Ultrasound-guided thrombin injection for treatment of femoral artery pseudoaneurysm with concomitant AV-fistula - a retrospective single centre experience.

BACKGROUND: Increasing volume of complex percutaneous endovascular procedures in highly anticoagulated patients generate a not negligible percentage of femoral pseudoaneurysms (PSA) with concomitant arteriovenous fistulas (AVF). While ultrasound-guided thrombin injection (UGTI) is the therapy of choice for PSA, concomitant AVF is regarded as a contraindication for UGTI, as venous thromboembolism is feared. In this retrospective, register-based cohort study, we report on and evaluate the use of UGTI for the treatment of PSA with AFV. PATIENTS AND METHODS: All patients (n = 523), who underwent UGTI for femoral PSA at the German Heart Centre Munich from January 2011 until January 2018, were retrospectively reviewed for the presence of a concomitant AVF and outcomes were recorded. RESULTS: Forty femoral PSA/AVFs treated by UGTI were identified. The mean enddiastolic arterial-flow-velocity above the AVF, an estimate of the AVF size, was 14.61 ± 1.7 cm/sec. The Majority of patients exhibited flow-velocities < 25 cm/sec (n = 31; 77.5 %) and were on either uninterrupted oral anticoagulation (n = 32; 80 %) or dual antiplatelet therapy (n = 8). Twenty-eight (70 %) PSA/AVFs could be successfully closed by UGTI. In eight multicompartmental PSAs, partial obliteration necessitated combined treatment with manual compression, while one partial occlusion was treated by observation. There were three failures, of which two underwent covered-stent-graft-implantation and one surgical repair. One DVT (2.5 %) occurred two days after UGTI in the by far largest AVF (60 cm/sec) included in the study. Besides two late PSA recurrences treated by surgery, no other complications were observed. AVF persisted in 65 %, all of them asymptomatic. The mean follow-up was 6 ± 15.5 months. CONCLUSIONS: UGTI appears to be a treatment option in femoral PSA/AVF, at least under oral anticoagulation in small fistulas with enddiastolic arterial-flow-velocities ≤ 25 cm/sec. However, caution is necessary in larger AVFs, which should remain a contraindication for UGTI.

Stent thrombosis after drug-eluting stent implantation: incidence, timing, and relation to discontinuation of clopidogrel therapy over a 4-year period.

AIMS: To assess the incidence, timing, and relation of drug-eluting stent (DES) thrombosis to discontinuation of clopidogrel therapy. METHODS AND RESULTS: This prospective observational cohort study included 6816 consecutive patients that underwent successful DES implantation. Primary endpoint was definite stent thrombosis (ST). During 4 years of follow-up, definite ST was observed in 73 patients, corresponding to a cumulative incidence of 1.2%. Cumulative incidence of ST at 30 days was 0.5 and 0.8% at 1 year, respectively. Discontinuation of clopidogrel therapy was significantly associated with ST only in the first 6 months after the procedure (P < 0.001). During that period, the median time interval from clopidogrel discontinuation to ST was 9 days [interquartile range (IQR) 5.5-22.5] while thereafter it was 104.3 days (IQR 7.4-294.8). CONCLUSION: The 4 year incidence of ST after DES implantation is low. A relevant number of ST occur early after discontinuation of clopidogrel therapy. The dependence of ST on discontinuation of clopidogrel therapy seems to be mostly confined to the first 6 months after DES implantation. However, specifically designed randomized studies are required to establish the optimal length of clopidogrel therapy after DES implantation.

Predictive factors for in-stent late loss and coronary lesion progression in patients with type 2 diabetes mellitus randomized to rosiglitazone or placebo.

