This article is more than 5 years old. Information may no longer be current.
The Take Home: ESC Congress
This year’s European Society of Cardiology Congress held in Amsterdam attracted more than 29,000 attendees to the 5-day meeting. The annual event has become known for the breadth of data presented, and this year was no exception with its more than 4,000 scheduled presentations and four Hot Line sessions featuring 20 major trials.
Cardiology Today’s Intervention was onsite throughout the meeting and spoke with several experts on some of the most heavily discussed data presented. Among them were Cardiology Today’s Intervention Chief Medical Editor Deepak L. Bhatt, MD, MPH, with Harvard Medical School; Cardiology Today’s Intervention Editorial Board members Christian W. Hamm, MD, with Kerckhoff Heart Center, Bad Nauheim, Germany, and Gregg W. Stone, MD, with Columbia University College of Physicians and Surgeons; Society for Cardiovascular Angiography and Interventions President Theodore A. Bass, MD, with the University of Florida, Jacksonville; and European Association of Percutaneous Cardiovascular Interventions representatives Petr Kala, MD, with Masaryk University and University Hospital Brno, Czech Republic, Christoph K. Naber, MD, PhD, with Essen University Hospital, Germany, and Marco Roffi, MD, with the University of Switzerland in Geneva.
TASTE
Bhatt: The TASTE trial was a large study of 7,244 patients with STEMI undergoing primary PCI in Sweden who enrolled in the Swedish registry (pretty much everybody gets enrolled in the registry). Patients were randomly assigned to manual thrombus aspiration with a catheter (n=3,621) or to stenting alone (n=3,623). The idea was to see whether mortality would be favorably influenced by the removal of a thrombus before stenting. There had been meta-analyses — in fact I was a senior author for two of them — that showed a lower rate of MACE and even a lower rate for mortality in the 6- to 12-month range. As it turned out, this large, well-powered study did not show any significant difference in mortality (thrombus-aspiration, 2.8% vs. PCI-only, 3%; HR=0.94; P=.63). However, it was a 30-day endpoint that was presented here, so we really need to see what happens with longer term follow-up, and such follow-up is planned in this registry at 1 year, 3 years and 5 years. With these longer-term data, we’ll have a better sense of whether there is or isn’t a reduction in mortality.
Deepak L. Bhatt
Secondary endpoints in TASTE, such as MI, were reduced, although not to a statistically significant extent, just trends. Some practicality endpoints were reduced: The ability to direct stent was improved; and the stent length was reduced with the strategy of manual thrombus aspiration before stenting, which is something many interventional cardiologists have observed in practice because it makes it easier to place the stent without pre-dilating with the balloon. So it’s a simple procedure, relatively inexpensive and doesn’t add much time to the procedure. As for myself, I probably will keep doing thrombus aspiration in patients who present with STEMI prior to stenting. On the other hand, one has to acknowledge that this large, well-done trial didn’t find the mortality difference. I should mention, however, there is another large randomized clinical trial that is ongoing — the TOTAL trial — which the group at McMaster University is coordinating, so we really should wait and see what this trial and longer-term follow-up from the TASTE trial show before making any decisions regarding whether to abandon thrombus aspiration using a catheter.
Theodore A. Bass
Bass: Trials assessing the value of adjunctive aspiration thrombectomy before TASTE were much smaller, a little inconsistent and had more focal endpoints, such as myocardial blush. TASTE instead looked at a hard clinical endpoint of 30-day all-cause mortality. The endpoint wasn’t reached in TASTE, indicating that there was no clinical benefit in performing aspiration thrombectomy. With the TAPAS trial, at 1 year they did show a mortality benefit, so the question is why TASTE did not. Although I can’t definitively answer that question, I can say that this only looked at 1-month data, and perhaps positive effects will manifest at 1 year.
