José Suárez de Lezo

Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis

BACKGROUND Whether the two drug-eluting stents approved by the US Food and Drug Administration-a sirolimus-eluting stent and a paclitaxel-eluting stent-are associated with increased risks of death, myocardial infarction, or stent thrombosis compared with bare-metal stents is uncertain. Our aim was to compare the safety and effectiveness of these stents. METHODS We searched relevant sources from inception to March, 2007, and contacted investigators and manufacturers to identify randomised controlled trials in patients with coronary artery disease that compared drug-eluting with bare-metal stents, or that compared sirolimus-eluting stents head-to-head with paclitaxel-eluting stents. Safety outcomes included mortality, myocardial infarction, and definite stent thrombosis; the effectiveness outcome was target lesion revascularisation. We included 38 trials (18,023 patients) with a follow-up of up to 4 years. Trialists and manufacturers provided additional data on clinical outcomes for 29 trials. We did a network meta-analysis with a mixed-treatment comparison method to combine direct within-trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. FINDINGS Mortality was similar in the three groups: hazard ratios (HR) were 1.00 (95% credibility interval 0.82-1.25) for sirolimus-eluting versus bare-metal stents, 1.03 (0.84-1.22) for paclitaxel-eluting versus bare-metal stents, and 0.96 (0.83-1.24) for sirolimus-eluting versus paclitaxel-eluting stents. Sirolimus-eluting stents were associated with the lowest risk of myocardial infarction (HR 0.81, 95% credibility interval 0.66-0.97, p=0.030 vs bare-metal stents; 0.83, 0.71-1.00, p=0.045 vs paclitaxel-eluting stents). There were no significant differences in the risk of definite stent thrombosis (0 days to 4 years). However, the risk of late definite stent thrombosis (>30 days) was increased with paclitaxel-eluting stents (HR 2.11, 95% credibility interval 1.19-4.23, p=0.017 vs bare-metal stents; 1.85, 1.02-3.85, p=0.041 vs sirolimus-eluting stents). The reduction in target lesion revascularisation seen with drug-eluting stents compared with bare-metal stents was more pronounced with sirolimus-eluting stents than with paclitaxel-eluting stents (0.70, 0.56-0.84; p=0.0021). INTERPRETATION The risks of mortality associated with drug-eluting and bare-metal stents are similar. Sirolimus-eluting stents seem to be clinically better than bare-metal and paclitaxel-eluting stents.

Una clasificación simple de las lesiones coronarias en bifurcación

Las lesiones coronarias localizadas en una bifurcacion presentan una amplia gama de morfologias angiograficas y anatomicas en funcion de la distribucion de la placa en el segmento afectado. Se han propuesto y se usan diferentes clasificaciones para definir estas lesiones1-3. Dichas clasificaciones ilustran con precision todas las posibles combinaciones, pero resulta dificil memorizar las diferentes posibilidades. Basandonos en los tres componentes en que puede ser dividida una bifurcacion: vaso principal proximal (VPP), vaso principal distal (VPD) y ramo secundario (RS), y respetando esta secuencia, proponemos una nueva clasificacion facil, sencilla e intuitiva, que no exige memorizacion alguna. Esta clasificacion consiste en asignar un valor binario (1,0) dependiendo de si hay o no compromiso de los segmentos de la bifurcacion previamente definidos. En la figura 1 se muestran las 7 morfologias posibles. Con respecto a las clasificaciones previas, creemos que este nuevo enfoque facilita la descripcion de la anatomia de las bifurcaciones, lo que tiene implicaciones tecnicas y estrategicas a la hora de afrontar el tratamiento percutaneo y valorar su resultado. Asimismo, facilita la inclusion de parametros descriptivos en las bases de datos que analizan los resultados del tratamiento percutaneo de las bifurcaciones y permite a su vez una unificacion del lenguaje a la hora de comparar diferentes series y tecnicas.

