Cover Story: Now Showing Highlights From ACC.16 The Best of 2016 ... So Far | By Rick McGuire

CardioSource WorldNews Interventions | For several years, a good share of breaking news at the major meetings has been transcatheter aortic valve replacement (TAVR—or TAVI for Euro investigators who refer to the implantation itself as opposed to the intervention performed). We noted at the 2015 TCT meeting that TAVR did not take up nearly the amount of prime-time space as years past. Well, TAVR is back in the spotlight again, this time at ACC.16 and the Cardiovascular Research Technologies (CRT) annual meetings. Often the main hall seemed to be showing Inside Out, featuring a range of emotions as many highly anticipated trials turned out to be negative. There were plenty of sequels, too, as we continue to learn from classic trials, plus a few superheroes: after all, the new Food and Drug Administration commissioner, cardiologist Robert Califf, MD, MACC, presented the ACC.16 Eugene Braunwald Lecture. Overall, the marquee presentations included plenty of interventional news and CardioSource World News: Interventions Executive Editor Rick McGuire reports on both meetings.

Meta-analysis: Long-term Use of DAPT

One of the ACCEL reports in this issue features the 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy (DAPT) in patients with coronary artery disease. Before the documents were released, immediately prior to ACC.16, Zaher Fanari, MD, an interventional fellow in the Cardiology Division of the University of Kansas, KS, presented the results of a meta-analysis of DAPT at CRT.16.

The study was an analysis of six randomized controlled trials, including 47,734 patients. Data were analyzed based on the use of long term DAPT (L-DAPT; n = 27,657), defined as use for more than 12 months or long-term aspirin (L-ASA; n = 20,077), defined as those receiving either long-term aspirin monotherapy or DAPT for < 6 months. The six trials studied: CHARISMA, DAPT, ITALIC, PEGASUS, PRODIGY, and DES-LATE.

L-DAPT was associated with a significant decrease in the composite of death, myocardial infarction (MI) and stroke (TABLE). This effect was significant in patients with prior MI but not in those who underwent PCI with DES but no history of MI (p = 0.21).

The reduction in the primary endpoint was evident with post-PCI patients on prasugrel (3.10% vs. 5.90%; p < 0.001) but only in those with prior MI taking clopidogrel (4.89% vs. 6.28%; p < 0.01) or ticagrelor (6.95% vs. 5.72%; p = 0.001). Long-term use of DAPT was associated with significant increase in major bleeding.

According to Dr. Fanari, “It looks like the patients who will benefit the most (from long-term DAPT) are the ones who had prior MI or presented with acute coronary syndrome. While the ones who got drug-eluting stents with no prior MI—treated (with PCI) for stable angina or symptoms—these guys didn’t benefit much from long-term dual antiplatelet therapy; they just got the burden of severe bleeding.”

No Need to DEFER Stenting

Numerous approaches have been evaluated trying to improve upon primary PCI. The DANAMI-3-DEFER trial was the largest trial yet to evaluate whether delaying stent implantation would improve patient survival and reduce risk of heart failure (HF) or reinfarction. It seems there is no need to bring patients back for an encore.

Investigators evaluated a staged revascularization approach in patients with acute STEMI who were randomly assigned to standard PCI (n = 612) or immediate minimally invasive balloon angioplasty with the aim to quickly restore flow followed by stenting 3 days later in a more stable patient (n = 603).

In results published simultaneously in The Lancet, the DEFER investigators reported that routine deferred stent implantation did not reduce the occurrence of death, HF, MI, or repeat revascularization compared with conventional PCI.

First-author Henning Kelbaek, MD, University of Copenhagen, Denmark, called the results “disappointing,” but quickly added “others will be relieved, because they don’t have to treat patients twice.” If there is a silver lining for Dr. Kelbaek and colleagues, the 3.5 years of follow-up data at least suggest it’s okay to wait if you want. Thomas Engstrøm, MD, PhD, also of the University of Copenhagen, Denmark, said, “It’s important to bear in mind that DANAMI-3-DEFER also showed that it is feasible to delay stenting for 2 days, it was very safe. So, in case you have a situation where you have very complex anatomy, you may end up with very complex stenting procedures.” In that case, he said, “It’s safe to wait 2 days.”

