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In late August, the European Society of Cardiology Congress brought together a record 33,000 cardiology professionals in Rome. Commenting on research germane to interventional cardiology are Sripal Bangalore, MD, MHA, from New York University Langone School of Medicine; Samir Kapadia, MD, from Cleveland Clinic; Cardiology Today’s Intervention Editorial Board member Ajay J. Kirtane, MD, SM, from Columbia University Medical Center/NewYork-Presbyterian Hospital and the Cardiovascular Research Foundation; Cardiology Today’s Intervention Associate Medical Editor Roxana Mehran, MD, from Icahn School of Medicine at Mount Sinai and the Cardiovascular Research Foundation; and Cardiology Today’s Intervention Editorial Board Member Gregg W. Stone, MD, from Columbia University Medical Center/NewYork-Presbyterian Hospital and the Cardiovascular Research Foundation.
NORSTENT
Stone: The NORSTENT study certainly led to a lot of discussion about whether the role of bare-metal stents should be re-examined for the treatment of CAD vs. drug-eluting stents. Many people have interpreted the study that way. I interpret it differently.
At 6 years, the primary outcome of all-cause mortality or nonfatal spontaneous MI occurred in 16.6% of the DES group vs. 17.1% of the BMS group (HR = 0.98; 95% CI, 0.88-1.09). There were no significant differences between the groups in all-cause death (HR = 1.1; 95% CI, 0.94-1.29) or all spontaneous acute MI (HR = 0.91; 95% CI, 0.8-1.03). The DES group had lower risk for repeat revascularization (16.5% vs. 19.8%; HR = 0.76; 95% CI, 0.85) and definite stent thrombosis (0.8% vs. 1.2%; HR = 0.64; 95% CI, 0.41-1; P = .0498) compared with the BMS group.
The study showed, in what is actually a rather modest sample size of less than 10,000 patients, that DES compared with BMS do what they’re supposed to do: reduce clinical restenosis. There was approximately a 50% reduction in target lesion revascularization, which has been seen in prior studies, and there was a statistically significant reduction in stent thrombosis, which is fairly extraordinary with the contemporary technologies. The concern with first-generation DES was an increase in stent thrombosis, but now there is a decrease.
The lack of a difference in mortality may just have to do with the study being underpowered; mortality was low in an unselected patient population. There was a trend toward reduction in cardiac mortality with DES. A large-scale meta-analysis of five randomized controlled trials comparing everolimus-eluting stents (EES) with BMS has suggested there may be a reduction in mortality with DES.
The bottom line is that BMS are yesterday’s technology and, for the most part, should be relegated as such. DES should be the standard of care in almost all patients with CAD undergoing PCI. There may still be a rare patient who is appropriately treated with a BMS if financial considerations are a concern of if there is a question about dual antiplatelet therapy being discontinued within the first 1 to 3 months. That issue has been less than optimally studied with contemporary DES.
Kirtane: There was a lot of press on the NORSTENT trial, even though I don’t think it will make a great impact. A lot was made of BMS vs. DES in the primary endpoint and the fact that the trial was so big, but, in reality, most of what we expect to happen with a DES as opposed to a BMS is a reduction in restenosis and in TLR, which was cut by 50%. That flew under the radar while many focused on there being no real differences between the stent types in death or MI. The results were touted as something that could have a lot of implications, but they did not reveal anything different from previous studies. Of interest is that the rates of stent thrombosis were low with both stent types at 6-year follow-up. My view is that it has to be explained by underreporting and ascertainment issues. It’s not easy to diagnose stent thrombosis in a large registry study.
Kapadia: It’s unbelievable that this trial got so much press and was published in The New England Journal of Medicine. Nobody in the United States uses BMS anymore. It is not a clinical question. No study has shown that BMS is superior, just noninferior if you select a population where they work well. There is no benefit to using BMS other than saving money. Currently in clinical practice, we are using DES 99% of the time. The vendors don’t even make very good BMS anymore. The issues relating to polymers and stent thrombosis in DES have been solved. This study is an interesting observation, but it will not affect what we do.
Bangalore: Most comparisons of DES vs. BMS have been with older-generation BMS. This study is important because it is a first-of-its-kind, large, randomized, head-to-head comparison of newer-generation DES and newer-generation thin-strut BMS.
