Jung Min Ahn

Randomized Trial of Stents versus Bypass Surgery for Left Main Coronary Artery Disease

BACKGROUND Percutaneous coronary intervention (PCI) is increasingly used to treat unprotected left main coronary artery stenosis, although coronary-artery bypass grafting (CABG) has been considered to be the treatment of choice. METHODS We randomly assigned patients with unprotected left main coronary artery stenosis to undergo CABG (300 patients) or PCI with sirolimus-eluting stents (300 patients). Using a wide margin for noninferiority, we compared the groups with respect to the primary composite end point of major adverse cardiac or cerebrovascular events (death from any cause, myocardial infarction, stroke, or ischemia-driven target-vessel revascularization) at 1 year. Event rates at 2 years were also compared between the two groups. RESULTS The primary end point occurred in 26 patients assigned to PCI as compared with 20 patients assigned to CABG (cumulative event rate, 8.7% vs. 6.7%; absolute risk difference, 2.0 percentage points; 95% confidence interval [CI], -1.6 to 5.6; P=0.01 for noninferiority). By 2 years, the primary end point had occurred in 36 patients in the PCI group as compared with 24 in the CABG group (cumulative event rate, 12.2% vs. 8.1%; hazard ratio with PCI, 1.50; 95% CI, 0.90 to 2.52; P=0.12). The composite rate of death, myocardial infarction, or stroke at 2 years occurred in 13 and 14 patients in the two groups, respectively (cumulative event rate, 4.4% and 4.7%, respectively; hazard ratio, 0.92; 95% CI, 0.43 to 1.96; P=0.83). Ischemia-driven target-vessel revascularization occurred in 26 patients in the PCI group as compared with 12 patients in the CABG group (cumulative event rate, 9.0% vs. 4.2%; hazard ratio, 2.18; 95% CI, 1.10 to 4.32; P=0.02). CONCLUSIONS In this randomized trial involving patients with unprotected left main coronary artery stenosis, PCI with sirolimus-eluting stents was shown to be noninferior to CABG with respect to major adverse cardiac or cerebrovascular events. However, the noninferiority margin was wide, and the results cannot be considered clinically directive. (Funded by the Cardiovascular Research Foundation, Seoul, Korea, and others; PRECOMBAT ClinicalTrials.gov number, NCT00422968.).

Optimal Duration of Dual Antiplatelet Therapy after Drug-Eluting Stent Implantation: A Randomized Controlled Trial

Background— The risks and benefits of long-term dual antiplatelet therapy remain unclear. Methods and Results— This prospective, multicenter, open-label, randomized comparison trial was conducted in 24 clinical centers in Korea. In total, 5045 patients who received drug-eluting stents and were free of major adverse cardiovascular events and major bleeding for at least 12 months after stent placement were enrolled between July 2007 and July 2011. Patients were randomized to receive aspirin alone (n=2514) or clopidogrel plus aspirin (n=2531). The primary end point was a composite of death resulting from cardiac causes, myocardial infarction, or stroke 24 months after randomization. At 24 months, the primary end point occurred in 57 aspirin-alone group patients (2.4%) and 61 dual-therapy group patients (2.6%; hazard ratio, 0.94; 95% confidence interval, 0.66–1.35; P=0.75). The 2 groups did not differ significantly in terms of the individual risks of death resulting from any cause, myocardial infarction, stent thrombosis, or stroke. Major bleeding occurred in 24 (1.1%) and 34 (1.4%) of the aspirin-alone group and dual-therapy group patients, respectively (hazard ratio, 0.71; 95% confidence interval, 0.42–1.20; P=0.20). Conclusions— Among patients who were on 12-month dual antiplatelet therapy without complications, an additional 24 months of dual antiplatelet therapy versus aspirin alone did not reduce the risk of the composite end point of death from cardiac causes, myocardial infarction, or stroke. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01186146.

