Mathias Vrolix

Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial

BACKGROUND If percutaneous coronary intervention (PCI) is required in patients taking oral anticoagulants, antiplatelet therapy with aspirin and clopidogrel is indicated, but such triple therapy increases the risk of serious bleeding. We investigated the safety and efficacy of clopidogrel alone compared with clopidogrel plus aspirin. METHODS We did an open-label, multicentre, randomised, controlled trial in 15 centres in Belgium and the Netherlands. From November, 2008, to November, 2011, adults receiving oral anticoagulants and undergoing PCI were assigned clopidogrel alone (double therapy) or clopidogrel plus aspirin (triple therapy). The primary outcome was any bleeding episode within 1 year of PCI, assessed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769938. FINDINGS 573 patients were enrolled and 1-year data were available for 279 (98·2%) patients assigned double therapy and 284 (98·3%) assigned triple therapy. Mean ages were 70·3 (SD 7·0) years and 69·5 (8·0) years, respectively. Bleeding episodes were seen in 54 (19·4%) patients receiving double therapy and in 126 (44·4%) receiving triple therapy (hazard ratio [HR] 0·36, 95% CI 0·26-0·50, p<0·0001). In the double-therapy group, six (2·2%) patients had multiple bleeding events, compared with 34 (12·0%) in the triple-therapy group. 11 (3·9%) patients receiving double therapy required at least one blood transfusion, compared with 27 (9·5%) patients in the triple-therapy group (odds ratio from Kaplan-Meier curve 0·39, 95% CI 0·17-0·84, p=0·011). INTERPRETATION Use of clopiogrel without aspirin was associated with a significant reduction in bleeding complications and no increase in the rate of thrombotic events. FUNDING Antonius Ziekenhuis Foundation, Strect Foundation.

Three-Year Outcome After Coronary Stenting Versus Bypass Surgery for the Treatment of Multivessel Disease

Background—The primary results of Arterial Revascularization Therapy Study reported a greater need for repeated revascularization after percutaneous coronary intervention with stenting (PCI). However, PCI was less expensive than coronary artery bypass grafting (CABG) and offered the same degree of protection against death, stroke, and myocardial infarction. Methods and Results—Patients with multivessel disease (n=1205) were randomly assigned to either CABG or PCI and followed up for up to 3 years. Survival rates without stroke or myocardial infarction were similar in each group at 1 year and 3 years (90.5% versus 91.4% for PCI versus CABG at 1 year and 87.2% versus 88.4% for PCI versus CABG at 3 years). However, the respective repeat revascularization rates were 21.2% and 26.7% at 1 and 3 years in patients allocated to PCI, compared with 3.8% and 6.6% in patients allocated to CABG (P <0.0001). Diabetes (P <0.0009) and maximal pressure for stent deployment (P <0.002) are the strongest independent predictors of events at 3 years after PCI, whereas left anterior descending coronary artery grafting (P <0.006) is the best predictor of event-free survival at 3 years after CABG. The incremental cost of surgery compared with PCI for an event-free patient was 19 257 &OV0556; at 1 year but decreased to 10 492 &OV0556; at 3 years. It remained at 142 391 &OV0556; at 3 years when revascularization procedures were excluded in the efficacy end point, however. Conclusions—Three-year survival rates without stroke and myocardial infarction are identical in both groups, and the cost/benefit ratio of stenting is determined primarily by the increasing need for revascularization in the PCI group.

A Multicenter Randomized Trial Comparing Amphilimus- With Paclitaxel-Eluting Stents in De Novo Native Coronary Artery Lesions

