[Exposure Therapy with the Help of a Wearable Defibrillator Device used in the Treatment of Severe Obsessive-Compulsive Disorder and Congenital LQTS - An Example for Interdisciplinary Treatment]. / Expositionsbehandlung mithilfe einer Defibrillatorweste bei schwerer Zwangsstörung und angeborenem Long-QT-Syndrom.

We report on a case of a young female suffering from both obsessive-compulsive disorder (OCD) and a severe underlying cardiac disease. Due to the somatic comorbidity, treatment according to guidelines with exposure and reaction prevention was not initially conducted, due to potentially fatal risks to the patient. However, through collaboration with a cardiology clinic, we were able to find an innovative solution which allowed for the continuation of the exposure therapy. This case report demonstrates a successful interdisciplinary collaboration and is intended to sensitize the reader to the need for checking for somatic contraindications before conducting exposure therapy.

Vascular complications after percutaneous mitral valve repair and venous access closure using suture or closure device.

OBJECTIVE: The aim of this study was to assess the impact of different access-site closure strategies, suture or closure device (Proglide, Abbott Vascular), on vascular and bleeding complications after percutaneous mitral valve repair (MitraClip, Abbott Vascular). BACKGROUND: Considering the high-risk profile in patients receiving percutaneous mitral valve repair, complications related to the large 24 Fr access sheath and its relation to the closure technique have not been evaluated so far. METHODS AND RESULTS: Between 2009 and 2015, 277 consecutive high-risk patients with severe mitral valve regurgitation (MR) underwent percutaneous mitral valve repair at our institution using Z-suture (n = 150) or closure device (n = 127) to close the access-site. Duplex sonography was performed in all patients. The primary endpoint was access-site related complications according to the Valve Academic Research Consortium (VARC) criteria. Secondary outcomes were the incidence of bleeding complications and mortality. Access-site related VARC2 major and minor complications were comparable after closure with Z-suture or closure device (2,7% vs 3.1%, P = 0.81 and 15,3% vs 15.7%, P = 0.92). Three patients (2%) in the suture and four patients (3.1%) in the closure device group experienced unplanned endovascular intervention at the access site. Access-site related major bleeding was observed in 4 (2.7%) suture and 4 (3.1%) closure device treated patients (P = 0.81). No access site related mortality occurred. CONCLUSION: Both Z-suture and closure device use after percutaneous mitral valve repair are feasible and safe. However, there is no benefit of one strategy over the other according to VARC2 major and minor complications.

Predictors for long-term survival after transcatheter edge-to-edge mitral valve repair.

OBJECTIVES: To determine predictors for long-term outcome in high-risk patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) for severe mitral regurgitation (MR). BACKGROUND: There is no data on predictors of long-term outcome in high-risk real-world patients. METHODS: From August 2009 to April 2011, 126 high-risk patients deemed inoperable were treated with TMVR in two high-volume university centers. RESULTS: MR could be successfully reduced to grade ≤2 in 92.1% of patients (116/126 patients). Long-term clinical follow-up up to 5 years (95.2% follow-up rate) revealed a mortality rate of 35.7% (45/126 patients). Repeat mitral valve treatment (surgery or intervention) was needed in 19 patients (15.1%). Long-term clinical improvement was demonstrated with 69% of patients being in NYHA class ≤II. In a multivariable Cox regression analysis, the post-procedural grade of MR (hazard ratio [HR] 1.55 per grade, P = 0.035), the left ventricular ejection fraction (HR 0.58 for difference between 75th and 25th percentile, P = 0.031) and the glomerular filtration rate (HR 0.33 for 75th vs 25th percentile, P < 0.001) were independent predictors for long-term mortality. Patients with primary MR and a post-procedural MR grade ≤1 had the most favorable long-term outcome. CONCLUSIONS: This study determines predictors of long-term clinical outcome after TMVR and demonstrates that the grade of residual MR determines long-term survival. Our data suggest that it might be of benefit reducing residual MR to the lowest possible MR grade using TMVR-especially in selected high-risk patients with primary MR who are not considered as candidates for surgical MVR.

Paclitaxel-eluting balloons, paclitaxel-eluting stents, and balloon angioplasty in patients with restenosis after implantation of a drug-eluting stent (ISAR-DESIRE 3): a randomised, open-label trial.

