We aimed to describe the impact of the vascular access used when patients are treated with primary percutaneous coronary intervention (PPCI) and to assess whether this translates into differences in ...angiographic outcomes. Patients with ST-elevation myocardial infarction who underwent PPCI were divided into 3 groups: successful radial access (RA), successful femoral access (FA), and Crossover (failed RA with need for bailout FA) groups. Vascular access–related time (VART) was defined as the delay in PPCI that can be attributed to vascular access–related issues. Study end point was the final corrected Thrombolysis In Myocardial Infarction frame count. Multivariable analysis was used to identify predictors of RA failure (RAF: FA + Crossover). We included 241 patients (RA, n = 172; FA, n = 49; Crossover, n = 20). Mean VART was longer in Crossover (10.3 8.8 to 12.4 minutes), relative to RA (4.1 3.2 to 5.5 minutes) and FA (4.6 3.4 to 8.4 minutes, p <0.001). A similar situation was found for time-to-first device (Crossover 22.5 20.3 to 32.0, RA 15.0 12.0 to 19.8; FA 17.9 13.5 to 22.3 minutes, p <0.001) and total procedure time (Crossover 60.3 51.6 to 71.5, RA 46.8 38.1 to 59.7, FA 52.3 41.9 to 74.7 minutes, p <0.001). No differences in corrected Thrombolysis In Myocardial Infarction frame count were observed (Crossover 26 18 to 32 frames, RA 24 18 to 32 frames, FA 25 16 to 34 frames, p = 0.625). Killip class IV (odds ratio OR 3.628, 95% confidence interval CI 1.098 to 11.981, p = 0.035), cardiopulmonary resuscitation before arrival (OR 3.572, 95% CI 1.028 to 12.407, p = 0.045), and glomerular filtration rate (OR 0.861, 95% CI 0.758 to 0.978, p = 0.021) were independent predictors of RA failure. In conclusion, in the setting of PPCI, radial-to-FA crossover can lead to VART delays that do not affect angiographic outcomes, in comparison with successful RA.
The study aimed to evaluate inclacumab for the reduction of myocardial damage during a percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction.
...P-selectin is an adhesion molecule involved in interactions between endothelial cells, platelets, and leukocytes. Inclacumab is a recombinant monoclonal antibody against P-selectin, with potential anti-inflammatory, antithrombotic, and antiatherogenic properties.
Patients (N = 544) with non-ST-segment elevation myocardial infarction scheduled for coronary angiography and possible ad hoc PCI were randomized to receive 1 pre-procedural infusion of inclacumab 5 or 20 mg/kg or placebo. The primary endpoint, evaluated in patients who underwent PCI, received study medication, and had available efficacy data (n = 322), was the change in troponin I from baseline at 16 and 24 h after PCI.
There was no effect of inclacumab 5 mg/kg. Placebo-adjusted geometric mean percent changes in troponin I with inclacumab 20 mg/kg were -24.4% at 24 h (p = 0.05) and -22.4% at 16 h (p = 0.07). Peak troponin I was reduced by 23.8% (p = 0.05) and area under the curve over 24 h by 33.9% (p = 0.08). Creatine kinase-myocardial band yielded similar results, with changes of -17.4% at 24 h (p = 0.06) and -16.3% at 16 h (p = 0.09). The incidence of creatine kinase-myocardial band increases >3 times the upper limit of normal within 24 h was 18.3% and 8.9% in the placebo and inclacumab 20-mg/kg groups, respectively (p = 0.05). Placebo-adjusted changes in soluble P-selectin level were -9.5% (p = 0.25) and -22.0% (p < 0.01) with inclacumab 5 and 20 mg/kg. There was no significant difference in adverse events between groups.
Inclacumab appears to reduce myocardial damage after PCI in patients with non-ST-segment elevation myocardial infarction. (A Study of RO4905417 in Patients With Non ST-Elevation Myocardial Infarction Non-STEMI Undergoing Percutaneous Coronary Intervention; NCT01327183).