BACKGROUND: Type 2 diabetics (DM2) are at increased risk for restenosis as well as nonculprit coronary artery lesion (NCCL) progression. Rosiglitazone (RSG) favorably modifies many of the altered biologic processes in DM2, although recent reports have questioned its safety. We conducted a double-blind randomized trial to assess the effects of RSG versus placebo on in-stent late lumen loss (LL) and angiographic progression of NCCL. METHODS: A total of 65 DM2 were randomized to RSG (4 mg/d) (n = 32) or placebo (n = 33) at the time of stenting and underwent clinical and laboratory analysis at 1 and 4 months and 8-month angiography (n = 46 patients). Rapid angiographic progression (RAP) was defined as > or =20% diameter reduction of preexisting NCCL by quantitative coronary angiography, or a new narrowing > or =30%. RESULTS: Mean LL in RSG (n = 33 lesions) was not different from that of placebo (0.62 +/- 0.59 vs 0.70 +/- 0.67, P = NS). Seven (13.5%) of 52 NCCLs have RAP in RSG versus 9 (16.1%) of 56 in placebo (P = NS). High-sensitivity C-reactive protein (hs-CRP) was the only predictor of RAP. Patients with a 120-day hs-CRP > or =75th percentile had an OR of 7.35 (95% CI 2.35-23) for RAP versus those below. Although RSG treatment also lowered log (hs-CRP) at 4 months (RSG 0.10 +/- 0.37 vs placebo 0.26 +/- 0.49, P = .06), it did not decrease the likelihood of plaque progression while also raising LDL and N-terminal brain naturetic peptide. CONCLUSIONS: Rosiglitazone appears not to lower LL or reduce angiographic progression of NCCL in DM2 and had complex effects on markers of cardiac risk.

Culotte stenting technique in coronary bifurcation disease: angiographic follow-up using dedicated quantitative coronary angiographic analysis and 12-month clinical outcomes.

AIMS: Percutaneous treatment of coronary bifurcation disease remains challenging. In patient subsets in which a two-stent strategy is necessary, the culotte technique is a widely used method. We sought to examine the clinical and angiographic outcomes of patients treated in this manner at our institution. As quantitative coronary angiographic analysis using standard measurement programmes is problematic, we used a dedicated bifurcation analysis system. METHODS AND RESULTS: We prospectively enrolled patients undergoing culotte stenting with drug-eluting stents (Cypher, Endeavor, polymer-free rapamycin-eluting, Taxus) in two German centres. Lesions were classified according to the Medina classification. Angiographic follow-up was scheduled between 6 and 12 months post-index procedure. Clinical follow-up was available up to 12 months. Culotte technique was used in 134 lesions in 132 patients. Of these, 124 (92.5%) represented 'true bifurcation' lesion morphology. Kissing balloon inflation was used in 62% of patients. Procedural angiographic success was achieved in all lesions. Follow-up coronary angiography was performed in 108 (81.8%) patients. Median (IQR) late lumen loss was 0.10 (-0.04-0.38) mm in the proximal main vessel, 0.34 (0.03-0.66) mm in the distal main branch, and 0.30 (-0.01-0.72) mm in the side branch. The incidence of binary angiographic restenosis was 22% for the whole bifurcation lesion, 0% in the proximal main vessel, 9.1% in the distal main branch, and 16% in the side branch. At 12 months, 28 of 132 (21%) patients had undergone target lesion revascularization. The incidence of stent thrombosis (at 1 year) was 1.5%. Predictors of angiographic restenosis were older age, increasing bifurcation angle, more severe distal main branch stenosis, and smaller side branch reference diameter; kissing balloon post-dilatation tended to have a protective effect. CONCLUSION: The culotte stenting technique is associated with high procedural success and a relatively low risk of angiographic restenosis. Safety results in our cohort were favourable in terms of a low risk of stent thrombosis.

Randomized trial of three rapamycin-eluting stents with different coating strategies for the reduction of coronary restenosis.

