Comparison of Antiplatelet Monotherapies After Percutaneous Coronary Intervention According to Clinical, Ischemic, and Bleeding Risks.

BACKGROUND: Clopidogrel was superior to aspirin monotherapy in secondary prevention after percutaneous coronary intervention (PCI). OBJECTIVES: The purpose of this study was to evaluate the benefits of clopidogrel across high-risk subgroups METHODS: This was a post hoc analysis of the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of coronary artery diseases-EXtended Antiplatelet Monotherapy) trial that randomly assigned patients who were event free for 6 to 18 months post-PCI on dual antiplatelet therapy (DAPT) to clopidogrel or aspirin monotherapy. Two clinical risk scores were used for risk stratification: the DAPT score and the Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention (TRS 2°P) (the sum of age ≥75 years, diabetes, hypertension, current smoking, peripheral artery disease, stroke, coronary artery bypass grafting, heart failure, and renal dysfunction). The primary composite endpoint was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission because of acute coronary syndrome, and major bleeding (Bleeding Academic Research Consortium type ≥3) at 2 years after randomization. RESULTS: Among 5,403 patients, clopidogrel monotherapy showed a lower rate of the primary composite endpoint than aspirin monotherapy (HR: 0.73; 95% CI: 0.59-0.90). The benefit of clopidogrel over aspirin was consistent regardless of TRS 2°P (high TRS 2°P [≥3] group: HR: 0.65 [95% CI: 0.44-0.96]; and low TRS 2°P [<3] group: HR: 0.77 [95% CI: 0.60-0.99]) (P for interaction = 0.454) and regardless of DAPT score (high DAPT score [≥2] group: HR: 0.68 [95% CI: 0.46-1.00]; and low DAPT score [<2] group: HR: 0.75 [95% CI: 0.59-0.96]) (P for interaction = 0.662). The association was similar for the individual outcomes. CONCLUSIONS: The beneficial effect of clopidogrel over aspirin monotherapy was consistent regardless of clinical risk or relative ischemic and bleeding risks compared with aspirin monotherapy. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis- EXtended Antiplatelet Monotherapy [HOST-EXAM]; NCT02044250).

Effects of Prolonged Dual Antiplatelet Therapy in ST-Segment Elevation vs. Non-ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The benefits and risks of prolonged dual antiplatelet therapy (DAPT) have not been studied extensively across a broad spectrum of acute coronary syndromes. In this study we investigated whether treatment effects of prolonged DAPT were consistent in patients presenting with ST-segment elevation myocardial infarction (STEMI) vs. non-STEMI (NSTEMI).Methods and Results:As a post hoc analysis of the SMART-DATE trial, effects of ≥12 vs. 6 months DAPT were compared among 1,023 patients presenting with STEMI and 853 NSTEMI patients. The primary outcome was a composite of recurrent myocardial infarction (MI) or stent thrombosis at 18 months after the index procedure. Compared with the 6-month DAPT group, the rate of the composite endpoint was significantly lower in the ≥12-month DAPT group (1.2% vs. 3.8%; hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.12-0.77; P=0.012). The treatment effect of ≥12- vs. 6-month DAPT on the composite endpoint was consistent among NSTEMI patients (0.2% vs. 1.2%, respectively; HR 0.20, 95% CI 0.02-1.70; P=0.140; Pinteraction=0.718). In addition, ≥12-month DAPT increased Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding among both STEMI (4.4% vs. 2.0%; HR 2.18, 95% CI 1.03-4.60; P=0.041) and NSTEMI (5.1% vs. 2.2%; HR 2.37, 95% CI 1.08-5.17; P=0.031; Pinteraction=0.885) patients. CONCLUSIONS: Compared with 6-month DAPT, ≥12-month DAPT reduced recurrent MI or stent thrombosis regardless of the type of MI at presentation.

Clinical Usefulness of PRECISE-DAPT Score for Predicting Bleeding Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: An Analysis From the SMART-DATE Randomized Trial.