BACKGROUND: The best way to manage restenosis in patients who have previously received a drug-eluting stent is unknown. We investigated the efficacy of paclitaxel-eluting balloons (PEB), paclitaxel-eluting stents (PES), and balloon angioplasty in these patients. METHODS: In this randomised, open-label trial, we enrolled patients older than 18 years with restenosis of at least 50% after implantation of any limus-eluting stent at three centres in Germany between Aug 3, 2009, and Oct 27, 2011. Patients were randomly assigned (1:1:1; stratified according to centre) to receive PEB, PES, or balloon angioplasty alone by means of sealed, opaque envelopes containing a computer-generated sequence. Patients and investigators were not masked to treatment allocation, but events and angiograms were assessed by individuals who were masked. The primary endpoint was diameter stenosis at follow-up angiography at 6-8 months. Primary analysis was done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00987324. FINDINGS: We enrolled 402 patients, of whom 137 (34%) were assigned to PEB, 131 (33%) to PES, and 134 (33%) to balloon angioplasty. Follow-up angiography at 6-8 months was available for 338 (84%) patients. PEB was non-inferior to PES in terms of diameter stenosis (38·0% [SD 21·5] vs 37·4% [21·8]; difference 0·6%, one-sided 95% CI 4·9%; p(non-inferiority)=0·007; non-inferiority margin of 7%). Findings were consistent in per-protocol analysis (p(non-inferiority)=0·011). PEB and PES were superior to balloon angioplasty alone (54·1% [25·0]; p(superiority)<0·0001 for both comparisons). Frequency of death, myocardial infarction, or target lesion thrombosis did not differ between groups. INTERPRETATION: By obviating the need for additional stent implantation, PEB could be a useful treatment for patients with restenosis after implantation of a drug-eluting stent. FUNDING: Deutsches Herzzentrum.

Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction.

BACKGROUND: The combination of glycoprotein IIb/IIIa inhibitors and heparin has not been compared with bivalirudin in studies specifically involving patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). We compared the two treatments in this patient population. METHODS: Immediately before PCI, we randomly assigned, in a double-blind manner, 1721 patients with acute non-ST-segment elevation myocardial infarction to receive abciximab plus unfractionated heparin (861 patients) or bivalirudin (860 patients). The study tested the hypothesis that abciximab and heparin would be superior to bivalirudin with respect to the primary composite end point of death, large recurrent myocardial infarction, urgent target-vessel revascularization, or major bleeding within 30 days. Secondary end points included the composite of death, any recurrent myocardial infarction, or urgent target-vessel revascularization (efficacy end point) and major bleeding (safety end point) within 30 days. RESULTS: The primary end point occurred in 10.9% of the patients in the abciximab group (94 patients) and in 11.0% in the bivalirudin group (95 patients) (relative risk with abciximab, 0.99; 95% confidence interval [CI], 0.74 to 1.32; P=0.94). Death, any recurrent myocardial infarction, or urgent target-vessel revascularization occurred in 12.8% of the patients in the abciximab group (110 patients) and in 13.4% in the bivalirudin group (115 patients) (relative risk, 0.96; 95% CI, 0.74 to 1.25; P=0.76). Major bleeding occurred in 4.6% of the patients in the abciximab group (40 patients) as compared with 2.6% in the bivalirudin group (22 patients) (relative risk, 1.84; 95% CI, 1.10 to 3.07; P=0.02). CONCLUSIONS: Abciximab and unfractionated heparin, as compared with bivalirudin, failed to reduce the rate of the primary end point and increased the risk of bleeding among patients with non-ST-segment elevation myocardial infarction who were undergoing PCI. (Funded by Nycomed Pharma and others; ISAR-REACT 4 ClinicalTrials.gov number, NCT00373451.).

Percutaneous edge-to-edge repair of the mitral valve in patients with degenerative versus functional mitral regurgitation.

OBJECTIVES: To prospectively assess the outcome of percutaneous edge-to-edge repair in patients with degenerative versus functional mitral regurgitation (MR). BACKGROUND: The optimal patient population eligible for percutaneous edge-to-edge repair has yet to be defined. METHODS: We analyzed 119 patients treated by percutaneous edge-to-edge repair for symptomatic MR, 72 patients with degenerative and 47 patients with functional MR. The primary endpoints were defined as procedural success (MR grade reduction ≥1 grade) as well as a composite endpoint defined as freedom from MR 3+ or 4+, mitral valve reintervention and death 12 months after clip implantation. In patients with successful clip placement we further analyzed MR grade, New York Heart Association (NYHA) functional class, distance in the 6 min walking test and left ventricular volumes 12 months after clip implantation. RESULTS: The primary success rate of all intended clipping procedures was 83.3% for degenerative and 89.4% for functional MR (P = 0.42). Regarding the composite endpoint we observed an event free survival of 59.7% in patients treated for degenerative MR and 63.8% in patients treated for functional MR (P = 0.73). We observed a highly significant reduction in MR grade as well as improvement in NYHA functional status in both groups 12 months after clip implantation. However, there was a more pronounced MR grade reduction in patients treated for degenerative MR compared with patients treated for functional MR. CONCLUSIONS: Percutaneous edge-to-edge repair of the mitral valve is feasible and comparably effective in patients with degenerative and functional MR.

