On the heels of horrifying attacks on Las Ramblas, more than 31,000 cardiology-minded folk arrived to the Fira Gran Via conference center in Barcelona, Spain to see armed guards, a multitude of security personnel, sniffer dogs and luggage scanning machines along their way to the sessions. Yet come they did as the world of cardiology convened for the European Society of Cardiology Congress 2017, bringing with them both a generalized (but not overwhelming) discomfort with the recent violence mixed with a clear enthusiasm for their purpose.

While perhaps not of the same caliber as confirming the inflammation hypothesis whilst taking a whack at cancer (as the CANTOS trial arguably did), the interventional cardiology world learned of some new data that provides incremental and important information to those conducting PCI. We’ll share just six trials here – three related to coronary stenting and three related to the treatment of atrial fibrillation (AFib).

Delayed healing of the stented artery and incomplete neointimal coverage of an implanted stent increases the risk of late stent thrombosis and prolongs the need for dual antiplatelet therapy (DAPT). It would stand to reason, then, that the extent of early strut coverage after stent implantation might impact the safety of early discontinuation of DAPT. The “Early strut coverage in patients receiving new-generation DES and its implications for DAPT: a randomized controlled trial” tested this hypothesis.

Researchers from seven centers, led by Myeong-Ki Hong, MD, PhD, randomly assigned stable patients to receive either an everolimus-eluting stent (EES; Xience) or a biodegradable polymer biolimus-eluting stent (BES; Nobori). Patients were also randomly assigned to undergo either optical coherence tomography- (OCT-) guided stent implantation or angiography-guided implantation.

The trial was prematurely terminated because of slow recruitment, the low event rate seen in patients on DAPT for 3 months and the unexpected halt in production of Nobori stents by the manufacturer. Therefore, only 894 (81.3 percent) of the planned 1,100-strong cohort were enrolled.

Strut coverage at the three-month follow-up OCT — the primary study endpoint — was similar for EES and BES. However, OCT-guided DES implantation resulted in better strut coverage than angiography-guided implantation, with 7.5 percent of struts still uncovered at three months for OCT-guided implantation vs. 9.9 percent with angiography (p = 0.009).

Those with ≤6.0 percent of struts left uncovered at three months were eligible to stop their clopidogrel and remain on only aspirin, while those with >6 percent uncovered struts continued clopidogrel for 12 months. A secondary outcome — a composite of cardiac death, myocardial infarction (MI), stent thrombosis and major bleeding at 12 months — did not differ between those who had only three months of DAPT and those who continued to 12 months. Indeed, the event rates were quite low, said Hong, with only one stent thrombosis in the first group and only one major bleed in the second group (p = 0.79).

The interventional cardiology world learned of some new data that provides incremental and important information to those conducting PCI. We’ll share just six trials here – three related to coronary stenting and three related to the treatment of atrial fibrillation (AFib).

In a subsequent discussion of the trial, Hong was asked why there is such a push to get patients off DAPT, especially when some trials have indicated that longer is better. His answer was that guidance is needed for the safe stopping of DAPT for “the 15 to 20 percent of patients who return to the clinic” after DES implantation needing a non-cardiac surgery, a dental procedure or even a cataract surgery, where their care must be delayed because they are taking DAPT.

Emmanouil S. Brilakis, MD, PhD, FACC, shared with attendees the findings of the DIVA trial, which was a randomized, blinded comparison of DES and bare metal stents (BMS) for saphenous vein graft PCI. Put simply, the trial found no significant differences in either short- or long-term outcomes between stent types.

His trial follows several previous trials comparing DES and BMS in saphenous vein graft lesions, but updates the evidence by increasing the sample size enrolled, employing second-generation DES in 89 percent of patients and routine angiographic follow-up, and by using embolic protection in a majority (69 percent) of patients.

Of the four prior studies, three of them — SOS, ISAR-CABG and BASKET-SAVAGE – all showed superior benefit for DES over BMS. “The fourth one — the RRISC trial — actually found higher events with its DES arm,” said Brilakis.

DIVA included 597 patients enrolled at 25 Veterans Affairs hospitals, of whom 592 were included in a 12-month follow-up analysis of primary and secondary outcomes, and 555 were followed for up to 60 months. The study had 86 percent power based on the actual number of events in the study to determine a difference between stents.

No significant difference was seen in the primary endpoint of target vessel failure (TVF) at 12 months, with event rates of 17 percent for DES and 19 percent for BMS (p = 0.67). TVF was defined as a composite of cardiac death, target vessel MI or target vessel revascularization (TVR).

There was also no difference in the occurrence of TVF at long-term follow-up completed at a median of 2.7 years (p = 0.46). These findings were consistent across multiple subgroups, including those with and without diabetes, those with one or more target lesions and those with newer (<13.5 years) and older saphenous vein grafts.

No meaningful differences were seen at short- or long-term follow-up for any of the individual endpoints of death, cardiac death, MI, and target vessel MI, PCI, CABG, TVR, definite stent thrombosis, or definite/probable stent thrombosis. The use of antiplatelet medication (aspirin or P2Y12 inhibitor) was also similar between the two groups.

