point to these studies. de Lemos also singled out the diabetes safety trials as the biggest news in clinical cardiology in 2016, noting that EMPA-REG, as well as the LEADER and SUSTAIN-6 trials of liraglutide and semaglutide, respectively, reduced the risk of major cardiovascular events, and in some cases, reduced the risk of cardiovascular and all-cause mortality.
Another important development in the heart failure field, Butler added, was the update to practice guidelines recommending as “Class I” the option of switching certain patients taking ACE-inhibitors or angiotensin receptor blockers—the standard of care for decades—to sacubitril/valsartan (Entresto; Novartis).
- Todd Neale
According to Suneet Mittal, MD (Valley Hospital Health System, Ridgewood, NJ), the major developments in heart rhythm management occurred in three areas: A-fib, diagnostic monitoring, and devices.
Highlights included the FIRE AND ICE trial showing that radiofrequency point-by-point pulmonary vein isolation (PVI) and cryoballoon PVI performed similarly in patients with drug-refractory A-fib. “Although we’ve had both technologies approved for a while, there had been no head-to-head studies,” he said. “We now have confidence that either of these technologies can be used in our patients to treat atrial fibrillation.”
In terms of diagnostic monitoring, acceptance this year within the neurology and cardiology communities about the utility of long-term ECG monitoring in patients with stroke has been critical, Mittal said. “Initially, the data were most clear for cryptogenic stroke, because many of these patients have unidentified atrial fibrillation. But more recently the European Society of Cardiology guidelines suggest that there may be a role for ECG monitoring in all patients with ischemic stroke, because many of the risk factors that lead to ischemic stroke are also the same risk factors that put people at risk for atrial fibrillation.”
In the device realm, Mittal highlighted both cost-efficacy data and a growing recognition of the importance of Heart Rhythm Society guidelines recommending that all patients with an implantable device be remotely monitored as opposed to having calendar-based, in-office follow-up. The leadless pacemaker, which was approved by the FDA in April, “is a real advance in the way that we think about pacing technology,” he said.
- Todd Neale
Several physicians who spoke with TCTMD highlighted the MACRA (Medicare Access & CHIP Reauthorization Act) as not only the biggest health policy news, but according to Butler, it’s “the biggest news in medicine in general.”
Although MACRA was passed last year, its ongoing implementation coupled with the incoming Trump administration make it still top health policy issue facing physicians now and in the years to come, said Jack Lewin, MD (Cardiovascular Research Foundation, New York, NY, and National Coalition on Health Care, Washington, DC). Bundled payments for cardiovascular services may also dramatically transform practice, he added, but it may not be full-steam ahead for MACRA just yet.
According to Lewin, Trump’s nominee for Secretary of Health and Human Services, Rep. Tom Price, MD (R-GA), wants to slow down the MACRA implementation process and has expressed concerns over the concept of value-based healthcare. “It would appear that this is a policy that will survive into the Trump administration,” Lewin predicted, “but Price’s skepticism for what he considers to be valid definitions of ‘value’ and how they will measure it, casts some doubt on whether CMS will move in that direction.
- L.A. McKeown
The field of digital health has garnered increased attention in the past few years as technology companies and healthcare organizations have partnered on ways to improve patient care.
In 2016 specifically, two practice-changing technologies were most notable, according to Paddy Barrett, MD (Scripps Translational Science Institute, La Jolla, CA). First, he called the Philips Lumify handheld, smartphone-connected ultrasound device a “big leap forward” since it enables easier examination of patients at the bedside and reduces the need for “often unnecessary” and costly testing. Interestingly, Barrett said, this device was released on the 200th anniversary of the stethoscope, but it will likely replace this older technology in the coming years.
Secondly, Barrett named AliveCor’s Kardia Band as another important development, especially within the field of cardiology. This device connects to an Apple Watch and allows for the capture of instant single-lead electrocardiogram that can either be uploaded to the cloud for automatic analysis or to a physician. While the technology has been available for several years, Barrett said, this is the first time it has been incorporated into a wearable device for consumers.
Lastly, the past year has “seen a huge growth [in the] accessibility of artificial intelligence and the network technologies we will use to integrate all this information,” Barrett commented.
With more tempered optimism, Euan Ashley, MB ChB, DPhil (Stanford University, CA), said 2016 was a “mixed year” for digital health. Several published studies “dampened the enthusiasm” for some long-awaited technologies and gave a “sanity check” to researchers. But he acknowledged that “with any new technology there's always this hype phase and then there's a sort of more realistic phase as we incorporate the technology and really understand its strengths and its limitations.” Looking to the future, Ashley anticipates a “very progressive and clear and gradual incorporation of the technology into the work that we do, and that's what we're seeing.”
-Yael L. Maxwell
How well did experts predict the big news of 2016 a year ago today? Find out in this December 2015 episode of On Record.
- Ashley reports that Samsung and Intel have provided small numbers of wearable devices for testing that were used for demonstration.
- Blaha reports having served on an advisory board for Amgen, having received grant money from Amgen, and serving as a member of the Endocrinologic and Metabolic Drug Advisory Committee for the FDA.
- Butler reports receiving research support from the National Institutes of Health, European Union, and PCORI and serving as a consultant for Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer, CVRx, Janssen, Medtronic, Merck, Novartis, Relypsa, and ZS Pharma.
- Dauerman reports consulting for and receiving research grants from Medtronic and Boston Scientific.
- de Lemos has reported consulting/advisory board work for Roche Diagnostics, Abbott Diagnostics; Siemens Health Care, and Radiometer.
- Gray reports consulting for Boston Scientific, Medtronic, and WL Gore.
- Kapadia reports being an unpaid member of steering committees for Portico, Direct Flow Medical, and the PARTNER 3 trial.
- Latib has reported grant/research support and consulting fees/honoraria from Direct Flow, Medtronic, Mitralign, Millipede, Amaranth Medical, 4tech, Valtech Cardio, Spectranetics, ACIST Medical, and Abbott Vascular.
- Min has reported a financial interest/arrangement or affiliation with GE Healthcare, HeartFlow, AstraZeneca, Cleerly, MDDX, and Autoplaq.
- Mintz reports receiving grant/research support from Volcano, Boston Scientific, Infraredx, and St. Jude and consulting fees/honoraria from Volcano, Boston Scientific and ACIST.
- Mittal reports receiving speaking fees from Medtronic.
- Asgar and Barrett report no relevant conflicts of interest.