OBJECTIVES This study sought to demonstrate the noninferiority of polymer-free amphilimus-eluting stents (Cre8, CID, Saluggia, Italy) versus permanent-polymer paclitaxel-eluting stents (Taxus Liberté, Boston Scientific, Natick, Massachusetts) in de novo percutaneous coronary intervention. BACKGROUND Although the efficacy of the drug-eluting stent has been well established, the risk-benefit balance is still suboptimal, and the safety of polymers remains uncertain. METHODS Patients undergoing percutaneous coronary intervention for de novo lesions were randomly assigned 1:1 to Cre8 or Taxus Liberté stents. Primary endpoint was 6-month angiographic in-stent late lumen loss (LLL) within a noninferiority scope. Six-month intravascular ultrasound was performed in 20% of the patients. All patients will be clinically followed up to 5 years. RESULTS Out of 323 patients enrolled, 162 received Cre8 and 161 Taxus Liberté stents. In-stent LLL was significantly lower in Cre8 group (0.14 ± 0.36 mm vs. 0.34 ± 0.40 mm, p noninferiority <0.0001, p superiority <0.0001). Clinical endpoints (cardiac death, myocardial infarction, target lesion revascularization, and stent thrombosis) up to 12 months did not differ significantly between the groups. CONCLUSIONS The Cre8 stent in de novo lesions showed significantly lower in-stent LLL at 6 months than the Taxus Liberté stent did, with a trend toward better 12-month clinical safety and efficacy results. (International Randomized Comparison Between DES Limus Carbostent and Taxus Drug-Eluting Stents in the Treatment of De Novo Coronary Lesions [NEXT]; NCT01373502).

Self-Expanding Versus Balloon-Expandable Stents in Acute Myocardial Infarction: Results From the APPOSITION II Study: Self-Expanding Stents in ST-Segment Elevation Myocardial Infarction

OBJECTIVES This study sought to investigate whether self-expanding stents are more effective than balloon-expandable stents for reducing stent malapposition at 3 days after implantation in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. BACKGROUND Acute myocardial infarction is associated with vasoconstriction and large thrombus burden. Resolution of vasoconstriction and thrombus load during the first hours to days after primary percutaneous coronary intervention may lead to stent undersizing and malapposition, which may subsequently lead to stent thrombosis or restenosis. In addition, aggressive stent deployment may cause distal embolization. METHODS Eighty patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomized to receive a self-expanding stent (STENTYS, STENTYS SA, Paris, France) (n = 43) or a balloon-expandable stent (VISION, Abbott Vascular, Santa Clara, California; or Driver, Medtronic, Minneapolis, Minnesota) (n = 37) at 9 European centers. The primary endpoint was the proportion of stent strut malapposition at 3 days after implantation measured by optical coherence tomography. Secondary endpoints included major adverse cardiac events (cardiac death, recurrent myocardial infarction, emergent bypass surgery, or clinically driven target lesion revascularization). RESULTS At 3 days after implantation, on a per-strut basis, a lower rate of malapposed stent struts was observed by optical coherence tomography in the self-expanding stent group than in the balloon-expandable group (0.58% vs. 5.46%, p < 0.001). On a per-patient basis, none of the patients in the self-expanding stent group versus 28% in the balloon-expandable group presented ≥5% malapposed struts (p < 0.001). At 6 months, major adverse cardiac events were 2.3% versus 0% in the self-expanding and balloon-expandable groups, respectively (p = NS). CONCLUSIONS Strut malapposition at 3 days is significantly lower in ST-segment elevation myocardial infarction patients allocated to self-expanding stents when than in those allocated to balloon-expandable stents. The impact of this difference on clinical outcome and the risk of late stent thrombosis need to be evaluated further. (Randomized Comparison Between the STENTYS Self-expanding Coronary Stent and a Balloon-expandable Stent in Acute Myocardial Infarction [APPOSITION II]; NCT01008085).

Efficacy of a Device to Narrow the Coronary Sinus in Refractory Angina

BACKGROUND Many patients with coronary artery disease who are not candidates for revascularization have refractory angina despite standard medical therapy. The balloon-expandable, stainless steel, hourglass-shaped, coronary-sinus reducing device creates a focal narrowing and increases pressure in the coronary sinus, thus redistributing blood into ischemic myocardium. METHODS We randomly assigned 104 patients with Canadian Cardiovascular Society (CCS) class III or IV angina (on a scale from I to IV, with higher classes indicating greater limitations on physical activity owing to angina) and myocardial ischemia, who were not candidates for revascularization, to implantation of the device (treatment group) or to a sham procedure (control group). The primary end point was the proportion of patients with an improvement of at least two CCS angina classes at 6 months. RESULTS A total of 35% of the patients in the treatment group (18 of 52 patients), as compared with 15% of those in the control group (8 of 52), had an improvement of at least two CCS angina classes at 6 months (P=0.02). The device was also associated with improvement of at least one CCS angina class in 71% of the patients in the treatment group (37 of 52 patients), as compared with 42% of those in the control group (22 of 52) (P=0.003). Quality of life as assessed with the use of the Seattle Angina Questionnaire was significantly improved in the treatment group, as compared with the control group (improvement on a 100-point scale, 17.6 vs. 7.6 points; P=0.03). There were no significant between-group differences in improvement in exercise time or in the mean change in the wall-motion index as assessed by means of dobutamine echocardiography. At 6 months, 1 patient in the treatment group had had a myocardial infarction; in the control group, 1 patient had died and 3 had had a myocardial infarction. CONCLUSIONS In this small clinical trial, implantation of the coronary-sinus reducing device was associated with significant improvement in symptoms and quality of life in patients with refractory angina who were not candidates for revascularization. (Funded by Neovasc; COSIRA ClinicalTrials.gov number, NCT01205893.).

