Featured Science and Key Takeaways From TCT 2020 (Part 2)

This is Part 2 of a two-part summary.
Click to access: Part 1 | Part 2

Introduction
This year's Transcatheter Cardiovascular Therapeutics 2020 (TCT 2020), the annual scientific symposium of the Cardiovascular Research Foundation, was virtual. Like the 2020 American College of Cardiology (ACC) Annual Scientific Session Together with World Congress of Cardiology and other virtual cardiovascular meetings occurring during the coronavirus pandemic, TCT 2020 still provided significant evolving science and clinical experience.

This two-part summary of late-breaking clinical trials from TCT 2020 is a slight departure from our usual trial summaries. We offer succinct excerpts from ACC.org meeting coverage to summarize the trials' results, emphasizing shorter expert commentary from members of the ACC Interventional Council. The full ACC.org summaries are referenced and linked for easy access. A new feature is the inclusion of two videos discussing the relevance of trial results. The goal of these videos is to support efficient application of the science to clinical practice.

We look forward to your response to this new format.

Video: What's Practical and Actionable for Interventionalists From TCT 2020 (Part 2)

Drs. George Vetrovec and Roxana Mehran discuss key takeaways for interventionalists from late-breaking clinical trials presented at TCT 2020, including the NACMI Registry (3:30), IREMMI (8:51), ULTIMATE (10:32), and TICO-STEMI (13:00).

Quick Takes

  • Findings from the NACMI (North American COVID Myocardial Infarction) Registry support primary percutaneous coronary intervention (PCI) as both preferable and feasible in patients with coronavirus disease 2019 (COVID-19), with door-to-balloon times similar across all groups.
  • The Global EXPAND study demonstrated that the third generation MitraClip NTR and XTR systems (Abbott Vascular; Abbott Park, IL) provided significant mitral regurgitation (MR) reduction from baseline, which was maintained through 1 year.
  • ULTIMATE (A Multicenter, Prospective, Randomized Trial Comparing Intravascular Ultrasound-Guided Versus Angiography-Guided Implantation of Drug-Eluting Stent in All-Comers) showed that intravascular ultrasound (IVUS)-guided PCI was superior to angiography-guided PCI at preventing target vessel failure.
  • HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases-Comparison of Reduction of Prasugrel Dose or Polymer Technology in ACS Patients) showed that after 1 month of regular-dose dual antiplatelet therapy (DAPT), reduced-dose prasugrel (5 mg) is superior to regular-dose prasugrel (10 mg) when used along with low-dose aspirin for acute coronary syndrome (ACS) PCI.
  • The COBRA-REDUCE (COBRA PzF Stenting to REDUCE Duration of Triple Therapy) trial failed to show that an experimental stent (impregnated with a Polyzene-F nanocoating) was superior to a standard stent at reducing bleeding events.
  • VOYAGER PAD (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) showed that rivaroxaban added to aspirin following peripheral vascular intervention reduced major adverse cardiac and vascular events and that use of drug-coated devices was safe.

COVID-19 Updates (NACMI Registry)
By Frederick G. P. Welt, MD, FACC
University of Utah Health Sciences Center
Salt Lake City, UT

ACC.org Excerpt
Key findings of the NACMI Registry showed COVID+ patients had higher in-hospital mortality and in-hospital stroke with longer length of stay compared with those under investigation for COVID, or those in the historical control group. Additionally, ST-Elevation occurred more frequently in Blacks, Hispanics and diabetic COVID+ patients, compared with the other two groups. Researchers also noted that COVID+ patients with ST-Elevation were also more likely to present with atypical symptoms, as well as cardiogenic shock (but not cardiac arrest) with lower left ventricular ejection fraction. They were also more likely to receive medical therapy vs. angiography.1