Trial of Everolimus-Eluting Stents or Bypass Surgery for Coronary Disease

BACKGROUND Most trials comparing percutaneous coronary intervention (PCI) with coronary-artery bypass grafting (CABG) have not made use of second-generation drug-eluting stents. METHODS We conducted a randomized noninferiority trial at 27 centers in East Asia. We planned to randomly assign 1776 patients with multivessel coronary artery disease to PCI with everolimus-eluting stents or to CABG. The primary end point was a composite of death, myocardial infarction, or target-vessel revascularization at 2 years after randomization. Event rates during longer-term follow-up were also compared between groups. RESULTS After the enrollment of 880 patients (438 patients randomly assigned to the PCI group and 442 randomly assigned to the CABG group), the study was terminated early owing to slow enrollment. At 2 years, the primary end point had occurred in 11.0% of the patients in the PCI group and in 7.9% of those in the CABG group (absolute risk difference, 3.1 percentage points; 95% confidence interval [CI], -0.8 to 6.9; P=0.32 for noninferiority). At longer-term follow-up (median, 4.6 years), the primary end point had occurred in 15.3% of the patients in the PCI group and in 10.6% of those in the CABG group (hazard ratio, 1.47; 95% CI, 1.01 to 2.13; P=0.04). No significant differences were seen between the two groups in the occurrence of a composite safety end point of death, myocardial infarction, or stroke. However, the rates of any repeat revascularization and spontaneous myocardial infarction were significantly higher after PCI than after CABG. CONCLUSIONS Among patients with multivessel coronary artery disease, the rate of major adverse cardiovascular events was higher among those who had undergone PCI with the use of everolimus-eluting stents than among those who had undergone CABG. (Funded by CardioVascular Research Foundation and others; BEST ClinicalTrials.gov number, NCT00997828.).

Randomized Trial of Stents Versus Bypass Surgery for Left Main Coronary Artery Disease 5-Year Outcomes of the PRECOMBAT Study

BACKGROUND In a previous randomized trial, we found that percutaneous coronary intervention (PCI) was not inferior to coronary artery bypass grafting (CABG) for the treatment of unprotected left main coronary artery stenosis at 1 year. OBJECTIVES This study sought to determine the 5-year outcomes of PCI compared with CABG for the treatment of unprotected left main coronary artery stenosis. METHODS We randomly assigned 600 patients with unprotected left main coronary artery stenosis to undergo PCI with a sirolimus-eluting stent (n = 300) or CABG (n = 300). The primary endpoint was a major adverse cardiac or cerebrovascular event (MACCE: a composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target vessel revascularization) and compared on an intention-to-treat basis. RESULTS At 5 years, MACCE occurred in 52 patients in the PCI group and 42 patients in the CABG group (cumulative event rates of 17.5% and 14.3%, respectively; hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 0.84 to 1.90; p = 0.26). The 2 groups did not differ significantly in terms of death from any cause, myocardial infarction, or stroke as well as their composite (8.4% and 9.6%; HR, 0.89; 95% CI, 0.52 to 1.52; p = 0.66). Ischemia-driven target vessel revascularization occurred more frequently in the PCI group than in the CABG group (11.4% and 5.5%, respectively; HR: 2.11; 95% CI: 1.16 to 3.84; p = 0.012). CONCLUSIONS During 5 years of follow-up, our study did not show significant difference regarding the rate of MACCE between patients who underwent PCI with a sirolimus-eluting stent and those who underwent CABG. However, considering the limited power of our study, our results should be interpreted with caution. (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease [PRECOMBAT]; NCT00422968).

Outcomes After Unrestricted Use of Everolimus-Eluting and Sirolimus-Eluting Stents in Routine Clinical Practice A Multicenter, Prospective Cohort Study

Background— It remains unclear whether there are differences in the safety and efficacy outcomes between everolimus-eluting stents (EES) and sirolimus-eluting stents (SES) in contemporary practice. Methods and Results— We prospectively enrolled 6166 consecutive patients who received EES (3081 patients) and SES (3085 patients) between April 2008 and June 2010, using data from the Interventional Cardiology Research In-Cooperation Society-Drug-Eluting Stents Registry. The primary end point was a composite of death, nonfatal myocardial infarction (MI), or target-vessel revascularization (TVR). At 2 years of follow-up, the 2 study groups did not differ significantly in crude risk of the primary end point (12.1% for EES versus 12.4% for SES; HR, 0.97; 95% CI, 0.84–1.12, P=0.66). After adjustment for differences in baseline risk factors, the adjusted risk for the primary end point remained similar for the 2 stent types (HR, 0.96; 95% CI, 0.82–1.12, P=0.60). There were also no differences between the stent groups in the adjusted risks of the individual component of death (HR, 0.93; 95% CI, 0.67–1.30, P=0.68), MI (HR, 0.97; 95% CI, 0.79–1.18, P=0.74), and TVR (HR, 1.10; 95% CI, 0.82–1.49, P=0.51). The adjusted risk of stent thrombosis also was similar (HR, 1.16; 95% CI, 0.47–2.84, P=0.75). Conclusions— In contemporary practice of percutaneous coronary intervention procedures, the unrestricted use of EES and SES showed similar rates of safety and efficacy outcomes with regard to death, MI, sent thrombosis, and TVR. Future longer-term follow-up is needed to better define the relative benefits of these drug-eluting stents. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01070420.

Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data

BACKGROUND Numerous randomised trials have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for patients with coronary artery disease. However, no studies have been powered to detect a difference in mortality between the revascularisation strategies. METHODS We did a systematic review up to July 19, 2017, to identify randomised clinical trials comparing CABG with PCI using stents. Eligible studies included patients with multivessel or left main coronary artery disease who did not present with acute myocardial infarction, did PCI with stents (bare-metal or drug-eluting), and had more than 1 year of follow-up for all-cause mortality. In a collaborative, pooled analysis of individual patient data from the identified trials, we estimated all-cause mortality up to 5 years using Kaplan-Meier analyses and compared PCI with CABG using a random-effects Cox proportional-hazards model stratified by trial. Consistency of treatment effect was explored in subgroup analyses, with subgroups defined according to baseline clinical and anatomical characteristics. FINDINGS We included 11 randomised trials involving 11 518 patients selected by heart teams who were assigned to PCI (n=5753) or to CABG (n=5765). 976 patients died over a mean follow-up of 3·8 years (SD 1·4). Mean Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score was 26·0 (SD 9·5), with 1798 (22·1%) of 8138 patients having a SYNTAX score of 33 or higher. 5 year all-cause mortality was 11·2% after PCI and 9·2% after CABG (hazard ratio [HR] 1·20, 95% CI 1·06-1·37; p=0·0038). 5 year all-cause mortality was significantly different between the interventions in patients with multivessel disease (11·5% after PCI vs 8·9% after CABG; HR 1·28, 95% CI 1·09-1·49; p=0·0019), including in those with diabetes (15·5% vs 10·0%; 1·48, 1·19-1·84; p=0·0004), but not in those without diabetes (8·7% vs 8·0%; 1·08, 0·86-1·36; p=0·49). SYNTAX score had a significant effect on the difference between the interventions in multivessel disease. 5 year all-cause mortality was similar between the interventions in patients with left main disease (10·7% after PCI vs 10·5% after CABG; 1·07, 0·87-1·33; p=0·52), regardless of diabetes status and SYNTAX score. INTERPRETATION CABG had a mortality benefit over PCI in patients with multivessel disease, particularly those with diabetes and higher coronary complexity. No benefit for CABG over PCI was seen in patients with left main disease. Longer follow-up is needed to better define mortality differences between the revascularisation strategies. FUNDING None.

Fractional flow reserve and pressure-bounded coronary flow reserve to predict outcomes in coronary artery disease

Aims Fractional flow reserve (FFR) has proven to its prognostic and therapeutic value. However, the additive prognostic value of coronary flow reserve (CFR) remains unclear. This study sought to investigate the clinical utility of combined FFR and CFR measurements to predict outcomes. Methods and results Using the prospective, multicentre Interventional Cardiology Research Incooperation Society-FFR registry, a total of 2088 lesions from 1837 patients were included in this substudy. Based on baseline and hyperaemic pressure gradients, we computed physiologic limits of CFR [the so called pressure-bounded (pb) CFR] and classified lesions as low (<2) or high (≥2). The primary endpoint was major adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction, and revascularization) analysed on a per-patient basis. During a median follow-up of 1.9 years (inter-quartile range: 1.0-3.0 years), MACE occurred in 5.7% of patients with FFR ≤0.80 vs. 2.8% of patients with FFR >0.80 [adjusted hazard ratio (aHR): 2.15, 95% confidence interval (CI): 1.19-3.89; P = 0.011. In contrast, the incidence of MACE did not differ between patients with pb-CFR < 2 vs. pb-CFR ≥ 2 (4.2% vs. 4.2%; aHR: 0.98, CI: 0.60 to 1.58; P = 0.92). Incorporation of FFR significantly improved model prediction of MACE (global χ2 38.8-48.1, P = 0.002). However, pb-CFR demonstrated no incremental utility to classify outcomes (global χ2 48.1-48.2, P > 0.99). Conclusions In this large, prospective registry of over 2000 coronary lesions, FFR was strongly associated with clinical outcomes. In contrast, a significant association between pb-CFR and clinical events could not be determined and adding knowledge of pb-CFR did not improve prognostication over FFR alone.

