Definite Thrombosis Research Articles

5-year outcomes in patients with acute coronary syndrome treated with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents

Abstract Background Newest generation drug-eluting stents (DES) combining ultrathin cobalt chromium platforms with biodegradable polymers may reduce target lesion failure (TLF) as compared to second generation DES among patients with acute coronary syndrome (ACS). While previous studies indicated a potential benefit within the first two years after percutaneous coronary intervention (PCI), it remains uncertain whether the clinical benefit persists after complete degradation of the polymer coating. Purpose To compare the long-term effects of ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) versus thin-strut durable polymer everolimus-eluting stents (DP-EES) for PCI in patients with ACS. Methods We performed a subgroup analysis of ACS patients included into the BIOSCIENCE trial (NCT01443104), a randomized trial comparing BP-SES with DP-EES. The primary endpoint of the present post-hoc analysis was TLF, a composite of cardiac death, target vessel myocardial infarction (MI) and clinically indicated target lesion revascularization (TLR), at 5 years. Results Among 2,119 patients enrolled between March 2012 and May 2013, 1,131 (53%) presented with ACS (ST-segment elevation myocardial infarction, 36%). Compared to patients with stable CAD, ACS patients were younger, had a lower baseline cardiac risk profile, including a lower prevalence of hypertension, hypercholesterolaemia, diabetes mellitus, and peripheral artery disease, and had a greater incidence of previous revascularization procedures. At 5 years, TLF occurred similarly in 89 patients (cumulative incidence, 16.9%) treated with BP-SES and 85 patients (16.0%) treated with DP-EES (RR 1.04; 95% CI 0.78–1.41; p=0.78) in patients with ACS, and in 109 patients (24.1%) treated with BP-SES and 104 patients (21.8%) treated with DP-EES (RR 1.11; 95% CI 0.85–1.45; p=0.46) in stable CAD patients (p for interaction=0.77) (Figure 1, Panel A). Cumulative incidences of cardiac death (8% vs. 7%; p=0.66), target vessel MI (5.2% vs. 5.8%; p=0.66), clinically indicated TLR (8.9% vs. 8.3%; p=0.63) (Figure 1, Panel B-D), and definite thrombosis (1.4% vs. 1.0%; p=0.57) at 5 years were similar among ACS patients treated with ultrathin-strut BP-SES or thin-strut DP-EES. Overall, there was no interaction between clinical presentation and treatment effect of BP-SES versus DP-EES. Conclusion In a subgroup analysis of the BIOSCIENCE trial, we found no difference in long-term clinical outcomes between ACS patients treated with ultrathin-strut BP-SES or thin-strut DP-EES at five years. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Unrestricted research grant to the institution from Biotronik AG, Switzerland

P1968Five-year outcomes in patients with diabetes mellitus treated with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents

Abstract Background Patients with diabetes mellitus (DM) remain at higher risk for adverse events after percutaneous coronary intervention (PCI) compared with non-diabetic individuals. Among available drug-eluting stents (DES), thin-strut durable polymer everolimus-eluting stents (DP-EES) were shown to provide the best safety and efficacy profile in diabetics. Whether biodegradable polymer DES provide additional long-term clinical benefit compared with DP-EES among diabetic patients remains uncertain. Purpose To compare the long-term performance of ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) versus DP-EES for PCI in patients with insulin-requiring and non-insulin-requiring DM. Methods We performed a prespecified subgroup analysis of the randomized, multicenter, non-inferiority BIOSCIENCE trial (NCT01443104). Patients with stable coronary artery disease or acute coronary syndrome were randomly assigned to treatment with ultrathin-strut BP-SES or thin-strut DP-EES. Patients were further divided according to diabetic status. The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target-vessel myocardial infarction (MI) and clinically-indicated target lesion revascularization (TLR), within 12 months. Results Among 2'119 patients enrolled between March 2012 and May 2013, 486 (22.9%) presented with DM (insulin-requiring, 33.1%). Compared with non-diabetics, patients with DM were older and had a greater baseline cardiac risk profile, including higher prevalence of hypertension, hypercholesterolaemia, peripheral artery disease, chronic renal failure and prior PCI, coronary artery bypass graft surgery, or stroke. At 5 years, TLF occurred similarly in 74 patients (cumulative incidence, 31.0%) treated with BP-SES and 57 patients (25.8%) treated with DP-EES (RR 1.23; 95% CI 0.87–1.73; p=0.24) in diabetics, and in 124 patients (16.8%) treated with BP-SES and 132 patients (16.8%) treated with DP-EES (RR 0.98; 95% CI 0.77–1.26; p=0.90) in non-diabetics (p for interaction=0.31). Cumulative incidences of cardiac death (14.9% vs. 9.5%; p=0.10), target-vessel MI (11.4% vs. 11.0%; p=0.81), clinically-indicated TLR (16.9% vs. 15.8%; p=0.68), and definite thrombosis (3.0% vs. 2.5%; p=0.63) at 5 years were similar among diabetic patients treated with ultrathin-strut BP-SES or thin-strut DP-EES. Overall, there was no interaction between diabetic status and treatment effect of BP-SES versus DP-EES. Conclusion In a prespecified subgroup analysis of the BIOSCIENCE trial, we found no difference in clinical outcomes throughout five years between diabetic patients treated with ultrathin-strut BP-SES or thin-strut DP-EES. Acknowledgement/Funding BIOSCIENCE was an investigator-initiated trial supported by a dedicated research grant from Biotronik, Bülach, Switzerland

A Case of Pheochromocytoma Initially Manifesting as Acute Myocardial Infarction

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors arising from chromaffin cells in the adrenal medulla. Typical classic triad are consisted of headaches, palpitations, and profuse diaphoresis. But some patients with pheochromocytomas have other cardiovascular manifestations such as left ventricular hypertrophy, congestive heart failure, and cardiac arrhythmia. Rarely, pheochromocytomas manifest as acute myocardial infarction leading to delayed diagnosis and treatment. We experienced one case of pheochromocytoma initially manifesting as acute myocardial infarction which showed normal coronary artery on coronary angiography. Pheochromocytoma should be suspected and evaluated in patients with acute myocardial infarction whose coronary angiography shows normal coronary without definite thrombosis.

CLINICAL AND ANGIOGRAPHIC CHARACTERISTICS OF PATIENTS WITH STENT THROMBOSIS

Stent thrombosis (TS) after percutaneous coronary intervention (PCI) is a rare but potentially fatal complication with an incidence of 1% to over 5%. Risk factors for TS can be divided into factors related to the patient, procedure, stent type and characteristics of the lesion. One thousand fifty-five patients who underwent PCI during 2009 and 2010 were included into the study and followed during the next year. Patients with and without definite TS formed the study (TS+) and control group (TS+), respectively. Twenty-three patients had TS (2,2%). Early, late and very late TS were noted in 69,5%, 13,1% and 17,4% of patients, respectively. Acute myocardial infarction with STsegment elevation was the most frequent clinical presentation (56,6%). Discontinuation of aspirin and/or clopidogrel (34.8%) and resistance to these drugs (34.7%) were the main patient-related factors for TS. A higher percentage of stenosis of lesions (92 ± 12 vs 86 ± 14), greater average stent length (19.69 vs 17.01 mm), lower pressure stent insufflation (14.84 vs. 16.02 atm) and coronary artery dissection (26.1%) were significant reasons for the occurrence of TS. Similar stent type BMS („bare metal stents) and DES („drug eluting stents“) were applied in both of patient groups. STEMI patients and those with impaired systolic left ventricular function are at highest risk of TS, which is reported in more than two thirds of them in the first 30 days after PCI. Discontinuation of aspirin and/or clopidogral or resistance to these drugs led to TS. Greater stent length, small diameter of the stent (underestimated lesion), lower pressure insufflation and dissection of the coronary artery are the most common procedural reasons for the occurrence of TS. Type of stent (BMS and DES) had no significant effect on the occurrence of TS. Acta Medica Medianae 2013;52(4):5-11.

