ACC.23/WCC in New Orleans, U.S. has received a lot of attention from cardiovascular physicians around the world, and ACC.23/WCC International Cardiovascular Conference has come to a perfect end! The meeting released the several breaking clinical trials, effectively promoting the development of clinical treatment, here we discuss several clinical trials during the meeting below.
Statins significantly reduce cardiovascular disease risk by lowering low-density lipoprotein cholesterol (LDL-C) levels. The YELLOW III study was designed to evaluate changes in coronary plaque and peripheral blood mononuclear cell (PBMC) gene expression analysis by intravascular imaging (OCT and NIRS/IVUS) in patients with cardiovascular disease who had received the maximum tolerated dose of statin for 26 weeks after receiving Evolocumab. The primary endpoints of the study were minimum fibrous cap thickness (FCT) change assessed by OCT and maximum maxLCBI4 mm change assessed by NIRS. Secondary endpoints were changes in maximum lipid arc, lipid length, lipid volume index, macrophage accumulation, and calcification assessed by OCT; changes in percent atheromatous plaque volume (PAV) and total atheromatous plaque volume (TAV) assessed by IVUS; and changes in PBMC gene expression. A total of 137 patients were included in the study, and 110 patients eventually completed the trial follow-up. The study results showed that total cholesterol, LDL-C, and the ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C) were significantly reduced in biochemical parameters after 26 weeks of intensive lipid-lowering therapy compared with baseline levels. The imaging primary endpoints showed significant improvement in FCT and maxLCBI4 mm compared to the previous levels. Among them, OCT showed an increase in FCT from 70.9 μm to 97.3 μm, a decrease in the proportion of patients with FCT < 65 μm from 48% to 13%, and a thickening of the fibrous cap in 80% of patients. NIRS results showed a statistically significant decrease in maxLCBI4 mm from 306.8 to 213.1. Among the secondary imaging study endpoints, OCT results showed a significant improvement in max/mean lipid arc, lipid length, and lipid volume index after 26 weeks of intensive lipid-lowering therapy compared with the previous period, and a similarly significant decrease in max/mean macrophage arc, macrophage length, and volume index. In calcification, only the decrease in calcification length was statistically significant (p = 0.03), and no significant change in maximal/mean calcification arc was observed. Significant decreases in the PAV and TAV were also observed in IVUS results, as well as in LCBI in NIRS results. This is the first report of a multimodality imaging study in stable patients with non-obstructive lesions and low baseline LDL-C levels, and these findings further support an intensive lipid-lowering strategy for patients, while the PBMC transcriptomic results help to establish a predictive model for screening subjects with a significant response of plaque morphology to PCSK9 inhibitors.
The TARGET trial was an investigator-initiated, prospective, multicenter, randomized control trial involving 1,216 patients with symptoms of stable angina and coronary artery disease (CAD). Patients were randomly assigned in a 1:1 ratio to the CT-FFR care group (guideline-directed medical therapy [GDMT] or invasive coronary angiography [ICA] guided by on-site CT-FFR) or the standard care group (GDMT or ICA guided by stress tests). In the CT-FFR group, If the CT-FFR was less than or equal to 0.80 in one or more major coronary arteries, the patient was referred directly for ICA; if the CT-FFR was more than 0.80, optimal medical therapy was recommended; while in the control group, if stress test results were positive, ICA was recommended. The primary endpoint was the proportion of patients undergoing invasive coronary angiography without obstructive CAD or with obstructive disease who did not undergo intervention within 90 days. Secondary endpoints included major adverse cardiovascular events (MACE), quality of life, symptoms of angina, and medical expenditure at 1 year. A total of 421 of 608 patients (69.2%) in the CT-FFR care group and 483 of 608 patients (79.4%) in the standard care group underwent invasive coronary angiography. Compared to standard care, the proportion of patients undergoing invasive coronary angiography without obstructive CAD or with obstructive disease not undergoing intervention was significantly reduced in the CT-FFR care group (28.3% [119/421] vs. 46.2% [223/483], p < 0.001). Overall, more patients underwent revascularization in the CT-FFR care group than in the standard care group (49.7% [302/608] vs. 42.8% [260/608], p = 0.02), but of MACE at 1 year did not differ (HR:0.88; 95%CI: 0.59-1.30). Quality of life and symptoms improved similarly during follow-up in both groups and there was a trend towards lower costs in the CT-FFR care group (difference, -¥4233; 95%CI: -¥8165 to ¥973, p = 0.07). These findings suggested that the field-based machine learning CT-FFR strategy is feasible, safe, and effective.
The BIOVASC study is a prospective, open-label, multicenter, randomized, noninferiority trial in which enrolled patients were randomly assigned to immediate complete revascularization (ICR) or culprit-only plus staged complete revascularization (SCR). In the ICR arm, all significant stenotic lesions were treated during the index procedure. In the SCR arm, all other lesions except for culprit lesion were treated during the first hospitalization or through a readmission within 6 weeks. The primary endpoint of the study was a composite of all-cause mortality, myocardial infarction, any unplanned ischemia-driven revascularization, or cerebrovascular events at 1 year. A total of 1525 patients underwent randomization grouping, of whom 764 underwent ICR and 761 underwent culprit-only plus SCR. Of the 1506 patients at 1-year follow-up, 57 patients (7.6%) in the ICR arm met the primary endpoint, compared with 71 (9.4%) in patients in the SCR arm (HR: 0.78, 95% CI: 0.55 -1.11, p = 0.001). All-cause death occurred in 14 patients (1.9%) in the immediate group and 9 patients (1.2%) in the staged group, with no significant difference in the incidence of all-cause death between the two groups. Myocardial infarction occurred in 14 patients (1.9%) in the immediate group. Thirty-four patients (4.5%) were in the staged group (HR: 0.41, 95% CI: 0.22-0.76, p = 0.005). The incidence of unplanned stenting was higher in the staging group (6.7%) compared with the immediate group (4.2%) (HR: 0.61, 95% CI: 0.39-0.95, p = 0.030). The incidence of stroke was similar in both groups (1.5% vs. 1.6%). In addition, the subgroup analyses (men versus women and younger versus older patients) showed the similar results. Robert Diletti, MD, showed that immediate complete revascularization was not inferior to staged complete revascularization in patients with ACS with multi-vessel disease at 1-year follow-up, and that immediate complete revascularization ensured that patients did not have another heart attack while waiting for the second procedure. The team will continue to follow the patients for five years, and we're looking forward to further results.