AIMS: The objective of this study was to assess the non-inferiority, in terms of anti-restenotic efficacy, of both biodegradable-polymer (BP) and polymer-free (PF) stents compared with permanent-polymer rapamycin-eluting (PP; Cypher) stent. METHODS AND RESULTS: Patients with de novo coronary lesions in native vessels were randomly assigned to receive a BP stent, a PF stent or a PP stent. The primary endpoint was in-stent late lumen loss at follow-up angiogram. A total of 605 patients were enrolled: 202 patients received BP stents, 202 were treated with PP stents, and 201 received PF stents. Repeat angiography was available for 492 patients (81.3%). Mean late lumen loss at 6-8-month angiographic follow-up was 0.17 +/- 0.45 mm in the BP stent group, 0.23 +/- 0.46 mm in the PP cohort, and 0.47 +/- 0.56 mm in the PF stent group. The BP stent met pre-specified criteria for non-inferiority (P < 0.001), whereas the PF stent did not (P = 0.94). There were no differences in safety outcomes. CONCLUSION: Both BP and PF stents have a 1-year safety profile similar to that of the PP stent. Whereas the PF stent provided an inferior efficacy, the BP stent is at least as effective as the PP stent in terms of anti-restenotic efficacy.

Age-dependent effect of abciximab in patients with acute coronary syndromes treated with percutaneous coronary interventions.

BACKGROUND: No studies have specifically performed an age-based analysis of the efficacy of abciximab in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention (PCI). The aim of the study was to assess whether there are age-dependent differences in the clinical benefit of abciximab in patients with acute coronary syndrome treated with PCI. METHODS AND RESULTS: We performed this retrospective analysis of 2022 patients with acute coronary syndrome enrolled in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 2) study and randomized to receive abciximab or placebo during a PCI procedure. The incidence of major adverse cardiac events (MACE) during the 30 days after PCI was the primary end point of the study. On the basis of the cutoff age value provided by logistic regression in connection with bootstrap resampling, patients were divided into those younger (n=1220) and older (n=802) than 70 years. Among younger patients, the incidence of MACE was 7.7% in the abciximab group versus 13.3% in the placebo group (relative risk 0.57, 95% confidence interval 0.40 to 0.80, P=0.001). In contrast, no difference was observed among older patients: The incidence of MACE was 10.9% in the abciximab group versus 9.9% in the placebo group (relative risk 1.10, 95% confidence interval 0.72 to 1.69, P=0.65). After adjustment for other variables, including cardiac troponin, there was a significant interaction between age and abciximab (P=0.04) with respect to MACE reduction, with abciximab being more effective in younger patients. CONCLUSIONS: In patients with non-ST-elevation acute coronary syndromes undergoing PCI, the efficacy of abciximab appears to be age-dependent, with greater benefit among younger patients.

Impact of diabetes mellitus on long-term outcomes in the drug-eluting stent era.

BACKGROUND: Diabetes mellitus is associated with an increased risk of restenosis, stent thrombosis, and death after percutaneous coronary interventions. Little is known about the late outcome of patients with diabetes mellitus who receive drug-eluting stents (DES). METHODS: This study includes a prospective database of 2557 consecutive patients with coronary artery disease who underwent DES implantation in native coronary arteries in 2 German hospitals. The primary end points of the study were mortality and clinical restenosis (target lesion revascularization). Secondary end points were binary angiographic restenosis, stent thrombosis, and the composite of death or myocardial infarction. RESULTS: Within a median follow-up period of 2.3 years, stent thrombosis occurred in 14 patients with diabetes versus 17 patients without diabetes: 3-year Kaplan-Meier estimates of stent thrombosis were 2.2% versus 1.0%, with a relative risk of 2.17 (95% CI 1.09-4.33, P = .027). Binary angiographic restenosis was observed in 87 patients with diabetes and 208 patients without diabetes (15.2% vs 13.5%, P = .32). Target lesion revascularization was needed in 93 patients with diabetes and 219 patients without diabetes (12.8% vs 12.0%, P = .56). There were 93 deaths among diabetic patients versus 118 deaths among nondiabetic patients: 3-year Kaplan-Meier estimates of mortality were 17.3% versus 7.8%, with a relative risk of 2.10 (95% CI 1.61-2.74, P < .001). After adjustment in the multivariable analyses, diabetes remained an independent predictor of 3-year mortality with a hazard ratio of 1.63 (95% CI 1.23-2.17, P < .001), but not of angiographic (P = .92) or clinical restenosis (P = .97). CONCLUSION: Although DES attenuate diabetes-associated excess risk of restenosis, risk of death and thrombotic complications remains higher in patients with diabetes than in nondiabetic patients in the DES era.

