Summary and take home messages of the late-breaking clinical trials presented during #TCTConnect 2020
Reported from the TCT Congress 2020
Vijay Kunadian provides a summary of the coronary & structural late-breaking studies presented during TCT Connect 2020 and shares some take-home messages. See how these studies might influence your daily practice!
The pandemic has caused disruption to all aspects of daily life. But that really does not seem to have dampened the efforts and enthusiasm of interventional cardiology community in the fight against heart disease through life-saving interventional procedures driven by evidence-based research. This year TCT took place virtually with late-breaking presentations from clinical trialists and researchers from around the world addressing most aspects of interventional cardiology. Here is a summary of those trials (coronary and structural) and new information that these studies provide and how they might influence daily practice.
1. COVID and STEMI
The North American COVID-19 STEMI registry consisted of 594 patients. COVID +ve patients compared with COVID suspected patients presented with more cardiogenic shock (20% vs. 14%) and had high mortality (32% vs. 12%). PPCI was performed in 71% vs. 80% respectively and many patients in the COVID +ve group were treated medically (20% vs. 12%). This registry is ongoing and so is our fight against COVID-19!
2. Plaque, imaging, plaque modification
Since the presentation of PROSPECT I study in 2009, the question that remained unanswered is what we do about those non-obstructive plaques that we see during ACS PCI. The PROSPECT II study using NIRS-IVUS imaging showed that non-culprit lesion related MACE occurred in 8% (vs. 4.6% in culprit lesions) during a follow-up of ~4 years driven by MI and angina. The combination of lipid-rich plaque (max LCBI 4mm ≥324.7) and large plaque burden (≥70%) vs. PB <70% and max LCBI 4mm <324.7 identified vulnerable plaques at high risk of future MACE (7% vs. 0.2%; Odds ratio 36.73). The COMBINE (OCT–FFR) study using OCT imaging in patients with diabetes showed that thin cap fibro-atheroma (TCFA) occurred in ~25% of patients and led to increased event rate (13.3% vs. 3%-no TCFA) in intermediate lesions with negative FFR.
The PROSPECT ABSORB showed that the use of ABSORB BVS in lesions with IVUS plaque burden ≥65% (diameter stenosis <70%) led to enlarged minimum lumen area MLA (6.9mm2 vs. 3.0mm2) compared with guideline-recommended medical therapy alone with fewer patients presenting with angina (1% vs. 9%) at ~25-month follow-up. This is a pilot study needing further studies to determine the benefit of treatment of these lesions.
The ULTIMATE study showed that IVUS-guided vs angiography guided DES implantation in de novo lesions led to significant reduction in target vessel failure (TVF) at 1 year (2.9% vs. 5.4%, p=0.02) and at 3 years (6.6% vs. 10.7%, p=0.01) driven by TVR (4.5% vs. 6.9%, p=0.05) and stent thrombosis (0.1% vs. 1.1%, p=0.02) favouring IVUS arm.
With an ageing population, dealing with calcified coronary lesions is a major challenge. Disruption of severe coronary calcification using shockwave was evaluated in the Disrupt CAD III study. 384 patients (aged 71.2±8.6 years) with severe coronary calcification were recruited (calcium length 47.9±18.8mm). The study showed that stent delivery was successful in 99.2% of cases with 30-day freedom from MACE in 92.2%. Procedural success in 92.4% and angiographic success (<50% stenosis) in 96.4%.
3. Antiplatelet/antithrombotic therapy
Despite significant progress in antiplatelet and antithrombotic therapy in patients with CAD, balancing ischaemic and bleeding risk is an ongoing challenge to determine the appropriate therapy to individualise care. The COMPARE CRUSH study showed that prehospital crushed vs. uncrushed Prasugrel in STEMI did not lead to improvements in TIMI 3 flow (31% vs. 32.7%) or ST-segment resolution (59.9% vs. 57.3%) despite significant inhibition of platelet reactivity.
The TICO-STEMI study showed that Ticagrelor monotherapy vs Ticagrelor with Aspirin in STEMI showed that there was no difference in NACE (3.7% vs. 5%, p=0.27) but there was significant reduction in TIMI major bleeding with monotherapy (0.9% vs. 2.9%, p=0.02).
Using Xience stents in the XIENCE 90/28 study, 3-month or 1-month DAPT in high bleeding risk patients, there was a significant reduction in BARC 3-5 bleeding (superiority Xience 28 2.2% vs. Xience V US 4.5%, p=0.001; Xience 90 2.2% vs. Xience V US 6.3%) without affecting ischemic outcomes (all-cause death and MI-non-inferior).
