The Take Home: TCT Connect
Due to the COVID-19 pandemic, the Transcatheter Cardiovascular Therapeutics meeting was held virtually. TCT Connect, which ran from Oct. 14 to 18, offered the latest in cutting-edge science for interventional cardiologists.
Healio and Cardiology Today asked experts for their opinions on key presentations. Weighing in were Cardiology Today Editorial Board Member Anita W. Asgar, MD, MSc, FRCPC, FACC, from the University of Montreal; Morton J. Kern, MD, from the University of California, Irvine, and VA Long Beach Health Care System; Amar Krishnaswamy, MD, from Cleveland Clinic; Roxana Mehran, MD, from Icahn School of Medicine at Mount Sinai; and Srihari S. Naidu, MD, FACC, FAHA, FSCAI, from Westchester Medical Center.
Editor’s Note: All coverage from TCT Connect can be found here.
NACMI
Naidu: The take-home message of the first data from the North American COVID-19 STEMI Registry (NACMI) is that it was feasible to do a very rapid registry format between multiple sites in all of North America, including Canada, and to do that in a pandemic, in a very short duration, to provide timely answers.
Of the 594 patients who were evaluated, only about 30% were COVID-19-positive. A large percentage of patients that were under investigation still ended up being standard STEMI patients. It’s important that we still manage that patient population since the minority is COVID-19-positive.
I was struck by the fact that COVID-positive STEMI is a disease, in particular of African American and Hispanic patients, and that really jumps out the data almost to the point that if you’re not African American or Hispanic, you’re more likely to be COVID-negative.
Primary PCI was still the majority treatment across the board: 80% in COVID-negative patients and 70% in COVID-positive patients. The door-to-balloon times were still within acceptable metrics for all the patients. However, I was struck by the fact that the mortality was extremely high in the COVID-19-positive patients, even though the vast majority did have primary PCI with a good door-to-balloon time. I’m concerned that the benefits of primary PCI are unclear.
What happened to the patients with COVID-19 who underwent medical therapy, those 30% or so who did not get primary PCI? They may have had multiple comorbidities or cardiac arrest. Was their mortality rate even higher? It would be nice to see what the relative risk reduction of primary PCI was in the COVID-positive patients.
I’d also like to see why the COVID-negative patients still had mortality rates higher than a mass population. The control population is a Midwest population and may not be the same as throughout the United States and Canada. However, mortality was still twice as much in the COVID-negative population compared to a standard-of-care, non-COVID-19, non-pandemic-based population.
That means either the population is different, which did not look like it in the demographics, or that there are other problems with processes. What happened to these patients, even though the door-to-balloon time was good? What happened to them afterward? Were the ICUs full of COVID-19 patients? Are we able to prioritize these patients after the fact in terms of their care? Was the care standard or were the hospital systems distracted by the pandemic? Those are areas of system improvement we need, to look at how do we address the whole system of care around MI, both in and out of the hospital, in the confines of a pandemic. You would imagine that the mortality should be the same as the mass population if they had a run-of-the-mill STEMI, were negative for COVID-19 and got primary PCI. That was concerning to me.
These data tell us that in suspected COVID-19, you need to work fast and assume that the majority of these patients are actually having a true STEMI with a true culprit lesion that can be fixed, and the mortality will be one-third of what the COVID-19-positive patients are. You have to assume those patients are more likely to be non-COVID-19 and will have a good outcome, including length of stay and mortality.
In the COVID-positive patients, we need more data. We need to understand whether primary PCI is benefiting or harming patients. We don’t know that unless we do a randomized trial, or we try to address all the confounders of selection bias in that population and do a comparison to the ones that get medical therapy.
My suspicion is that primary PCI is still the way to go. However, when you do primary PCI in a COVID-19-positive patient with dyspnea and lung findings that are related to the pneumonia, primary PCI may be helpful in terms of evaluating the cardiac situation, but it may be harmful in delaying other treatment, including potentially intubation, proning or ICU care for the COVID-19 pneumonia and other aspects of the COVID disease state. Some of these patients do not have culprit lesions that require a PCI, and so it’s very important to determine how best to treat that population. I think that this registry, while extremely helpful, still does not fully answer whether primary PCI benefits these patients or not.
XIENCE 90/28
Krishnaswamy: There is significant clinical interest in how we can optimize post-PCI care for patients by minimizing risk and optimizing benefit of medical therapies. An important part of this management is the need for dual antiplatelet therapy after stent implantation, most commonly with aspirin and clopidogrel. This dichotomy of risk and benefit is especially profound for those patients who present with high bleeding risk. While prolonged DAPT may be beneficial regarding long-term CV outcomes in some patients, those with high bleeding risk are especially prone to complications of the same. Therefore, minimizing the duration of DAPT is paramount to optimizing short- and long-term outcomes.
