Undeclared Veil of Secrecy Behind TCT2020
Byeong-Keuk Kim, MD, PhD, et al., used a prespecified cohort of 1,103 STEMI patients from 38 centers in South Korea who were enrolled in the broader TICO trial. Stratified randomization was performed based on the presence of STEMI, with 546 patients assigned to receive ticagrelor monotherapy after three-month DAPT and 557 patients assigned to receive ticagrelor-based 12-month DAPT. Results highlighted that major bleeding risk was reduced in the ticagrelor monotherapy group and there were no significant differences observed between the two treatment groups in terms of major adverse cardiac and cerebrovascular events. “This is the first report assessing the feasibility of the ticagrelor monotherapy after short-term DAPT for STEMI patients with [drug-eluting stent],” Kim said. However, he noted that “care should be taken in applying these results to the overall STEMI population, especially those at high risk for ischemia.”
CONTRIBUTION TO LITERATURE - The TICO trial showed that ticagrelor monotherapy after 3 months of DAPT was superior at preventing ischemia and bleeding after PCI for ACS.
Description - The goal of the trial was to evaluate ticagrelor monotherapy after 3 months of dual antiplatelet therapy (DAPT) compared with 12 months of DAPT after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS).
STUDY DESIGN - randomized, parallel, stratification, open-label
Patients undergoing PCI for ACS were randomized to ticagrelor monotherapy after 3 months of DAPT (n = 1,527) versus standard therapy (n = 1,529).
- Total number of enrollees: 3,056
- Duration of follow-up: 12 months
- Mean patient age: 61 years
- Percentage female: 21%
- Percentage with diabetes: 27%
- ACS treated with the ultrathin bioresorbable polymer sirolimus-eluting stent (Orsiro)
- ≥19 years of age
- >80 years of age
- Increased risk of bleeding
- Need for oral anticoagulation therapy
- Current or potential pregnancy
- Hepatic dysfunction
OTHER SALIENT FEATURES/CHARACTERISTICS
- Clinical presentation: unstable angina 29%, non-NSTEMI 35%, STEMI 36%
PRINCIPAL FINDINGS - The primary outcome, net adverse clinical events (death, MI, stent thrombosis, stroke, target vessel revascularization, or Thrombolysis in Myocardial Infarction [TIMI] major bleeding) at 12 months, occurred in 3.9% of the ticagrelor monotherapy after 3 months of DAPT group compared with 5.9% of the standard therapy group (p = 0.01). Association of ticagrelor monotherapy after 3 months of DAPT vs. standard therapy on the primary outcome: overall hazard ratio (HR) = 0.66, no multivessel disease HR = 0.41, multivessel disease HR = 0.86 (p for interaction = 0.04). Landmark analysis at 3 months for ticagrelor monotherapy vs. standard therapy for the primary outcome: (HR 0.41, p = 0.001).
- Major bleeding at 12 months: 1.7% of the ticagrelor monotherapy after 3 months group compared with 3.0% of the standard therapy group (p = 0.02)
- Stent thrombosis at 12 months: 0.4% of the ticagrelor monotherapy after 3 months group compared with 0.3% of the standard therapy group (p = 0.53)
- TICO-STEMI subgroup analysis: Major adverse cardiac and cerebrovascular events at 12 months: 2.7% of the ticagrelor monotherapy after 3 months group compared with 2.5% of the standard therapy group (p = 0.81)
INTERPRETATION - Among ACS patients who underwent PCI with an ultrathin biodegradable-polymer sirolimus-eluting stent, ticagrelor monotherapy after 3 months of DAPT was superior to standard therapy of DAPT for 12 months. Ticagrelor monotherapy was effective at preventing net composite ischemic and bleeding events. Bleeding events were defined by the TIMI criteria, which by way of reminder includes fatal bleeding, overt bleeding with drop in hemoglobin ≥5 g/dl or a 15% drop in hematocrit, and any intracranial hemorrhage.