Importance of adjunctive heart failure optimization immediately after implantation to improve long-term outcomes with cardiac resynchronization therapy

Despite improvement in morbidity and mortality with cardiac resynchronization therapy (CRT), disease progression continues to affect a subset of patients and there is limited effort to identify contributing factors. Our objective was to investigate if a protocol-driven approach incorporated in a management strategy of heart failure immediately after implantation would provide incremental benefits beyond usual care after implantation. We reviewed 114 consecutive patients with CRT implanted from 2005 through 2009 who received usual care after implantation or underwent protocol-driven CRT care after implantation. Preimplantation characteristics in patients receiving usual versus protocol-driven care were similar in left ventricular (LV) dimension (LV internal diastolic diameter 6.2 ± 0.8 vs 6.4 ± 1.0 cm), LV ejection fraction (26 ± 8% vs 25% ± 8%), QRS width, and medication usage. Major adjustments during the protocol-driven approach were uptitration of neurohormonal blockers (64%), echocardiographically guided atrioventricular optimization (50%), heart failure education (42%), arrhythmia management (19%), and LV lead repositioning (7%). Although positive LV remodeling was noted in the 2 groups at 6 months, extent was significantly greater in the protocol-driven approach compared to usual care (change in LV internal diastolic diameter 0.7 ± 0.6 cm vs 0.2 ± 1.2 cm, p = 0.01; change in LV ejection fraction 11 ± 7% vs 7 ± 9%, p = 0.01), which was associated with fewer major adverse events (14% vs 53%, p <0.001). In conclusion, a protocol-driven approach for patients with CRT started immediately after implantation is associated with incremental favorable effects on reverse remodeling and fewer adverse events compared to usual care after implantation. These effects appeared to be driven not only by changes in device settings and arrhythmia management but also by concomitant medication optimization and heart failure education.

Optical coherence tomography study of healing characteristics of paclitaxel-eluting balloons vs. everolimus-eluting stents for in-stent restenosis: the SEDUCE (Safety and Efficacy of a Drug elUting balloon in Coronary artery rEstenosis) randomised clinical trial

AIMS Little is known about the respective healing responses and clinical efficacy and safety of drug-eluting balloons (DEB) and the second generation of drug-eluting stents (DES) when used to treat in-stent restenosis (ISR). In this study, we set out to compare prospectively the healing characteristics, as assessed by optical coherence tomography (OCT), of DEB versus DES after treatment of ISR in bare metal stents (BMS). METHODS AND RESULTS Fifty patients with BMS ISR were randomised to treatment with a paclitaxel-eluting balloon vs. an everolimus-eluting stent (EES). The primary endpoint was the percentage of uncovered struts, assessed with OCT at nine months, as a marker of vessel wall healing. A mean of 366±135 and 636±184 struts were analysed per patient in the DEB and EES groups, respectively. The percentage of uncovered struts per patient was significantly lower with DEB vs. EES (1.4% vs. 3.1%, p=0.025). Mean neointimal hyperplasia area was 2.4±1.08 mm in DEB vs. 1.92±0.67 mm in EES (p=0.1806), while the percentage of malapposed struts per patient was very low in both groups (0.2% vs. 0.3%, p=0.699). At nine months, angiographic in-stent MLD (minimum lumen diameter) was lower (2.13 vs. 2.54 mm, p=0.006), while diameter stenosis (26.4 vs. 11.4%, p=0.002), and LLL (0.28 vs. 0.07 mm, p=0.1) were higher after DEB compared to EES. During one-year follow-up, we did not observe differences in the rates of death, TLR (target lesion revascularisation) or stent thrombosis. CONCLUSIONS DEB appears to be associated with better healing characteristics, as assessed by stent strut coverage with OCT, but tended to be slightly less effective compared to EES. These findings give support to the use of either DEB or EES as valuable treatment options for ISR. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Unique identifier: NCT 01065532.