In this regard, the XIENCE 90/28 trial provides important outcomes data for patients with high bleeding risk who received the durable polymer Xience everolimus-eluting stent (Abbott Vascular) with DAPT limited to either 1 or 3 months. Importantly, in comparison to a historical group of patients receiving the same stent under the XIENCE V protocol of 12 months DAPT, there was no increase in ischemic outcomes — importantly, no numerical increase in stent thrombosis — but a very clear reduction in significant bleeding with both of the shorter DAPT regimens.
There were 1,693 patients (mean age, 75 years; 35% women) from the XIENCE 90 trial who were event-free at 3 months and 1,392 patients (mean age, 76 years; 33% women) from the XIENCE 28 trial event-free at 1 month.
From 3 to 12 months, the primary endpoint of all-cause death or MI occurred in 5.4% of patients in the XIENCE 90 trial and 5.4% in the historical control group (P for noninferiority = .0063).
From 1 to 6 months, the primary endpoint of all-cause death or MI occurred in 3.5% of patients in the XIENCE 28 trial and 4.3% in the historical control group (P for noninferiority = .0005).
The data are congruent with other trials that have been recently published supporting 3-month DAPT for patients with high bleeding risk using the biodegradable polymer Synergy (Boston Scientific) EES and 1-month DAPT for high bleeding risk patients using the durable polymer Resolute Onyx (Medtronic) zotarolimus-eluting stent.
These latter two stents have FDA approval for these respective shortened DAPT durations; the current data should provide evidence for a similar shorter DAPT indication among high bleeding risk patients for the Xience platform.
In summary, XIENCE 90/28 is an important trial for physicians who take care of patients at high bleeding risk and have had a coronary drug-eluting stent implanted, as it provides reassurance with regard to coronary and stent safety outcomes with a shorter DAPT duration to minimize bleeding. Further, as many patients still undergo bare-metal stent implantation due to concerns of long-term bleeding and the desire to minimize DAPT as a result of stent thrombosis risks with prior-generation DES, the current trial adds to the foundation of data that there appears to be less and less reason to implant a BMS with the current generation of DES, even in patients with high bleeding risk.
TICO-STEMI
Mehran: The investigators did an amazing job with TICO-STEMI, which consisted of about one-third of the patients from the TICO study. It is the only trial that has looked at ticagrelor (Brilinta, AstraZeneca) monotherapy after 3-month DAPT in this population. But it’s open-label and has a small number of patients (n = 1,103).
In the intention-to-treat population, net adverse clinical events occurred in 3.7% of the monotherapy group and 5% of the DAPT group at 1 year (HR = 0.73; 95% CI, 0.42-1.29). In the as-treated population, net adverse clinical events were lower at 1 year in those who had monotherapy compared with those who had DAPT (2.3% vs. 5.2%; HR = 0.44; 95% CI, 0.23-0.86). TIMI major bleeding at 1 year was significantly lower in the monotherapy group, regardless of whether it was the intention-to-treat population (0.9% vs. 2.9%; HR = 0.32; 95% CI, 0.12-0.87) or the as-treated population (0.8% vs. 2.9%; HR = 0.26; 95% CI, 0.09-0.77).
The net adverse clinical events for the ticagrelor monotherapy group did not meet the P value seen in the overall TICO trial, but that does not mean these findings are less important. There was a reduction in bleeding, as expected, without a real increase in ischemic endpoints. This study is in line with the main TICO trial, but given that it is a smaller sample size, we need a larger prospective randomized study in patients with STEMI. Our team hopes to accomplish this with TWILIGHT-STEMI.
Until then, decisions about antiplatelet therapy after PCI for STEMI should be made on a case-by-case basis.
There are a lot of differences between TICO and TWILIGHT, which did not include patients with STEMI. TWILIGHT had a 3-month open-label period, after which patients underwent randomization if they were event-free. In TICO, the randomization occurred straight up at the time of PCI. The TICO researchers say to be cautious in the case of complex patients at high risk for ischemia. It’s important to use good clinical judgment.
SCOPE 2
Asgar: In my opinion, the most important take-home messages from SCOPE 2, a head-to-head randomized trial of the Acurate neo (Boston Scientific) and CoreValve Evolut (Medtronic) self-expanding transcatheter aortic valve replacement systems in 796 patients, are:
No. 1, direct randomized TAVR device comparisons are important to understand the performance of newer valves against those that have an established evidence base and have been well-studied.
No. 2, overall, the study missed the noninferiority endpoint just slightly for the primary endpoint of all-cause death or stroke at 1 year (Acurate, 15.8%; CoreValve, 13.9%; one-sided upper 95% CI limit, 6.1%; P for noninferiority = .0549). However, this is the second trial in which this iteration of the device fails to compare favorably with the two most-studied devices: Sapien 3 (Edwards Lifesciences) and CoreValve Evolut.