Gentle, Graded Reperfusion Fails

Speaking of Dr. Engstrøm, he was at ACC.16 to present another trial looking at whether abrupt reperfusion by angioplasty may itself damage the heart muscle. “The thinking was that performing reperfusion in a gentle, graded fashion would protect the heart against reperfusion injury,” he said.

In a word: no. “All we found was that the number of patients who ended up with left ventricular ejection fraction above 45% was larger in the group who received ischemic post-conditioning,” said Dr. Engstrøm.

The DANAMI-3 iPOST trial evaluated ischemic post-conditioning, involving 30-second bursts of blood flow interspersed with 30-second pauses to restore blood flow to the heart of 617 patients undergoing primary PCI. Results were compared to 617 patients randomized to conventional primary PCI. Use of iPOST during primary angioplasty failed to reduce the primary composite endpoint of all-cause mortality and hospitalization for HF. Ischemic post-conditioning did reduce the secondary endpoint of all-cause mortality by 25% but this did not reach statistical significance.

“This may translate into improved survival over more years of follow-up,” Dr. Engstrøm said. (Patients were followed for a minimum of 2 years, with an average follow-up of 39 months).

EARLY-BAMI Has No Punch

While on the subject of failed trials, intravenous beta blockers before primary PCI is safe; it just doesn’t offer any clinical benefit.

There was reason for optimism. In 2013, the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CINC) evaluated early intravenous metoprolol and suggested active therapy was associated with reduced infarct size and improved left ventricular (LV) function among patients with anterior STEMI undergoing reperfusion with PPCI.

The Early Beta-blocker Administration before primary PCI in STEMI (EARLY-BAMI) trial was conducted in the Netherlands and Spain. Investigators enrolled patients (average age 62; 75% male) with acute STEMI symptoms of < 12 hours duration who were randomly assigned to receive metoprolol (n = 336) or placebo (n = 346) before PCI. The STEMI could be in any distribution, not limited to anterior infarction like METOCARD-CINC.

Of the patients randomized, 342 (55%) had the primary endpoint assessment of infarct size by magnetic resonance imaging (MRI) at 30 days. Among these patients, there was no effect of pre-PPCI intravenous metoprolol on infarct size (15.3% vs. 14.9%; p = 0.616). However, patients who did not undergo MRI were different (older, more often women, and had fewer first contacts at a referring hospital or PCI center) from those who did, which may have resulted in bias in the primary endpoint assessment.

First-author Vincent Roolvink, MD, Isala Klinieken, Zwolle, Netherlands, said, “Early intravenous metoprolol before primary PCI was not associated with reduction in infarct size although it did reduce the incidence of malignant arrhythmias in the acute phase and was not associated with an increase in adverse events.”

Also, he noted that EARLY-BAMI may not be the end of beta blockers for acute STEMI patients. “I think there is still room for another large trial that includes patients at higher risk, with large heart size, who are given a higher dose of a beta blocker than we used in this study and as soon as possible after diagnosis to see if beta blockers have any place in STEMI patients.”

“Invasive Procedure? Sure, Go for It”

Guidelines emphasize shared decision-making between clinician and patient when determining the best approach for managing coronary artery disease (CAD). So, what happens when patients are asked what to do? You might think they want a prescription and a discharge. Yet, when asked for their preferences, many CAD patients prefer more invasive measures over medical therapy. One downside: these patients tend to underestimate the risk of complications associated with invasive procedures.

The data come from investigators at the Duke Clinical Research Institute (DCRI), who surveyed 98 patients undergoing angiography. Only 6% of patients said their physician should make treatment decisions alone. A similar-sized group (9%) of very independent patients said they wanted to decide on their own. That left 85% of patients preferring some form of shared decision-making.

