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The Take Home: AHA
The American Heart Association Scientific Sessions were held Nov. 10 to 12, 2018, in Chicago, during which several trials of interest to the interventional cardiology community were presented. Cardiology Today’s Intervention was on-site and discussed key findings with several opinion leaders, including Sripal Bangalore, MD, MHA, from NYU Langone Health; Cardiology Today’s Intervention Associate Medical Editor Roxana Mehran, MD, from Icahn School of Medicine at Mount Sinai and the Cardiovascular Research Foundation; and American College of Cardiology President C. Michael Valentine, MD, from Stroobants Cardiovascular Center, Centra Health.
FREEDOM Follow-On
Mehran: I was pleased to see follow-up of patients from the original FREEDOM trial, which evaluated CABG vs. PCI in patients with diabetes and multivessel disease, extended for another 6 years.
Although the researchers had issues obtaining full follow-up on all of the cohorts studied, they were able to get the vital status of 943 patients and found a benefit of CABG over PCI and a reduction in mortality with CABG vs. PCI with first-generation drug-eluting stents in patients with diabetes and multivessel disease (18.7% vs. 23.7%; HR = 1.32; 95% CI, 0.97-1.78) over a mean follow-up of 7.5 years.
These data provided important, consistent validation of the fact that, at the moment, patients with diabetes and multivessel disease in need of revascularization should preferably be treated with CABG over PCI. It is worth noting that PCI in FREEDOM was performed with first-generation DES and we have come a very long way since then. To go back and conduct a trial such as FREEDOM all over again with next-generation stents would be wonderful, but I do not think that will happen any time soon.
Valentine: The FREEDOM Follow-On data solidify our guidelines and recommendations that patients with diabetes and multivessel disease have better long-term outcomes with surgical revascularization. I believe that especially applies to this group, in which 99% had left anterior descending artery disease. The ability to get an arterial bypass to the LAD is crucial in these patients. We think having LAD disease is one of the main determinants of how well patients do long-term. If the patients had not had LAD disease, the results may have been much closer.
FREEDOM Follow-on is a long-term follow-up of a well-done study. Some criticisms might include the fact that only 50% of patients stayed in the long-term study. Others might say that our techniques have changed with third-generation stents. However, I think the lessons are pretty solid and these findings will keep our guidelines intact.
Door-to-Unload in STEMI Pilot Trial
Valentine: In this study, 50 patients with anterior STEMI were assigned to LV unloading with the Impella CP device (Abiomed) followed by immediate reperfusion or delayed reperfusion after 30 minutes of unloading. Traditional 30-day MACCE rates were low and not significantly different in the immediate vs. delayed reperfusion groups (8% vs. 4%, respectively). Rates of total composite MACCE that also included vascular complications were not different between the two study arms (immediate group, 8%; delayed group, 12%; P = .99).
Many interventionalists with whom I spoke after the presentation were surprised about many aspects of the trial. No. 1, they were surprised that the researchers would conduct a trial with LV unloading without patients with cardiogenic shock. No. 2, they were surprised that the researchers excluded patients with cardiogenic shock, as that is the one group that we know benefits.
Additionally, while we do understand the concept, it was such a small pilot study that it would take very little change from one group to the other to lead to significant results. Yet, there was no significant change in infarct size.
Many interventionalists were also surprised that investigators would conduct this trial because unloading the ventricle has not been shown to be favorable in all-comers, nor has it been shown to be favorable in this subgroup of patients with anterior MI but without cardiogenic shock.
In light of these results, several interventional cardiologists with whom I spoke did not see a reason to support a larger trial because they did not see any significant benefits or even a trend toward significant benefits that would justify further investigation.
T-TIME
Valentine: T-TIME tested a hypothesis that thousands of interventional cardiologists have thought about in the last 20 years — whether adjunctive alteplase at the time of intervention could help microperfusion and long-term LV function. In 440 patients who had primary PCI for STEMI, there was no significant difference at 2 to 7 days after MI in the amount of microvascular obstruction between those assigned alteplase 20 mg or placebo (P = .32) and between those assigned alteplase 10 mg or placebo (P = .28).
Many interventional cardiologists wondered why the trial had not been performed before. There were many different trials in which there was “drip and ship,” but this occurred at the time of primary PCI. And, many were hoping that there would be a positive result out of this trial because it made clinical sense. It would have been great if a significant difference had been observed in one of the arms. We are all disappointed that we did not see any improvement. However, it was an interesting trial and a question that needed to be answered.
