Year in Review: Physicians Select the Most Important News of 2015, in Interventional Cardiology and Beyond
The past 12 months have seen new drugs and devices approved, while others were passed over or sent back for further testing. TCTMD journalists asked a range of experts in interventional medicine and in cardiology more broadly about what developments shook the field in 2015 or, at the very least, caused some tremors.
David E. Kandzari, MD, of Piedmont Heart Institute (Atlanta, GA), chose the DAPT Study, published in late 2014, as 2015’s most influential study in cardiovascular medicine, saying “its impact really didn’t start to be assimilated into practice until this year.”
The study offers insight into the risk-benefit tradeoffs of continuing dual therapy among patients who have been on it for 1 year and are clinically stable without prior events, he said. Notably, it also showed that the benefits of extending therapy also were seen with newer DES and that BMS-treated patients, while at greater risk of events than DES-treated patients, can still benefit from continued dual antiplatelet therapy. Other key trials, Kandzari added, are those forming the growing body of evidence on complete revascularization, the TOTAL trial of thrombectomy, and the ABSORB studies—particularly ABSORB III—on bioresorbable scaffolds (BRS).
Sunil V. Rao, MD, of Duke University Medical Center (Durham, NC), also singled out ABSORB III, “not because the results are so overwhelming—I think we all expected better overall outcomes—but it was a very exciting development.” Strong data on BRS “is something we’ve all been waiting for, at least since 2006, if not even longer. I expect and hope the device will be commercially available in the United States this year.”
Even bigger news, in Rao’s opinion, was the 8,000-patient MATRIX trial, which “definitively showed that the radial approach is superior to the femoral approach in high-risk patients with acute coronary syndrome. I think it’s going to be very difficult moving forward to do any more randomized trials, when the body of literature is so robust.”
Finally, a third trial, “which may have flown under the radar for a lot of people,” was LEADERS-FREE, Rao commented. “The reason this is such a great study is that they took patients who, for all intents and purposes, would have been excluded from many of the drug-eluting stent trials…and assigned them in a randomized fashion to this new polymer-free stent and showed that the outcomes were superior in these patients who could not tolerate prolonged dual antiplatelet therapy.”
- Caitlin Cox
Philip Meyers, MD, of Columbia University Medical Center (New York, NY), pointed to the series of trials published over the past 12 months establishing the effectiveness of mechanical thrombectomy performed with stent retrievers in patients with acute strokes caused by large proximal intracranial occlusions. “The blockbuster news in 2015 is intervention for acute ischemic stroke,” he said. “Multiple trials have now unequivocally shown the benefit of mechanical thromboembolectomy for treatment of severe stroke due to a large cerebral artery occlusion in carefully selected patients. In the history of neurointervention, this is one of the greatest opportunities to have an impact on public health.”
David Thaler, MD, PhD, of Tufts Medical Center (Boston, MA), had a similar view, calling 2015 “a seminal moment in medicine where the field is changed completely and convincingly really within a matter of months.” Thaler also noted the approval of the Watchman device (Boston Scientific) in March 2015. “I think it’s very early yet to know who are the right patients for the Watchman device and who can continue with anticoagulants, keeping in mind that the newer anticoagulants are so much easier to manage than was warfarin,” he observed. “I’m a big fan of the new anticoagulants, and I’m a big fan of alternatives to anticoagulation altogether for atrial fibrillation. So I think the approval of the Watchman device is exciting.”
- Todd Neale
Both John Webb, MD, of St Paul’s Hospital (Vancouver, Canada) and Alain Cribier, MD, University of Rouen (France) highlighted the use of TAVR in lower-risk patients, “even though the US and EU guidelines still limit the indication to nonoperable or high-surgical–risk patients,” Cribier said. “All recent data suggest better outcome with TAVR in lower-risk patients, equivalent to surgery in propensity matching.”
Similarly, Webb pointed out that the 1% mortality rate in moderate-risk patients “is as good as surgery in lower risk patients in most centers, so I think it will take some time to convince the FDA, but I don’t think physicians are going to need a lot more convincing.”
Cribier pointed out that over the last 10 years, more than 200,000 patients have undergone TAVR and that it is now being performed in 60 countries internationally. “In 2015, TAVR is clearly turning into a routine practice … driven by increased operator experience, better patient selection, and improved 3D adjunctive imaging,” he said.
Webb also mentioned progress with mitral interventions, acknowledging that the field is still in the “very early days and the clinical outcomes have been variable.” That being said, “you can see that mitral valve replacement is feasible, it’s reproducible, and it’s going to have to evolve a little bit but it’s for real,” he continued, adding, “The question is, can it be as safe as repair? And I don’t know the answer.”
Asked whether concerns over leaflet thrombosis would make his list of key valve news in 2015, Webb said: “It’s a key issue in terms of being of interest to regulatory authorities and it’s a new unexpected thing that came up, ... but I don’t think it’s going to be a game changer or anything. It’s just a question of how best to manage patients with biological valves, whether they are transcatheter or surgical.”