Earlier research on ambulatory patients with CAD suggested patients show a preference for medical management compared with PCI or coronary artery bypass graft surgery (CABG). In this study, Jacob Doll, MD, and colleagues wanted to explore the preferences of CAD patients undergoing coronary angiography.

Most patients said they would prefer PCI to medical therapy alone or CABG if they were offered a choice by their physician. Obviously, patients were already about to undergo an invasive procedure, which might explain the discrepancy with previous data suggesting patients generally prefer less invasive treatments.

What concerns Dr. Doll is the lack of knowledge within this population. Most patients underestimated the risk of major complications (death, MI, or stroke) associated with PCI (which was underestimated by 70% of the patients surveyed) and CABG (91% missed the mark in estimating risk).

“There’s not a lot of knowledge out there,” said Dr. Doll. “It’s not obvious to patients how risky some of these therapies really are.”

Also, Don’t Ask Patients to Estimate Their CV Risk

Patients can provide a lot of information and, as just seen, they may tell you a more invasive approach is fine with them; but, don’t bother asking them to estimate their own risk. Ann Marie Navar, MD, also of DCRI, and colleagues surveyed 2,856 U.S. patients 40 years of age and older without cardiovascular disease to estimate their 10-year risk. They then compared the patient answers with risk as determined using the calculator recommended by the current 2013 ACC/AHA Guidelines. The researchers found no correlation between patients’ estimates of their risk and calculated CVD risk estimates. Only 27.3% of patients estimated their risk within 10 points of their calculated risk, and most people overestimated their risk of heart disease.

“We were surprised by this, because other studies have shown high rates of ‘optimistic bias,’ where people think they are healthier than they really are,” said Dr. Navar. Women and younger adults tended to overestimate their risk, while men and older adults, on average, underestimated their risk.

Given that most individuals overestimate their risk, the researchers noted the possible unintended consequences of interventions that focus on communicating 10-year risk to patients. “What happens when you tell someone who thinks they have an 80% chance of heart attack or stroke in the next 10 years that it’s only 10%?” Dr. Navar asked. “We need to better understand how what we tell patients about risk affects their behavior.”

Valve Hemodynamic Deterioration in TAVR Patients

Evidence of valve deterioration after TAVR got a lot of attention at the 2015 TCT meeting. At ACC.16, there were reassuring data presented from the DCRI in an analysis of data from the Society of Thoracic Surgeons (STS)/ACC TVT Registry™. Sreekanth Vemulapalli, MD, conducted a retrospective study of 10,099 registry patients to determine whether TAVR valve deterioration is associated with adverse cardiac events.

He and his colleagues detected valve deterioration following TAVR in 2.1% of patients in the first 30 days and in 2.5% of patients in the 30-day to 1-year period post-procedure. Valve deterioration did not seem to be associated with an excess of cardiovascular events, based on cumulative incidence of the composite measure that included death, stroke, MI, and aortic valve re-intervention. Patient factors linked to valve deterioration included AF or atrial flutter, age, severe lung disease, and high body mass index (BMI).

Said Dr. Vemulapalli: “Our finding—including the low incidence of valve deterioration and apparent lack of association with major cardiovascular events up to 18 months after the procedure—may help to inform TAVR care. The information on patient risk factors may aid in patient selection, surveillance and preventive strategies.”

Yes, Interventionalists Respond to Data

Given the vast amount of new data and so little time to absorb it all, there is always a question as to whether news makes its way to clinical practice. A report from the ACC’s CathPCI Registry® shows how well PCI operators are paying attention.

Bivalirudin for PCI in the United States increased until 2013 in patients with acute MI, followed by a rapid early decline in early 2014, corresponding to the release of HEAT-PPCI (How Effective are Antithrombotic Therapies in PPCI?) involved a “real-world” population of patients to evaluate bivalirudin + ‘bailout’ glycoprotein IIb/IIIa inhibitors (GPI) (n = 905) versus heparin + ‘bailout’ GPI (n = 907), per guideline-directed recommendations for such use.