This trial is like the similarly designed but placebo-controlled TWILIGHT trial. Neither of these trials addressed if aspirin monotherapy, instead of ticagrelor monotherapy in the 3- to 12-month period, would be equally effective. Ticagrelor monotherapy appears to be an emerging strategy, especially for patients with increased bleeding risk, after a short duration of DAPT.
- Presented by Dr. Byeong-Keuk Kim at the Transcatheter Cardiovascular Therapeutics Virtual Meeting (TCT Connect), October 14, 2020.
- Presented by Dr. Byeong-Keuk Kim at the American College of Cardiology Virtual Annual Scientific Session Together With World Congress of Cardiology (ACC 2020/WCC), March 30, 2020.
PCI of angiographically mild lesions with large plaque burden was safe, substantially enlarged the follow-up minimum lumen area (MLA), and was associated with favorable long-term clinical outcomes, said researchers presenting findings from the PROSPECT ABSORB Trial Oct. 14 during TCT 2020.
The study, which was simultaneously published in the Journal of the American College of Cardiology, used three-vessel imaging and a combination intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) catheter in 898 patients presenting with myocardial infarction following successful PCI of all flow-limiting coronary lesions. Those patients with an angiographically non-obstructive stenosis not intended for PCI but with IVUS plaque burden ≥65% (N=192) were randomized to treatment of the lesion with either a bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) or GDMT alone.
The primary powered effectiveness endpoint was the IVUS-derived MLA at protocol-driven 25-month follow-up. Additionally, the primary safety endpoint was randomized target lesion failure at 24 months and the secondary clinical effectiveness endpoint was randomized lesion-related major adverse cardiac events (MACE) at latest follow-up.
Results showed the median angiographic diameter stenosis of the randomized lesions was 41.6%, while the NIRS-IVUS median plaque burden was 73.7%. The median MLA was 2.9 mm2, and median maximum lipid plaque content was 33.4%. Angiographic follow-up at 25 months was completed in 167 patients. The follow-up MLA in BVS-treated lesions was 6.9±2.6 mm2 compared with 3.0±1.0 mm2 in those treated with GDMT alone. Researchers also noted that the rates of target lesion failure at 24 months were similar across both groups. Randomized lesion-related MACE occurred in 4.3% of patients in the BVS-treated group compared with 10.7% in the GDMT-alone group (P=0.12).
Among the limitations to the study: it was not powered for clinical outcomes, and the present PCI results only apply to the first generation everolimus-eluting Absorb BVS. “Whether the results would be superior with a thinner-strut BVS or a contemporary metallic DES is unknown,” said Gregg W. Stone, MD, FACC. However, Stone and colleagues note that the “the favorable randomized lesion-related MACE rates observed after BVS treatment compared with GDMT alone warrants the performance of an adequately powered randomized trial to determine whether PCI treatment of focal vulnerable plaques improves patient outcomes.” But they also add, that “until such a study, PCI of non-ischemic lesions, even those with high-risk morphologic features, cannot be routinely recommended.”
The PROSPECT ABSORB study was embedded in the PROSPECT II study, also presented at TCT 2020.
CONTRIBUTION TO LITERATURE - PCI of proximal non–flow-limiting stenosis with angiographic stenosis <70%, FFR/iFR negative, and plaque burden on IVUS ≥65% with Absorb BVS resulted in a larger MLA on IVUS follow-up, with no difference in clinical endpoints at 24 months.
DESCRIPTION - The goal of the trial was to assess the safety and efficacy of percutaneous coronary intervention (PCI) of non–flow-limiting stenosis with Absorb bioresorbable vascular scaffold (BVS) compared with control, using near-infrared spectroscopy–intravascular ultrasound (NIRS-IVUS) to understand plaque burden.