Comparison of vascular closure devices vs manual compression after femoral artery puncture: the ISAR-CLOSURE randomized clinical trial.

IMPORTANCE: The role of vascular closure devices (VCD) for the achievement of hemostasis in patients undergoing transfemoral coronary angiography remains controversial. OBJECTIVE: To compare outcomes with the use of 2 hemostasis strategies after diagnostic coronary angiography performed via transfemoral access-a VCD-based strategy with 2 types of devices, an intravascular device and an extravascular device, vs standard manual compression. The primary hypothesis to be tested was that femoral hemostasis achieved through VCD is noninferior to manual compression in terms of vascular access-site complications. A secondary objective was the comparison of the 2 types of VCD. DESIGN, SETTING, AND PARTICIPANTS: Randomized, large-scale, multicenter, open-label clinical trial. We enrolled 4524 patients undergoing coronary angiography with a 6 French sheath via the common femoral artery from April 2011 through May 2014 in 4 centers in Germany. Last 30-day follow-up was performed in July 2014. INTERVENTIONS: After angiography of the access site, patients were randomized to hemostasis with an intravascular VCD, extravascular VCD, or manual compression in a 1:1:1 ratio. MAIN OUTCOMES AND MEASURES: Primary end point: the composite of access site-related vascular complications at 30 days after randomization with a 2% noninferiority margin. Secondary end points: time to hemostasis, repeat manual compression, and VCD failure. An α-level of .025 was chosen for primary and secondary comparisons. RESULTS: Of the 4524 enrolled patients, 3015 were randomly assigned to a VCD group (1509 received intravascular VCD and 1506 received extravascular VCD) and 1509 patients were randomly assigned to the manual compression group. Before hospital discharge, duplex sonography of the access site was performed in 4231 (94%) patients. The primary end point was observed in 208 patients (6.9%) assigned to receive a VCD and 119 patients (7.9%) assigned to manual compression (difference, -1.0% [1-sided 97.5% CI, 0.7%]; P for noninferiority<.001). Time to hemostasis was significantly shorter in patients with VCD (1 minute [interquartile range {IQR}, 0.5-2.0]), vs manual compression (10 minutes [IQR, 10-15]; P < .001). Time to hemostasis was significantly shorter among patients with intravascular VCD (0.5 minute [IQR, 0.2-1.0]), vs extravascular VCD (2.0 minutes [IQR, 1.0-2.0]; P <.001) and closure device failure was also significantly lower among those with intravascular vs extravascular VCD (80 patients [5.3%], vs 184 patients [12.2%]; P < .001). CONCLUSIONS AND RELEVANCE: In patients undergoing transfemoral coronary angiography, VCDs were noninferior to manual compression in terms of vascular access-site complications and reduced time to hemostasis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01389375.

Sex-related effectiveness of bivalirudin versus abciximab and heparin in non-ST-segment elevation myocardial infarction.

BACKGROUND: Female sex independently predicts bleeding risk after percutaneous coronary intervention (PCI). Bivalirudin is safer than abciximab plus heparin in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Thus, a greater benefit of bivalirudin in women would be expected. METHODS: We performed a sex-based analysis of the patients with NSTEMI (n = 1,721, 399 women) enrolled in the ISAR-REACT 4 trial and randomized to receive bivalirudin or abciximab plus heparin. Main outcome was a 30-day composite of death, large recurrent myocardial infarction, urgent target vessel revascularization, or major bleeding. Secondary outcome was 1-year composite of death, myocardial infarction, or target vessel revascularization. RESULTS: No difference in the main outcome was observed in groups with bivalirudin or abciximab plus heparin: 12.6% versus 15.5% (hazard ratio [HR] 0.81, 95% CI 0.48-1.37) among women and 10.6% versus 9.5% (HR 1.12, 95% CI 0.77-1.64) among men. Major bleeding occurred in 4.5% in the bivalirudin group versus 7.5% in the abciximab plus heparin group (HR 0.60, 95% CI 0.26-1.39) among women and 2.0% versus 3.8% (HR 0.52, 0.27-1.02) among men. At 1 year, the secondary outcome was observed in 24.1% in the bivalirudin group versus 28.7% in the abciximab plus heparin group among women, HR of 0.80 (95% CI 0.55-1.17), and in 20.6% and 19.0%, respectively, HR of 1.10 (95% CI 0.86-1.40) among men. CONCLUSION: Despite a higher peri-PCI bleeding risk in women, bivalirudin is as effective as and safer than abciximab plus heparin in women and men with NSTEMI undergoing PCI.