For the primary outcome of major acute coronary events (MACE) at 28 days (a combined endpoint including death, stroke, reinfarction, and target lesion revascularization [TLR]), bivalirudin was associated with significantly more events (8.7% vs. 5.7%, RR 1.52; p = 0.01), mostly due to an increase in MI/stent thrombosis. Moreover, while decreased bleeding is often touted as the predominant reason to use bivalirudin, HEAT PPCI showed no major bleeding reduction with bivalirudin. The authors concluded that their results suggest substantial savings in drug costs with heparin plus selective (‘bailout’) glycoprotein inhibition.

The new NCDR® analysis was based on an analysis of 1,066,384 PCIs (49% STEMI) performed from July 2009, through Dec. 2014. Bivalirudin monotherapy use increased linearly from 2009 through 2013 (increasing from 26.3% to 50.4%) followed by a decline in 2014 (42.4% by the 4th quarter of the year). Conversely, there was a sharp increase in unfractionated heparin (UFH) monotherapy starting in 2014, jumping from 18.7% early in the year to 27.5% in the 4th quarter. Operators were more likely to use bivalirudin during PCI for NSTEMI and GPIs during PCI for STEMI.

Having said that, clearly there remains significant variation in bivalirudin and GPI use during PCI for acute MI that persists in the U.S.

What about the bleeding issue? Does bivalirudin really have no impact on bleeding? One of the problems with the data has been the unbalanced use of GPI with UFH in comparator arms. Eric Secemsky, MD, of Harvard and associated centers, and colleagues, who reported the data above on time trends in anticoagulant use in PCI for acute MI, had another study at ACC.16, this time examining the comparative effectiveness of bivalirudin versus UFH in the same setting.

In the largest, real-world population examined to date, bivalirudin data came from 550,396 patients and UFH data from another 515,988 patients. After instrumental variable analysis, bivalirudin was associated with a 2.59% absolute reduction in bleeding (p < 0.01) but with no difference in mortality (p = 0.35) and a 0.23% increase in repeat PCI for stent thrombosis (p < 0.01). Bleeding reductions were greatest in STEMI patients but negligible for those undergoing PCI via trans-radial access (remember this for another study reported below).

PCI Operator Volume: It Varies (a lot)

Due to increasing procedural success and safety, the 2013 ACC/AHA/SCAI clinical competence statement for PCI reduced the recommended annual minimum number of PCI procedures performed by each operator to 50. Again, using NCDR® CathPCI Registry® data, a team of DCRI investigators analyzed about 99% of operators (the National Provider Identifier number was missing for fewer than 1% of the registry participants).

The overall number of PCIs has stabilized since 2010 in the West and South and since 2011 in the Northeast and Midwest. Median annual operator volume was 60, with 44% of operators performing fewer than the recommended 50 procedures per year. Other findings:

  • Patient characteristics were similar for low- (< 50 procedures), medium- (50 to 100), and high-volume (> 100) centers.
  • Low-volume operators practiced at smaller hospitals with lower average annual PCI volumes.
  • Low-volume operators attempted more emergent PCIs.
  • High-volume operators more often used drug-eluting stents, radial access, and UFH; they less often used GPIs.

Of course, operators may perform PCIs at non-CathPCI hospitals (such as Veterans Administration hospitals), which means the data for these procedures are not included in this study.

Operator volume varied substantially across the U.S., with significant differences in procedure type and interventional practice patterns. The authors concluded that further research on procedure appropriateness and outcomes are needed before the guideline-based volume standards are enforced.

Which Strategies Impact 30-day Readmission After PCI?

Estimated rates vary, but it seems safe to say that more than one in 10 PCI patients are readmitted to the hospital within 30 days of discharge. These patients are at increased risk of adverse events and poorer short-term outcomes.