Clinical presentation and predictors of Stent thrombosis after drug-eluting stent implantation for chronic coronary occlusions

The objective of this study was to evaluate the incidence of stent thrombosis, as well as the clinical presentation and related factors in patients with chronic total coronary occlusions (CTO) treated with drug-eluting stents. Methods: The CIBELES (ChronIc coronary occlusion treated By EveroLimus Eluting Stent) trial allocated 207 patients with CTO to everolimus or sirolimus stent in 13 centers from Spain and Portugal. Stent thrombosis episodes accordingly to the Academic and Research Consortium (ARC) criteria were codified through a 12 month period. Results: During a 12 month follow-up, 3 episodes of definitive or probable stent thrombosis were diagnosed: 2 definitive thrombosis (1 and 117 days after the procedure), and 1 probable stent thrombosis (9 days after the procedure). Therefore, the incidence of definitive or probable stent thrombosis at 1 year was 1.4% (early stent thrombosis 0.9%, late stent thrombosis 0.5%). No death or Q-wave myocardial infarction occurred in these patients (clinical presentation was non-Q-wave acute myocardial infarction in 2, and unstable angina in 1 case). At univariate analysis, the risk of stent thrombosis was higher with left anterior descending coronary artery as treated vessel (3.5% vs 0.0%, p=0.037), single vessel disease (3.3% vs 0.0%, p=0.049), and treatment with sirolimus-eluting stent (3.,0% vs 0.0% in patients treated with everolimus-eluting stent, p=0.074). Patients with stent thrombosis had lower minimum lumen diamerer (1.3±0.6 mm vs. 2.6±0.5 mm, p<0.001), and higher % stenosis immediately after the procedure (43±14% vs 20±10%, p<0.001). At multivariate analysis, the only independent predictor of stent thrombosis was the minimum lumen diameter after the procedure. Conclusions: Incidence of definitive or probable stent thrombosis after drug-eluting stent implantation in CTO is low (1.5%), especially in patients treated with everolimus-eluting stents. The only independent predictor of stent thrombosis in these patients was minimum lumen diameter after stenting. Clinical presentation was relatively benign in all cases.

Performance of Spin-Echo and Gradient-Echo T1-Weighted Sequences for Evaluation of Dural Venous Sinus Thrombosis and Stenosis

Dural venous sinus abnormalities are clinically important but can potentially be overlooked using various MRI techniques. This study evaluates the diagnostic accuracy of spin-echo (SE) T1-weighted imaging, 3D gradient-recalled echo (GRE) T1-weighted imaging, and contrast-enhanced MR venography (MRV) for the detection of dural venous sinus thrombosis and transverse sinus (TS) stenosis. Seventy-three patients underwent MRI evaluation with unenhanced and contrast-enhanced axial SE T1-weighted imaging, contrast-enhanced sagittal 3D GRE T1-weighted imaging, and contrast-enhanced MRV sequences. Three neuroradiologists each evaluated these 219 total datasets in a randomized blinded fashion for the presence or absence of TS stenosis and for dural venous sinus thrombosis in each of 10 venous sinus segments (730 total segments). Diagnostic performance characteristics and kappa statistics were calculated for each technique. Thirteen patients (37 segments) had suspected dural venous sinus thrombosis by one or more readers; of those 13 patients, nine (23 segments) were thought to have definite thrombosis on contrast-enhanced MRV. Compared with contrast-enhanced MRV, the positive predictive value (PPV) and negative predictive value (NPV) for thrombosis were 60% and 97%, respectively, for both unenhanced and contrast-enhanced SE T1-weighted imaging and 100% and 98% for 3D GRE T1-weighted imaging. Kappa values calculated per venous segment were as follows: 0.41 for SE T1-weighted imaging, 0.72 for 3D GRE T1-weighted imaging, and 0.95 for contrast-enhanced MRV. Thirty patients (58 segments) had TS stenosis suspected by one or more readers; of those 30 patients, TS stenosis was deemed to be definite on contrast-enhanced MRV in 25 patients (50 segments). Compared with contrast-enhanced MRV, the PPV and NPV were 75% and 80%, respectively, for SE T1-weighted imaging and 91% and 92% for 3D GRE T1-weighted imaging for the detection of stenosis. Kappa values calculated per patient were -0.038 for SE T1-weighted imaging, 0.58 for 3D GRE T1-weighted imaging, and 0.98 for contrast-enhanced MRV. Contrast-enhanced 3D GRE T1-weighted imaging is superior to SE T1-weighted imaging for the detection of dural venous sinus thrombosis and TS stenosis but does not substitute for dedicated MRV. Hyperintensity on unenhanced SE T1-weighted imaging is unreliable for the detection of dural venous sinus thrombosis.

Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis

The relative safety of drug-eluting stents and bare-metal stents, especially with respect to stent thrombosis, continues to be debated. In view of the overall low frequency of stent thrombosis, large sample sizes are needed to accurately estimate treatment differences between stents. We compared the risk of thrombosis between bare-metal and drug-eluting stents. For this network meta-analysis, randomised controlled trials comparing different drug-eluting stents or drug-eluting with bare-metal stents currently approved in the USA were identified through Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. 49 trials including 50,844 patients randomly assigned to treatment groups were analysed. 1-year definite stent thrombosis was significantly lower with cobalt-chromium everolimus eluting stents (CoCr-EES) than with bare-metal stents (odds ratio [OR] 0·23, 95% CI 0·13-0·41). The significant difference in stent thrombosis between CoCr-EES and bare-metal stents was evident as early as 30 days (OR 0·21, 95% CI 0·11-0·42) and was also significant between 31 days and 1 year (OR 0·27, 95% CI 0·08-0·74). CoCr-EES were also associated with significantly lower rates of 1-year definite stent thrombosis compared with paclitaxel-eluting stents (OR 0·28, 95% CI 0·16-0·48), permanent polymer-based sirolimus-eluting stents (OR 0·41, 95% CI 0·24-0·70), phosphorylcholine-based zotarolimus-eluting stents (OR 0·21, 95% CI 0·10-0·44), and Resolute zotarolimus-eluting stents (OR 0·14, 95% CI 0·03-0·47). At 2-year follow-up, CoCr-EES were still associated with significantly lower rates of definite stent thrombosis than were bare-metal (OR 0·35, 95% CI 0·17-0·69) and paclitaxel-eluting stents (OR 0·34, 95% CI 0·19-0·62). No other drug-eluting stent had lower definite thrombosis rates compared with bare-metal stents at 2-year follow-up. In randomised studies completed to date, CoCr-EES has the lowest rate of stent thrombosis within 2 years of implantation. The finding that CoCr-EES also reduced stent thrombosis compared with bare-metal stents, if confirmed in future randomised trials, represents a paradigm shift. The Cardiovascular Research Foundation.

The natural history of pelvic vein thrombosis on magnetic resonance venography after vaginal delivery

Venous thromboembolism constitutes the leading cause of direct maternal mortality in the developed world. To date, there are no studies using magnetic resonance venography (MRV) to delineate the incidence and natural history of intraluminal filling defects in the postpartum period in patients with low thrombosis risk. This was a prospective cohort study of women at low thrombosis risk postvaginal delivery undergoing MRV in the early postpartum period. In 30 eligible and consenting participants, independently adjudicated MRV, conducted on a median of postpartum day 1, identified definite thrombosis in 30% (95% confidence interval [CI], 13.6-46.4%) of study participants. All episodes of definite thrombosis were identified in the iliac and ovarian veins. Probable thrombosis was identified in an additional 27% of study participants (95% CI, 10.3-41.7%), and possible thrombosis in an additional 10% (95% CI, 0-20.7%). In this group of low-risk postpartum patients, we identified a high prevalence of definite pelvic vein intraluminal filling defects of uncertain clinical significance. This study suggests that some degree of pelvic vein intraluminal filling defect may be a normal finding after uncomplicated vaginal delivery.