Five-year clinical outcomes of a polymer-free sirolimus-eluting stent versus a permanent polymer paclitaxel-eluting stent: final results of the intracoronary stenting and angiographic restenosis - test equivalence between two drug-eluting stents (ISAR-TEST) trial.

BACKGROUND: Limited evidence exists regarding the long-term performance of polymer-free (PF) drug-eluting stents (DES) in comparison to permanent polymer DES. This study investigated the 5-year efficacy and safety of a PF sirolimus-eluting stent (PF-SES) versus a permanent polymer paclitaxel-eluting stent (PES) in the setting of the Intracoronary Stenting and Angiographic Restenosis-Test Equivalence Between Two Drug-Eluting Stents (ISAR-TEST) randomized trial. METHODS AND RESULTS: A total of 450 patients undergoing percutaneous coronary intervention were randomized to receive either PF-SES (Yukon, Translumina; n = 225) or PES (Taxus, Boston Scientific; n = 225). Clinical follow-up was performed to 5 years after enrollment. The endpoints were major adverse cardiac events (MACE), target lesion revascularization (TLR), the composite of death or any myocardial infarction (MI) and stent thrombosis (ST). The incidence of MACE at 5 years was 27.3% (57 patients) in the PF-SES group and 31.7% (65 patients) in the PES group [hazard ratio (HR) = 0.87 [95% confidence interval (95% CI) = 0.61-1.24]; P = 0.40]. The combined incidence of death or MI was 16.6% (34 patients) in the PF-SES group and 20.0% (39 patients) in the PES group (HR = 0.86 [95% CI = 0.54-1.36]; P = 0.52). The incidence of TLR was 16.5% (34 patients) in the PF-SES group and 16.4% (33 patients) in the PES group (HR = 1.03 [95% CI = 0.64-1.66]; P = 0.89). ST occurred in 0.5% (one patient) in the PF-SES group and 1.6% (three patients) in the PES group (HR = 0.33 [95% CI = 0.03-3.14]; P = 0.32). CONCLUSION: Overall there was no significant difference in clinical outcomes between PF-SES and PES to 5 years. Extended follow-up supports the durability of efficacy and safety of PF-SES.

Second-versus first-generation "Limus"-eluting stents in diabetic patients with coronary artery disease: a randomized comparison in setting of ISAR-TEST-4 trial.

BACKGROUND: Patients with diabetes mellitus remain at higher risk for adverse events following percutaneous coronary intervention and the identification of the optimum drug eluting stents (DES) in these patients is of high clinical relevance. We compared effectiveness of everolimus-eluting stents (EES; Xience) versus sirolimus-eluting stents (SES; Cypher) in patients with diabetes mellitus enrolled in the Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting Stents (ISAR-TEST-4) trial. METHODS: In the setting of the ISAR-TEST-4 trial, 1304 patients with broad inclusion criteria were randomized to treatment with EES or SES. The focus of the present analysis is on a cohort of 377 patients with diabetes mellitus assigned to receive EES (n = 184) or SES (n = 193). The primary endpoint was the composite of cardiac death, myocardial infarction (MI) related to the target vessel, or target lesion revascularization (TLR) at 3-year follow-up. Secondary endpoints were parameters of angiographic and clinical restenosis (in-stent late lumen loss, binary restenosis, and TLR), all-cause mortality and definite/probable stent thrombosis. RESULTS: EES was comparable to SES concerning the incidence of the primary endpoint (21% vs. 24%, respectively; relative risk = 0.87; 95% CI, 0.57-1.34; P = 0.53). Concerning the secondary endpoint, TLR at 3 years with EES versus SES stents was not statistically different (14.7% vs. 16.6%, respectively; relative risk = 0.85; 95% CI, 0.51-1.43; P = 0.55). In terms of angiographic outcomes patients treated with EES as compared to SES had significantly lower late lumen loss (0.22 ± 0.46 mm vs. 0.44 ± 0.66 mm, respectively; P < 0.001) and binary restenosis (8.4% vs. 17%, respectively; P = 0.02) at 6- to 8-month angiographic follow-up. EES was comparable to SES concerning the incidence of all-cause death (10% vs. 16%, respectively; relative risk = 0.66; 95% CI, 0.37-1.18; P = 0.16) and stent thrombosis (1.1% vs. 3.1%, respectively; P = 0.19). CONCLUSIONS: In patients with diabetes mellitus enrolled in a real-world randomized control trial, EES is comparable to SES in terms of clinical efficacy and safety out to 3 years; angiographic markers of antirestenotic efficacy favored EES.

Collagen plug vascular closure devices and reduced risk of bleeding with bivalirudin versus heparin plus abciximab in patients undergoing percutaneous coronary intervention for non st-segment elevation myocardial infarction.