We do know that risk-standardized readmission rates (RSRR) post-PCI vary substantially across hospitals, but little is known about what processes or organizational structures impact 30-day readmissions.

Karl E. Minges, PhD, MPH, Yale-New Haven Hospital, and colleagues sought to determine hospital strategies independently and significantly associated with lower RSRR. They surveyed 500 hospitals (81% response rate) participating in the CathPCI Registry.

They performed weighted multivariate regression using CathPCI Registry data to determine the association between specific hospital strategies and hospital 30-day RSRR. They found 5 hospital strategies significantly associated with lower RSRRs, including:

  1. Review of CathPCI Registry data by cardiology leadership (seen in 65.8% of surveyed sites; p = 0.003);
  2. Regular meetings with cardiac rehabilitation to review the care of cardiac patients (44%; p = 0.016);
  3. Ability to retain high quality staff (64.8%; p = 0.023);
  4. Rapid adoption of new technologies used for PCI (75.1%; p = 0.012); and
  5. Discharge with the date and time of a follow-up appointment already arranged (58.3%; p = 0.003).

Hospitals varied in terms of numbers of strategies employed and, despite the effectiveness of these strategies, only a minority of hospitals used all five approaches. However, institutions that did employ a greater number of strategies demonstrated superior outcomes.

Impact of Bleeding Avoidance Strategies

Periprocedural bleeding is among the most common complications following PCI and is associated with increased risk for short- and long-term mortality, stroke, longer hospital stay, and higher cost. Multiple bleeding avoidance strategies have been developed to reduce the incidence of bleeding, but which ones work?

Unlike the Yale study above looking at strategies that reduce 30-day readmission rates, this study of CathPCI data had less promising results.

In data presented at ACC.16 and published subsequently in JACC Interventions, Vora and colleagues from DCRI analyzed records from almost 2.5 million procedures at 1,358 sites between 2009 and 2013. In conducting their analysis, they adjusted for patient risk, including variables such as gender, age, body mass index, the presence of cerebrovascular disease, prior PCI, and diabetes.

The detected substantial variation in bleeding rates, despite the fact that bleeding avoidance strategies use was high (median hospital rate of any such strategy was 86.6%). Importantly, patient mix explained just one-fifth of the overall hospital level variation in bleeding.

After adjusting for individual patient risk for bleeding, hospital rates for bleeding varied from 2.6% to 9.3%. With bleeding avoidance strategies having only a small effect on overall hospital-level variation, about 70% of the variation among hospitals remains unexplained.

They did show that when hospitals used bleeding avoidance strategies in more than 85% of patients, bleeding rates were lower.

Amit N. Vora, MD, MPH, the study’s lead author and a cardiologist with the Duke Clinical Research Institute in Durham, NC, addressed limitations associated with using post-procedure bleeding as a performance measure for hospitals. Because such a high percentage of bleeding rates remain unexplained, he said, “The stringent use of bleeding rate measures to determine reimbursement rates or to penalize institutions by payers and regulators may be premature at this time.”

He and his colleagues did show that higher use of bleeding avoidance strategies was associated with reduced levels of bleeding at the hospital level. That means that efforts to broaden the use of these strategies in all patients might be a reasonable way to reduce overall variation in hospital bleeding rates.

Bleeding avoidance strategies were more commonly used in lower risk patients and lower volume hospitals. The analysis showed a 5.85% reduction with bivalirudin anticoagulation and a 0.88% reduction with the use of a vascular closure device. In an accompanying editorial comment, Eric Bates, MD, FACC, University of Michigan Medical Center, Ann Arbor, MI, noted that the big surprise in this report was that radial artery access had almost no impact on bleeding variation (a 1.26% reduction in variation in bleeding rates with transradial access). In an earlier patient-level analysis from the same registry, Dr. Bates noted that there was a reported significant absolute reduction (8.0% for women, 4.1% for men) in bleeding risk with radial artery access.