Expert Commentary
The NACMI Registry was presented by Dr. Tim Henry at TCT 2020. The registry is an ongoing collaboration among the Society for Cardiovascular Angiography & Intervention, the Canadian Association of Interventional Cardiology, and the ACC Interventional Council. The effort is collecting from several North American hospitals data regarding patients who are either confirmed COVID-19 positive or persons under investigation (PUI). Enrollment includes patients with ST-segment elevation or new left bundle branch block and chest pain or other manifestation of ischemia. Patients can be enrolled regardless of therapeutic strategy, including primary PCI, fibrinolysis with or without angiogram and subsequent PCI, or medical therapy alone. Patients are divided into groups determined by their eventual COVID-19 positivity (confirmed COVID-19 positive and PUI but COVID-19 negative) and compared to historical controls. Outcomes of interest include etiologies of ST-segment elevation, major adverse cardiovascular events (MACE), individual components of MACE, electrocardiographic and angiographic characteristics, and analysis of groups of interest.

Dr. Henry presented the results for the first 594 patients enrolled. One of the remarkable observations made is the high percentage of African American (27%) and Hispanic (24%) patients represented; these numbers are much higher than in most cardiovascular registries. Patients with confirmed COVID-19 or PUI also had higher rates of diabetes and lower ejection fractions. Compared to historical controls, patients with COVID-19 or PUI were more likely to have angiograms deferred (21% and 5%, respectively, compared to 0% in the propensity-matched cohort; p < 0.001). Thrombolytic agents were used sparsely, and the majority of patients underwent primary PCI. In terms of outcomes, compared to PUI patients or matched controls, mortality for COVID-19 patients with ST-segment elevation myocardial infarction (MI) was dramatically higher (32% vs. 12% in PUI and 6% in matched controls). There also was an excess of strokes noted in COVID-19 positive patients compared with matched controls (3.4% vs. 0.6%; p = 0.039).

Dr. Henry concluded that although mortality is certainly higher in COVID-19-positive patients, primary PCI remains the therapy of choice in the patient presenting with ST-segment elevation MI. The registry continues to enroll.

Global EXPAND
By Neal S. Kleiman, MD, FACC
Houston Methodist Hospital
Houston, TX

ACC.org Excerpt
Global EXPAND is the first contemporary report of one-year outcomes in patients with both primary and secondary mitral regurgitation (MR) treated with the third generation MitraClip NTR and XTR systems. The study enrolled 1,041 subjects at 57 centers in the U.S. and Europe. Overall results found significant MR reduction from baseline through one year was maintained. Additionally, investigators noted significant reduction in MR was associated with sustained improvements in quality of life and heart failure symptoms.2

Expert Commentary
The MitraClip (Abbott Vascular; Abbott Park, IL) was first approved for transcatheter edge-to-edge repair in 2013, and the indication was expanded to include secondary MR in 2019. Since then, the device has undergone a number of iterations that have made the device easier to use with the intent of increasing the likelihood of successful repair. At the same time, operators have become more experienced. The Global EXPAND registry studied the XTR and NTR versions of MitraClip. In contrast to the preceding generation, the delivery system has become more torqueable, and arms of the clips are longer (now 9 mm and 12 mm) to facilitate easier leaflet grasping. In this report by Dr. Saibal Kar and colleagues, approximately half of patients had primary MR and half had secondary MR. Procedural outcomes were significantly better than those reported for previous clip iterations: MR graded by the echocardiography core laboratory at 4+ was reduced from 23.7% to 0%, and at 1 year MR ≤1+ was achieved in 89.2% of patients. In comparison, in the STS/ACC TVT Registry, site-reported MR of <1% was achieved by inexperienced operators in 65% of patients and by experienced operators in 80%. Importantly, the longer arms of the XTR and NTR devices allow inclusion of more tissue, raising concerns about inducing mitral stenosis and leaflet injury. However, mitral stenosis at 1 year was present in only 0.5% of patients, leaflet injury occurred in 0.4%, and single leaflet device attachment in 1.7%. Mortality at 1 year was 14%, and 80% were classified as New York Heart Association Class I or II. Kansas City Cardiomyopathy Questionnaire scores improved by an average of 21.6 points, with almost no difference between patients with primary or secondary MR. In contrast, patients in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial had an average 12.5% improvement in scores. Although comparison between registries and among registries and clinical trials is always speculative, these findings provide evidence that technical iterations in the design of the MitraClip (perhaps coupled with increased operator experience) have led to improved procedural and clinical success in transcatheter edge-to-edge repair without introducing additional safety concerns and may ultimately lead to expansion of the device's indications.

