Nae Hee Lee

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.)

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.

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).

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.

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.

Additive beneficial effects of valsartan combined with rosuvastatin in the treatment of hypercholesterolemic hypertensive patients.

Background and Objectives We compared the efficacy and safety of valsartan and rosuvastatin combination therapy with each treatment alone in hypercholesterolemic hypertensive patients. Subjects and Methods Patients who met inclusion criteria were randomized to receive 1 of the following 2-month drug regimens: valsartan 160 mg plus rosuvastatin 20 mg, valsartan 160 mg plus placebo, or rosuvastatin 20 mg plus placebo. The primary efficacy variables were change in sitting diastolic blood pressure (sitDBP) and sitting systolic blood pressure (sitSBP), and percentage change in low-density lipoprotein-cholesterol (LDL-C) in the combination, valsartan, and rosuvastatin groups. Adverse events (AEs) during the study were analyzed. Results A total of 354 patients were screened and 123 of them were finally randomized. Changes of sitDBP by least squares mean (LSM) were -11.1, -7.2, and -3.6 mm Hg, respectively, and was greater in the combination, as compared to both valsartan (p=0.02) and rosuvastatin (p<0.001). Changes of sitSBP by LSM were -13.2, -10.8, and -4.9 mm Hg, and was greater in the combination, as compared to rosuvastatin (p=0.006) and not valsartan (p=0.42). Percentage changes of LDL-C by LSM were -52, -4, and -47% in each group, and was greater in the combination, as compared to valsartan (p<0.001), similar to rosuvastatin (p=0.16). Most AEs were mild and resolved by the end of the study. Conclusion Combination treatment with valsartan and rosuvastatin exhibited an additive blood pressure-lowering effect with acceptable tolerability, as compared to valsartan monotherapy. Its lipid lowering effect was similar to rosuvatatin monotherapy.

Spontaneous Systemic Tumor Embolism Caused by Tumor Invasion of Pulmonary Vein in a Patient with Advanced Lung Cancer

We describe a 72-year-old man who presented with left hemiparesis due to acute cerebral infarction in the right fronto-temporal lobe. Three months prior to admission, he was hospitalized for right hemiparesis due to the acute cerebral infarction in the left anterior cerebral artery territory. To investigate the cause of his recurrent embolic event, a chest computed tomography scan and echocardiography were performed, which revealed advanced lung cancer invading contiguously through the pulmonary veins to the right main pulmonary artery and left atrium. Tumor embolism is a rare cause of stroke, occurring with primary or metastatic neoplasms of the lung. Echocardiography is a useful tool in patients with cerebral embolic episodes.

Double anchoring balloon technique for recanalization of coronary chronic total occlusion by retrograde approach.

A retrograde approach through the collateral channels is considered to improve the success rate of percutaneous coronary intervention for coronary chronic total occlusion (CTO). Various kinds of strategies and techniques are required to improve the success rate of this novel approach. We describe a case in which a CTO was successfully recanalized by the retrograde approach, using a new anchoring balloon technique (double anchoring balloon technique) which enabled the successful balloon passage through the hard CTO lesion.

Blood Pressure and Cholesterol-lowering Efficacy of a Fixed-dose Combination With Irbesartan and Atorvastatin in Patients With Hypertension and Hypercholesterolemia: A Randomized, Double-blind, Factorial, Multicenter Phase III Study

PURPOSE A fixed-dose combination of a stain and an antihypertensive drug may be useful for the treatment of patients with hypertension and hyperlipidemia. It may also improve patient drug compliance to help control risk factors of cardiovascular disease. This study was designed to evaluate the blood pressure-lowering and cholesterol-lowering effect of a fixed-dose combination of irbesartan-atorvastatin compared with monotherapy by either agent over an 8-week treatment period. METHODS Patients with comorbid hypertension and hypercholesterolemia were screened for this randomized, double-blind, Phase III study. Eligible study patients were randomly assigned to test groups receiving a combination of irbesartan 300 mg and atorvastatin 40 mg or 80 mg (IRB300 + ATO40 and IRB300 + ATO80). Comparator groups comprised monotherapy groups with irbesartan 300 mg (IRB300) or atorvastatin 40 mg (ATO40) or atorvastatin 80 mg (ATO80), or placebo. Patients who were eligible at screening were subjected to a 4- to 6-week washout period before commencing 8 weeks of therapy per their assigned group. The primary efficacy end points were percent change in LDL-C and sitting diastolic blood pressure (DBP) levels from baseline to end of therapy. Tolerability profiles of combination therapy were compared with other groups. FINDINGS A total of 733 patients with comorbid hypertension and hypercholesterolemia were screened for this study; 230 eligible patients were randomized to treatment. The mean age of patients was 58.9 (8.5) years, and their mean body mass index was 25.8 (3.2) kg/m2. More than two thirds (70.9%) of the study patients were male. Mean LDL-C and sitting DBP levels at baseline were 149.54 (29.19) mg/dL and 92.32 (6.03) mm Hg, respectively. Percent reductions in LDL-C after 8 weeks were 46.74% (2.06%) in the IRB300 + ATO40 group and 48.98% (2.12%) in the IRB300 + ATO80 group; these values were 47.13% (3.21%) and 48.30% (2.98%) in the ATO40 and ATO80 comparator groups. Similarly, a reduction in sitting DBP after 8 weeks was -8.50 (1.06) mm Hg in the IRB300 + ATO40 group and 10.66 (1.08) mm Hg in the IRB300 + ATO80 group compared with 8.40 (1.65) mm Hg in the IRB300 group. The incidence rate for treatment-emergent adverse events was 22.27% and was similar between the monotherapy and combination groups. IMPLICATIONS A once-daily combination product of irbesartan and atorvastatin provided an effective, safe, and more compliable treatment for patients with coexisting hypertension and hyperlipidemia. ClinicalTrials.gov identifier: NCT01442987.

Response to Letter Regarding Article, “Optimal Duration of Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation: A Randomized, Controlled Trial”

We thank Dr Sardar and colleagues for their interest in our recent article1 and appreciate the opportunity to reply. We agree that medication adherence is associated with clinical outcomes and remains an important issue in clinical drug trials. Unfortunately, there are no definite methods for assessing adherence to medications. In our study, pill count was used to determine medication adherence, and pharmacy data were electronically checked by medical insurance system. Medical adherence in this type of study is considered generally poor. Even in the Platelet Inhibition and Patient Outcome (PLATO) trial, medical adherence was ≈80%.2 In this context, we believe that medical adherence in our study seems to be acceptable. Time from index procedure to randomization was rather variable, but most patients were enrolled between 12 …