Dr. Bates noted, “U.S. interventionalists have been criticized for being slow to adopt radial artery access. And yet, the radialists need to avoid hubris and prove to the skeptics that they are not wearing the emperor’s new clothes when they promote the superiority of radial artery access over femoral artery access for all patients.”

Importantly, he added, the study by Vora et al. does not support the use of bleeding rate as a hospital-level PCI performance measure.

Fire and Ice

Current guidelines recommend (Class I, level A) catheter ablation with pulmonary-vein isolation (PVI) as treatment for drug-refractory paroxysmal atrial fibrillation (AF). Two approaches are widely marketed: radiofrequency ablation (RFA) using electroanatomical mapping (THERMOCOOL, Biosense Webster, Inc.) and cryoballoon ablation using fluoroscopic guidance (Arctic Front, Medtronic, Inc.).

The FIRE AND ICE trial was a multicenter, randomized effort comparing RFA PVI to cryoballoon PVI in 762 symptomatic patients. There was a 90-day blanking period after the procedure, only after which were endpoint events counted.

The rates of the primary efficacy endpoint (the first documented AF recurrence, occurrence of atrial flutter or atrial tachycardia, use of antiarrhythmic drugs, or repeat ablation) were 34.6% for RFA ablation and 35.9% for cryoballoon (p < 0.001 for noninferiority). There was no difference, either, in the occurrence of the primary safety endpoint (a composite of death, cerebrovascular events, or serious treatment-related adverse events; hazard ratio, 0.78; p = 0.24).

What does it mean that cryoballoon ablation was noninferior to RFA (and safety was similar between approaches)? The study was presented by Karl-Heinz Kuck, MD, PhD, FACC, St. Georg Hospital, Hamburg, Germany. He said, “Radiofrequency ablation for atrial fibrillation is the most challenging procedure in cardiology, but with the cryoballoon, it becomes a very simple procedure. So, with a single-step approach, we should be to able to achieve the main goal of treatment which is isolation of the pulmonary vein.”

“Freezing usually produces better lesions,” he added. “The lesion is very precise, very discrete, very sharp line between normal and frozen tissue. While a radiofrequency lesion is completely different; it’s diffuse and there is a lot of overlap between normal tissue and necrosis.”

Stents Disappear but Questions Do Not

Compared with bare-metal stents (BMS), drug-eluting stents (DES) decrease the risk of restenosis without increasing the risk of death and MI. However, unlike their bare-metal counterparts they are associated with hypersensitivity reactions, delayed healing, and incomplete endothelialization, which may increase the risk of late and very late stent thrombosis. And, of course, current guidelines recommend extended DAPT after DES placement, increasing bleeding risk, requiring good patient compliance, and added cost.

Bioresorbable vascular scaffolds (BVS) were proposed as an answer to this dilemma. Efforts to develop the devices began more than 20 years ago, but the world first learned of their clinical use in 2000. The “disappearing” stent became commercially available 11 years later, when Abbott’s Absorb™ BVS became the first of its kind to be approved for use in Europe. The everolimus-eluting device, made of a poly-L-lactide polymer, won its approval based on results of clinical trials demonstrating that the stent restored blood flow by opening a blocked vessel, providing support to that vessel until it dissolved after about 2 years.

Since then, the BVS concept has hit a few snags. Yes, the conformability and superior flexibility of BVS allows for minimal changes of vessel geometry and along with the eventual absorption of the lumen-protruding struts attenuate the unfavorable hemodynamic changes typical of rigid stents. Plus, elimination of late-acquired malapposition (an established trigger of stent thrombosis) or edge-related vascular responses in the long term are additional theoretical benefits of BVS. On the other hand, strut thickness is larger compared with new-generation DES, leading to suboptimal crossing profiles, limiting the ability to treat complex (e.g., excessively tortuous or calcified) lesions or to implant overlapping BVS, resulting in inferior immediate, post-procedural angiographic outcomes of device performance.