First-in-Human Evaluation of a Bioabsorbable Polymer–Coated Sirolimus-Eluting Stent: Imaging and Clinical Results of the DESSOLVE I Trial (DES With Sirolimus and a Bioabsorbable Polymer for the Treatment of Patients With De Novo Lesion in the Native Coronary Arteries)

OBJECTIVES This first-in-human multicenter study sought to examine prospectively the safety and efficacy of a new, cobalt chromium thin-strut, coronary absorbable polymer-coated, sirolimus-eluting stent. BACKGROUND Bioabsorbable polymers on drug-eluting stents may lower the long-term risks of inflammation, delayed healing, and adverse events. METHODS We enrolled patients with symptomatic coronary artery disease with stable or unstable angina pectoris and >50% diameter stenosis, amenable to coverage with a ≤23-mm long stent in a vessel 2.5 to 3.5 mm in diameter. All patients received dual antiplatelet therapy after implantation. Patients, in groups of 10, underwent repeat angiography, intravascular ultrasound, and optical coherence tomography at 4, 6, or 8 months, and all patients were seen or contacted at 18 months of follow-up. RESULTS The median (range) in-stent late lumen loss (LLL) was 0.03 mm (-0.22 to 0.21 mm), 0.10 mm (-0.03 to 1.2 mm), and 0.08 mm (-0.01 to 0.28 mm), at 4, 6, and 8 months, respectively. At 18 months, the median in-stent LLL was 0.08 mm (-0.30 to 0.46 mm). On optical coherence tomography, the proportion of uncovered stent struts decreased from a median of 7.3% (range 0.4% to 46.3%) at 4 months to 0% (range: 0% to 3.4%) at 18 months. The percentage of neointimal volume obstruction by intravascular ultrasound increased from a median of 5.3% to 9.1% between 4 and 6 months and remained nearly unchanged thereafter through 18 months of follow-up. The only recorded major adverse cardiac event was a myocardial infarction. CONCLUSIONS At 18 months of follow-up, this absorbable polymer-coated, cobalt chromium sirolimus-eluting stent was associated with a low and stable in-stent LLL, complete strut coverage, and no stent thrombosis. (First-In-Human Trial of the MiStent Drug-Eluting Stent [DES] in Coronary Artery Disease [DESSOLVE-I]; NCT01247428).

Reply: The C-CURE Randomized Clinical Trial (Cardiopoietic stem Cell therapy in heart failURE).

We appreciate the interest of Dr. Mielewczik and colleagues in the C-CURE (Cardiopoietic stem Cell therapy in heart failURE) trial. As outlined in our paper [(1)][1], feasibility and safety were the primary endpoints in this first-in-man study that assessed cardiogenically-oriented, autologous bone

Uninterrupted oral anticoagulation versus bridging in patients with long-term oral anticoagulation during percutaneous coronary intervention : subgroup analysis from the WOEST trial

AIMS To investigate the optimal periprocedural antithrombotic strategy in patients on long-term oral anticoagulation (OAC) who require percutaneous coronary intervention with stenting. METHODS AND RESULTS The WOEST study was a randomised controlled trial which recruited 573 patients on long-term OAC who underwent PCI. The periprocedural treatment strategy was left to the operators discretion. To assess the safety and feasibility of uninterrupted oral anticoagulation (UAC) and bridging therapy (BT), bleeding complications and MACCE were assessed in patients treated according to UAC (n=241) and BT (n=322) regimen. After 30 days, as well as after one year, there were no significant differences in bleeding complications (HR 1.14, 95% CI: 0.77-1.69, p=0.51, and HR 1.26, 95% CI: 0.94-1.69, p=0.12, respectively) and MACCE. MACCE tended to be less frequent in the UAC group (respectively HR 0.48, 95% CI: 0.15-1.51, p=0.21, and HR 0.72, 95% CI: 0.46-1.14, p=0.16). Additionally, adjustment with a propensity score revealed no significant differences. Periprocedural INR was not associated with bleeding or MACCE. CONCLUSIONS In the WOEST study, UAC was not associated with an increase of bleeding or MACCE compared to bridging therapy. This is the largest study up to now to support the current guidelines. The WOEST trial is registered with ClinicalTrials.gov, number NCT00769938.