Thrombosis of Second-Generation Drug-Eluting Stents in Real Practice: Results From the Multicenter Spanish Registry ESTROFA-2 (Estudio Español Sobre Trombosis de Stents Farmacoactivos de Segunda Generacion-2)

This study sought to evaluate second-generation drug-eluting stent (DES) thrombosis in clinical practice. First-generation DES are associated with a significant incidence of late thrombosis. There is paucity of data regarding real practice late thrombosis incidence and predictors with second-generation DES, zotarolimus-eluting stent (ZES), and everolimus-eluting stents (EES). A prospective, large-scale, non-industry-linked multicenter registry was designed. Complete clinical-procedural data and systematic follow-up of all patients treated with these stents was reported in a dedicated registry supported by the Spanish Working Group on Interventional Cardiology. From 2005 to 2008, 4,768 patients were included in 34 centers: 2,549 treated with ZES, and 2,219 with EES. The cumulative incidence of definite/probable thrombosis for ZES was 1.3% at 1 year and 1.7% at 2 years and for EES 1.4% at 1 year and 1.7% at 2 years (p = 0.8). The increment of definite thrombosis between the first and second year was 0.2% and 0.25%, respectively. In a propensity score analysis, the incidence remained very similar. Ejection fraction (adjusted hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.95 to -0.99; p = 0.008), stent diameter (adjusted HR: 0.37; 95% CI: 0.17to 0.81; p = 0.01) and bifurcations (adjusted HR: 2.1; 95% CI: 1.14 to 3.7; p = 0.02) emerged as independent predictors of thrombosis. In the subgroup of patients with bifurcations, the use of ZES was independently associated with a higher thrombosis rate (adjusted HR: 4; 95% CI: 1.1 to 13; p = 0.03). In a real practice setting, the incidence of thrombosis at 2 years with ZES and EES was low and quite similar. The incidence of very late thrombosis resulted lower than was reported in registries of first-generation DES. In the subset of bifurcations, the use of ZES significantly increased the risk of thrombosis.

Comparison of incidence and angiography patterns in definite thrombosis between drug-eluting and bare-metal stents

Stent thrombosis is a feared complication of percutaneous coronary intervention due to its catastrophic consequences. We analysed the incidence of angiographically-confirmed thrombosis in 5011 consecutive patients treated with drug-eluting stents or bare-metal stents. Although the incidence of thrombosis was similar between the two groups (0.8%), angiographically-documented late thrombosis was a relatively unusual complication after implantation of either stent, though it was more common with drug-eluting stents than bare-metal stents (0.25 vs. 0.06%, P = .03).

Pelvic Magnetic Resonance Venography Reveals High Rate of Pelvic Vein Thrombosis After Cesarean Section