Recent randomized trials have raised concerns about the possibility of higher stent thrombosis (ST) with BVS. Thus, Alok Saurav, MD, et al. of Creighton University Medical Center, Omaha, NE, conducted a meta-analysis of five randomized and three observational trials, including data on 2,760 BVS patients and 2,212 receiving DES. He presented the data at CRT.16.

All patients were on DAPT for at least 1 year. They reported a strong trend towards higher ‘definite ST’ (RR: 1.8; p = 0.06). Clinical outcomes were similar for death (RR: 0.74; p = 0.57), cardiac death (RR: 0.83; p = 0.66), TVR (RR: 1.0; p = 0.95); and ischemia-driven TVR (RR: 1.0; p = 0.6). The difference? That would be MI, which was significantly higher with BVS (RR: 1.35; p = 0.049).

ORBIT II 3-year Results

Nearly 25 years have passed since the introduction of rotational atherectomy (RA). While RA facilitates PCI for complex de novo lesions with severe calcification, a strategy of routine RA has not led to a reduction in restenosis or MACE. While effective in ablating calcified lesions, RA still produces procedural complications, such as slow flow and perforation.

The persistence of angiographic and clinical complications of RA underscores the need for improvements in technique and technology for severely calcified coronary lesions. The orbital atherectomy (OA) system, distinct from RA, works on the principle of elliptical burr movement, with variation in effective burr size based on rotational speed. Compared to RA, the Orbital system is designed for easier set up and use, better device control in the operating field, and a smaller (0.012) guidewire and tip (0.014) that are compatible with 6-Fr guiding catheters. Consequently, practitioners have experienced a faster learning curve and less slow flow than with RA, plus fewer procedural complications.

The ORBIT II (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) trial demonstrated a TVR rate of 5.9% at 1 year with OA. Importantly, this was in a patient population (n = 440) who all had severely calcified lesions. ORBIT II met both primary safety and efficacy endpoints by significant margins. Investigators demonstrated low rates of 30-day MACE (10.4%), cardiac death (0.2%); MI (9.7%), and target vessel revascularization (1.4%).

At CRT.16, ORBIT II 3-year results were presented showing a cumulative cardiac death rate of 6.7%. For target vessel and target lesion revascularization (TVR/TLR), the 3-year rate was 10.2%, including a TVR rate of 3.4% (non-TLR) and TLR rate of 7.8%.

According to Jeff Chambers, MD, director of the cardiac catheterization laboratory at the Metropolitan Heart and Vascular Institute, Mercy Hospital, Minneapolis, MN, “Using the coronary Orbital atherectomy system as a lesion preparation tool prior to stent implantation offers an effective treatment option, with durable long term results, in these complex patients with severely calcified coronary lesions.”

TAVR Takes the Stage Again: Next Gen TAVR Device Scores in Intermediate-risk Patients

2015 was quite the interesting year for transcatheter aortic valve replacement (TAVR). We now know from the PARTNER trial that mortality from the first to the fifth year is much the same whether high-risk patients with aortic stenosis are treated with TAVR or surgery (SAVR).

The success in the high-risk setting has led to interest in moving TAVR to intermediate-risk patients. Susheel Kodali, MD, FACC, director of the heart valve program at New York-Presbyterian/Columbia University Medical Center in New York City, NY, told the media last year (ACC.15), “We now have intermediate-risk data where we’re getting to a 30-day 1% mortality risk and a 1% stroke risk with TAVR; how much better data do we need?” He added “maybe the conversation shouldn’t be ‘TAVR when surgery’s not a good option’ but rather TAVR is the preferred option—at least in 80-year olds.” (Average age at baseline in this trial was 82.6 years.)

One year later, it’s ACC.16 and the argument still holds. The lower-profile, next-generation valve was evaluated in PARTNER trial patients. “Improvements with the SAPIEN 3 valve have made this an easier procedure to perform,” said Vinoid Thourani, MD, Emory University School of Medicine, Atlanta, GA, “And this study shows that we can do it with an extremely low risk of complications and mortality.”