ACCOAST
Marco Roffi
Roffi: The question addressed in ACCOAST was whether in patients with non-ST-elevation ACS (NSTEACS), pretreatment with prasugrel (Effient, Daiichi Sankyo/Eli Lilly) 30 mg was beneficial compared with a strategy of giving 60 mg prasugrel at the time of PCI. The study was totally negative in terms of ischemic complications, which were similar between groups at 7 days (pretreatment HR=1.02; 95% CI, 0.84-1.25) and 30 days (HR=0.997; 95% CI, 0.83-1.20). In addition, the strategy of pretreatment with 30 mg prasugrel was deleterious with respect to TIMI major bleeding episodes at both 7 (HR=1.9; 95% CI, 1.19-3.02) and 30 (HR=1.97; 95% CI, 1.26-3.08) days. Because of this, the study was prematurely stopped.
One consideration is that the time from loading dose to coronary angiography was very short, less than 4.5 hours. This was mandated by the protocol design, which stated you could include the patient only if you foresee that within 24 hours you will bring this patient to the cath lab. This actually doesn’t correspond to European guidelines, which gives us 72 hours to treat the patient, with the exception of patients who are extremely high risk. The pretreatment phase may have been too short to allow for a beneficial effect at the coronary level. However, it should be emphasized that the level of platelet aggregation inhibition at the time of PCI in patients pretreated was adequate, as demonstrated by a platelet function substudy. The extent of major bleeding associated with pretreatment observed in ACCOAST was surprising to me. It was more than I would have expected.
In TRITON-TIMI 38, which was the other study assessing prasugrel, the treatment was given after coronary angiography, so assuming the patient would have bled prior or during catheterization, the patient likely would have not been enrolled in the trial. We know that by enrolling patients prior to coronary angiography, we enroll higher-risk patients. If you look at the bleeding complications, some were access-related and we can understand that pretreatment with a potent P2Y12 inhibitor would increase this complication. On the other hand, there were also non-access site complications. This is more difficult to understand because all the patients then received prasugrel anyway.
These data clearly challenge the current European and US guidelines. For patients with non-STEMI in whom we foresee a very short delay going to the cath lab, I would definitely say there is no indication for pretreatment. It would be important to see whether this also translates to STEMI patients. Again, ACCOAST was of non-STEMI patients, but there is a very similar study that will likely be presented in 2014: the ATLANTIC study, also by Gilles Montalescot, MD, PhD, looking at pretreatment with ticagrelor (Brilinta, AstraZeneca), this time in the ambulance vs. ticagrelor at the time of PCI in STEMI patients. It will be interesting to see whether there will be differences in the results of the ACCOAST and ATLANTIC trials. The upside for potent platelet inhibition is that the thrombotic risk is higher in STEMI patients and virtually all of them undergo PCI. The downside is that the pretreatment times are shorter and at the time of PCI, the platelets may be insufficiently inhibited. Finally, the results of upstream glycoprotein IIb/IIIa inhibitors in STEMI were quite disappointing.
Christoph K. Naber
Naber: For me, the outcomes of ACCOAST are unfortunate because I thought we would get an additional tool and advice on how we could preload our patients with non-STEMI with one of the new drugs. However, the trial failed to show any benefit and in fact showed a significant increase in bleeding. So, again, we don’t have good evidence to recommend preloading our patients with prasugrel. This adds yet another question to the field of antiplatelet therapy. We don’t know about the duration of antiplatelet therapy in elective patients with stenting. We don’t know about the best duration for patients with ACS despite the fact that it is recommended for 1 year. We’ve seen in all the analyses that it’s in the first month that the patients really benefit the most. So I think that the ACCOAST trial was for me a negative trial because it does not contribute to the thematic guidance of daily practice, but rather increases the confusion at the moment and I still don’t know what to do. What I do in my clinical practice is I preload patients who are not elective and have ACS with clopidogrel and then keep track of them to see how they do.
PRAMI
Gregg W. Stone
Stone: When primary PCI is performed, at least half the patients will have multivessel disease, and there are other lesions beyond those in the infarct vessel that often need to be treated as well. Whether such non-infarct-related lesions should be treated during the acute infarct setting (currently contraindicated), in a staged fashion, or not at all (unless refractory recurrent ischemia occurs) is not known. The PRAMI researchers tested a “preventive” strategy of treating non-culprit lesions in STEMI patients from five UK centers during the acute infarct setting, representing the first reasonably sized trial to examine this issue. They randomly assigned 465 patients with multivessel disease who had a successful primary PCI to either treat the non-infarct lesions immediately or not, unless recurrent ischemia later required it.