Sex and effect of abciximab in patients with acute coronary syndromes treated with percutaneous coronary interventions: results from Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2 trial.

BACKGROUND: It is not known whether there exists a sex-dependent difference in the clinical benefit of abciximab in patients with acute coronary syndromes (ACS) undergoing a percutaneous coronary intervention (PCI). METHODS: We performed this retrospective analysis of 2022 patients (498 women) with ACS enrolled in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2 trial and randomized to receive abciximab or placebo during a PCI procedure. The incidence of major adverse cardiac events (MACE) during the 30 days after PCI was the primary end point of the study. RESULTS: Among men, the 30-day incidence of MACE was 8.6% in the abciximab group compared with 12.6% in the placebo group, relative risk (RR) 0.69 (95% confidence interval [CI] 0.50-0.94), P = .01. The 30-day incidence of MACE in women was 9.7% in the abciximab group compared with 9.9% in the placebo group, RR 0.98 (95% CI, 0.56-1.72), P = .97. After adjustment for baseline clinical and angiographic characteristics, there was no significant interaction between sex and abciximab (P = .71); adjusted RR was 0.70 (95% CI, 0.34-1.34) in women and 0.60 (95% CI, 0.40-0.90) in men. The incidence of major bleeding was significantly greater in women (3.6%) than in men (0.7%), RR 5.5 (95% CI, 2.54-11.9), P < .001, without any dependence on the form of therapy received. CONCLUSIONS: In patients with non-ST elevation ACS undergoing a PCI, the benefit with abciximab is greater in men than in women. This is apparently the result of sex-based differences in risk profile.

Relationship between platelet count and 30-day clinical outcomes after percutaneous coronary interventions. Pooled analysis of four ISAR trials.

Platelets play an important role in the development of major adverse cardiac events (MACE) following percutaneous coronary intervention (PCI). The impact of platelet count on the outcome of patients undergoing PCI after pre-treatment with clopidogrel is unknown. The study included 5,256 patients enrolled in four randomized trials - ISAR-REACT, ISAR-SMART2, ISAR-SWEET, and ISAR-REACT2 - which assessed the value of abciximab in patients with coronary artery disease (CAD) undergoing PCI after pre-treatment with 600 mg of clopidogrel. Platelet count was measured at baseline before PCI. Primary endpoint was the 30-day incidence of MACE, secondary endpoint was mortality. The tertiles of platelet counts were: lower tertile (<198 x 10(9)/L; n = 1,726), middle tertile (198-244 x 10(9)/L; n = 1,750) and upper tertile (>244 x 10(9)/L; n = 1,780). The 30-day incidence of MACE was 6.7% (n = 116) among patients of the lower tertile, 6.3% (n = 111) among patients of the middle tertile, and 7.0% (n = 124) among patients of the upper tertile (P = 0.76). The 30-day mortality was 1.2% (n = 22) among patients of the upper tertile, 0.5% (n = 9) among patients of middle tertile and 0.6% (n = 11) among patients of the lower tertile (P = 0.04). Q-wave myocardial infarction occurred in 1.3% of patients (n = 23) in the upper tertile, 0.7% of patients (n = 13) in the middle tertile and 0.5% of patients (n = 8) in the lower tertile (P = 0.02). Platelet count was an independent correlate of 30-day mortality (hazard ratio 2.69, 95% confidence interval 1.08-6.67; P = 0.033 for the third vs. the first tertile). In conclusion, in patients with CAD undergoing PCI after pre-treatment with 600 mg clopidogrel, baseline platelet count predicts 30-day mortality.

Durability of antirestenotic efficacy in drug-eluting stents with and without permanent polymer.

