Duk Woo Park

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

BACKGROUND The 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. METHODS In 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. RESULTS The 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). CONCLUSIONS The 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

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.).

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

OBJECTIVES The 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. BACKGROUND Whether ZES might provide similar clinical and angiographic outcomes in a broad spectrum of patients compared with SES or PES is undetermined. METHODS We 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. RESULTS Baseline 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). CONCLUSIONS In 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).

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).

Drug-Eluting Versus Bare-Metal Stents in Unprotected Left Main Coronary Artery Stenosis: A Meta-Analysis

OBJECTIVES We undertook a meta-analysis to assess outcomes for drug-eluting stents (DES) and bare-metal stents (BMS) in percutaneous coronary intervention for unprotected left main coronary artery (ULMCA) stenosis. BACKGROUND Uncertainty exists regarding the relative performance of DES versus BMS in percutaneous coronary intervention for unprotected left main coronary stenosis. METHODS Of a total of 838 studies, 44 met inclusion criteria (n = 10,342). The co-primary end points were mortality, myocardial infarction (MI), target vessel/lesion revascularization (TVR/TLR), and major adverse cardiac events (MACE: mortality, MI, TVR/TLR). RESULTS Event rates for DES and BMS were calculated at 6 to 12 months, at 2 years, and at 3 years. Crude event rates at 3 years were mortality (8.8% and 12.7%), MI (4.0% and 3.4%), TVR/TLR (8.0% and 16.4%), and MACE (21.4% and 31.6%). Nine studies were included in a comparative analysis (n = 5,081). At 6 to 12 months the adjusted odds ratio (OR) for DES versus BMS were: mortality 0.94 (95% confidence interval [CI]: 0.06 to 15.48; p = 0.97), MI 0.64 (95% CI: 0.19 to 2.17; p = 0.47), TVR/TLR 0.10 (95% CI: 0.01 to 0.84; p = 0.01), and MACE 0.34 (95% CI: 0.15 to 0.78; p = 0.01). At 2 years, the OR for DES versus BMS were: mortality 0.42 (95% CI: 0.28 to 0.62; p < 0.01), MI 0.16 (95% CI: 0.01 to 3.53; p = 0.13), and MACE 0.31 (95% CI: 0.15 to 0.66; p < 0.01). At 3 years, the OR for DES versus BMS were: mortality 0.70 (95% CI: 0.53 to 0.92; p = 0.01), MI 0.49 (95% CI: 0.26 to 0.92; p = 0.03), TVR/TLR 0.46 (95% CI: 0.30 to 0.69; p < 0.01), and MACE 0.78 (95% CI: 0.57 to 1.07; p = 0.12). CONCLUSIONS Our meta-analysis suggests that DES is associated with favorable outcomes for mortality, MI, TVR/TLR, and MACE as compared to BMS in percutaneous coronary intervention for unprotected left main coronary artery stenosis.

Comparison of the Efficacy and Safety of Zotarolimus-, Sirolimus-, and Paclitaxel-Eluting Stents in Patients With ST-Elevation Myocardial Infarction

Drug-eluting stents (DESs) are increasingly used for treatment of acute ST-segment elevation myocardial infarction (STEMI), but there are few comparisons of outcomes of various types of DES. We compared the efficacy and safety of zotarolimus-eluting stents (ZESs), sirolimus-eluting stents (SESs), and paclitaxel-eluting stents (PESs) in primary intervention for STEMI. This multicenter, prospectively randomized ZEST-AMI trial included 328 patients at 12 medical centers who were randomly assigned to ZES (n = 108), SES (n = 110), or PES (n = 110) deployment. The primary end point was major adverse cardiac events (death, MI, and ischemia-driven target vessel revascularization) at 12 months. Secondary end points included the individual components of the primary end point, late loss, angiographic restenosis, and stent thrombosis. Baseline clinical and angiographic characteristics were well matched. In-segment late loss (0.28 +/- 0.42 vs 0.46 +/- 0.48 vs 0.47 +/- 0.50 mm, respectively, p = 0.029) and restenosis rate (2.7% vs 15.9% vs 12.3%, respectively, p = 0.027) at 8 months were lowest in the SES group compared to the ZES and PES groups. At 12 months, cumulative incidence rates of primary end points in the ZES, SES, and PES groups were 11.3%, 8.2%, and 8.2%, respectively (p = 0.834). There were 2 acute (in the SES group) and 5 subacute (2 in the SES group and 3 in the PES group) stent thromboses. Incidence of death, recurrent MI, or ischemia-driven target vessel revascularization did not differ among the 3 groups. In conclusion, despite the difference in restenosis rate, the efficacy and safety of the 3 different DESs showed similar, acceptable results in the treatment of STEMI.