BACKGROUND: Although the current guidelines endorse the PRECISE-DAPT score (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy) to inform clinical decisions regarding duration of DAPT in patients undergoing percutaneous coronary intervention, use of the PRECISE-DAPT score to guide duration of DAPT has not been properly validated by randomized trials focused on the population with acute coronary syndrome. This study aimed to evaluate the usefulness of the PRECISE-DAPT score for predicting future bleeding and ischemic events and to compare clinical outcomes of short-term and long-term DAPT duration according to the PRECISE-DAPT score in patients with acute coronary syndrome. METHODS: This was a substudy of the SMART-DATE trial (6- Versus 12-Month or Longer Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome), in which patients with acute coronary syndrome undergoing percutaneous coronary intervention were randomly assigned to either 6- (n=1357) or 12-month or longer DAPT (n=1355). Major bleeding (Bleeding Academic Research Consortium type 3-5) and ischemic (myocardial infarction, stent thrombosis, or ischemic stroke) events at 18 months after the index procedure were compared between the 6- and 12-month or longer DAPT groups, according to PRECISE-DAPT score. RESULTS: The PRECISE-DAPT score was moderately effective at predicting bleeding events (area under the curve, 0.754 [95% CI, 0.655-0.854]; P<0.001). In patients with nonhigh PRECISE-DAPT score (<25, n=1967 [72.5%]), 6-month DAPT was associated with higher ischemic risk (2.7% versus 1.3%; HR, 2.01 [95% CI, 1.03-3.91]; P=0.040; absolute risk difference, +1.3%; P=0.035) with similar bleeding risk (0.4% versus 0.3%; HR, 2.00 [95% CI, 0.37-10.94]; P=0.422; absolute risk difference, +0.2%; P=0.498), compared with 12-month or longer DAPT. Among patients with high PRECISE-DAPT score (≥25, n=745 [27.5%]), 6-month DAPT presented a similar ischemic risk (4.8% versus 3.4%; HR, 1.43 [95% CI, 0.68-2.98], P=0.348; absolute risk difference, +1.5%; P=0.327) but significantly reduced major bleeding risk (0.6% versus 2.3%; HR, 0.25 [95% CI, 0.05-1.17]; P=0.079; absolute risk difference, -1.7%; P=0.045). CONCLUSIONS: Consistent with current guidelines, determination of the duration of DAPT according to PRECISE-DAPT score could improve the clinical outcomes in patients with acute coronary syndrome after percutaneous coronary intervention with current-generation drug-eluting stents. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01701453.

6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial.

BACKGROUND: Current guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus a P2Y12 inhibitor for at least 12 months after implantation of drug-eluting stents (DES) in patients with acute coronary syndrome. However, available data about the optimal duration of DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention are scant. We aimed to investigate whether a 6-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT in this population. METHODS: We did a randomised, open-label, non-inferiority trial at 31 centres in South Korea. Patients were eligible if they had unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and underwent percutaneous coronary intervention. Enrolled patients were randomly assigned, via a web-based system by computer-generated block randomisation, to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation, and diabetes. Assessors were masked to treatment allocation. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population. Secondary endpoints were the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2-5 bleeding at 18 months after the index procedure. The primary endpoint was also analysed per protocol. This trial is registered with ClinicalTrials.gov, number NCT01701453. FINDINGS: Between Sept 5, 2012, and Dec 31, 2015, we randomly assigned 2712 patients; 1357 to the 6-month DAPT group and 1355 to the 12-month or longer DAPT group. Clopidogrel was used as a P2Y12 inhibitor for DAPT in 1082 (79·7%) patients in the 6-month DAPT group and in 1109 (81·8%) patients in the 12-month or longer DAPT group. The primary endpoint occurred in 63 patients in the 6-month DAPT group and in 56 patients in the 12-month or longer DAPT group (cumulative event rate 4·7% vs 4·2%; absolute risk difference 0·5%; upper limit of one-sided 95% CI 1·8%; pnon-inferiority=0·03 with a predefined non-inferiority margin of 2·0%). Although all-cause mortality did not differ significantly between the 6-month DAPT group and the 12-month or longer DAPT group (35 [2·6%] patients vs 39 [2·9%]; hazard ratio [HR] 0·90 [95% CI 0·57-1·42]; p=0·90) and neither did stroke (11 [0·8%] patients vs 12 [0·9%]; 0·92 [0·41-2·08]; p=0·84), myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 [1·8%] patients vs ten [0·8%]; 2·41 [1·15-5·05]; p=0·02). 15 (1·1%) patients had stent thrombosis in the 6-month DAPT group compared with ten (0·7%) in the 12-month or longer DAPT group (HR 1·50 [95% CI 0·68-3·35]; p=0·32). The rate of BARC type 2-5 bleeding was 2·7% (35 patients) in the 6-month DAPT group and 3·9% (51 patients) in the 12-month or longer DAPT group (HR 0·69 [95% CI 0·45-1·05]; p=0·09). Results from the per-protocol analysis were similar to those from the intention-to-treat analysis. INTERPRETATION: The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation DES. Prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care. FUNDING: Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors Inc, and Dong-A ST.

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.

Impact of insulin resistance on 1-year clinical outcomes in non-diabetic patients undergoing percutaneous coronary intervention with drug-eluting stents.