INTRODUCTION: In ISAR-REACT-4 (abciximab and heparin vs. bivalirudin for non-ST-elevation myocardial infarction [NSTEMI]), bivalirudin reduced the risk of bleeding after percutaneous coronary intervention (PCI) compared with unfractionated heparin plus abciximab (UFH + abciximab). Vascular closure devices (VCDs) may also prevent bleeding complications, and thus attenuate the benefit of bivalirudin. This analysis examined whether there exists an interaction on bleeding between VCDs and bivalirudin versus UFH + abciximab after PCI. METHODS: Patients with NSTEMI were randomly assigned to either receive UFH + abciximab or bivalirudin for PCI. The use of a VCD after femoral access was left to the operator's discretion. The effect of randomized treatment in patients who received a VCD was compared to that in patients with manual compression of the femoral access site. The primary end-point of this analysis was the 30-day incidence of ISAR-REACT-4 major bleeding. RESULTS: A total of 1,711 patients were enrolled in this analysis. Among the 365 (21.3%) patients receiving a VCD, 188 (51.5%) were treated with UFH + abciximab and 177 (48.5%) with bivalirudin. ISAR- REACT-4 major bleeding was higher with UFH + abciximab than with bivalirudin, independent of whether a VCD was used (4.8% vs. 2.3% with VCD and 4.6% vs. 2.7% without VCD, Pint = 0.76). There were also no interactions between randomized treatment and VCDs with respect to any of the ischemic end-points or net clinical outcome (Pint > 0.56). CONCLUSIONS: In patients undergoing PCI for NSTEMI, the reduction of major bleeding by bivalirudin compared with UFH + abciximab was not affected whether a VCD was used.

Polymer-free sirolimus- and probucol-eluting versus new generation zotarolimus-eluting stents in coronary artery disease: the Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol-Eluting versus Zotarolimus-eluting Stents (ISAR-TEST 5) trial.

BACKGROUND: Durable polymer coatings have been implicated in mid- and long-term adverse events after drug-eluting stent implantation. A polymer-free dual-drug sirolimus- and probucol-eluting stent and a new generation permanent polymer zotarolimus-eluting stent are recently developed technologies demonstrating encouraging results. METHODS AND RESULTS: In a clinical trial with minimal exclusion criteria, we randomly assigned 3002 patients to treatment with sirolimus- and probucol-eluting stents versus zotarolimus-eluting stents. The trial was designed to demonstrate noninferiority of the sirolimus- and probucol-eluting stents. The primary end point was the combined incidence of cardiac death, target-vessel-related myocardial infarction, or target-lesion revascularization at 1-year follow-up. Follow-up angiography was scheduled at 6 to 8 months. The sirolimus- and probucol-eluting stent was noninferior to the zotarolimus-eluting stent in terms of occurrence of the primary end point (13.1% versus 13.5%, respectively, P(noninferiority)=0.006; hazard ratio=0.97, 95% confidence interval, 0.78 to 1.19; P(superiority)=0.74). The incidence of definite/probable stent thrombosis was low in both groups (1.1% versus 1.2%, respectively; hazard ratio=0.91 [95% confidence interval, 0.45 to 1.84], P=0.80). With regard to angiographic efficacy, there were no differences between the sirolimus- and probucol-eluting stent and the zotarolimus-eluting stent in terms of either in-segment binary angiographic restenosis (13.3% versus 13.4% respectively; P=0.95) or in-stent late luminal loss (0.31±0.58 mm versus 0.29±0.56 mm, respectively; P=0.46). CONCLUSION: In this large-scale study powered for clinical end points, a polymer-free sirolimus- and probucol-eluting stent was noninferior to a new generation durable polymer-based zotarolimus-eluting stent out to 12 months. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier NCT 00598533.

Drug-eluting versus bare-metal stents in saphenous vein graft lesions (ISAR-CABG): a randomised controlled superiority trial.