Venous thromboembolism (VTE) not only remains the major cause of direct maternal mortality in developed countries worldwide, but reportedly causes more than half of direct maternal deaths in the United States. Although cesarean section increases the risk of pregnancy-associated VTE, postpartum thromboprophylaxis is not uniformly recommended. Magnetic resonance venography (MRV) appears to be a highly sensitive and specific means of detecting deep venous thrombosis (DVT) in the upper and lower extremities. The investigators report preliminary findings of an ongoing randomized, controlled trial that uses MRV to identify pelvic DVT after operative delivery. Observations were made during the run-in phase of a trial of thromboprophylaxis in women at moderate to high risk of DVT based on a family history of VTE or a personal history of superficial phlebitis, current major illness or infection, immobility for longer than 4 days, obesity, or age greater than 35 years. Other risk factors included gross varicose veins, preeclampsia, parity of 4 or more, emergency cesarean section, and extended surgery such as cesarean hysterectomy. The women were assigned to receive or not to receive open-label tinzaparin, a low-molecular-weight heparin, by subcutaneous injection. Two radiologists independently and blindly assessed the MRV studies. Participants included 15 women with a mean age of 33 years. None of them had compression leg ultrasound findings of DVT. The MRV findings were interpreted as showing definite thrombosis in 46% of women, all of whom were asymptomatic. Clots were found chiefly in the iliac veins, although one patient had thrombosis in the common femoral artery. All clots were less than 1 cm in size and only one occluded the affected vein. Nearly half of these moderate- or high-risk women were found to have definite pelvic DVT after cesarean delivery-many more than expected. The clinical significance of this finding remains to be determined. It is possible that pelvic vein thrombosis is a normal finding after cesarean delivery and also that DVT may be present in lower-risk women. MRV would seem to be a useful measure of outcome in studies evaluating postpartum measures intended to prevent DVT.

The color Doppler-guided compression therapy of pseudoaneurysms. The authors' own experiences and a review of the literature

The common use of interventional angiographic techniques and the sensitive detection of this vascular complication by ultrasound are major factors contributing to the increasing incidence of femoral artery pseudoaneurysms. ultrasound-guided compression repair of femoral artery pseudoaneurysms was prospectively evaluated. 11 femoral artery pseudoaneurysms were detected in 10 patients who ranged from 45 to 79 years of age. In one patient two ipsilateral pseudoaneurysms occurred. All patients were considered to be candidates for ultrasound-guided compression repair. Successful compression repair was achieved in 9 of 11 pseudoaneurysms (82%) with a mean diameter of 2.2 +/- 1.0 cm. In two recurrent lesions (22%) definitive thrombosis required a second treatment. Compression was maintained between 10 and 40 minutes (mean 22 +/- 11 minutes). No complications have been observed. Ultrasound-guided compression repair provides an efficient, noninvasive and safe treatment of femoral artery pseudoaneurysms. More than 80% of pseudoaneurysms can be occluded successfully. In recurrent lesions a second attempt is valuable.

Urokinase plus heparin versus aspirin in unstable angina and non-Q-wave myocardial infarction

The pivotal role of thrombosis in unstable angina and non-Q-wave myocardial infarction has been established recently. To assess the value and safety of thrombolytic therapy compared to conventional antithrombotic therapy (aspirin) in arresting progression in this setting to recurrent ischemic endpoints, 25 patients presenting with unstable angina and an electrocardiogram showing subendocardial ischemia were randomized to receive either aspirin 325 mg daily, or urokinase 3 × 10 6 U intravenously, over 30 minutes followed by heparin. Incidence of endpoints (intractable ischemia requiring mechanical intervention, new myocardial infarction or death) was determined over 7 days. Coronary arteriography was performed at 24 to 72 hours to determine extent of coronary artery disease and morphologic severity of the culprit lesion, graded by a semiquantitative scoring system ranging from 4+ (definite thrombosis) to 0 (chronic lesion). In the first 24 hours, 7 of 13 aspirin versus 1 of 12 urokinase patients exhibited ischemia progression (p < 0.05). By 7 days, progression to a primary ischemic endpoint occurred in 8 of 13 aspirin patients (3 myocardial infarctions and 5 intractable ischemias) versus 3 of 12 urokinase patients (2 intractable ischemias and 1 death) (p = 0.18). The apparent benefit of urokinase followed by heparin compared to conventional aspirin therapy in arresting early progression of unstable angina or non-Q-wave myocardial infarction was not associated with enhanced culprit lesion morphology (mean lesion severity score 2.7 ± 1.5 vs 2.8 ± 1.6 in aspirintreated patients). Large scale, randomized trials to assess the clinical utility of urokinase for unstable angina are warranted.