ISAR-TEST 4
Bangalore: In the ISAR-TEST 4 trial, the researchers randomly assigned patients in a 2:1:1 fashion to PCI with a new-generation sirolimus-eluting stent with a biodegradable polymer (Yukon Choice PC, Translumina; n = 1,299), a new-generation everolimus-eluting stent with a permanent polymer (Xience, Abbott Vascular; n = 652) or an early-generation SES with a permanent polymer (Cypher, Cordis; n = 652).
At 10 years, the incidence of MACE was different across treatment groups (P =.003), which was mainly driven by an 18% to 21% RR reduction with both new-generation DES vs. the early-generation DES. Specifically, when compared with the early-generation permanent-polymer SES (54.9%), the incidence of MACE was lower with both the new-generation biodegradable-polymer SES (47.7%; HR = 0.82; 98.3% CI, 0.69-0.96) and the new-generation permanent-polymer EES (46%; HR = 0.79; 98.3% CI, 0.65-0.96). The incidence of MACE, however, was not significantly different with the new-generation biodegradable-polymer SES vs. the new-generation permanent-polymer EES (HR = 1.04; 98.3% CI, 0.87-1.24).
The results are very clear. If you compare second-generation durable-polymer DES or biodegradable-polymer DES vs. first-generation durable-polymer DES, there is not only a significant reduction in MACE, but there is also a significant reduction in death and stent thrombosis. And, if we look at the other endpoints, they are numerically lower when compared with the first-generation durable-polymer DES.
One take-home message is that improvement in stent design can have meaningful impact on hard outcomes, including death and/or MI. Finally, I want to emphasize that if we look at current-generation DES, after 1 year, the MACE rate accrues at a staggering rate of 3.3% per year, so we need to make continued progress in stent or scaffold technology and perhaps a focus beyond biodegradable polymer technology is warranted.
TiCAB
Mehran: The TiCAB trial showed that the use of ticagrelor (Brilinta, AstraZeneca) monotherapy vs. aspirin failed to improve rates of MACE or bleeding at 1 year in 1,893 patients undergoing CABG — the 1-year primary endpoint of CV death, MI, stroke or repeat revascularization was 9.7% in the ticagrelor group and 8.2% in the aspirin group (HR = 1.19; 95% CI, 0.87-1.62) — and raised some important questions.
Currently, it remains unknown whether or not patients could benefit from P2Y12 inhibitors after CABG. Unfortunately, this study, though informative, did not show a benefit of ticagrelor on graft patency. However, the researchers only had clinical follow-up as opposed to angiography and other important aspects of follow-up that would have provided more insight into the results. Therefore, it was not a definitive study. I still believe there is an unmet need in trying to understand how to treat these patients who have had CABG — whether or not they should be on an antiplatelet regimen and, if so, which regimen and for how long. We do know from previous studies that the direct oral anticoagulant rivaroxaban (Xarelto, Janssen/Bayer) improves outcomes over aspirin alone in patients who have had prior CABG, but we need to know more. This is an important question for us to address in the future.
REGROUP
Mehran: The REGROUP study yielded intriguing results. The researchers found that there were no significant differences between open vein graft harvesting and endoscopic vein graft harvesting in risk for MACE in 1,150 veterans who underwent CABG. At a median follow-up of 2.78 years, the primary outcome of nonfatal MI, all-cause death or repeat revascularization occurred in 15.5% of the open group and 13.9% of the endoscopic group (HR = 1.12; 95% CI, 0.83-1.51).
Previous studies had shown that endoscopic vein graft harvesting may not be as good as open vein graft harvesting, but this study actually refuted this notion while also demonstrating a good safety profile, which is an interesting take on the topic.
Disclosures: Bangalore reports he is a consultant for or serves on the advisory board of Abbott Vascular, Amgen, Biotronik and Pfizer and has received research grants from Abbott Vascular and the NHLBI. Mehran reports she has received research grants from AstraZeneca, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, CSL Behring, Eli Lilly/Daiichi Sankyo, Medtronic, Novartis Pharmaceuticals and Roundish; has ownership interest in Claret Medical and Elixir Medical; is a consultant or serves on the advisory board for Abbott Laboratories, Abiomed, Boston Scientific, Bristol-Myers Squibb, Medscape, Roivant Sciences, Siemens Medical Solutions, Spectranetics and The Medicines Company; and has other financial relationships with Janssen Pharmaceuticals, Osprey Medical and Watermark Research Partners. Valentine reports no relevant financial disclosures.