STUDY DESIGN - Eligible
patients were randomized in a 1:1 fashion to either PCI with Absorb BVS
(n = 93) or control (n = 89). Both arms got optimal guideline-directed
medical therapy (GDMT).
undergoing PCI for ACS were randomized to ticagrelor monotherapy after 3
months of DAPT (n = 1,527) versus standard therapy (n = 1,529).
- Total number of enrollees: 182
- Duration of follow-up: 4.1 years
- Mean patient age: 64years
- Percentage female: 18%
- Percentage with diabetes: 11%
- Successful PCI of all flow-limiting lesions
- Angiographic diameter stenosis <70% (with negative fractional flow reserve [FFR] or instantaneous wave-free ratio [iFR] required if diameter stenosis was >40%)
- Reference vessel diameter 2.5-4.0 mm
- Lesion length ≤50 mm
- IVUS plaque burden ≥65%
- The primary endpoint, MLA on IVUS, for PCI + GDMT vs. GDMT alone, was 6.9 vs. 3.0 mm2 (p < 0.0001).
- Across the entire lesion (including 5 mm margins): 5.2 vs. 2.9 mm2 (p < 0.0001)
SECONDARY ENDPOINTS for IVUS, for PCI + GDMT vs. GDMT alone
- Target lesion failure: 4.3% vs. 4.5% (p = 0.96)
- Target vessel myocardial infarction (TV-MI): 3.3% vs. 1.1%
- Lesion-related major adverse cardiac events (MACE): 4.3% vs. 10.7% (p = 0.12)
- Scaffold thrombosis: 1.1% vs. 0%
INTERPRETATION - The results of this pilot trial indicate that PCI of proximal non–flow-limiting stenosis with angiographic stenosis <70%, FFR/iFR negative, and plaque burden on IVUS ≥65% with Absorb BVS resulted in a larger MLA on IVUS follow-up, with no difference in clinical endpoints at 24 months. MACE rates were numerically lower with Absorb BVS PCI, while TV-MI rates were slightly higher.
- Stone GW, Maehara A, Ali ZA, et al, on behalf of the PROSPECT ABSORB Investigators. Percutaneous Coronary Intervention for Vulnerable Coronary Atherosclerotic Plaque. J Am Coll Cardiol 2020;Oct 14:[Epub ahead of print].
- Presented by Dr. Gregg Stone at the Transcatheter Cardiovascular Therapeutics Virtual Meeting (TCT Connect), October 14, 2020.
Combined fractional flow reserve (FFR) and optical coherence tomography (OCT) can improve the accuracy of predicting adverse event outcomes in patients with diabetes mellitus (DM), according to Elvin Kedhi, MD, presenting results from the COMBINE (OCT-FFR) trial Oct. 14 during TCT 2020.
As part of the trial, 500 DM patients with stable or acute coronary syndromes and who had ≥1 (non-culprit) target lesion with a 40-80% diameter stenosis underwent FFR assessment. FFR-negative patients underwent OCT assessment and were given further medical treatment. Patients were then divided into two groups depending on the presence (Group A) or absence of (Group B) a thin cap fibroatheroma (TCFA). Patients with FFR-positive target lesions were revascularized and placed in a third group (Group C). The primary endpoint was a composite of cardiac death, target-lesion myocardial infarction, clinically-driven target lesion revascularization or hospitalization due to unstable angina at 1.5 years between groups A and B.
COMBINE (OCT-FFR) showed for the first time that in patients with DM more than 25% of all FFR-negative lesions represent high-risk plaques, said Kedhi, who also noted that the presence of TCFA appears to be a strong predictor of future major adverse cardiac events, despite lack of ischemia. Additionally, Kedhi and colleagues observed that patients with TCFA had a significant increase in target-lesion-related major adverse cardiovascular events and myocardial infarction compared with patients without TCFA.
Kedhi, et al., note that their findings offer new insights into the treatment of DM patients who tend to have worse outcomes in terms of FFR-negative lesions compared with those without DM. They also suggest that “ischemia and future adverse events represent, to a large extent, two separate concepts,” and should be studied further.