- Shelley Wood
Acute Coronary Syndromes
On the ACS front, Daniel Simon, MD, of UH Case Medical Center (Cleveland, OH), pointed to the final results of the PEGASUS-TIMI 54 study, which led to the approval of ticagrelor (Brilinta, AstraZeneca) 60 mg twice daily in patients with a history of MI beyond the first year. “I think it really establishes that you can reduce myocardial infarction, or let’s say atherothrombotic events like myocardial infarction and stroke, if you have more potent antiplatelet inhibition,” said Simon. Most patients in PEGASUS had received a stent so the trial is really an affirmation of the DAPT Study, in that it established the benefit of dual antiplatelet therapy in this patient group, he added.
Given the need to balance the increase in bleeding risk with the reduction in ischemic events, Simon also pointed the emergence of the DAPT score, which can be used to determine the payoff of extending dual antiplatelet therapy beyond 1 year. “The DAPT score finally gives the practicing interventionalist and general cardiologist a clinical score to say which of my patients are likely to benefit from prolonged [DAPT] and which of my patients are less likely,” said Simon.
- Michael O'Riordan
Atherosclerosis and Cholesterol
For C. Michael Gibson, MD, Beth Israel Deaconess Medical Center (Boston, MA), the IMPROVE-IT study and the failure of ezetimibe to garner an event-reduction claim from an FDA advisory panel were big news in 2015. “We’ve had a lot of big wins so far in improving outcomes and taking on the low-hanging fruit,” said Gibson. “I think from here on out, the improvements are going to be fought in those 0.5% to 1% increments. As a community, we have to get used to the fact that the gains in the future are going to be modest. Regulators and clinicians have to expect, approve, and embrace modest gains against a very immodest killer. We have to adjust our perception.”
IMPROVE-IT was pivotal, however, in confirming the LDL hypothesis, namely that lower LDL cholesterol levels translate into a reduction in clinical events. That hypothesis gave a boost to the other big lipid newsmaker in 2015: PCSK9 inhibitors, Gibson observed. The 2 new monoclonal antibodies—alirocumab (Praluent; Sanofi/Regeneron) and evoculamab (Repatha; Amgen)—gained FDA approval based on their ability to lower LDL cholesterol levels. At present, the PCSK9 inhibitors cost approximately $14,000 per year in the United States and are given as an injection once every 2 or 4 weeks, depending on the dose.
Gibson also drew attention to another compound that in 2015 has only completed phase 1 studies, but may prove to be even bigger news. The agent, ALN-PCScs (Alnylam/The Medicines Company), works by interfering with the synthesis of PCSK9 at the RNA level. “At this point, we’re almost thinking of looking at a vaccine, in a certain way,” said Gibson. “People are talking about developing oral drugs [with the PCSK9 inhibitors], but you can’t beat the compliance with a 6-month injection. You’re not going to beat it.”
- Michael O'Riordan
Peripheral Vascular Interventions
Christopher J. White, MD, of the Ochsner Heart and Vascular Institute (New Orleans, LA), named data on drug-coated balloons (DCBs), notably LEVANT-2 in femoropopliteal artery disease, as one of the most significant advances. “The findings are in contrast to the troubled history that DCBs have had when used against DES in CAD. We now have a very strong signal of the benefit of the balloon with drug on it compared to any other treatment in the leg … it’s a paradigm shift,” he said.
Also of note, the Dutch ERASE trial of endovascular therapy plus exercise vs exercise alone in PAD patients with claudication showed—somewhat surprisingly—that there is synergy between both treatments and that neither one alone is preferred, White added. In the past, some physicians would push a conservative approach, whereas “if you talked to plumbers we would tell you that endovascular therapy is better, and this trial pretty clearly says we’re both right and we need to do both things together for our patients.”
William A. Gray, MD, of Columbia University Medical Center (New York, NY), called out DCB use in the superficial femoral artery (SFA) in the IN.PACT SFA trial as well as the emergence of a second DES for use in the SFA. The Eluvia (Boston Scientific) and Zilver PTX (Cook Medical) stents will be pitted against each other in the currently enrolling IMPERIAL trial, he noted. “That’s an exciting trial and something we’ve all been wanting to see—a comparison among these SFA therapies—because right now there’s so much data, it’s improved tremendously, but we’re lacking some of the head-to-head data that we need to make decisions at the bedside.”
Lastly, Gray pointed to the ACT I trial, which compared carotid artery stenting and surgery in asymptomatic patients younger than 80 years with standard surgical risk, showing equivalent results for the primary composite endpoint of any stroke, MI, or death within 30 days. This provides support for the idea that carotid stenting should be considered on par with endarterectomy in this population, Gray said.