Experience with bioresorbable vascular scaffolds (BVSs) outside clinical trials is scarce, and data from "real-world" use are needed. In particular, there are few data on scaffold thrombosis (ST). We ...report our experience with ST in our all-comer BVS population (n = 339) and review the literature on the topic. Four cases (1.2%) of early definite ST were identified. Multiple risk factors were present in all 4 cases. Optical coherence tomography ruled out mechanical causes of ST in 2 cases, whereas scaffold underexpansion was observed in 1 case. Twelve BVS series have been published to date. Total sample size includes 1393 patients, with 13 cases of definite ST (0.9%), which is similar to long-term second-generation drug-eluting stent thrombosis rate (1.0%). Eleven of these cases were early ST (8 during the first week). Six of these 11 cases occurred in patients who received a BVS in the setting of an acute coronary syndrome (ACS). It can be speculated that the prothrombotic milieu of ACS, coupled with the unfavorable peristrut rheology of BVSs, might promote ST early after implantation, particularly if other concomitant risk factors are present.
Summary Background Oxidative stress and inflammation are involved in the pathophysiology of atherosclerosis. Our aim was to assess the effects of the antioxidant succinobucol (AGI-1067) on ...cardiovascular outcomes in patients with recent acute coronary syndromes already managed with conventional treatments. Methods After an acute coronary syndrome occurring 14–365 days before recruitment, 6144 patients were randomly assigned with a computer-generated randomisation list, stratified by study site, to receive succinobucol (n=3078) or placebo (n=3066) in addition to standard of care. Enrolment began in July, 2003; this event-driven trial was stopped in August, 2006, after the prespecified number of primary outcome events had occurred. The composite primary endpoint was time to first occurrence of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, unstable angina, or coronary revascularisation. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00066898. Findings All randomised patients were included in the efficacy analyses. Succinobucol had no effect on the primary endpoint (530 events in succinobucol group vs 529 in placebo group; hazard ratio 1·00, 95% CI 0·89–1·13, p=0·96). The composite secondary endpoint of cardiovascular death, cardiac arrest, myocardial infarction, or stroke occurred in fewer patients in the succinobucol group than in the placebo group (207 vs 252 events; 0·81, 0·68–0·98, p=0·029). The tertiary endpoint of new-onset diabetes developed in fewer patients without diabetes at baseline in the succinobucol group than in such patients in the placebo group (30 of 1923 vs 82 of 1950 patients; 0·37, 0·24–0·56, p<0·0001). New-onset atrial fibrillation occurred more often in the succinobucol group than in the placebo group (107 of 2818 vs 55 of 2787 patients; 1·87, 1·67–2·09, p=0·0002). Although the number of patients who reported any treatment emergent adverse event was much the same in the two groups, more patients in the succinobucol group than in the placebo group reported bleeding episodes or anaemia (32 vs 18 and 37 vs ten, respectively) as serious adverse events. Relative to treatment with placebo, succinobucol increased LDL cholesterol and systolic blood pressure, and decreased HDL cholesterol and glycated haemoglobin (p<0·0001 for all). Interpretation Although succinobucol had no effect on the primary endpoint, changes in the rates of other clinical outcomes—both beneficial and harmful—will need to be further assessed before succinobucol is used in patients with atherosclerosis or as an antidiabetic agent. Funding AtheroGenics Inc.
A better understanding of the central role of inflammation in the development of coronary artery disease (CAD) has been the impetus for the evaluation of therapeutic strategies targeting the ...interleukin-1ß/interleukin-6 cytokine signaling pathway, involved in both chronic atherogenesis and in triggering of atherosclerotic plaque rupture. As an inexpensive pharmacologic agent with relatively few adverse effects that tend to be mild and tolerable, the role of colchicine in secondary prevention of atherothrombotic events has been the focus of multiple recent large-scale randomized controlled trials involving patients with stable CAD (Low-Dose Colchicine LoDoCo and LoDoCo2 trials), a recent myocardial infarction (Colchicine Cardiovascular Outcome Trial COLCOT, Colchicine in Patients With Acute Coronary Syndrome COPS, and Colchicine and Spironolactone in Patients With Myocardial Infarction/Synergy Stent Registry CLEAR SYNERGY trials), and undergoing percutaneous coronary interventions (Colchicine in Percutaneous Coronary Intervention COLCHICINE-PCI trial). Based on this evidence, low-dose colchicine (0.5 mg once daily) should be considered in patients with recent myocardial infarctions—within 30 days and, ideally, within 3 days—or with stable CAD to improve cardiovascular outcomes. Colchicine should not be used in patients with severe renal or hepatic disease because of the risk of severe toxicity. No serious adverse effect was associated with the combined use of colchicine and high-intensity statin therapy in large trials. The impact of colchicine in high-risk populations of patients with peripheral arterial disease and in those with diabetes for the primary prevention of CAD remains to be established.