BACKGROUND: Comparative assessment of clinical outcomes after use of drug-eluting stents versus bare-metal stents for treatment of aortocoronary saphenous vein graft lesions has not been undertaken in large randomised trials. We aimed to undertake a comparison in a randomised trial powered for clinical endpoints. METHODS: In this randomised superiority trial, patients with de-novo saphenous vein graft lesions were assigned by computer-generated sequence (1:1:1:3) to receive either drug-eluting stents (one of three types: permanent-polymer paclitaxel-eluting stents, permanent-polymer sirolimus-eluting stents, or biodegradable-polymer sirolimus-eluting stents) or bare-metal stents. Randomisation took place immediately after crossing of the lesion with a guidewire, and was stratified for each participating centre. Investigators assessing data were masked to treatment allocation; patients were not masked to allocation. The primary endpoint was the combined incidence of death, myocardial infarction, and target lesion revascularisation at 1 year. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00611910. FINDINGS: 610 patients were allocated to treatment groups (303 drug-eluting stent, 307 bare-metal stent). Drug-eluting stents reduced the incidence of the primary endpoint compared with bare-metal stents (44 [15%] vs 66 [22%] patients; hazard ratio [HR] 0.64, 95% CI 0.44-0.94; p=0.02). Target lesion revascularisation rate was reduced by drug-eluting stents (19 [7%] vs 37 [13%] patients; HR 0.49, 95% CI 0.28-0.86; p=0.01). No significant differences were seen between drug-eluting stents and bare-metal stents regarding all-cause mortality (15 [5%] vs 14 [5%] patients; HR 1.08, 95% CI 0.52-2.24; p=0.83), myocardial infarction (12 [4%] vs 18 [6%]; HR 0.66, 95% CI 0.32-1.37; p=0.27), or definite or probable stent thrombosis (2 [1%] in both groups; HR 1.00, 95% CI 0.14-7.10; p=0.99). INTERPRETATION: In patients undergoing percutaneous coronary intervention for de-novo saphenous vein graft lesions, drug-eluting stents are the preferred treatment option because they reduce the risk of adverse events compared with bare-metal stents. FUNDING: Deutsches Herzzentrum.

Bivalirudin versus unfractionated heparin during percutaneous coronary intervention.

BACKGROUND: Whether bivalirudin is superior to unfractionated heparin in patients with stable or unstable angina who undergo percutaneous coronary intervention (PCI) after pretreatment with clopidogrel is unknown. METHODS: We enrolled 4570 patients with stable or unstable angina (with normal levels of troponin T and creatine kinase MB) who were undergoing PCI after pretreatment with a 600-mg dose of clopidogrel at least 2 hours before the procedure; 2289 patients were randomly assigned in a double-blind manner to receive bivalirudin, and 2281 to receive unfractionated heparin. The primary end point was the composite of death, myocardial infarction, urgent target-vessel revascularization due to myocardial ischemia within 30 days after randomization, or major bleeding during the index hospitalization (with a net clinical benefit defined as a reduction in the incidence of the end point). The secondary end point was the composite of death, myocardial infarction, or urgent target-vessel revascularization. RESULTS: The incidence of the primary end point was 8.3% (190 patients) in the bivalirudin group as compared with 8.7% (199 patients) in the unfractionated-heparin group (relative risk, 0.94; 95% confidence interval [CI], 0.77 to 1.15; P=0.57). The secondary end point occurred in 134 patients (5.9%) in the bivalirudin group and 115 patients (5.0%) in the unfractionated-heparin group (relative risk, 1.16; 95% CI, 0.91 to 1.49; P=0.23). The incidence of major bleeding was 3.1% (70 patients) in the bivalirudin group and 4.6% (104 patients) in the unfractionated-heparin group (relative risk, 0.66; 95% CI, 0.49 to 0.90; P=0.008). CONCLUSIONS: In patients with stable and unstable angina who underwent PCI after pretreatment with clopidogrel, bivalirudin did not provide a net clinical benefit (i.e., it did not reduce the incidence of the composite end point of death, myocardial infarction, urgent target-vessel revascularization, or major bleeding) as compared with unfractionated heparin, but it did significantly reduce the incidence of major bleeding. (ClinicalTrials.gov number, NCT00262054.)

Prognostic value of sensitive troponin T in patients with stable and unstable angina and undetectable conventional troponin.

BACKGROUND: high-sensitivity cardiac troponin assays enable the measurement of cardiac troponin concentrations in the majority of patients with coronary artery disease. The objective of this study was to investigate the prognostic value of sensitive cardiac troponin in patients with stable and unstable angina presenting with undetectable levels of conventional troponin. METHODS: this study included 1,057 patients with stable (808 patients) or unstable (249 patients) angina who presented with undetectable conventional cardiac troponin T and underwent coronary artery revascularization. The cardiac troponin T was measured with conventional and high-sensitivity assays, in parallel, using the same plasma sample. The primary end point was 4-year mortality. RESULTS: the total sensitive troponin T level (median [interquartile range]) was 0.008 (0.005-0.014) microg/L. Variables independently associated with an elevated level of sensitive troponin T were elderly age, male sex, higher body mass index, presence of diabetes, unstable angina, increased New York Heart Association class, reduced left ventricular ejection fraction, elevated level of N-terminal pro-brain natriuretic peptide, reduced glomerular filtration rate, and elevated level of C-reactive protein. During the follow-up period, there were 83 deaths. The sensitive troponin T level was an independent predictor of 4-year mortality (adjusted hazard ratio = 1.47 with 95% CI 1.17-1.84, P < .001 for each unit increase in the natural logarithm of the sensitive troponin T). CONCLUSIONS: the elevated levels of sensitive cardiac troponin T in patients with stable or unstable angina presenting with undetectable conventional cardiac troponin T are significantly associated with reduced survival.