Intravascular Ultrasound Versus Angiography-Guided Drug-Eluting Stent Implantation (ULTIMATE)
By Michael N. Young, MD, RPVI
Dartmouth-Hitchcock Medical Center
Geisel School of Medicine at Dartmouth
Lebanon, NH

ACC.org Excerpt
The ULTIMATE trial showed that IVUS-guided PCI was superior to angiography-guided PCI at preventing target vessel failure. The primary outcome, target vessel failure at 12 months (cardiac death, MI, or target vessel revascularization), occurred in 2.9% of the IVUS-guided PCI group compared with 5.4% of the angiography-guided PCI group (p = 0.019). Among those who met the criteria for optimal IVUS-guided PCI, there appeared to be enhanced benefit from the use of IVUS compared with angiography-guided PCI.3

Expert Commentary
At TCT 2020, Dr. Xiao-Fei Gao and colleagues presented the highly anticipated 3-year results of the ULTIMATE trial. This was a large, multicenter study conducted at 8 Chinese centers that randomized 1,448 patients to either IVUS-guided or angiographic-guided PCI, with 724 patients in each comparator group. The initial 12-month findings of ULTIMATE had been previously published in the Journal of the American College of Cardiology,4 and the investigators now report the longitudinal outcomes of this important trial.

At 3 years, the IVUS-guided group exhibited 6.6% target vessel failure compared to 10.7% in the angiography-guided group (p = 0.01). This was primarily driven by a lower occurrence of clinically driven target vessel revascularization in the IVUS group (4.5% vs. 6.9%; p = 0.05). Furthermore, stent thrombosis was favorably lower for IVUS-guided PCI as well (0.1% vs. 1.1%; p = 0.02). The ULTIMATE investigators also emphasized that a significant reduction in 3-year target vessel failure was observed for IVUS-defined optimal versus suboptimal procedures, an important element of the trial design. IVUS-defined criteria for optimal stent deployment required all 3 of the following elements:

  • Minimal lumen area in the stented segment >5.0 mm2 or 90% of the minimal lumen area at the distal reference segments
  • Plaque burden 5 mm proximal or distal to the stent edge <50%
  • No edge dissection involving media with a length >3 mm

In summary, these findings presented by Dr. Gao and the ULTIMATE investigators further support the benefits of intracoronary imaging with IVUS now out to 3 years. In this trial, IVUS was clearly favorable for both the defined efficacy and safety endpoints. Furthermore, these data emphasize one important take-home message: not only the use of IVUS, but also its optimal employment, is key to ensuring improved long-term outcomes post-PCI. Note that the trial also included only high-volume operators (>200 annual cases). To conclude, the ULTIMATE 3-year results add to the ever-growing evidence base that intracoronary imaging should be considered the standard of care in contemporary PCI practice.