No. 3, very concerning, however, was the statistically significant increase in cardiac deaths in the Acurate neo group compared with Evolut, mostly due to HF (30 days, 2.8% vs. 0.8%; P = .03; 1 year, 8.4% vs. 3.9%; P = .01). This occurred in the setting of increased moderate to severe aortic insufficiency, mainly paravalvular, at 30 days, which is likely a contributing factor.
No. 4, permanent pacemaker implantation and new left bundle branch block were lower in the Acurate neo group compared with the Evolut group.
Given the literature and evidence from SCOPE 1 and now SCOPE 2, it would appear that this iteration of the device is not noninferior to the Sapien 3 or Evolut devices, therefore changes need to be made. Device changes addressing sizing, in particular larger available sizes, and strategies to mitigate paravalvular leak will be essential in the next generation to remain competitive with the industry standards.
For this particular version of the device, no further data are needed. In order for the device to have a future, newer iterations will have to show improvements and be compared once more to establish that there are safe alternatives to current available devices.
It is reassuring to see this kind of research study published because it highlights that the results of TAVR are not a class effect and new devices in the field need to demonstrate their noninferiority or superiority to industry standards prior to widespread adoption. Not all devices are created equal.
DEFINE-FLOW
Kern: DEFINE-FLOW was a very well-conducted study of 430 patients with coronary artery lesions. It showed what happens to patients with a discordance between coronary flow reserve (CFR) and fractional flow reserve.
People with abnormal values of both FFR and CFR had the highest event rates at 2 years (14.4%), even after PCI. People with normal CFR and FFR values had the lowest event rate (5.8%), typical of people who have stable asymptomatic coronary disease. The discordant groups — abnormal FFR/normal CFR and abnormal CFR/normal FFR — had nearly the same in event rates (10.8% and 12.4%, respectively), higher than FFR–/CFR– but lower than FFR+/CFR+.
In this analysis, the abnormal FFR/normal CFR group was not noninferior to the group with normal values of both, meaning that if your FFR was positive even if your CFR was negative, you still had a slightly worse event rate (difference, 5%; 95% CI, –1.5 to 11.5; P for noninferiority = .065).
What does this mean to guide us in practice? While we don’t routinely measure CFR, if we do and it’s low, the patient is at greater odds for events regardless of whether the FFR is positive or negative. CFR carries its own adverse prognosis. It’s not certain why that is, but people with low CFRs often have hypertrophy, diabetes, myocardial scarring, fibrosis, advanced age and other comorbidities. In the past several decades, the Amsterdam group, which studied CFR extensively, found that even in patients without coronary disease, those who had abnormal CFR still had more adverse events.
Decision-making for stable ischemic heart disease relies on what one trusts most. Since we don’t measure CFR routinely, we have to trust FFR or a nonhyperemic pressure ratio such as instantaneous wave-free ratio, diastolic resting pressure ratio, resting full-cycle ratio, etc. All of those physiologic indices are similar for stable angina and will likely result in similar outcomes. If you throw CFR in the mix, it becomes even more complicated.
Part of our problem with the data in DEFINE-FLOW is that we do not sort out the population with coronary disease well enough. Someone with stable CAD and diabetes is not the same as someone with stable CAD and no other risk factors or someone with stable CAD and a prior CV event. To make blanket statements for the stable CAD population, we would need evidence in thousands of patients.
Nonetheless, the first step toward optimizing decision-making is to be sure we are treating a lesion that needs to be treated. We can look to the ISCHEMIA trial to help. Can we justify continued medical therapy based on the patient’s clinical course or will our patient get more mileage out of revascularization? That decision requires an individual discussion with the patient. A 50-year-old executive with an FFR of 0.82 and symptoms might do better with revascularization. But for an 85-year-old sedentary individual with an FFR of 0.82, giving them a stent may increase their chance of stent thrombosis or bleeding due to dual antiplatelet therapy, and maybe they should be treated medically.
I still trust FFR. I believe it works and the long-standing data are consistent. I also believe iFR (and other nonhyperemic pressure ratios) works in this population. If CFR is normal, I am comfortable that the patient will do well if they do not have much coronary disease. But patients with normal CFR and lots of coronary disease (ie, FFR+) may have higher event rates, and FFR will tell you that. I would trust FFR for revascularization decisions and predict outcomes based on CFR in patients without CAD. If your CFR is normal, you are in good shape. If it is abnormal, then look at the lesion-specific problem.
Unfortunately, the study did not give us a stronger answer to the question of whether flow is better than pressure, because it depends in whom you are making the measurements.
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