Like Dr. Kodali 1 year earlier, Dr. Thourani concluded: “In intermediate-risk patients with severe aortic stenosis, SAPIEN 3-TAVR compared with surgery improves clinical outcomes and is the preferred therapy.”

One other interesting report: in a large data set of more than 40,000 TAVR cases performed in the first 4 years after the technology was approved by the US Food and Drug Administration, John Carroll, MD, FACC, of the University of Colorado Hospital, Denver, CO, said, “TAVR outcomes are improving but the one (question) that needed to be studied was volume. This analysis shows that the effect of TAVR volume on risk adjusted in-hospital mortality is statistically significant and clinically meaningful.”

CoreValve at 3 Years

Let’s move to the CoreValve (Medtronic). The investigators previously hypothesized that the reasons for the survival benefit favoring TAVR versus surgery in high-risk patients might be related to reduced peri-procedural complications. It makes sense that, in patients with severe aortic stenosis at increased risk for surgery, early differences bleeding, acute kidney injury, post-operative atrial fibrillation, improved aortic valve hemodynamics, lower rates of prosthesis patient mismatch, and more rapid recovery with improved health status might influence early survival, but then the 2-year data showed a continuing separation of the survival curves.

In data presented at ACC.16 and published simultaneously in JACC, investigators reported the 3-year clinical and echoicardiographic outcomes for the CoreValve U.S. Pivotal High Risk Randomized Trial. Of 797 patients with severe symptomatic AS deemed at high risk for surgery underwent randomization at 45 U.S. centers, 750 patients had an attempted procedure.

Three-year all-cause mortality or stroke was 37.3% in the TAVR arm compared with 46.7% with SAVR arm (p = 0.006), which translated into a 20.1% relative risk reduction and a 9.4% absolute risk reduction with TAVR. Significant reductions also were seen in all- cause mortality (32.9% vs. 39.1%, respectively; p = 0.068), stroke (12.6% vs. 19.0%, respectively; p = 0.034), and major adverse cardiovascular or cerebrovascular events (40.2% vs. 47.9%, respectively; p = 0.025).

Vascular complications, re-intervention and the need for new permanent pacemaker implantation were more common with TAVR, whereas life-threatening or major bleeding and acute kidney injury was more common with SAVR.

Aortic valve hemodynamics were also better at 3 years with TAVR (mean aortic valve gradient, 7.62 mm Hg versus 11.40 mm Hg with SAVR; p < 0.001), but moderate-severe residual aortic regurgitation was higher with TAVR (6.8% vs. 0.0% in SAVR; p < 0.001). There was no evidence of clinical valve thrombosis or structural valve deterioration in either group.

The investigators concluded that in high-risk patients with severe symptomatic aortic stenosis, 3-year clinical outcomes significantly favored self-expanding TAVR over SAVR. Aortic valve hemodynamics were also more favorable in TAVR patients with no differences noted in structural valve deterioration or clinical valve thrombosis. The incidence of moderate or greater aortic regurgitation significantly favored SAVR.

Study presenter G. Michael Deeb, MD, of the University of Michigan Medical Center, noted in his presentation that although these are still “short-term data,” going forward the shape and the divergence of the survival curves will depend on the two valve types. “Whether these curves continue to separate may be determined by the improved benefit of the hemodynamics with the transcatheter valve. If the curves come together, well maybe the amount of aortic insufficiency and pacemaker implants has an impact.” He stressed that further follow-up is important.

Read the full May/June issue of CardioSource WorldNews Interventions at ACC.org/CSWNI

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Interventions and Coronary Artery Disease

Keywords: CardioSource WorldNews Interventions, Aspirin, Composite Resins, Coronary Artery Disease, Myocardial Infarction, Randomized Controlled Trials as Topic, Stroke, Transcatheter Aortic Valve Replacement, United States Food and Drug Administration


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