Restenosis and adverse clinical events after successful percutaneous mitral valvuloplasty: immediate post-procedural mitral valve area as an important prognosticator

AIMS We sought to investigate the factors associated with restenosis and its potential association with late clinical deterioration after successful percutaneous mitral valvuloplasty (PMV). METHODS AND RESULTS We analysed echocardiographic (median 74 months) and clinical (median 109 months) follow-up data of 329 patients who achieved procedural success, defined as mitral valve area (MVA) > or =1.5 cm(2) and mitral regurgitation (MR) < or =2/4, between 1995 and 2000. Clinical events included cardiovascular death, mitral valve surgery, and repeat PMV. The 1, 3, 5, 7, and 9 year rates of restenosis-free survival were 99 +/- 1%, 97 +/- 1%, 95 +/- 1%, 86 +/- 3%, and 72 +/- 4%, respectively. The 1, 3, 5, 7, and 9 year rates of event-free survival were 99.7 +/- 0.3%, 96.4 +/- 1.0%, 94.5 +/- 1.3%, 90.8 +/- 1.6%, and 90.0 +/- 1.7%, respectively. Immediate post-PMV MVA and commissural MR or splitting, indicators of procedural adequacy, were independent predictors of both restenosis and clinical events. The best immediate post-PMV MVA cut-off value for predicting both restenosis and clinical events within 5 years after successful PMV were 1.8 cm(2) [95% confidence interval (CI) = 1.7-1.9] and 1.9 cm(2) (95% CI = 1.7-2.0), respectively. Patients with immediate post-PMV MVA <1.8 cm(2) showed significantly lower event-free survival rate than those with post-PMV MVA > or =1.8 cm(2) (P < 0.001). CONCLUSION Immediate post-PMV MVA> or =1.8 cm(2) was an important predictor of both restenosis- and clinical event-free survival and this value should be considered as a component of optimal result.

Benefits and risks of long-term duration of dual antiplatelet therapy after drug-eluting stenting: A meta-analysis of randomized trials

BACKGROUND The potential benefits and risks of at least 1-year dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) implantation remain uncertain. METHODS AND RESULTS PubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched from database inception to December 2011 for randomized controlled trials that compared longer DAPT versus shorter DAPT duration after DES. Unpublished data were obtained from investigators. Trial-specific odds ratios (ORs) with 95% confidence interval (CI) were calculated and pooled using fixed-effects or random-effects model as appropriate. Data were independently extracted by 2 reviewers. Three randomized controlled trials comprising 5622 participants were included. Compared with patients receiving short-term therapy, participants receiving longer DAPT duration had a pooled OR of 1.26 (95% CI, 0.88 to 1.80; P=0.21, random-effects) for the primary outcome of cardiac death, myocardial infarction or stroke, OR of 1.29 (95% CI, 0.85 to 1.93; fixed-effects) for all-cause death, 1.23 (95% CI, 0.78 to 1.93; fixed-effects) for cardiac death, 0.91 (95% CI, 0.58 to 1.42; random-effects) for myocardial infarction, 1.93 (95% CI, 1.01 to 3.69; fixed-effects) for stroke and 2.51 (95% CI, 1.10 to 5.71, fixed-effects) for TIMI major bleeding. The number needed to treat for an additional harmful outcome was 217.6 for stroke and 243 for TIMI major bleeding. CONCLUSIONS This meta-analysis provides no evidence of benefits with longer DAPT duration as compared with a shorter course of therapy. It also reports significant harms with respect to major bleeding and stroke associated with prolonged DAPT use.