OBJECTIVES: We sought to assess changes in antirestenotic efficacy of drug-eluting stents (DES) by restudying subjects at 2 time points after coronary stenting (6 to 8 months and 2 years) and to compare differences in time courses of late luminal loss (LLL) between 3 different DES platforms in use at our institution. BACKGROUND: DES therapy is associated with low levels of LLL at 6 to 8 months. The temporal course of neointimal formation after this time point remains unclear. METHODS: This prospective, observational, systematic angiographic follow-up study was conducted at 2 centers in Munich, Germany. Patients underwent stenting with permanent-polymer rapamycin-eluting stents (RES), polymer-free RES, or permanent-polymer paclitaxel-eluting stents (PES). The primary end point was delayed LLL (the difference in in-stent LLL between 6 to 8 months and 2 years). RESULTS: Of 2,588 patients undergoing stenting, 2,030 patients (78.4%) had 6- to 8-month angiographic follow-up and were enrolled in the study. Target lesion revascularization was performed in 259 patients; these patients were not considered for further angiographic analysis. Of 1,771 remaining patients, 1,331 had available 2-year reangiographic data (75.2%). Overall mean (SD) delayed LLL was 0.12 +/- 0.49 mm (0.17 +/- 0.50 mm, 0.01 +/- 0.42 mm, and 0.13 +/- 0.50 mm in permanent-polymer RES, polymer-free RES, and permanent-polymer PES groups, respectively [p < 0.001]). In multivariate analysis, only stent type (in favor of polymer-free RES) predicted delayed LLL. CONCLUSIONS: Ongoing erosion of luminal caliber beyond 6 to 8 months after the index procedure is observed following DES implantation. Absence of permanent polymer from the DES platform seems to militate against this effect.

Long-term risk of adverse outcomes and new malignancies in patients treated with oral sirolimus for prevention of restenosis.

OBJECTIVES: We sought to investigate the long-term efficacy of oral sirolimus therapy and its impact on the incidence of de novo malignancies in the OSIRIS (Oral Sirolimus to Inhibit Recurrent In-Stent Stenosis) trial population. BACKGROUND: The OSIRIS trial showed a significant reduction of angiographic restenosis with an oral adjunctive sirolimus treatment for in-stent restenosis. The long-term efficacy of oral sirolimus therapy is unknown. METHODS: Three hundred patients with in-stent restenosis were randomly assigned to receive placebo, a cumulative loading dose of 8 mg (usual-dose), or 24 mg (high-dose) of sirolimus over 3 days (2 days before and the day of intervention) followed by maintenance therapy of 2 mg/day for 7 days. The primary outcome of this analysis was the incidence of composite of death, myocardial infarction, and target vessel revascularization at 4-year follow-up. Secondary outcome was the incidence of newly diagnosed malignancies. RESULTS: No significant differences were observed between placebo, usual-, and high-dose sirolimus treatment groups regarding primary outcome (33.3%, 39.4%, and 31.3%, respectively; p = 0.46), death (5.9%, 9.1%, and 11.1%, respectively; p = 0.41), target vessel revascularization (30.4%, 30.3%, and 22.2%, respectively; p = 0.33), and rate of newly diagnosed malignancies (7.8%, 3.0%, and 11.1%, respectively; p = 0.09). CONCLUSIONS: The benefit in the reduced need for repeat intervention observed at 1 year with high-dose oral sirolimus therapy was attenuated over 4 years. Moreover, this regimen was associated with numerical yet not a significant increase in newly diagnosed malignancies without augmenting the malignancy-induced risk of death. (Oral Sirolimus for In-Stent Restenosis [OSIRUS] trial; NCT00859183).

Paclitaxel- versus sirolimus-eluting stents for unprotected left main coronary artery disease.

