Soo Jin Kang

Duration of dual antiplatelet therapy after implantation of drug-eluting stents.

BACKGROUNDnThe potential benefits and risks of the use of dual antiplatelet therapy beyond a 12-month period in patients receiving drug-eluting stents have not been clearly established.nnnMETHODSnIn two trials, we randomly assigned a total of 2701 patients who had received drug-eluting stents and had been free of major adverse cardiac or cerebrovascular events and major bleeding for a period of at least 12 months to receive clopidogrel plus aspirin or aspirin alone. The primary end point was a composite of myocardial infarction or death from cardiac causes. Data from the two trials were merged for analysis.nnnRESULTSnThe median duration of follow-up was 19.2 months. The cumulative risk of the primary outcome at 2 years was 1.8% with dual antiplatelet therapy, as compared with 1.2% with aspirin monotherapy (hazard ratio, 1.65; 95% confidence interval [CI], 0.80 to 3.36; P=0.17). The individual risks of myocardial infarction, stroke, stent thrombosis, need for repeat revascularization, major bleeding, and death from any cause did not differ significantly between the two groups. However, in the dual-therapy group as compared with the aspirin-alone group, there was a nonsignificant increase in the composite risk of myocardial infarction, stroke, or death from any cause (hazard ratio, 1.73; 95% CI, 0.99 to 3.00; P=0.051) and in the composite risk of myocardial infarction, stroke, or death from cardiac causes (hazard ratio, 1.84; 95% CI, 0.99 to 3.45; P=0.06).nnnCONCLUSIONSnThe use of dual antiplatelet therapy for a period longer than 12 months in patients who had received drug-eluting stents was not significantly more effective than aspirin monotherapy in reducing the rate of myocardial infarction or death from cardiac causes. These findings should be confirmed or refuted through larger, randomized clinical trials with longer-term follow-up. (ClinicalTrials.gov numbers, NCT00484926 and NCT00590174.)

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

BACKGROUNDnPercutaneous 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.nnnMETHODSnWe 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.nnnRESULTSnThe 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).nnnCONCLUSIONSnIn 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

BACKGROUNDnMost trials comparing percutaneous coronary intervention (PCI) with coronary-artery bypass grafting (CABG) have not made use of second-generation drug-eluting stents.nnnMETHODSnWe 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.nnnRESULTSnAfter 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.nnnCONCLUSIONSnAmong 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.).

Comparison of Zotarolimus-Eluting Stents With Sirolimus- and Paclitaxel-Eluting Stents for Coronary Revascularization The ZEST (Comparison of the Efficacy and Safety of Zotarolimus-Eluting Stent with Sirolimus-Eluting and PacliTaxel-Eluting Stent for Coronary Lesions) Randomized Trial

OBJECTIVESnThe aim of this study was to evaluate the relative efficacy and safety of zotarolimus-eluting stents (ZES) in comparison with the established and widely used sirolimus- (SES) and paclitaxel-eluting stents (PES) in routine clinical practice.nnnBACKGROUNDnWhether ZES might provide similar clinical and angiographic outcomes in a broad spectrum of patients compared with SES or PES is undetermined.nnnMETHODSnWe performed a single-blind, multicenter, prospectively randomized trial to compare ZES with SES and PES in 2,645 patients undergoing percutaneous coronary intervention. The primary end point was a composite of major adverse cardiac events (MACE) (death, myocardial infarction, and ischemia-driven target vessel revascularization) at 12 months. A noninferiority comparison (ZES vs. SES) and a superiority comparison (ZES vs. PES) were performed for the primary end point.nnnRESULTSnBaseline clinical and angiographic characteristics were similar in the 3 groups. At 12 months, the ZES group showed noninferior rates of MACE compared with the SES group (10.2% vs. 8.3%, p for noninferiority = 0.01, p for superiority = 0.17) and significantly fewer MACE than the PES group (10.2% vs. 14.1%, p for superiority = 0.01). The incidence of death or myocardial infarction was similar among the groups (ZES vs. SES vs. PES, 5.8% vs. 6.9% vs. 7.6%, respectively, p = 0.31). The incidence of stent thrombosis was significantly lower in the SES group (ZES vs. SES vs. PES, 0.7% vs. 0% vs. 0.8%, respectively, p = 0.02).nnnCONCLUSIONSnIn this large-scale, practical randomized trial, the use of ZES resulted in similar rates of MACE compared with SES and in fewer MACE compared with PES at 12 months. (Comparison of the Efficacy and the Safety of Zotarolimus-Eluting Stent Versus Sirolimus-Eluting Stent and PacliTaxel-Eluting Stent for Coronary Lesions; NCT00418067).