Characteristics of Earlier Versus Delayed Presentation of Very Late Drug‐Eluting Stent Thrombosis: An Optical Coherence Tomographic Study

Background The pathophysiology underlying very late drug‐eluting stent (DES) thrombosis is not sufficiently understood. Using optical coherence tomography, we investigated characteristics of very late stent thrombosis (VLST) according to different onset times. Methods and Results A total of 98 patients from 10 South Korean hospitals who underwent optical coherence tomography for evaluation of very late DES thrombosis were retrospectively included in analyses. VLST occurred at a median of 55.1 months after DES implantation. All patients were divided into 2 equal groups of earlier versus delayed presentation of VLST, according to median onset time. In total, 27 patients were treated with next‐generation DES and 71 with first‐generation DES. Based on optical coherence tomography findings at thrombotic sites, main VLST mechanisms were as follows, in descending order: neoatherosclerosis (34.7%), stent malapposition (33.7%), and uncovered struts without stent malapposition or evagination (24.5%). Compared with patients with earlier VLST, patients with delayed VLST had lower frequency of uncovered struts without stent malapposition or evagination (34.7% versus 14.3%, respectively; P=0.019). Conversely, the frequency of neoatherosclerosis was higher in patients with delayed versus earlier VLST (44.9% versus 24.5%, respectively; P=0.034). The frequency of stent malapposition was not different between patients with earlier and delayed VLST (34.7% versus 32.7%, respectively; P=0.831). The frequency of stent malapposition, evagination, and uncovered struts was still half of delayed VLST. Conclusions The pathological mechanisms of very late DES thrombosis changed over time. Delayed neointimal healing remained a substantial substrate for VLST, even long after DES implantation.

Predictors for Paravalvular Regurgitation After TAVR With the Self-Expanding Prosthesis: Quantitative Measurement of MDCT Analysis.

Paravalvular regurgitation (PVR) remains a major concern of transcatheter aortic valve replacement (TAVR) as it is associated with poorer outcomes. PVR after TAVR results from several factors, including, device undersizing, aortic valve calcification, and prosthesis malposition [(1)][1]. We sought

Impact of metabolic syndrome on subclinical atherosclerosis in asymptomatic individuals

BACKGROUND Little is known about subclinical atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic individuals with metabolic syndrome (MetS). METHODS AND RESULTS We analyzed 5,213 asymptomatic individuals who underwent CCTA. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Of the study participants, 2,042 (39.2%) had MetS. MetS was an independent predictor of significant coronary artery disease (CAD) in at least 1 coronary artery (odds ratio [OR]=1.992, 95% confidence interval [CI]=1.623-2.445, P<0.001) and significant CAD in the left main (LM) or proximal left anterior descending (LAD) artery (OR=2.151, 95% CI=1.523-3.037, P<0.001). During the follow-up period (median 28.1 [interquartile range, 19.2-36.5] months), 111 individuals had 114 cardiac events. Individuals with MetS were significantly associated with more cardiac events than those without (RR [rate ratio]=1.67, 95% CI=1.15-2.43, P=0.007). In the MetS group, individuals with significant CAD had the majority of cardiac events (RR=64.33, 95% CI=29.17-141.88, P<0.001). Furthermore, in the MetS with significant CAD group, those with significant CAD in the LM or proximal LAD had more cardiac events (RR=2.63, 95% CI=1.51-4.59, P=0.001). CONCLUSIONS MetS was associated with subclinical atherosclerosis on CCTA with subsequent high risk for cardiac events. These findings suggest the importance of reducing unfavorable metabolic conditions in asymptomatic individuals.