A New Classification of Coronary Bifurcation Lesions

Coronary lesions located at a bifurcation present a wide range of angiographic and anatomical morphologies depending upon the distribution of the plaque in the segment affected. Different classifications have been proposed and used to define these lesions.1-3 Although these classifications clearly define all the possible combinations, they are difficult to memorise. For our classification we use the 3 components of a bifurcation: the main branch proximal (MBP), the main branch distal (MBD), and the side branch (SB). Respecting that sequence, we propose a new simple intuitive classification which does not demand memorisation. It consists in giving a binary value (1, 0) according to whether each of the segments previously defined is compromised or not. Figure shows the 7 possible morphologies. We consider that this new approach, compared to previous classifications, makes the description of the anatomy of coronary bifurcations much more simple, a factor which is technically and strategically significant when facing percutaneous treatment and assessing its results. Likewise, it could also facilitate the inclusion of descriptive parameters in the data base which analyses the result of percutaneous treatment of bifurcations. Last, we consider that it allows for homogenous terminology when comparing different series and techniques.

Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis

Objective To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus. Design Collaborative network meta-analysis. Data sources Electronic databases (Medline, Embase, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, book chapters, and proceedings of advisory panels for the US Food and Drug Administration. Manufacturers and trialists provided additional data. Review methods Network meta-analysis with a mixed treatment comparison method to combine direct within trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. Overall mortality was the primary safety end point, target lesion revascularisation the effectiveness end point. Results 35 trials in 3852 people with diabetes and 10 947 people without diabetes contributed to the analyses. Inconsistency of the network was substantial for overall mortality in people with diabetes and seemed to be related to the duration of dual antiplatelet therapy (P value for interaction 0.02). Restricting the analysis to trials with a duration of dual antiplatelet therapy of six months or more, inconsistency was reduced considerably and hazard ratios for overall mortality were near one for all comparisons in people with diabetes: sirolimus eluting stents compared with bare metal stents 0.88 (95% credibility interval 0.55 to 1.30), paclitaxel eluting stents compared with bare metal stents 0.91 (0.60 to 1.38), and sirolimus eluting stents compared with paclitaxel eluting stents 0.95 (0.63 to 1.43). In people without diabetes, hazard ratios were unaffected by the restriction. Both drug eluting stents were associated with a decrease in revascularisation rates compared with bare metal stents in people both with and without diabetes. Conclusion In trials that specified a duration of dual antiplatelet therapy of six months or more after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes.

Immediate and follow-up findings after stent treatment for severe coarctation of aorta

Experimental studies have shown that stents implanted at the aorta become incorporated within the aortic wall and can be further expanded in growing animals. Few clinical studies have shown that the stent repair of severe coarctation of aorta provides excellent initial results, and little is known on the follow-up of these patients. We assessed the immediate and follow-up results obtained in a series of 48 patients (mean age 14+/-12 years) with severe coarctation of the aorta who were treated by Palmaz stent implantation; 30 of them (63%) underwent angiographic follow-up studies at a mean of 25+/-11 months after treatment. Quantitative serial analysis of the aortogram (baseline, after treatment, and at follow-up) was performed. Significant relief (mean residual gradient 3+/-4 mm Hg) was always obtained after stent implantation. The isthmus, when hypoplastic (60%), was always expanded with the stent. One associated aneurysm became occluded after the implant. Complications included aortic disruption, stent migration, and decreased or absent femoral pulses. At angiographic follow-up, the stent remained always in place, without recoil. In 22 patients (73%), there were no detectable neointimal proliferation at late angiogram; however, 8 patients (27%) had some degree of intimal thickening (1 to 5 mm), causing mild restenosis in 3 patients treated at early age, and nonsignificant lumen reduction in 5. The serial aortogram analysis revealed a minor but significant increase in nonstented aortic diameters that seemed related to the normal growth of children. No need for stent reexpansion was observed at 2-year follow-up (mean). Two patients (7%) developed late small aneurysm formation at the stented wall; both were occluded by the insertion of coils through the stent orifices. We conclude that stent treatment for severe coarctation of aorta provides excellent immediate and long-term results in young adults and children. However, at early age, restenosis by intimal growth may develop.