CONTRIBUTION TO LITERATURE - In the COMPARE CRUSH trial, crushed prasugrel did not improve TIMI 3 flow at first angiography or complete ST-segment resolution at 1 hour post-PCI compared with integral prasugrel, both of which were administered as a 60 mg load in the ambulance prior to PPCI among patients with suspected STEMI.
DESCRIPTION - The goal of the trial was to assess the efficacy of prehospital crushed vs. integral prasugrel among ST-segment elevation myocardial infarction (STEMI) patients being considered for primary percutaneous coronary intervention (PPCI).
STUDY DESIGN - Eligible patients were randomized in a 1:1 fashion to either crushed (n = 369) or integral (n = 358) tablets of 60 mg prasugrel in the ambulance. They also received aspirin and heparin. Rapamycin target eluting stent (Firehawk MicroPort Medical, Shanghai, China) was used as the preferred stent.
- Total screened: 1,669
- Total number of enrollees: 727
- Duration of follow-up: 48 hours
- Mean patient age: 62 years
- Percentage female: 23%
- Suspected STEMI and symptom onset within 6 hours
- Initially managed by a mobile emergency medical care unit
- Plan for PPCI
- History of a cerebral vascular accident
- Recent gastrointestinal bleeding
- Recent major surgery
- Indication for chronic oral anticoagulation therapy
- Dependent on hemodialysis
- Unable to swallow oral medication
- Presented with cardiogenic shock or cardiac arrest
OTHER SALIENT FEATURES/CHARACTERISTICS
- Symptom onset to first medical contact: 58 minute
- Anterior MI: 38%
- Use of glycoprotein inhibitors: 12%, opioids: 15%
-The primary endpoint, Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the infarct-related artery at first angiography, between crushed vs. integral prasugrel, was 31.0% vs. 32.7% (p = 0.64).
- Complete ST-segment resolution 1-hour post-PPCI: 59.9% vs. 57.3% (p = 0.55)
- Across the entire lesion (including 5 mm margins): 5.2 vs. 2.9 mm2 (p < 0.0001)
SECONDARY ENDPOINTS for crushed vs. integral prasugrel
- High platelet reactivity at start of PCI (P2Y12 inhibitor reactivity units >208): 43.3% vs. 62.6% (p < 0.01)
- Any bleeding: 3.3% vs. 3.9% (p = 0.63)
- Stent thrombosis: 0.6% vs. 0.7% (p = 1.0)
INTERPRETATION - The results of this trial indicate that crushed prasugrel did not improve TIMI 3 flow at first angiography or complete ST-segment resolution at 1 hour post-PCI compared with integral prasugrel, both of which were administered as a 60 mg load in the ambulance prior to PPCI among patients with suspected STEMI. Platelet reactivity was lower in the crushed prasugrel arm, but this did not translate into lower stent thrombosis events or need for less frequent bailout glycoprotein inhibitor. The trial was underpowered for the latter two endpoints.
There was no use of cangrelor in this study, which showed a reduction in intraprocedural and early stent thrombosis events compared with clopidogrel in the CHAMPION PHOENIX trial. In the ATLANTIC trial, no difference in myocardial perfusion markers was noted with prehospital vs. in-hospital administration of ticagrelor, although there was a benefit noted in stent thrombosis.
- Vlachojannis G, Wilschut JM, Vogel R, et al. Effect of pre-hospital crushed prasugrel tablets in patients with STEMI planned for primary percutaneous coronary intervention: the randomized COMPARE CRUSH trial. Circulation 2020;Oct 14:[Epub ahead of print].
- Presented by Dr. Georgios Vlachojannis at the Transcatheter Cardiovascular Therapeutics Virtual Meeting (TCT Connect), October 14, 2020.
CONTRIBUTION TO LITERATURE -
The ULTIMATE trial showed that IVUS-guided PCI was superior to angiography-guided PCI at preventing target vessel failure.