Sensitive troponin and N-terminal probrain natriuretic peptide in stable angina.

BACKGROUND: High-sensitivity cardiac troponin (hs-TnT) and N-terminal probrain natriuretic peptide (NT-proBNP) are powerful predictors of mortality in patients with stable coronary artery disease. Whether their combined use may further improve mortality prediction in these patients is unknown. MATERIALS AND METHODS: The study included 869 patients with stable coronary artery disease who underwent percutaneous coronary intervention. Hs-TnT and NT-proBNP were measured before angiography. Using median values of hs-TnT (0·008 µg L(-1)) and NT-proBNP (250·0 ng L(-1)) as cut-off points, patients were divided into four groups: low hs-TnT/low NT-proBNP group (293 patients with hs-TnT and NT-proBNP < median); low hs-TnT/high NT-proBNP group (142 patients with hs-TnT < median and NT-proBNP ≥ median); high hs-TnT/low NT-proBNP group (142 patients with hs-TnT ≥ median and NT-proBNP < median) and high hs-TnT/high NT-proBNP group (292 patients with hs-TnT and NT-proBNP ≥ median). The primary end point was all-cause mortality. RESULTS: The 4-year follow-up was complete in 90·7% of the patients. There were 76 deaths during the follow-up: seven in low hs-TnT/low NT-proBNP, 8 in low hs-TnT/high NT-proBNP, 10 in high hs-TnT/low NT-proBNP and 51 in high hs-TnT/high NT-proBNP groups (mortality estimates, 2·5%, 5·9%, 7·4% and 18·1%, respectively; odds ratio = 8·64, 95% confidence interval 3·85-19·4, P < 0·001 for high hs-TnT/high NT-proBNP vs. low hs-TnT/low NT-proBNP). Inclusion of hs-TnT and NT-proBNP in the multivariable model increased the discriminatory power of the model regarding mortality prediction compared with the model without biomarkers (absolute and relative integrated discrimination improvement 0·039 and 26·0%, P = 0·0015). CONCLUSIONS: Combined use of hs-TnT and NT-proBNP improves long-term risk prediction of mortality in patients with stable coronary heart disease.

ISAR-REACT 3A: a study of reduced dose of unfractionated heparin in biomarker negative patients undergoing percutaneous coronary intervention.

AIMS: Although a 140 U/kg dose of unfractionated heparin (UFH) was comparable with bivalirudin in terms of net clinical outcome in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 3 trial, it was associated with a higher risk of bleeding. We designed this study to assess whether a reduction in the UFH dose from 140 to 100 U/kg is associated with improved net clinical outcome. METHODS AND RESULTS: A total of 2505 biomarker negative patients undergoing percutaneous coronary intervention (PCI) after clopidogrel pre-treatment received a single bolus of 100 U/kg UFH. The primary endpoint was net clinical outcome-a quadruple endpoint of death, myocardial infarction, urgent target-vessel revascularization within 30 days, or in-hospital REPLACE 2 defined major bleeding. The primary comparison was with the historical UFH group of ISAR-REACT 3 (2281 patients). In a second analysis, we checked for non-inferiority against the historical bivalirudin arm of ISAR-REACT 3 (2289 patients). The incidence of the primary endpoint was 7.3% in the lower UFH dose group compared with 8.7% in the higher UFH dose group [hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.67-1.00; P = 0.045]. The incidence of major bleeding was 3.6% in the lower UFH dose group and 4.6% in the higher UFH dose group (HR 0.79; 95% CI 0.59-1.05; P = 0.11). The lower UFH dose met the criterion of non-inferiority compared with bivalirudin (P < 0.001). CONCLUSION: In biomarker negative patients undergoing PCI after clopidogrel loading, a reduced dose of 100 U/kg UFH provided net clinical benefit compared with the historical control of 140 U/kg UFH in the ISAR-REACT 3 trial. The benefit was mostly driven by reduction in bleeding. CLINICAL TRIAL REGISTRATION INFORMATION: URL www.clinicaltrials.gov; Unique identifier NCT00735280.

Abciximab in patients with acute ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention after clopidogrel loading: a randomized double-blind trial.