Une meilleure compréhension du rôle central de l'inflammation dans le développement de la coronaropathie (CP) a été à l'origine de l'évaluation de stratégies thérapeutiques ciblant la voie de signalisation des cytokines interleukine-1ß/interleukine-6, impliquée à la fois dans l'athérogénèse chronique et dans le déclenchement de la rupture de la plaque d'athérome. En tant qu'agent pharmacologique peu coûteux, dont les effets indésirables sont relativement peu nombreux et généralement légers et tolérables, le rôle de la colchicine dans la prévention secondaire des événements athérothrombotiques a fait l'objet de plusieurs essais contrôlés randomisés à grande échelle menés récemment auprès de patients atteints de CP stable (essais LoDoCo Low-Dose Colchicine et LoDoCo2), après un infarctus du myocarde récent (essais COLCOT Colchicine Cardiovascular Outcome Trial, COPS Colchicine in Patients With Acute Coronary Syndrome et CLEAR SYNERGY Colchicine and Spironolactone in Patients With Myocardial Infarction/Synergy Stent Registry) et pour des patients subissant une intervention coronarienne percutanée (ICP) (essai COLCHICINE-PCI). Sur la base de ces données, la colchicine à faible dose (0,5 mg une fois par jour) doit être envisagée chez les patients ayant subi un infarctus du myocarde récent - dans les 30 jours et, idéalement, dans les trois jours - ou présentant une CP stable afin d'améliorer le pronostic cardiovasculaire. La colchicine ne doit pas être utilisée chez les patients présentant une affection rénale ou hépatique sévère, en raison d'un risque de toxicité grave. Aucun effet indésirable grave n'a été associé à l'utilisation combinée de la colchicine et d'un traitement par statine de haute intensité dans les essais à grande échelle. L'impact de la colchicine dans les populations à haut risque des patients atteints de maladie artérielle périphérique et chez les diabétiques pour la prévention primaire de la CP reste à établir.
The objective of this study was to assess the efficacy of sealing intermediate nonobstructive coronary saphenous vein graft (SVG) lesions with drug-eluting stents (DES; paclitaxel- or ...everolimus-eluting stents) for reducing major adverse cardiac events (MACE).
This was a randomized controlled multicenter clinical trial that enrolled patients with a previous coronary artery bypass graft who had developed at least 1 intermediate nonobstructive SVG lesion (30%-60% diameter stenosis by visual estimation). Patients were randomized (1:1) to DES implantation (SVG-DES) or medical treatment (SVG-MT) of the target SVG lesion. The primary efficacy outcome was the first occurrence of MACE defined as the composite of cardiac death, myocardial infarction, or coronary revascularization related to the target SVG during the duration of follow-up (minimum of 2 years). Secondary efficacy outcomes included MACE related to the target SVG lesion and overall MACE. A total of 125 patients (mean age 70±9 years, 87% men) were included, with a mean time from coronary artery bypass graft of 12±5 years. Sixty and 65 patients were allocated to the SVG-DES and SVG-MT groups, respectively. There were no events related to the target SVG at 30 days. After a median follow-up of 3.4 (interquartile range: 2.8-3.9) years, the MACE rate related to the target SVG was not significantly different in the 2 groups (SVG-DES: 15.0%, SVG-MT: 20.0%; hazard ratio, 0.65; 95% confidence interval, 0.23-1.53; P=0.33). There were no significant differences between groups in MACE related to the target SVG lesion (SVG-DES: 10.0%, SVG-MT: 16.9%; hazard ratio, 0.53; 95% confidence interval, 0.20-1.43; P=0.21) or global MACE (SVG-DES: 36.7%, SVG-MT: 44.6%; hazard ratio, 0.73; 95% confidence interval, 0.42-1.27; P=0.26).