Bivalirudin vs Heparin in patients with MI (STEMI, NSTEMI), the individual pooled data (n=38565, from 832 sites, 55% STEMI patients) showed that the 30-day all-cause mortality for all patients was 1.9% vs. 2.1% in bivalirudin (B) vs heparin (H) group. The greatest benefit with bivalirudin vs. heparin (all-cause death 2.5% v 2.9%, cardiac death 2.1% vs 2.7%) seem to be in STEMI patients but at the expense of MI (2.4% vs. 1.7%) and stent thrombosis (1.7% vs. 1.2%) which seem to have been mitigated by the use of high dose bivalirudin infusion. Serious bleeding was observed in 3.4% vs. 5.7% (B vs. H). Of note radial procedures overall was performed in 47% vs. 53% femoral cases.
4. Physiological assessment
In the DEFINE-PCI study, patients with post-PCI residual ischemia (occurred 24% of patients) were evaluated using an iFR cut-off of <0.95 vs. ≥0.95 post PCI. Patients with <0.95 had experienced more adverse events vs. those with ≥0.95 (MACE-cardiac death, MI, TVR 5.7% vs. 1.8%, p=0.04; cardiac death/MI 3.2% vs. 0%, p=0.02; MI 2.8% vs. 0%, p=0.02). Patients with ≥0.95 have greater symptom improvement at one year.
The TARGET FFR is a RCT of physiology-guided PCI optimization. This study showed that patients with FFR ≥0.9 post PCI have reduced MACE. Proportion of patients with FFR ≤0.80 was significantly reduced in those that had further PCI optimisation compared to control (18.8% vs. 29.8%, p=0.045).
The DEFINE-FLOW is an observational study of deferred lesions after FFR and CFR assessment. Patients with FFR ≤0.80 were grouped into those with CFR ≥2 vs. CFR <2. At 2 year the natural history of both groups was not non-inferior (p=0.0065 for non-inferiority). If CFR was <2 the prognosis is poor even if FFR was >0.80 emphasising the fact that microvascular dysfunction is not benign!
FORECAST is a RCT of CTCA/FFRCT decision-making in patients with chest pain. This study randomised 1400 patients to regular care vs. FFRCT following CTCA. This study did not demonstrate significant difference in cost or any of the clinical outcomes (MACCE, angina, QOL) between the 2 groups. But coronary angiography was reduced by 14.1% (22% fewer patients) in the FFR CT group with no difference in the revascularisation rates.
5. Novel coronary stent design
The Host-Reduce-Polytech-ACS is a RCT of durable polymer vs. bioabsorbable polymer DES in ACS patients. This study showed that the use of durable polymer vs. bioabsorbable polymer DES was non-inferior (5.2% vs. 6.4%, p=0.146, p for non-inferiority <0.001) in terms of POCO-patient oriented clinical outcomes (All-cause death, non-fatal MI, stent thrombosis, repeat revasc) with a significant difference in TLR 1% vs. 1.8% (P=0.049). The stent thrombosis rate was very low (0.1% vs. 0.4%, p=0.174).
The COBRA-REDUCE is a RCT of a Thromboresistant Polyzene F-Coated Stent (n=495) with 14 days DAPT in HBR patients (taking OAC) compared with DES with 3-6 months of DAPT (n=501). This study showed that BARC >2 bleed was not different between the 2 groups (7.5% vs. 8.9%, p=0.477) nor the composite outcome of death, MI, definite/probable stent thrombosis, ischaemic stroke (7.7% vs. 5.2%).
OPTIMIZE is a RCT of a novel, ultra-low profile fixed-wire DES (SLENDER IDS) vs. DES where direct stenting was performed. This study showed that there was no difference between SLENDER vs. standard DES in terms of target lesion failure-TLF at 1 year (10.3% vs. 9.5%, p=0.61, p for non-inferiority=0.034, non-inferiority was not met) with no difference in rates of stent thrombosis (0.38% vs. 0.5%). Target vessel MI occurred in 9.3 vs. 8.2% p=0.48 respectively.
6. Structural intervention
Aortic valve
The SCOPE I RCT showed that there was no difference in all-cause death at 1 year in ACURATE Neo self-expanding valve vs. Sapien 3 valve (11.1% vs. 8.1%, p=ns) but more patients had paravalvular leaks in ACURATE valve. The self-expanding TAVI bioprostheses (ACURATE Neo vs. CoreValve Evolut) was evaluated in the SCOPE II RCT. This study did not meet the non-inferiority for the 2 valves Neo ACURATE vs. CoreValve Evolut (all-cause death/MI 15.8% vs. 13.9% at 1 year, p=0.0549; PPM implantation 10.5% vs. 8%, p<0.0027; and 30-day AR 9.6% vs. 2.9% respectively). The SOLVE-TAVI showed that there was no difference in 1-year composite endpoint between self-expanding (CoreValve Evolut) vs balloon-expandable TAVR (Edwards Sapien 3). However, the self-expanding valve was associated with fewer stroke events (1% vs. 6.9%, p=0.002). There was no difference in all-cause mortality with local or general anaesthesia.