New Stent Designs (Host-Reduce-Polytech-ACS, COBRA-REDUCE)
By Tanveer Rab, MD, FACC
Emory University School of Medicine
Atlanta, GA

ACC.org Excerpts
The HOST-REDUCE-POLYTECH-ACS trial showed that after 1 month of regular-dose DAPT, reduced-dose prasugrel (5 mg) is superior to regular-dose prasugrel (10 mg) when used along with low-dose aspirin for ACS PCI. For prasugrel 5 mg vs. 10 mg, the primary endpoint, net adverse events (death, MI, stent thrombosis, clinically driven revascularization, stroke, and Bleeding Academic Research Consortium [BARC] 2 or higher bleeding) at 1 year for prasugrel 5 mg vs. 10 mg, was 7.2% vs. 10.1% (hazard ratio 0.70, 95% confidence interval 0.52-0.92, p = 0.012). For DP vs. BP-DES, the primary endpoint (death, MI, stent thrombosis, and any repeat revascularization) for DP vs. BP-DES, was 5.2% vs. 6.4%, hazard ratio 0.81, 95% confidence interval 0.61-1.08 (p < 0.001 for noninferiority).5

The COBRA-REDUCE trial failed to show that an experimental stent was superior to a standard stent at reducing bleeding events. The co-primary outcome, major bleeding (BARC 2-5) at 14 days, occurred in 7.5% of the experimental stent/14-day DAPT group compared with 8.9% of the standard stent/3-6-month DAPT group (p = 0.48). The co-primary outcome, death, myocardial infarction, stroke, or stent thrombosis at 6 months occurred in 7.7% of the experimental stent/14-day DAPT group compared with 5.2% of the standard stent/3-6-month DAPT group (p for noninferiority = 0.061).6

Expert Commentary
The lower dose maintenance therapy with 5 mg of prasugrel and low-dose aspirin after ACS PCI may be beneficial beyond the Asian population for the frail and elderly in the United States and Western countries or those at higher bleeding risk. Additionally, there appeared to be no significant differences in MACE between durable polymer drug-eluting stents and bioabsorbable polymer drug-eluting stents.

The COBRA bare-metal stent with Polyzene-F nanocoating (to promote early healing and shorten DAPT) failed to demonstrate reduction in bleeding on DAPT at 14 days or MACE at 6 months in patients at high bleeding risk. Hence, there are no indications to justify use of this stent with favorable outcomes in recent trials of 1-month DAPT using durable polymer drug-eluting stents for patients at high bleeding risk.

VOYAGER PAD
By Alexander G. Truesdell, MD, FACC
Virginia Heart/Inova Heart and Vascular Institute
Falls Church, VA

ACC.org Excerpt
The VOYAGER PAD trial showed that rivaroxaban/aspirin was superior to aspirin at preventing major adverse limb and cardiovascular events. The primary efficacy outcome, cardiovascular death, acute limb ischemia, major amputation, myocardial infarction, or stroke, occurred in 17.3% of the rivaroxaban/aspirin group compared with 19.9% of the placebo/aspirin group (p = 0.0085). This association was similar among various tested subgroups. The primary safety outcome, Thrombolysis in Myocardial Infarction (TIMI) major bleeding, occurred in 2.7% of the rivaroxaban/aspirin group compared with 1.9% of the placebo/aspirin group (p = 0.069). Among diabetics, TIMI major bleeding occurred in 2.4% of the rivaroxaban/aspirin group compared with 1.0% of the placebo/aspirin group (p for interaction = 0.033).7

Expert Commentary
VOYAGER PAD, as initially presented at the 2020 ACC Annual Scientific Session Together with World Congress of Cardiology and most recently at TCT 2020, demonstrated two important outcomes. First, building on data from the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial, VOYAGER PAD offers further evidence to support the addition of low-dose rivaroxaban to aspirin to reduce risks of adverse cardiovascular and limb events (without increasing major bleeding) in patients with peripheral arterial disease with or without coronary artery disease undergoing peripheral vascular intervention. Accruing data such as this increasingly supports potentially practice-changing combined antithrombotic and antiplatelet therapy for life and limb protection in this high morbidity population. Second, a large subgroup analysis showed no mortality risk (nor benefit) associated with the use of paclitaxel drug-coated devices, further supporting their safety. Added to a growing body of literature challenging early reports of increased all-cause mortality with the use of paclitaxel drug-coated devices, VOYAGER PAD offers increasing reassurance for use of these devices in current vascular practice.