Sealing intermediate nonobstructive SVG lesions with DES was safe but was not associated with a significant reduction of cardiac events at 3-year follow-up.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01223443.
Abstract Background The antioxidant AGI-1067 was shown to reduce experimental atherosclerosis. The present study originally intended to study restenosis as a primary endpoint but was subsequently ...modified to primarily investigate the effects of AGI-1067 on coronary atherosclerosis. Methods and results This placebo-controlled randomized trial assessed the effects of AGI-1067 280 mg qd started before percutaneous coronary intervention (PCI) and administered for 12 months after PCI on atherosclerosis progression as assessed by coronary intravascular ultrasound (IVUS). Among patients with IVUS examinations considered technically adequate both at baseline and follow-up upon central laboratory assessments ( n = 232), plaque volume was not significantly modified with placebo (least squares mean change: −0.4 mm3 , P = 0.85 versus baseline), but was significantly reduced by −4.0 mm3 at end of treatment in the AGI-1067 group ( P = 0.001 versus baseline, P = 0.12 versus placebo). LDL-cholesterol varied by −9% and +4% in the placebo and AGI-1067 groups, respectively ( P < 0.05 between groups), and HDL-cholesterol was reduced by 1% with placebo and 14% with AGI-1067 ( P < 0.05 between groups). Plasma myeloperoxidase was reduced by 6% with AGI-1067 ( P < 0.05) but hs-CRP was not significantly different between groups. Conclusions Atherosclerosis regression (−4.0 mm3 ) was observed in patients treated with AGI-1067, although this was not significantly different from placebo. The anti-inflammatory effect of AGI-1067 is supported by reduced levels of myeloperoxidase.
AGI-1067, a metabolically stable modification of probucol, is an equipotent antioxidant to probucol but is pharmacologically distinct. In a multicenter trial, we studied whether AGI-1067 reduces ...restenosis assessed by intravascular ultrasound (IVUS) after percutaneous coronary intervention (PCI) compared with placebo and probucol used as a positive control.
Two weeks before PCI, 305 patients were randomly assigned to 1 of 5 treatment groups: placebo, probucol 500 mg BID, or AGI-1067 70, 140, or 280 mg once daily. Patients were treated for 2 weeks before and 4 weeks after PCI. Baseline and 6-month follow-up IVUS were interpreted by a blinded core laboratory. Stents were used in 85% of patients. Luminal area at the PCI site at follow-up was 2.66+/-1.58 mm2 for placebo, 3.69+/-2.69 mm2 for probucol, 2.75+/-1.76 mm2 for AGI-1067 70 mg, 3.17+/-2.26 mm2 for AGI-1067 140 mg, and 3.36+/-2.12 mm2 for AGI-1067 280 mg (P=0.02 for the dose-response relationship; P< or =0.05 for AGI-1067 280 mg and probucol versus placebo). There was a mean narrowing of 5.3 mm3 of reference segment lumen in the placebo group and an enlargement in the AGI-1067 140- and 280-mg groups at follow-up (P=0.05 for 140 mg). An increase in QTc interval >60 ms occurred in 4.8% of placebo patients, 17.4% of probucol patients, and 4.8%, 2.4%, and 2.5% of patients in the AGI-1067 groups (P=0.02).
AGI-1067 and probucol reduce restenosis after PCI. In contrast to probucol, AGI-1067 did not cause prolongation of the QTc interval and improved lumen dimensions of reference segments, suggestive of a direct effect on atherosclerosis.
Although lifestyle interventions are first-line treatment for individuals living with prediabetes and type 2 diabetes (T2D), they are rarely implemented effectively in routine clinical care.