The event rates were very low. A stent thrombosis rate of 1.2% in 6 years is extremely low. It’s a sign of the progress we have made in stent technology. Thinner struts have made a significant impact, which is great to see. Prior trials of older BMS and first-generation DES had higher stent thrombosis rates; in the SYNTAX trial, they were close to 6%.
The results are not surprising. There was a benefit with DES for reduction in revascularization and stent thrombosis, the latter of which has now been shown in various randomized trials and meta-analyses. That there was no difference between the two groups in the primary endpoint of death or MI has generated much discussion. But we have to be extremely careful in trying to interpret this. First, there were very few stent-related events. The stent can only prevent stent-related events. If 100 patients die, and stent-related deaths are a very small proportion of that, you need much more than 10,000 patients to show a difference — perhaps hundreds of thousands. Just because we didn’t see a difference here on the background of very low event rates, I don’t think we can completely rule out a difference in death or MI. Of interest, nonfatal spontaneous MI trended in favor of DES.
So the trends all point in the same direction, and the results will not prompt me to change anything in my clinical practice. These findings reinforce that there is an advantage — whether from a reduction in revascularization or stent thrombosis — of using a second-generation DMS compared with a BMS.
BASKET-SAVAGE
Mehran: Once again, we see that a DES is doing extremely well; in this case, in patients requiring saphenous vein graft intervention. It was good to see this issue re-examined.
At 12 months, MACE occurred in 2.3% of the DES group vs. 17.9% of the BMS group (HR = 0.15; P < .001), with the difference driven by target vessel revascularization (DES, 0%; BMS, 11.9%; HR = 0.04; P < .001) and nonfatal MI (DES, 2.3%; BMS, 11.9%; HR = 0.24; P = .025).
Limitations include that the study was stopped early because of slow enrollment and that a first-generation DES was used. Despite that, both early and long-term outcomes were in favor of DES over BMS. The efficacy of DES, even in vein grafts, is confirmed above and beyond over BMS.
I don’t think these results will change clinical practice, as DES are already very much in use in every scenario unless a patient is completely unable to take DAPT. Even with that, given what we know from the LEADERS FREE results, we’re using DES in almost every indication.
Despite all the data we have, there are less and less on saphenous vein graft interventions. It’s nice to see investigators are still researching that area even though it is less of an issue than it used to be. Better primary and secondary prevention has led to vein grafts being kept completely open or closed, so vein graft intervention has become a more uncommon procedure in the cath lab.
EROSION
Kirtane: The idea of being able to assess plaque erosion with OCT and then treating it pharmacologically after extruding the clot without having to put stents in is enticing. In the EROSION study, a majority of patients had thrombectomy, and if the clot was removed, and then the patient was treated with pharmacologic therapy, the rate of reinfarction was low, although the lumen remained somewhat compromised at follow-up. Among the cohort of 55 patients, 78.3% (95% CI, 65.8-87.9) met the primary endpoint of 50% reduction in thrombus volume at 1 month and 22 patients had no thrombus volume at 1 month.
Cases do come up where the clot can be removed in a patient with STEMI and there is no residual lesion, and it has been unclear whether we should stent or treat with medical therapy in that situation. This somewhat small study provides reassurance that if the residual stenosis is minimal, you can leave the vessel alone.
I would not advocate this approach in all cases. One of the issues with thrombectomy is, as shown in several trials and meta-analyses, increased risk for stroke. In addition, large randomized trials have shown no true benefit to thrombectomy vs. standard PCI. Most of us are not using routine thrombectomy, and the only way to tell there is erosion is to do the thrombectomy and then the OCT. It’s an interesting study, but the potential to change practice is somewhat limited.
DOCTORS
Kapadia: This was a study of 240 patients with non-ST-elevation ACS randomly assigned 1:1 to an angiogram alone or an angiogram plus OCT. It was a well-done trial that provided useful information. The primary endpoint was not clinical, but was related to how the modalities performed compared with fractional flow reserve. The primary endpoint was significantly better in the OCT group compared with the angiography group (FFR value, 0.94 vs. 0.92, P = .005). The OCT group also had more patients with FFR > 0.9 (82.5% vs. 64.2%; P = .0001). The non-clinical outcomes and the small sample size are limitations.