Transcatheter Aortic Valve Replacement With Early- and New-Generation Devices in Bicuspid Aortic Valve Stenosis

BACKGROUNDnFew studies have evaluated the clinical outcomes of transcatheter aortic valve replacement (TAVR) inxa0patients with bicuspid aortic valve stenosis (AS). Particularly, limited data exist comparing the results of TAVR with new-generation devices versus early-generation devices.nnnOBJECTIVESnThis study sought to evaluate the clinical outcomes of TAVR for bicuspid AS with early- and new-generation devices.nnnMETHODSnThe Bicuspid TAVR Registry is an international multicenter study enrolling consecutive patients with bicuspid AS undergoing TAVR between April 2005 and Mayxa02015.nnnRESULTSnOf 301 patients, 199 patients (71.1%) were treated with early-generation devices (Sapien XT [Edwards Lifesciences Corporation, Irvine, California]: nxa0= 87; CoreValve [Medtronic, Minneapolis, Minnesota]: nxa0= 112) and 102xa0with new-generation devices (Sapien 3 [Edwards Lifesciences Corporation]: nxa0= 91; Lotus [Boston Scientific Corporation, Marlborough, Massachusetts]: nxa0= 11). The mean Society of Thoracic Surgeons score was 4.7 ± 5.2 without significant differences between groups (4.6 ± 5.1 vs. 4.9 ± 5.4; pxa0= 0.57). Overall, all-cause mortality rates were 4.3% atxa030 days and 14.4% at 1 year. Moderate or severe paravalvular leak was absent and significantly less frequent with new-generation compared to early-generation devices (0.0% vs. 8.5%; pxa0= 0.002), which resulted in a higher device success rate (92.2% vs. 80.9%; pxa0= 0.01). There were no differences between early- and new-generation devices in stroke (2.5% vs. 2.0%; pxa0> 0.99), life-threatening bleeding (3.5% vs. 2.9%; p > 0.99), major vascular complication (4.5% vs. 2.9%; pxa0= 0.76), stage 2 to 3 acute kidney injury (2.5% vs. 2.9%; p > 0.99), early safety endpoints (15.1% vs. 10.8%; pxa0= 0.30), and 30-day all-cause mortality (4.5% vs. 3.9%; p > 0.99).nnnCONCLUSIONSnThe clinical outcomes of TAVR in patients with bicuspid AS were favorable. New-generation devices were associated with less paravalvular leak and, hence, a higher device success rate than early-generation devices. (Thexa0Bicuspid Aortic Stenosis Following Transcatheter Aortic Valve Replacement Registry [Bicuspid TAVR]; NCT02394184).

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.

Clinical Outcomes Following Transcatheter Aortic Valve Replacement in Asian Population