What they found was that at follow-up (mean, 23 months), there was significant reduction in the composite rate of cardiac mortality, MI or refractory angina with the preventive strategy compared with a more conservative watchful-waiting approach (nine events per 100 patients vs. 23 events per 100 patients; P<.001). The event curves diverged quite early. Before this trial, a strategy of immediate or preventive multivessel PCI was prohibited by the guidelines, except perhaps in patients with cardiogenic shock. On the basis of this study, we have to rethink our approach. However, the limitations of this relatively small trial must be carefully considered. It took more than 5 years to recruit 465 patients, and thus they were highly selected. Description of the randomized lesions wasn’t provided. We don’t know whether these were 90% irregular stenoses or 60% stable-appearing lesions. Fractional flow reserve was not used, and the role of this modality in the acute STEMI setting needs further study. The observed treatment effect may be unrealistically optimistic because the trial was stopped early. Nonetheless, this randomized trial should make us re-examine our beliefs. Specifically, PRAMI suggests lesions that appear stable in patients with STEMI may not be nearly as innocuous as we think they are; from PROSPECT and HORIZONS-AMI we know that non-infarct lesions are more likely fibroatheromas than in patients with stable CAD, and may frequently progress rapidly in the setting of systemic inflammation and platelet activation, which is present in patients with STEMI. So in contrast to COURAGE, there is a rationale for early treatment to prevent death and MI in this setting. PRAMI doesn’t answer the question, however, of whether we should treat such lesions immediately or wait a few additional days or weeks, but it certainly suggests that early treatment is preferable to a watchful-waiting strategy. Nonetheless, practice shouldn’t change completely on the basis of one modest-sized randomized trial, and additional studies are warranted.
TAO
Christian W. Hamm
Hamm: In the TAO trial, investigators compared unfractionated heparin plus eptifibatide (Integrilin, Merck) with otamixaban (Sanofi-Aventis), a factor Xa inhibitor, in patients with NSTEACS and a planned early invasive strategy. The TAO trial was a “negative trial” because the standard arm was doing quite well and otamixaban did not improve the primary efficacy outcome — defined as the composite of all-cause death or new MI through 7 days (otamixaban, 5.5% vs. unfractionated heparin plus eptifibatide, 5.7%; adjusted RR=0.99; 95% CI, 0.85-1.16) — but did increase TIMI major or minor bleeding at 7 days (3.1% vs. 1.5%; RR=2.13; 95% CI, 1.63-2.78). This trial teaches us a lesson in that if we increase bleeding we cannot improve outcomes in patients with NSTEACS. It looks like we’ve really reached the limits here with antiplatelet and anticoagulant therapy and that there will be no further improvement — we only increase the risk of bleeding. The standard therapy as we use it today of unfractionated heparin or bivalirudin (Angiomax, The Medicines Company) and then giving glycoprotein IIb/IIIa on top of it is probably the best therapy at the moment we can provide.
PARIS
Kala: Two-year data from the PARIS study showed that in 5,018 patients, 57.3% experienced any DAPT cessation, with the causes varying from physician-recommended discontinuation (40.8%), interruption for surgery (10.5%) and disruption due to noncompliance or because of bleeding (14.4%). The 2-year MACE rate was 11.5%, and primarily occurred while patients were taking DAPT (74%). Compared with patients on DAPT, there was a significantly increased risk for MACE in patients with disrupted DAPT usage (adjusted HR=1.5; P=.004), a decreased risk in patients who discontinued DAPT (HR=0.63; P=.004) and no significant difference in patients with interrupted DAPT (HR=1.41; P=.10).
This study addresses very important questions about DAPT cessation and its potential risks depending on whether it is based on clinician decision or if it is required by clinical status — by bleeding or for surgery. It’s clear from this study that discontinuation is best for the patient in general. What is also interesting is 80% of definite/probable stent thrombosis events occurred during DAPT duration. This is very important. Perhaps there is some correlation with antiplatelet therapy resistance, but this wasn’t studied in this registry. So these are very clear observations from the PARIS study and hypothesis-generating, but further research is needed to confirm the results.