However, some characteristics indicating suboptimal long-term results were discovered. The difference in quality of stent placement comes down to how much of a perfectionist an operator is, and perfectionism is only possible with accurate data. It’s questionable whether characteristics such as proper apposition, proper expansion and proper covering leads to better long-term outcomes. It makes clinical sense that those things would lead to better outcomes, but there is controversy over what level constitutes a problem. Should we do something about things we can see with OCT but not an angiogram, and if so, do we have better outcomes? That remains unanswered.
In my mind, operators who have not used OCT and IVUS should use them sometimes, so they can understand where in the angiogram they should anticipate being able to get more information from OCT or IVUS. Early in your career, you should learn when you are likely to see something and when you are not. But no trials have conclusively shown that additional imaging leads to improved clinical outcomes. Conducting such a trial would be challenging because there is no way to blind the investigator. Further, the people who use OCT and IVUS are those who know exactly what they’re going to find. So how would you convince people who are not believers in OCT and IVUS to do the trials? I don’t think we will ever be able to prove it, but it doesn’t matter as long as one uses the data properly.
ABSORB JAPAN
Kirtane: Bioresorbable stent or scaffold technology is a hot topic in interventional cardiology. In this study, in which 400 patients undergoing PCI were randomly assigned on a 2:1 basis to receive a bioresorbable vascular scaffold (BVS; Absorb, Abbott Vascular) or cobalt chromium EES (Xience, Abbott Vascular), the 2-year rates of target lesion failure were 7.3% in the BVS group and 3.8% in the EES group (P = .18), and the rates of very late scaffold thrombosis after 1 year were 1.6% in the BVS group and 0% in the EES group.
What was interesting about the presentation of ABSORB Japan was that there were some cases of scaffold thrombosis occurring at later follow-up. This is something we will have to keep a very close eye on. We must be sure that before the device completely dissolves, it is not dismantling inside the vessel and leading to adverse events. We should not overreact because these are small numbers, but we must be vigilant.
PRAGUE-18
Bangalore: This is an important study because, prior to this, it was either a guess or an indirect comparison as to whether prasugrel (Effient, Daiichi Sankyo/Eli Lilly) or ticagrelor (Brilinta, AstraZeneca) were superior. In that setting, it’s valuable information, and it’s good to see that there are no differences between the two treatment strategies.
In the study, 1,230 patients with STEMI (mean age, 62 years; 24% women) were randomly assigned upon arrival to a PCI center to receive prasugrel 60 mg orally followed by 10 mg per day for 1 year (5 mg per day for patients aged 75 years or older or weighing less than 60 kg) or ticagrelor 180 mg orally followed by 90 mg twice daily for 1 year. The trial was scheduled to enroll 2,500 patients, but was stopped early for futility after an interim analysis showed no difference in the primary endpoint of death, reinfarction, urgent TVR, stroke, serious bleeding leading to transfusion and prolonged hospitalization at 7 days (prasugrel group, 4%; ticagrelor group, 4.1%; P = .939; log-rank P = .935) or the key secondary endpoint of CV death, nonfatal MI or stroke at 30 days (prasugrel group, 2.7%; ticagrelor group, 2.5%; P = .864; log-rank P = .665).
That being said, there are a number of limitations, including the small sample size, which means the study is likely underpowered. There were also patients who crossed over. The short 7-day and 30-day endpoints are somewhat troublesome. I would like to see longer-term outcomes. There are some strengths, but many weaknesses we need to consider.
In terms of clinical practice, the findings somewhat reassure clinicians that choosing either of the two drugs means that patients are not worse off.
We definitely need longer-term, well-powered studies to determine if there are differences between prasugrel and ticagrelor. For 7-day endpoints, you need a lot more patients, especially when event rates are very low.
Disclosure: Bangalore reports serving on advisory boards for Abbott Vascular and AstraZeneca. Kirtane reports receiving institutional research grants from Abbott Vascular, Abiomed, Boston Scientific, Eli Lilly, Medtronic and St. Jude Medical. Kapadia, Mehran and Stone report no relevant financial disclosures.