The RENOVATE-COMPLEX-PCI study is an investigator-initiated, prospective, multicenter, open-label randomized study in which investigators randomly assigned the enrolled participants to the intravascular imaging-guided or angiography-guided group in a 2:1 ratio. The primary endpoints of the study were target-vessel failure, a composite of death from cardiac causes, target-vessel–related myocardial infarction, or clinically driven target-vessel revascularization. A total of 1639 patients underwent randomization, of whom 1092 underwent intravascular imaging-guided intervention and 547 underwent intravascular imaging-guided intervention. During a median follow-up time of 2.1 years, the primary endpoint event occurred in 76 patients (7.7%) in the intravascular imaging group and 60 patients (12.3%) in the angiography group (HR: 0.64, 95% CI: 0.45-0.89, p = 0.008). The rates of cardiac death, target-vessel-related myocardial infarction, and clinically driven target-vessel revascularization occurred in 1.7%, 3.7%, and 3.4% of patients in the intravascular imaging group, compared with 3.8%, 5.6%, and 5.5% in the angiography group, respectively. This study demonstrated that intravascular imaging-guided percutaneous coronary intervention (PCI) was superior to angiography-guided PCI in reducing the primary endpoints in patients with complex coronary lesions, providing new and reliable evidence for the current clinical application of intravascular image-guided PCI.
The LODESTAR study is a randomized, multicenter, noninferiority trial in patients with CAD treated at 12 centers in South Korea. Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20mg, or atorvastatin, 40mg. The primary endpoint was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points. The results of the study showed that in the treat-to-target group, 43% of patients were given moderate-intensity statin therapy, and 54% of patients were given high-intensity statin therapy, respectively. The mean 3-year LDL-C level was 69.1 mg/dl in this group and 68.4 mg/dl in the high-intensity statin group (p = 0.21). The primary endpoint occurred in 177 (8.1%) patients in the treat-to-target group and 190 (8.7%) patients in the high-intensity statin group. The above findings suggest that a treatment target strategy with LDL-C levels between 50-70 mg/dL is not inferior to high-intensity statins in patients with CAD. The results suggest that individualized and precise treatment with statins can be considered for patients within the LDL-C level target range.
During this session, Paul M. Ridker, MD, MPH, FACC, presented an interesting study showing that residual inflammation risk is a strong predictor of future major adverse cardiovascular events, cardiovascular death, and all-cause death. They did a collaborative analysis of patients with-or at high risk of-atherosclerotic disease, who were receiving contemporary statins and were participants in the multinational PROMINENT (n = 9988), REDUCE-IT (n = 8179), or STRENGTH (n = 13078) trials. The observed ranges for baseline high-sensitivity C-reactive protein (hsCRP) and LDL-C, and the relationships of each biomarker to subsequent cardiovascular event rates, were almost identical in the three trials. Residual inflammatory risk was significantly associated with incident MACE (highest hsCRP quartile vs lowest hsCRP quartile, adjusted HR:1.31, 95%CI:1.20-1.43, p < 0.0001), cardiovascular mortality (HR:2.68, 95%CI:2.22-3.23, p < 0.0001), and all-cause mortality (HR:2.42, 95%CI:2.12-2.77, p < 0.0001). By contrast, the relationship of residual cholesterol risk was neutral for MACE (highest LDL-C quartile vs lowest LDL-C quartile, adjusted HR:1.07, 95%CI:0.98-1.17, p = 0.11), and of low magnitude for cardiovascular death (HR:1.27, 95%CI:1.07-1.50, p = 0.0086) and all-cause death (HR:1.16, 95%CI:1.03-1.32, p = 0.025).The results of this study suggest that intensive lipid lowering combined with anti-inflammatory therapy may be the standard treatment strategy for atherosclerotic disease in the future.
Clinical Topics: COVID-19 Hub, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Stable Ischemic Heart Disease, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging, Chronic Angina
Keywords: ACC International, ACC Annual Scientific Session, ACC23, COVID-19, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Leukocytes, Mononuclear, PCSK9 protein, human, Proprotein Convertase 9, Cardiovascular Diseases, Transcriptome, Maximum Tolerated Dose, Follow-Up Studies, Calcinosis, Gene Expression Profiling, Macrophages, Lipids, Physicians, Lipoproteins, Coronary Artery Disease, Angina, Stable, Fractional Flow Reserve, Myocardial, Prospective Studies, Health Expenditures, Quality of Life, Coronary Angiography, Patient Readmission, Random Allocation, Myocardial Infarction, Percutaneous Coronary Intervention, Stroke, Atorvastatin, Rosuvastatin Calcium, C-Reactive Protein, Inflammation, Anti-Inflammatory Agents
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