Balloon-expandable stent repair of severe coarctation of aorta

Experimental studies have shown that stents implanted at the aorta become incorporated within the aortic wall and can be further expanded in growing animals. This study evaluates the feasibility and immediate results of balloon-expandable stent implantation in 10 patients with severe coarctation of aorta. The ages of the patients ranged from 1 month to 43 years; 1 was an infant, 8 were children (mean age 5.3 +/- 4 years), and 1 was an adult. All had an unfavorable anatomy for balloon angioplasty; 9 had isthmus hypoplasia. Balloon predilation was first performed and its immediate effect evaluated. Then a balloon-expandable stent that was 30 mm long and covered the isthmus and coarctation levels was deployed, and it was further expanded to the preselected final diameter (12 +/- 4 mm). A final hemodynamic and angiographic evaluation was then obtained. Full deployment of an incompletely expanded and distally displaced stent in the infant led to aortic disruption that was controlled by a second stent covering the disrupted zone and the isthmus. After balloon angioplasty alone was done, the mean gradient (43 +/- 12 vs 31 +/- 10 mm Hg) and the percentage stenosis (72% +/- 11% vs 54% +/- 11%) had an insufficient decrease. However, after stent implantation was done, the gradient almost disappeared (mean 2 +/- 3 mm Hg). The angiographic stenosis disappeared in 7 patients and was markedly reduced in 3. The ratio of isthmus/descending aorta changed from 0.65 +/- 0.14 to 1 +/- 0.08 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Transcatheter closure of perimembranous ventricular septal defects using the amplatzer membranous VSD occluder: Immediate and midterm results of an international registry

Objective: To report the immediate and midterm results of transcatheter closure of perimembranous ventricular septal defect (PmVSD) using the Amplatzer membranous VSD occluder (AMVSD). Methods: Between April 2002 and August 2004, 100 patients underwent an attempt of percutaneous device closure of PmVSD using the AMVSD in 24 international centers. The median age was 9.0 years (0.7–58 years) and the median weight was 27.5 kg (7–121 kg). Results: A device was successfully deployed in 93/100 (93%) patients. Reasons for procedural failure were an increased gradient across the left ventricle outflow tract in one patient, aortic regurgitation in 2 patients, and inability to securely position the device in 4 patients. The median VSD size by TEE was 7.0 mm (1.5–13 mm), median device size 10 mm (4–16 mm) and median fluoroscopy time 22.1 min (8.9–96.0 min). Weight below 10 kg (P = 0.0392), inlet extension of the VSD (P = 0.0139) and aortic cusp prolapse into the VSD (P = 0.0084) were significantly associated with a lower procedural success. Patients have been followed up for a median of 182 days (1–763 days). There were no procedure‐related deaths. Complications were encountered in 29/100 (29%) patients, including rhythm or conduction anomalies in 13 patients (two with complete heart block requiring permanent pacemaker implantation), new or increased aortic (9 patients) or tricuspid (9 patients) regurgitation, most of which were classified as trivial or mild. Patients with a weight below 10 kg had a significantly higher incidence of adverse events than patients with a weight above 10 kg (58.3% versus 25.0%, P = 0.0285). Immediately after device release complete closure of the defect was present in 54/93 (58.1%) patients, increasing to 46/55 (83.6%) patients at 6‐months follow‐up (P = 0.0012). Left ventricle end‐diastolic diameter decreased from a median of 44 mm prior to device closure to a median of 39 mm at 6‐months postprocedure (P = 0.0015). Conclusion: Closure of PmVSDs using the AMVSD occluder is safe and effective. However, longer follow‐up period is warranted prior to the wide spread use of this device.

Simple and complex stent strategies for bifurcated coronary arterial stenosis involving the side branch origin

Coronary lesions located in major bifurcations constitute a challenge for the use of stents. Although the occlusion of a side branch covered by a stent is infrequent, the maintenance of a patent, stenosis-free bifurcation may result in a complex procedure. Between September 1994 and April 1998, 70 patients were treated by stent implantation for coronary bifurcation stenosis. The side branch always had a diameter >2 mm. The pairs of treated arteries were: left anterior descending (LAD)/diagonal artery in 32 patients, circumflex/obtuse marginal in 26, right coronary/posterior descending artery in 5, and LAD/circumflex in 7. We applied 2 different techniques of stent implantation: (1) deployment of 1 stent in the parent vessel covering the takeoff of the side branch and subsequent angioplasty of the side branch across the metallic structure (group A, n = 47 patients), and (2) implantation of 1 stent at the ostium of the side branch and complete reconstruction of the entire bifurcation with additional implantation of 1 or 2 stents at the parent vessel (group B, n = 23 patients). There were no significant differences between groups at baseline variables. Procedural success was similar in both groups: 42 (89%) in group A versus 21 (91%) in group B. However, major cardiac events at 18 months follow-up were higher in group B (event-free probability 44% vs 75%, p <0.05). Selected patients with coronary stenosis at major bifurcations can be treated with an acceptable rate of primary and late success. Complex techniques providing radical stent reconstruction of the bifurcation seems to provide no advantages over the simpler stent jail followed by ostial side branch balloon dilation.