BACKGROUND: Insulin resistance (IR) is known to be a risk factor for coronary artery disease (CAD). We aimed to evaluate the impact of IR on 1-year clinical outcomes in non-diabetic CAD patients who underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). METHODS AND RESULTS: A total of 229 consecutive non-diabetic CAD patients treated with DESs were enrolled. Study population was divided into IR group [homeostasis model assessment (HOMA) index ≥ 2.5, n=54] and non-IR group (HOMA index<2.5, n=175). Baseline clinical and procedural characteristics were similar between the groups except higher incidence of high-sensitivity C-reactive protein and lower incidence of multivessel disease as the target vessel in the non-IR group. There was a trend toward longer restenosis lesion length in the IR group at 6 months angiographic follow up but composite major clinical outcomes up to 1 year were similar between the two groups. CONCLUSIONS: Despite worse trend in angiographic outcomes in the IR group (HOMA index ≥ 2.5), it was not translated into worse 1-year major clinical outcomes following PCI with DESs as compared to the non-IR group.

Catastrophic catecholamine-induced cardiomyopathy mimicking acute myocardial infarction, rescued by extracorporeal membrane oxygenation (ECMO) in pheochromocytoma.

Pheochromocytoma is a rare disorder and functioning tumor composed of chromaffin cells that secrete catecholamines. Patients with a pheochromocytoma 'crisis' have a high mortality in spite of aggressive therapy. We present a case with a severe acute catecholamine cardiomyopathy presenting ST segment elevation with cardiogenic shock after hemorrhage into a left suprarenal tumor. Intra-aortic balloon pump (IABP) support, combined with inotropic therapy, was performed. However, the patient deteriorated rapidly and was unresponsive to a full dose of inotropics and IABP. We decided to apply extracorporeal membrane oxygenation (ECMO) device for the patient. His clinical state began to improve 3 days after ECMO. After achieving hemodynamic stabilization, he underwent successful laparoscopic left adrenalectomy. He needed no further cardiac medication after discharge.

Left atrial volume measured by real-time 3-dimensional echocardiography predicts clinical outcomes in patients with severe left ventricular dysfunction and in sinus rhythm.

BACKGROUND: The clinical value of real-time 3-dimensional echocardiography assessments of left atrial volume in patients with left ventricular dysfunction has not been determined. METHODS: Real-time 3-dimensional echocardiography and 2-dimensional Doppler echocardiography were performed on the same day in 108 patients with severe left ventricular dysfunction and in sinus rhythm. End-systolic left atrial volumes were measured using real-time 3-dimensional echocardiography images (LAV-3D) and end-systolic left atrial volumes were calculated by the biplane area-length formula using 2-dimensional echocardiography (LAV-2D). Patients were observed clinically over 10 +/- 7 months. RESULTS: LAV-2D showed excellent correlation with LAV-3D (r = 0.88, P < .001), but the former was significantly smaller than the latter (-12 +/- 21 mL, P < .001). During follow-up, 31 patients (29%) showed clinical events, including 3 cardiac deaths and 28 hospitalizations as a result of heart failure. Patients with clinical events had larger initial LAV-3D (P < .05) and LAV-2D (P = .05), higher transmitral E velocity, higher E/E' ratio, more severe mitral and tricuspid regurgitation, and higher maximal velocity of tricuspid regurgitation than the 77 patients without events. LAV-3D (P < .001) and age (P < .05) were independent predictors of cardiac events by Cox proportional hazard model, whereas LAV-2D was negatively involved. Patients with initial LAV-3D less than 100 mL had a significantly higher 1-year event-free survival than those with LAV-3D greater than or equal to 100 mL (80 +/- 7 vs 48 +/- 10%, P < .001). CONCLUSIONS: LAV-3D is a major predictor of clinical events in patients with severe left ventricular dysfunction and in sinus rhythm. The clinical value of LAV-3D seems to be superior to that of LAV-2D.

Long-term outcome of simultaneous kissing stenting technique with sirolimus-eluting stent for large bifurcation coronary lesions.