- Laura McKeown
Health Policy and the Business of Medicine
Mary Norine Walsh, MD, of St. Vincent Indianapolis Hospital (Indianapolis, IN), said the passage of MACRA (Medicare Access & CHIP Reauthorization Act) is the biggest policy news of 2015 since it permanently repeals the Sustainable Growth Rate (SCR). “With the passage of MACRA, our lives as cardiologists … will change the most dramatically over the next few years as we move forward into a value-based system rather than volume-based,” she emphasized.
Additionally, Walsh raised an issue she believes “has gotten very little press,” namely the residency match, which occurred at the beginning of December. “There are some subspecialties of internal medicine that are no longer filling—residents are no longer electing to go into them. Cardiovascular disease is always well filled, but the specialties of infectious disease, nephrology, and rheumatology, as well as geriatrics, have a very low residency match rate,” she said, Walsh predicted that having inadequate numbers of physicians in those specialties will impact the way cardiologists currently practice medicine and that inadequate numbers of doctors treating complex diseases, specifically rheumatology and nephrology, “will seriously affect patient care going forward.”
- Yael Maxwell
Suzanne Oparil, MD, of the University of Alabama at Birmingham, identified the SPRINT trial as the biggest news in hypertension this year. The trial showed for the first time that lowering systolic blood pressure to a more aggressive goal, that being what was previously considered the upper limit of normal (120 mmHg), compared to the usual goal of less than 140 mm Hg, reduced total mortality and reduced the primary composite endpoint of MI, ACS other than MI, stroke, acute decompensated heart failure, and cardiovascular death.
SPRINT included nondiabetic individuals 50 years and older, and the findings were consistent across various subgroups. “So it’s pertinent to the large proportion of the hypertensive populations in the country that are being treated medically for their hypertension, about 16 million people,” she stressed. “This will encourage most people and particularly cardiologists, who are pretty aggressive with everything, to get the blood pressures lower.”
- Todd Neale
Ulrich Jorde, MD, of Albert Einstein College of Medicine (New York, NY), identified 2 big developments in heart failure this year. The first was the European approval of the HeartMate 3 device (Thoratec), which came with encouraging early data. The FDA requested a US study of the device, and that endeavor has already started enrolling patients, he noted.
The other major news was the European approval of the HeartMate percutaneous heart pump (also Thoratec). Jorde is 1 of 3 national principal investigators for the 452-patients US trial that has already begun comparing the pump to the Impella device (Abiomed). “Those are the 2 big device things that have been new and exciting,” he said. “They have just started [and] we have some early results, but this is basically looking forward to 2016, … when we’re going to get a lot more data on this.”
- Todd Neale
Jordan G. Safirstein, MD, of Morristown Medical Center (Morristown, NJ), when asked about advances in digital health innovations in 2015, called attention to institutions like the Cleveland Clinic and Brigham and Women’s Hospital that have made substantial investments in telemedicine programs this year. Even “administrators and healthcare pundits are buying into the concept of video-based telemedical follow-ups,” he said. This is important because the data show that “frequent follow-ups of any kind prevent readmissions and promote medication compliance,” he stressed.
On the app front, Safirstein noted that several were developed and promoted in 2015 to allow patients and physicians to better interact. “In our smartphone dominated world, there is little doubt that these apps will partner with larger healthcare systems to provide yet another option for patients down the line,” he observed.
But AliveCor—a mobile ECG smartphone app with medication and symptom tracking capabilities—“seems to be the only one that has broken through to actually turn one’s phone into a medical tool,” Safirstein said. “I have recommended it personally to many patients, particularly young patients with paroxysmal A-fib, rather than sending them to ERs, urgent care centers, or offices to get an expensive 12-lead ECG. This is by far the most patient-empowering, cost-saving, progressive app that has penetrated actual patient care.”
- Yael Maxwell
TCTMD also asked the Twittersphere to name the biggest digital health innovations of 2015. Here’s a sample of their responses.
- Cribier reports receiving consultant/honoraria/speaker’s fees from Edwards Lifesciences.
- Jorde reports being 1 of 3 national principal investigators for the SHIELD II trial of the HeartMate percutaneous heart pump.
- Kandzari reports receiving grant/research support from Abbott Vascular, Biotronik, Boston Scientific, Medtronic CardioVascular, and Thoratec as well as consulting fees/honoraria from Boston Scientific and Medtronic CardioVascular.
- Meyers reports being a past president of the Society of NeuroInterventional Surgery.
- Oparil reports being 1 of the principal investigators of the SPRINT trial.
- Rao reports receiving grant/research support from Bellerophon Therapeutics as well as consulting/honoraria/speaker's fees from AstraZeneca, Merck/Schering Plough, Terumo, and The Medicines Company.
- Safirstein serves on the advisory board for Google Healthcare.
- Simon reports serving on an advisory board for Medtronic.
- Webb reports grant support/research contracts from Boston Scientific, Edwards Lifesciences, and St. Jude Medical and consultant/honoraria/speaker’s fees from Edwards Lifesciences and St. Thaler, Gibson, and Walsh report no relevant conflicts of interest.