Treatment and Clinical Outcomes of Transcatheter Heart Valve Thrombosis

Background—Valve thrombosis has yet to be fully evaluated after transcatheter aortic valve implantation. This study aimed to report the prevalence, timing, and treatment of transcatheter heart valve (THV) thrombosis. Methods and Results—THV thrombosis was defined as follows (1) THV dysfunction secondary to thrombosis diagnosed based on response to anticoagulation therapy, imaging modality or histopathology findings, or (2) mobile mass detected on THV suspicious of thrombus, irrespective of dysfunction and in absence of infection. Between January 2008 and September 2013, 26 (0.61%) THV thromboses were reported out of 4266 patients undergoing transcatheter aortic valve implantation in 12 centers. Of the 26 cases detected, 20 were detected in the Edwards Sapien/Sapien XT cohort and 6 in the Medtronic CoreValve cohort. In patients diagnosed with THV thrombosis, the median time to THV thrombosis post–transcatheter aortic valve implantation was 181 days (interquartile range, 45–313). The most common clinical presentation was exertional dyspnea (n=17; 65%), whereas 8 (31%) patients had no worsening symptoms. Echocardiographic findings included a markedly elevated mean aortic valve pressure gradient (40.5±14.0 mm Hg), presence of thickened leaflets or thrombotic apposition of leaflets in 20 (77%) and a thrombotic mass on the leaflets in the remaining 6 (23%) patients. In 23 (88%) patients, anticoagulation resulted in a significant decrease of the aortic valve pressure gradient within 2 months. Conclusions—THV thrombosis is a rare phenomenon that was detected within the first 2 years after transcatheter aortic valve implantation and usually presented with dyspnea and increased gradients. Anticoagulation seems to have been effective and should be considered even in patients without visible thrombus on echocardiography.

Results of transvenous occlusion of secundum atrial septal defects with the fourth generation buttoned device: comparison with first, second and third generation devices☆

OBJECTIVES The purpose of this study was to assess safety and effectiveness of the fourth generation buttoned device in dosing atrial septal defects (ASDs) and to test the hypothesis that introduction of double button reduces unbuttoning rate without reducing effectiveness. BACKGROUND Because of the high unbuttoning rate (7.2%) with first, second and third generation buttoned devices, the device was modified (fourth generation) so that there were two radiopaque spring buttons 4 mm apart on the button loop attached to the occluder. METHODS During a four-year period ending in September 1997, 423 patients, ages 1.5 to 80 years (median 16 years), underwent closure of ASD at 40 medical centers around the world. RESULTS The ASD size varied between 5 and 30 mm (median 17 mm). The device size varied between 25 and 60 mm. Unbuttoning occurred in 4 (0.9%) of 423 patients. Effective occlusion, defined as no (n = 343) or trivial (n = 34) residual shunt on echo-Doppler studies performed within 24 h of the procedure, was demonstrated in 377 patients (90%). Thus, the unbuttoning rate (0.9 vs. 7.2%) decreased (p<0.01) while effective occlusion rate (90 vs. 92%) remained unchanged (p>0.1) with this device, compared with earlier generation devices. During follow-up from one month to five years (23+/-15 months), 21 (5%) of 417 patients required surgical (n = 12) or transcatheter (n = 9) reintervention, mostly to treat significant residual shunt. In the remaining patients there was gradual reduction and disappearance of the residual shunt. No wire integrity problems were observed. CONCLUSIONS These data suggest that the fourth generation buttoned device is as effective as earlier generation devices, but without significant unbuttoning. Follow-up results remained good, with a reintervention-free rate of 89% at five years.