OBJECTIVES: This study was conducted to evaluate the outcomes of simultaneous kissing stenting with sirolimus-eluting stent (SES). BACKGROUND: Percutaneous intervention for bifurcation coronary lesions is still challenging. METHODS: This study was designed to evaluate the long-term outcomes of 36 consecutive patients with large bifurcation coronary lesions who underwent simultaneous kissing stenting with SES. RESULTS: Lesion location was unprotected left main in 29 patients (81%) and anterior descending artery in 7 (19%). The patients received a combination of aspirin and clopidogrel for 6 months and cilostazol for 1 month. Mean proximal reference diameter was 4.05 +/- 0.68 mm. Compared with the side branch (SB), the main vessel (MV) involved longer lesions (25.8 +/- 17.0 mm vs. 10.2 +/- 10.8 mm, P < 0.001) and smaller preprocedural minimal lumen diameters (1.02 +/- 0.53 mm vs. 1.46 +/- 0.78 mm, P = 0.006) and was treated with larger stents (3.1 +/- 0.3 mm vs. 3.0 +/- 0.3 mm, P = 0.006). Angiographic success rate was 100%. Over the follow-up of 26.7 +/- 8.6 months, no deaths, myocardial infarctions or stent thromboses occurred. Target lesion revascularization was performed in five patients (14%). Overall angiographic restenosis occurred in 5/30 patients (17%), consisting of 4 (13%) at MV and 3 (10%) at SB. At follow-up angiography, a membranous diaphragm at the carina was identified in 14 patients (47%), but only one of whom was associated with angiographic restenosis. CONCLUSION: Simultaneous kissing stenting with SES appears a feasible stenting technique in large bifurcation coronary lesions. However, a new angiographic structure of carinal membrane developed in a half of patients at follow-up and its influence needs to be further investigated.

Results and predictors of angiographic restenosis and long-term adverse cardiac events after drug-eluting stent implantation for aorto-ostial coronary artery disease.

The correlates of angiographic and clinical outcomes after drug-eluting stent (DES) implantation for aorto-ostial lesions remain unknown. This study evaluated long-term results of DES implantation for aorto-ostial lesions and determined risk factors for restenosis and adverse cardiac events. In total, 184 consecutive patients who underwent DES implantation for aorto-ostial lesions were investigated (DES group) compared with 172 consecutive patients treated with bare metal stents before the introduction of DESs (pre-DES group). Major adverse cardiac events (MACEs) were defined as death, Q-wave myocardial infarction, and need for target lesion revascularization. The DES group had significantly higher risk clinical and procedural profiles than the pre-DES group. Procedural success rates were 99.5% in the DES group and 100% in the pre-DES group (p = 1.0). The DES group had a significantly lower incidence of in-segment restenosis (10.5% vs 26.0%, p = 0.001) and target lesion revascularization (4.3% vs 11.6%, p = 0.011). Cumulative MACE rates at 1 year were 6.5% in the DES group and 13.4% in the pre-DES group (p = 0.03). By multivariate analysis, treatment of bypass graft, treatment of in-stent restenosis, and reference vessel diameter were predictors of restenosis, and only reference vessel diameter (hazard ratio 0.20, 95% confidence interval 0.05 to 0.75, p = 0.017) inversely correlated with 1-year MACEs after DES implantation. In conclusion, DES implantation for aorto-ostial lesions is associated with a significant decrease in restenosis and MACEs compared with the pre-DES phase. Treatment of bypass graft and in-stent restenosis and reference vessel size were identified as predictors of restenosis and/or long-term MACEs after DES implantation.

Serial intravascular ultrasound evidence of both plaque stabilization and lesion progression in patients with ruptured coronary plaques: effects of statin therapy on ruptured coronary plaque.

Using serial intravascular ultrasound (IVUS), we evaluated the natural evolution of non-culprit/non-target lesion ruptured coronary plaques and assessed the impact of statin therapy. Twenty-eight patients with non-stenotic ruptured plaques underwent baseline and 12-month follow-up IVUS studies; half were treated with statins. Standard IVUS analyses were performed. Complete healing of ruptured plaques was observed in four (29%) statin-treated patients and no non-statin-treated patients (p=0.049). Statin-treated patients had an increase in lumen area of 0.4+/-0.8 mm2 (versus a decrease in lumen area of -0.6+/-1.0 mm2 in non-statin-treated patients, p=0.007) and no change in plaque area (versus an increase in plaque area of 0.6+/-0.9 mm2, p=0.051). During 1-year follow-up, target lesion revascularization was performed in three non-statin-treated patients (21%) and no statin-treated patient (p=0.11). Compared to lesions that did not require revascularization, lesions requiring revascularization had a decrease in lumen area (-1.7+/-1.4 mm2 versus 0.1+/-0.8 mm2, p=0.001) as well as an increase in plaque area (1.6+/-1.0 mm2 versus 0.1+/-0.7 mm2, p=0.002). In conclusion, the current observational follow-up IVUS study showed beneficial effects of statin treatment on reduction of revascularization rates and stabilization of non-culprit/non-target lesion plaque ruptures without significant stenosis. Conversely, healing of non-statin-treated non-culprit/non-target lesion plaque ruptures can be responsible for lesion progression requiring revascularization.