“The DIVA trial showed no difference in either short- or long-term outcomes between DES and BMS, which has important economic implications and also highlights the need for new strategies for treating severe vein graft lesions,” Brilakis said.

"The DIVA trial showed no difference in either short- or long-term outcomes between DES and BMS, which has important economic implications and also highlights the need for new strategies for treating severe vein graft lesions. " — Emmanouil S. Brilakis, MD, PhD, FACC

Commenting on ESC TV, William Wijns, MD, PhD, noted that the event rates in both arms of DIVA were “pretty high,” highlighting the difficultly inherent in revascularization of stenosed vein grafts, but he still marveled at the noninferiority between BMS and DES. “That’s new,” he said.

Masahiro Natsuaki, MD, presented five-year findings from the NEXT trial, which compared the Nobori biodegradable polymer biolimus-eluting stent (BP-BES) with the Xience/Promus durable polymer everolimus-eluting stent (DP-EES). The trial originally enrolled 3,200 patients scheduled for PCI across 98 centers in Japan.

Follow-up at one and three years was focused on the primary safety endpoint of death or MI and the primary efficacy endpoint of TLR, and showed no differences between stents. To assess the impact of the stents on long-term follow-up, an extended follow-up study enrolled 2,568 patients from 78 centers, with 2,408 (93.8 percent) completing five-year follow-up. Despite the all-comers design, only about 5 percent of patients had acute MI as their original diagnosis while about 84 percent underwent PCI for stable CAD. Mean SYNTAX score was low, at 10.

At five years and in a landmark analysis that looked at events from one to five years, the investigators found no differences in either of the primary safety or efficacy endpoints, nor in the individual endpoints of death, cardiac death, MI, stroke, and major or minor bleeding. The incidence of TLR was slightly, but significantly, higher in the BP-DES group, reported Natsuaki (8.1 percent vs. 5.9 percent; p = 0.04). The five-year stent thrombosis rates were 0.49 percent for BP-BES and 0.34 percent for DP-EES (p = 0.52).

“Advantages of biodegradable polymer DES over durable polymer DES were not apparent even at five-year follow-up after stent implantation,” concluded Natsuaki. “Very long-term follow-up of the extended NEXT study scheduled at 10 years will provide important information on the potential advantages of BP-DES over DP-DES.”

“For me it is very interesting to see this extremely low rate of stent thrombosis at five years,” said Michael Haude, MD, one of the session chairs.

Leading off the AFib trials was EMANATE, whose purpose was to compare rates of stroke and bleeding with apixaban vs. warfarin with heparin in anticoagulation-naïve patients scheduled for cardioversion of predominately new onset non-valvular AFib. Anticoagulation-naïve was defined as those receiving an anticoagulant for <48 hours during the index episode of AFib.

"In patients with atrial fibrillation undergoing cardioversion, apixaban with or without a loading dose was safe, resulting in few bleeding events and less strokes than conventional anticoagulant therapy. We expect these findings will be translated into clinical practice." — Michael D. Ezekowitz, MB, ChB, FACC

“In patients with atrial fibrillation undergoing cardioversion, apixaban with or without a loading dose was safe, resulting in few bleeding events and less strokes than conventional anticoagulant therapy,” reported Michael D. Ezekowitz, MB, ChB, FACC. “We expect these findings will be translated into clinical practice.”

This multicenter, prospective, open-label trial included 1,500 patients with AFib who were randomly assigned to apixaban administered orally at a dose of 5 mg twice a day (or 2.5 mg twice a day when two of the following conditions were met: age ≥80 years, weight ≤60 kg or serum creatinine ≥1.5 mg/dL) or parenteral heparin with warfarin. At the discretion of the local investigator, patients assigned to the study arm could also receive an initial 10 mg or 5 mg loading dose of apixaban (for study doses of 5 mg and 2.5 mg, respectively) if the cardioversion was immediate.

Patients treated with apixaban had fewer strokes and similar bleeding to those receiving usual care. There were no strokes in the 753 patients treated with apixaban compared with six strokes in the 747 receiving usual care (p = 0.02). There were no systemic embolic events in either group.

Major bleeding events occurred in three apixaban patients and in six heparin/vitamin K antagonist patients. Clinically-relevant non-major bleeds were seen in 11 and 13 patients, respectively. There were two deaths in the apixaban group and one in the heparin/warfarin group. (No p-values were given supporting these findings.)

Out of 753 patients in the apixaban group, 342 received a loading dose. In this subgroup, there were no strokes or systemic embolic events, one death, one major bleed and four clinically relevant non-major bleeds.

Commenting on the trial, Jens Cosedis Nielsen, MD, PhD, noted that, while the risk of stroke is lower in the apixaban arm, when the rate is combined with that for death, the difference is no longer significant. Nor is it significant if bleeding is added into the equation. He stressed that with an underpowered trial such as this one and a low event rate, “statistical comparisons should be interpreted with caution” and the study should only be considered “exploratory.” The trial adds, however, to “growing evidence suggesting that NOACs are a viable alternative to heparin in patients undergoing cardioversion for AFib,” Nielsen concluded.