DESCRIPTION - The goal of the trial was to evaluate intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) compared with angiography-guided PCI among an all-comers group of patients undergoing PCI.
STUDY DESIGN - Randomized, Parallel
Patients undergoing coronary revascularization were randomized to IVUS-guided PCI (n = 724) versus angiography-guided PCI (n = 724).
“Optimal IVUS-guided PCI” characteristics: minimal cross-sectional area >5.0 mm2 (or 90% of distal reference lumen cross-sectional area), plaque burden at proximal and distal stent edges <50%, no edge dissection involving media with length >3 mm.
- Total number of enrollees: 1,448
- Duration of follow-up: 12 months
- Mean patient age: 65 years
- Percentage female: 26%
- Percentage with diabetes: 31%
- All-comers group of patients undergoing PCI
- Had silent ischemia, stable or unstable angina, or myocardial infarction (MI; including both ST-elevation and non-ST-elevation MI) >24 hours from the onset of chest pain to admission
- Had de novo coronary lesion eligible for DES implantation
- Co-morbidity with life expectancy <12 months
- Intolerant of antithrombotic therapy
- Significant anemia, thrombocytopenia, or leucopenia
- History of major hemorrhage (intracranial, gastrointestinal, etc.)
- Chronic total occlusion lesion in either left anterior descending, left circumflex, or right coronary artery not re-canalized
- Severe calcification needing rotational atherectomy
PRINCIPAL FINDINGS - 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.
- Cardiac death: 0.7% of the IVUS-guided PCI group vs. 1.4% of the angiography-guided PCI group (p = 0.19)
- MI: 1.0% of the IVUS-guided PCI group vs. 1.5% of the angiography-guided PCI group (p = 0.34)
- Target vessel revascularization: 1.5% of the IVUS-guided PCI group vs. 2.9% of the angiography-guided PCI group (p = 0.07)
- Definite/probable stent thrombosis: 0.1% of the IVUS-guided PCI group vs. 0.7% of the angiography-guided PCI group (p = 0.10)
LONG-TERM OUTCOMES - Target vessel failure (cardiac death, target vessel MI, or clinically driven target vessel revascularization) at 3 years: 6.6% of the IVUS-guided PCI group vs. 10.7% of the angiography-guided PCI group (p = 0.01)
INTERPRETATION - Among an all-comers group of patients undergoing PCI, IVUS-guided PCI was beneficial. IVUS-guided PCI was associated with a lower frequency of target vessel failure up to 3 years compared with angiography-guided PCI. All components of the composite outcome were numerically lower in the IVUS-guided PCI group; however, the greatest benefit seemed to be at reducing target vessel revascularization. Multiple randomized trials now support the use of IVUS guidance in optimizing coronary stent implantation as a mechanism to reduce adverse cardiac events.
- Gao XF, Ge Z, Kong XQ, et al., on behalf of the ULTIMATE Investigators. Three-Year Outcomes of the ULTIMATE Trial Comparing Intravascular Ultrasound Versus Angiography-Guided Drug-Eluting Stent Implantation. JACC Cardiovasc Interv 2020;Oct 15:[Epub ahead of print].
- Presented by Dr. Junjie Zhang at the Transcatheter Cardiovascular Therapeutics Virtual Meeting (TCT Connect), October 15, 2020.
- Zhang J, Gao X, Kan J, et al. Intravascular Ultrasound Versus Angiography-Guided Drug-Eluting Stent Implantation: The ULTIMATE Trial. J Am Coll Cardiol 2018;72:3126-37.
- Editorial Comment: di Mario C, Koskinas KC, Räber L. Clinical Benefit of IVUS Guidance for Coronary Stenting: The ULTIMATE Step Toward Definitive Evidence? J Am Coll Cardiol 2018;72:3138-41.
- Presented by Dr. Junjie Zhang at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2018), San Diego, CA, September 24, 2018.