The TRANSIT study evaluated the treatment of failed TAVR with TAVR. Device success was 79%. The mortality rates were low (in-hospital 4%, 30 days 7%, 1-year 10%). AR grade 2-3 at 1 year occurred in 12.7%. The 5-year results of PARTNER 2 aortic valve in valve registry showed that all-cause mortality occurred in 50.6% vs. 73% in native valve, death/stroke occurred in 53.8%.
Cerebral embolization and infarction are a major consequence following TAVI procedures and it occurs in ~2.6% of cases. The REFLECT II RCT showed that cerebral embolic protection (CEP) during TAVR did not lead to reduction in all-cause mortality and stroke (Control [n=58]: 6.7% vs. TriGuard 3 CEP [n=121]: 9.8%). But there were more vascular complications with some reduction in cerebral lesion volume with CEP. The STS/ACC TVT registry study showed that CEP compared with no CEP during TAVI did not result in reduced in-hospital stroke (1.39% vs. 1.54%, p=0.41). But there was a difference in the propensity-matched analysis (1.3% vs. 1.58%, p=0.002).
Mitral valve
In the Global EXPAND study, the use of 3rd generation MitraClip NTR and XTR Systems showed that high rates of MR ≤1 was achieved at 1 year with sustained improvements in QOL, reverse LV remodelling and lower hospitalisation rates.
The use of MitraClip in Patients with acute MR in AMI with and without Cardiogenic Shock in the IREMMI study showed that procedural success was high at 90%. 30-day mortality very low 10% in shock cases vs. 2.3% (p=0.212) in those without shock. There was significant reduction in MR and NYHA class improvement of symptoms. In the MitraBridge study MitraClip treatment as bridge to heart transplantation was safe and effective. Nearly a quarter of the patients were removed from heart transplant waiting list due to clinical improvement with Mitraclip. The procedure success rate was 86%.
Iatrogenic ASD occurs in 24-50% of patients following TMVr. The MITHRAS RCT evaluated ASD closure after TMVr for iatrogenic ASD (QP:QS >1.3). It showed that there was no difference in the primary endpoint of 6-minute walk test (p=0.758) in the closure vs. no closure groups.
Conclusions and take-home messages:
- COVID continues to devastate patients with prior CVD and appears to lead to worse outcomes in those presenting with STEMI with excess cardiogenic shock presentation.
- We have made so much progress in our understanding of vulnerable plaques and coronary/microvascular physiology over the years, the studies presented at TCT suggest there is still so much unknown, emphasising the need for more studies to continue to optimise therapy for improved outcomes in our patients. The event rate on non-culprit lesions after ACS over 4 years is ~8%, emphasising the importance of aggressive secondary prevention therapy post ACS in these patients.
- Use of non-invasive measure (CTCA/FFRCT) to define coronary anatomy and physiology, unfortunately, was not cost-effective or effective at least in the UK population with stable CAD.
- Intravascular imaging during PCI though limited by availability and costs in many centres is beneficial in reducing future events.
- PCI optimisation using coronary physiology might also be a good strategy to identify patients at risk of future events and perhaps help initiate up-front aggressive pharmacotherapy.
- Novel coronary stent technologies have been evaluated but none of them appear to outperform the existing DES.
- Ageing population with co-morbidity is a current challenge in providing the optimal treatment for patients. In the catheter laboratory, calcified lesions pose challenges in achieving optimal results post PCI. In this setting use of Shockwave therapy provides promise with improved PCI outcomes.
- In high bleeding risk patients, use of short duration DAPT (1 or 3 months) leads to reduced severe bleeding without affecting clinical outcomes. Ticagrelor monotherapy in STEMI patients results in reduced bleeding without affecting ischaemic outcomes. Bivalirudin appears beneficial in STEMI patients at the expense of MI and stent thrombosis which appears to be mitigated by high dose infusion.
- In aortic valve intervention, unfortunately, the 2 studies that evaluated the use of cerebral embolic protection did not demonstrate significant benefit in terms of preventing clinically significant stroke. Valve in valve procedure is feasible with acceptable clinical outcomes.
- MitraClip appears to have good outcomes at 1 year and appears to be beneficial in patients as a bridge to heart transplantation and in those presenting with cardiogenic shock. Closure of iatrogenic ASDs following mitral procedures did not result in better outcomes.
Innovation with novel technologies and devices push the boundaries in the best care of patients with cardiovascular diseases. In this setting, some of the studies presented are hypothesis-generating needing further evaluation and thus interpretation of findings should be considered in this context.
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