CASTLE-AF was the first randomized trial to compare catheter ablation to antiarrhythmic drug (AAD) therapy for individuals with coexisting heart failure (HF) and AFib that focused on hard clinical outcomes of mortality and hospitalization for worsening HF. A total of 397 patients (mean age, 64 years) with symptomatic paroxysmal or persistent AFib and HF (left ventricular ejection fraction <35 percent) were randomly assigned to catheter ablation with pulmonary vein isolation or conventional standard therapy, either rate or rhythm control. To be eligible for the study, patients had to already have an implanted ICD with home-monitoring functionality.

Catheter ablation bested conventional therapy, with a 38 percent relative risk reduction in the composite endpoint of all-cause mortality and HF hospitalization at five years (HR, 0.62; p = 0.007), reported lead author Nassir F. Marrouche, MD.

For the secondary endpoint of all-cause mortality, the rates were 13.4 percent for catheter ablation and 25 percent for conventional therapy, offering a 47 percent reduction in relative risk (HR, 0.53; p = 0.011). Hospitalization for worsening HF was seen in 20.7 percent and 35.9 percent, respectively (HR, 0.56; p = 0.004). Cardiovascular mortality (HR, 0.49; p = 0.008) and cardiovascular hospitalization (HR, 0.72; p = 0.041) were also reduced with the interventional strategy compared with standard of care.

Commenting on the trial, Carina Blomström-Lundqvist, MD, PhD, called the findings “novel” because it’s the first trial to study hard outcomes (as compared with previous trials that looked at freedom from AFib as a primary endpoint) and, indeed, catheter ablation was superior to pharmacological therapy for those hard outcomes. She cautioned, however, that application of the findings will need to be in similar patients to those enrolled in the trial, which she noted was a relatively young and symptomatic group with long-standing AFib, reflecting, perhaps “a bias toward recruiting healthier patients who could tolerate the procedure of AFib ablation.” Despite this, she also suggested that the “take home message” is that “it’s time to offer AFib ablation procedures at an earlier stage in congestive heart failure patients with atrial fibrillation.”

The CAPTAF investigators also sought to change things up concerning AFib trial endpoints: they compared the efficacy of catheter ablation and optimized pharmacological therapy using — again, not AFib recurrence — but quality of life as the primary endpoint, “since that is actually the indication for the AFib ablation procedure,” noted principal investigator Blomström-Lundqvist. They also felt that continuous AFib rhythm monitoring to optimally assess AFib burden was important.

A total of 155 patients with symptomatic AFib who had failed at least one drug for either rate or rhythm control received an implantable cardiac monitor for a two-month run-in period and then were randomized to ablation with pulmonary vein isolation or AAD with adequate doses according to guidelines.

"The lack of a statistically significant difference between treatment groups in the reduction in AFib burden suggests that other mechanisms may explain the better improvement of quality of life and symptoms achieved with pulmonary vein isolation compared to antiarrhythmic drugs." — Carina Blomström-Lundqvist, MD, PhD

Patients who received catheter ablation reported significantly greater improvement in general health, as measured by the Short Form 36-item (SF-36) health survey, from baseline to 12 months (mean change, 11.0 vs. 3.1; p = 0.0084). As well, all quality of life SF-36 subscales, except for bodily pain and social functioning, improved significantly more in the ablation group compared with the AAD group.

AFib burden, or the proportion of time in AFib as obtained from the implantable cardiac monitor, was reduced in both groups from baseline to 12 months. While the reduction was numerically larger in the ablation arm, the magnitude of change from baseline did differ significantly between groups. The complication rate between treatment groups was also comparable.

Blomström-Lundqvist said: “The lack of a statistically significant difference between treatment groups in the reduction in AFib burden suggests that other mechanisms may explain the better improvement of quality of life and symptoms achieved with pulmonary vein isolation compared to antiarrhythmic drugs.” She suggested that the improved quality of life with ablation is related to the side effects of the drugs, “although this is not shown yet in this trial.”

“This study is a game changer in how we follow-up patients — it’s not the 30 seconds of AFib anymore, it’s quality of life, how our patients are feeling, which is very important,” said Marouche, the scheduled discussant for the trial. “The trial also showed yet again, that ablation is superior to antiarrhythmic drugs, anyway you look at it.”

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Click the cover image above to read the latest issue of Cardiology: Interventions in e-pub format or click here to read it on the web!

Keywords: ACC Publications, Cardiology Interventions, Inflammation, Angiography, Angiography, Anti-Arrhythmia Agents, Anticoagulants, Arteries, Aspirin, Atrial Fibrillation, Catheter Ablation, Diabetes Mellitus, Drug-Eluting Stents, Embolism, Emotions, Health Surveys, Heparin, Iatrogenic Disease, Metals, Myocardial Infarction, Neointima, Neoplasms, Pain, Platelet Aggregation Inhibitors, Polymers, Pulmonary Veins, Quality of Life, Sample Size, Saphenous Vein, Stents, Stroke, Thrombosis, Ticlopidine, Tomography, Optical Coherence, Veterans, Warfarin

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