OBJECTIVESnThis study describes the characteristics of a real-world Asian patient population treated with transcatheter aortic valve replacement (TAVR) and evaluates their clinical outcomes.nnnBACKGROUNDnNo previously reported randomized or observational studies adequately assess the safety and efficacy of TAVR in an Asian population.nnnMETHODSnThe Asian TAVR registry is an international multicenter study that enrolled patients with aortic stenosis who underwent TAVR in Asian countries.nnnRESULTSnIn total, 848 patients with mean STS score of 5.2 ± 3.8% were enrolled between March 2010 and September 2014 at 11 centers in 5 countries. The Edwards Sapien or Medtronic CoreValve was implanted in 64.7% and 35.3% of patients, respectively. The procedural success rate was 97.5%. The 30-day and 1-year mortality rates were 2.5% and 10.8%, respectively. There was no difference in 1-year mortality between devices (Sapien: 9.4%; CoreValve: 12.2%; log-rank pxa0= 0.40). The rates of stroke, life-threatening bleeding, major vascular complications and acute kidney injury (stage 2 to 3) were 3.8%, 6.4%, 5.0% and 3.3%, respectively. Moderate or severe paravalvular leakage was significantly more common with the CoreValve than Sapien (14.4% vs. 7.3%; pxa0= 0.001). According to the multivariate model, a higher STS score, lower body mass index, New York Heart Association functional class III-IV symptoms, diabetes mellitus, prior cerebrovascular accident, low mean gradient at baseline, and moderate or severe paravalvular leakage were significantly associated with reduced survival.nnnCONCLUSIONSnDespite anatomical features of concern, the clinical outcomes of TAVR in our Asian population werexa0favorable in comparison with those of previously published trials and observational studies. (The Asian Transcatheter Aortic Valve Replacement Registry [Asian TAVR]; NCT02308150).

Impact of arterial stiffness on regional myocardial function assessed by speckle tracking echocardiography in patients with hypertension.

Background Arterial stiffening may affect regional myocardial function in hypertensive patients with normal ejection fraction (EF). Methods Brachial-ankle pulse wave velocity (PWV) was measured in 70 patients, of mean age 48 ± 14 years, with untreated hypertension and EF > 55%. Using two-dimensional-speckle tracking echocardiography, we measured longitudinal and circumferential strain (ε) and strain rate (SR). Basal and apical rotations were measured using short axis views. Results The mean systolic and diastolic blood pressure in these patients was 152 ± 15 mmHg and 92 ± 11 mmHg, respectively. The mean value of PWV was 1578 ± 274 cm/s. PWV significantly correlated with age (r = 0.682, p < 0.001), body mass index (r = -0.330, p = 0.005), systolic blood pressure (r = 0.386, p = 0.001) and pulse pressure (r = 0.509, p < 0.001). PWV also significantly correlated with septal E velocity (r = -0.570, p < 0.001), E/A ratio (r = -0.414, p < 0.001), E/E ratio (r = 0.589, p < 0.001), systolic global longitudinal ε (r = 0.300, p = 0.012) and early diastolic SR (SRE) (r = -0.479, p < 0.001) suggesting impaired abnormal relaxation. PWV was also correlated with basal rotation (r = -0.301, p = 0.011) and basal-to-apical twist (r = -0.256, p = 0.032). The increases in apical rotation and basal-to-apical twist were attenuated in patients with PWV > 1700 cm/s compared to those with PWV ≤ 1400 cm/s or those with PWV 1400-1700 cm/s. Conclusion In hypertensive patients with normal ejection fraction, arterial stiffening contributes to impaired systolic and diastolic function of the regional myocardium. Compensatory increases in ventricular twist were diminished in patients with advanced stage of vascular stiffening.

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

AimsnFractional 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.nnnMethods and resultsnUsing 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 FFRu2009≤0.80 vs. 2.8% of patients with FFRu2009>0.80 [adjusted hazard ratio (aHR): 2.15, 95% confidence interval (CI): 1.19-3.89; Pu2009=u20090.011. In contrast, the incidence of MACE did not differ between patients with pb-CFRu2009<u20092 vs. pb-CFRu2009≥u20092 (4.2% vs. 4.2%; aHR: 0.98, CI: 0.60 to 1.58; Pu2009=u20090.92). Incorporation of FFR significantly improved model prediction of MACE (global χ2 38.8-48.1, Pu2009=u20090.002). However, pb-CFR demonstrated no incremental utility to classify outcomes (global χ2 48.1-48.2, Pu2009>u20090.99).nnnConclusionsnIn 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.