BACKGROUND: The glycoprotein IIb/IIIa receptor inhibitor abciximab has improved the efficacy of primary percutaneous coronary interventions in patients with acute myocardial infarction. However, it is not known whether abciximab remains beneficial after adequate clopidogrel loading in patients with acute ST-segment-elevation myocardial infarction. METHODS AND RESULTS: A total of 800 patients with acute ST-segment-elevation myocardial infarction within 24 hours from symptom onset, all treated with 600 mg clopidogrel, were randomly assigned in a double-blind fashion to receive either abciximab (n=401) or placebo (n=399) in the intensive care unit before being sent to the catheterization laboratory. The primary end point, infarct size measured by single-photon emission computed tomography with technetium-99m sestamibi before hospital discharge, was 15.7+/-17.2% (mean+/-SD) of the left ventricle in the abciximab group and 16.6+/-18.6% of the left ventricle in the placebo group (P=0.47). At 30 days, the composite of death, recurrent myocardial infarction, stroke, or urgent revascularization of the infarct-related artery was observed in 20 patients in the abciximab group (5.0%) and 15 patients in the placebo group (3.8%) (relative risk, 1.3; 95% CI, 0.7 to 2.6; P=0.40). Major bleeding complications were observed in 7 patients in each group (1.8%). CONCLUSIONS: Upstream administration of abciximab is not associated with a reduction in infarct size in patients presenting with acute myocardial infarction within 24 hours of symptom onset and receiving 600 mg clopidogrel.

Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal stents.

BACKGROUND: The long-term effects of treatment with sirolimus-eluting stents, as compared with bare-metal stents, have not been established. METHODS: We performed an analysis of individual data on 4958 patients enrolled in 14 randomized trials comparing sirolimus-eluting stents with bare-metal stents (mean follow-up interval, 12.1 to 58.9 months). The primary end point was death from any cause. Other outcomes were stent thrombosis, the composite end point of death or myocardial infarction, and the composite of death, myocardial infarction, or reintervention. RESULTS: The overall risk of death (hazard ratio, 1.03; 95% confidence interval [CI], 0.80 to 1.30) and the combined risk of death or myocardial infarction (hazard ratio, 0.97; 95% CI, 0.81 to 1.16) were not significantly different for patients receiving sirolimus-eluting stents versus bare-metal stents. There was a significant reduction in the combined risk of death, myocardial infarction, or reintervention (hazard ratio, 0.43; 95% CI, 0.34 to 0.54) associated with the use of sirolimus-eluting stents. There was no significant difference in the overall risk of stent thrombosis with sirolimus-eluting stents versus bare-metal stents (hazard ratio, 1.09; 95% CI, 0.64 to 1.86). However, there was evidence of a slight increase in the risk of stent thrombosis associated with sirolimus-eluting stents after the first year. CONCLUSIONS: The use of sirolimus-eluting stents does not have a significant effect on overall long-term survival and survival free of myocardial infarction, as compared with bare-metal stents. There is a sustained reduction in the need for reintervention after the use of sirolimus-eluting stents. The risk of stent thrombosis is at least as great as that seen with bare-metal stents.

A polymer-free dual drug-eluting stent in patients with coronary artery disease: a randomized trial vs. polymer-based drug-eluting stents.

AIMS: Long-term polymer residue in the coronary milieu is a consequence of current drug-eluting stent (DES) therapy and has been implicated in late adverse events. We developed a novel polymer-free rapamycin- and probucol-eluting stent (Dual-DES) and compared its efficacy against commercially available permanent polymer-based sirolimus-eluting (SES; Cypher) and zotarolimus-eluting (ZES; Endeavor) stents. METHODS AND RESULTS: Between March 2006 and July 2007, a total of 1007 patients undergoing coronary stenting of de novo lesions, in native vessels, were randomized to treatment with SES (n = 335), Dual-DES (n = 333), or ZES (n = 339). The primary endpoint was binary angiographic restenosis at 6-8 month follow-up angiography. Secondary endpoints were angiographic in-stent late loss; and target lesion revascularization (TLR), death/myocardial infarction and stent thrombosis at 12 months. Follow-up angiographic data were available for 828 (82.2%) patients. There was a significant difference in both binary restenosis and TLR across treatment groups (P = 0.003 and P < 0.001, respectively). Binary restenosis in the Dual-DES group (11.0%) was significantly lower than that in the ZES group (19.3%; P = 0.002) but comparable with that in the SES group (12.0%; P = 0.68). Similarly, TLR with Dual-DES (6.8%) was significantly lower than ZES (13.6%; P = 0.001) but not different to that of SES (7.2%; P = 0.83). These differences were mirrored in the extent of late loss across the groups. No differences were observed between stent groups in terms of death/myocardial infarction or stent thrombosis. CONCLUSION: A novel polymer-free Dual-DES is associated with high anti-restenotic efficacy without recourse to carrier polymer. Potential long-term clinical advantage of this platform remains subject to investigation. Study registered at ClinicalTrials.gov. Identifier number: NCT00332397.