References

  1. NACMI: Unique Registry Collaboration Aims to Improve Outcomes, Management of STEMI Patients With COVID-19 (ACC.org website). October 14, 2020. Accessed October 19, 2020. Available at https://www.acc.org/latest-in-cardiology/articles/2020/10/12/13/17/weds-1230pm-nacmi-north-american-covid-19-stemi-registry-tct-2020.
  2. Global EXPAND: One-Year Outcomes in MR Patients Treated With Third Generation MitraClip (ACC.org website). October 16, 2020. Accessed October 19, 2020. Available at https://www.acc.org/latest-in-cardiology/articles/2020/10/15/02/34/fri-115pm-global-expand-tct-2020.
  3. Bavry AA. A Multicenter, Prospective, Randomized Trial Comparing Intravascular Ultrasound-Guided Versus Angiography-Guided Implantation of Drug-Eluting Stent in All-Comers – ULTIMATE (ACC.org website). October 15, 2020. Accessed October 19, 2020. Available at https://www.acc.org/latest-in-cardiology/clinical-trials/2018/09/22/21/04/ultimate.
  4. Zhang J, Gao XF, Kan J, et al. Intravascular Ultrasound Versus Angiography-Guided Drug-Eluting Stent Implantation: The ULTIMATE Trial. J Am Coll Cardiol 2018;72:3126-37.
  5. Kumbhani DJ. Harmonizing Optimal Strategy for Treatment of coronary artery diseases-comparison of REDUCtion of prasugrEl dose or POLYmer TECHnology in ACS patients - HOST-REDUCE-POLYTECH-ACS (ACC.org website). October 17, 2020. Accessed October 19, 2020. Available at https://www.acc.org/latest-in-cardiology/clinical-trials/2020/08/29/12/40/host-reduce-polytech-acs.
  6. Bavry AA. COBRA PzF Stenting to REDUCE Duration of Triple Therapy - COBRA-REDUCE (ACC.org website). October 17, 2020. Accessed October 19, 2020. Available at https://www.acc.org/latest-in-cardiology/clinical-trials/2020/10/15/17/36/cobra-reduce.
  7. Bavry AA. Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease - VOYAGER PAD (ACC.org website). October 18, 2020. Accessed October 19, 2020. Available at https://www.acc.org/latest-in-cardiology/clinical-trials/2020/03/26/19/48/voyager-pad.

Keywords: TCT20, Transcatheter Cardiovascular Therapeutics, Angina, Stable, Atrial Fibrillation, Cardiac Surgical Procedures, Constriction, Pathologic, Coronary Artery Bypass, Coronary Artery Disease, Drug-Eluting Stents, Fractional Flow Reserve, Myocardial, Ischemia, Myocardial Infarction, Myocardial Revascularization, Percutaneous Coronary Intervention, Quality of Life, Stroke, Thrombosis, Ultrasonography, Natriuretic Peptide, Brain, Kidney Failure, Chronic, Myocardial Revascularization, Transcatheter Cardiovascular Therapeutics, Adrenergic beta-Antagonists, Cardiac Surgical Procedures, Cardiomyopathies, Coronary Artery Bypass, Echocardiography, Geriatrics, Heart-Assist Devices, Heart Failure, Heart Transplantation, Heart Valve Diseases, Mitral Valve Insufficiency, Myocardial Infarction, Myocardial Ischemia, Natriuretic Peptide, Brain, Percutaneous Coronary Intervention, Pulmonary Disease, Chronic Obstructive, Stroke, Stroke Volume, Angina Pectoris, Angina, Stable, Angina, Unstable, Angiography, Coronary Restenosis, Drug-Eluting Stents, Myocardial Infarction, Percutaneous Coronary Intervention, Sirolimus, Stents, Thrombosis, Ultrasonography, Interventional


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