OBJECTIVES: The aim of this trial was to compare the safety and efficacy of paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) for treatment of unprotected left main coronary artery (uLMCA) disease. BACKGROUND: Both PES and SES have reduced the risk of restenosis, particularly in high-risk patient and lesion subsets. However, their comparative performance in uLMCA lesions is not known. METHODS: In this randomized study, 607 patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention for uLMCA were enrolled: 302 were assigned to receive a PES (Taxus, Boston Scientific, Natick, Massachusetts) and 305 assigned to receive a SES (Cypher, Cordis, Johnson & Johnson, New Brunswick, New Jersey). The primary end point was the combined incidence of death, myocardial infarction, and target lesion revascularization (TLR) at 1 year. The secondary end point was angiographic restenosis on the basis of the LMCA area analysis at follow-up angiography. RESULTS: At 1 year the cumulative incidence of death, myocardial infarction, or TLR was 13.6% in the PES and 15.8% in the SES group (relative risk [RR]: 0.85, 95% confidence interval [CI]: 0.56 to 1.29, p = 0.44). One patient in the PES group (0.3%) and 2 patients in the SES group (0.7%) experienced definite stent thrombosis (p = 0.57). Mortality at 2 years was 10.7% in the PES and 8.7% in the SES group (RR: 1.14, 95% CI: 0.66 to 1.95, p = 0.64). Angiographic restenosis was 16.0% with PES and 19.4% with SES (RR: 0.82, 95% CI: 0.57 to 1.19, p = 0.30). CONCLUSIONS: Implantation of either PES or SES in uLMCA lesions is safe and effective; both of these drug-eluting stents provide comparable clinical and angiographic outcomes. (Drug-Eluting-Stents for Unprotected Left Main Stem Disease [ISAR-LEFT-MAIN]; NCT00133237).

Troponin level and efficacy of abciximab in patients with acute coronary syndromes undergoing early intervention after clopidogrel pretreatment.

OBJECTIVE: We investigated how does troponin level (TnT) affect the benefit achieved by abciximab in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) after pretreatment with a high loading dose of clopidogrel. METHODS: The Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 2) trial included 2,022 patients with non-ST elevation ACS undergoing PCI who were randomized to abciximab or placebo after pretreatment with 600 mg of clopidogrel. The patients were divided into groups with elevated TnT level (n = 1,049) and no elevated TnT level (n = 973). The primary end point of the trial was the composite of death, myocardial infarction and urgent reintervention at 30 days. RESULTS: In patients with elevated TnT level the incidence of the primary end point was 13.1% in the abciximab group Vs. 18.3% in the placebo group [relative risk (RR): 0.70; 95% confidence interval (CI), 0.52-0.95, P = 0.02]. The combined incidence of death or myocardial infarction was 12.9% in the abciximab group vs. 17.9% in the placebo group (RR: 0.71; 95% CI, 0.52-0.96, P = 0.03). In contrast, the incidence of the primary end point in patients with no elevated TnT level was identical in both treatment groups (4.6%). The risk of bleeding was not related to TnT level. CONCLUSIONS: Baseline troponin level affects the benefit of abciximab in patients with ACS undergoing PCI after pretreatment with a high loading dose of clopidogrel. Abciximab reduces the risk of ischemic events only in patients with ACS and elevated troponin level.

One-year clinical outcomes with abciximab vs. placebo in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention after pre-treatment with clopidogrel: results of the ISAR-REACT 2 randomized trial.

AIMS: The aim of this study is to investigate whether the benefit of abciximab in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACSs) undergoing percutaneous coronary intervention (PCI) after pre-treatment with 600 mg clopidogrel is sustained at 1 year. METHODS AND RESULTS: We performed 1-year follow-up of 2022 high-risk patients with NSTE-ACS undergoing urgent PCI, who were randomized to abciximab or placebo after pre-treatment with 600 mg clopidogrel in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2 trial. The combined incidence of death, myocardial infarction, or target vessel revascularization at 1 year was the primary outcome analysis. At 1 year, the primary outcome was reached in 23.3% of patients allocated to abciximab vs. 28.0% of patients allocated to placebo [relative risk (RR) 0.80, 95% confidence interval (CI) 0.67-0.95, P = 0.012]. The combined incidence of death or myocardial infarction was 11.6% in patients allocated to abciximab vs. 15.3% in patients allocated to placebo (RR 0.74, 95% CI 0.59-0.94, P = 0.015). CONCLUSION: In high-risk patients with NSTE-ACS undergoing a PCI after pre-treatment with 600 mg clopidogrel, adverse events occurred less frequently with abciximab and the early benefit was maintained at 1 year after administration.