We ...present a retrospective analysis of a 12-month, single-centre, structured multidomain lifestyle intervention clinic offered to individuals living with prediabetes and type 2 diabetes. The intervention consisted of expert-guided educational and nutritional counselling combined with a personalized physical exercise prescription, with the main goal of improving metabolic health and reaching remission. Anthropometric parameters, glucose, basal insulin, glycated hemoglobin (A1C), and lipid levels were measured at baseline and at 3, 6, and 12 months after the lifestyle intervention initiation. Remission of prediabetes and T2D were defined as a return of A1C at 6 months to <6.5% (or <5.7% for prediabetes) and persisting for at least 3 months in the absence of glucose-lowering pharmacotherapy.
After a multidomain, expert-guided lifestyle intervention, 117 individuals living with prediabetes and T2D had significantly improved metabolic profiles: Mean weight change at 12 months was −4.9 kg (95% confidence interval CI, −4.0 to −5.7; p<0.001), and mean change in A1C at 12 months was −0.6% (95% CI, −0.4 to −0.7; p<0.001). A substantial proportion of individuals reached the criteria for remission (20% among participants with prediabetes and 12% among those with T2D).
The results of this study suggest that prioritizing lifestyle changes in a multifaceted, progressive, 12-month intervention in this population improves anthropometric and insulin resistance measures, and has the potential to normalize metabolic values, even to the point of reaching the criteria of remission.
Bien que les interventions axées sur le mode de vie constituent le traitement de première ligne des individus vivant avec le prédiabète et le diabète de type 2 (DT2), elles sont rarement mises en œuvre de façon efficace dans le cadre des soins cliniques courants.
Nous présentons une étude rétrospective unicentrique d’une clinique d’interventions axées sur le mode de vie, multidomaines et structurées, de 12 mois, offertes aux patients vivant avec le prédiabète et le diabète de type 2. Les interventions consistaient en la combinaison d’un counseling éducationnel et nutritionnel par un expert et d’une prescription personnalisée ayant pour principal objectif l’amélioration de la santé métabolique et l’obtention de la rémission. Les paramètres anthropométriques et les concentrations de glucose, de l’insuline basale, de l’hémoglobine glyquée (A1c) et des lipides ont été mesurés au début et 3, 6 et 12 mois après l’amorce des interventions axées sur le mode de vie. La rémission du prédiabète et du DT2 a été définie par le retour de l’A1c après 6 mois à < 6,5 % (ou < 5,7 % lors de prédiabète) et son maintien durant au moins 3 mois en l’absence de pharmacothérapie hypoglycémiante.
Après les interventions multidomaines axées sur le mode de vie par des experts, 117 individus vivant avec le prédiabète et le DT2 avaient montré une amélioration significative de leurs profils métaboliques : le changement moyen du poids après 12 mois était −4,9 kg (intervalle de confiance IC à 95 %, de −4,0 à −5,7; p < 0,001), et le changement moyen de l’A1c après 12 mois était de −0,6 % (IC à 95 %, de −0,4 à −0,7; p < 0,001). Une proportion substantielle d’individus remplissait les critères de rémission (20 % chez les participants atteints de prédiabète et 12 % chez ceux atteints du DT2).
Les résultats de cette étude montrent que la priorisation des changements au mode de vie d’une intervention multifacette progressive de 12 mois dans cette population permet d’améliorer les mesures anthropométriques et de la résistance à l’insuline, et a le potentiel de normaliser les valeurs métaboliques, au point même de remplir les critères de rémission.
We sought to determine whether clopidogrel is at least as efficacious as ticlopidine.
Several trials have supported the enhanced safety and tolerability of clopidogrel compared with ticlopidine after ...coronary stent deployment. However, none of these individual trials were powered to detect possible differences in the efficacy for reducing ischemic end points.
Published data from trials and registries that compared clopidogrel with ticlopidine in patients receiving coronary stents were pooled, and a formal meta-analysis was performed. The rate of 30-day major adverse cardiac events (MACE), as defined in each trial, was used as the primary end point.
There were a total of 13,955 patients. The pooled rate of major adverse cardiac events was 2.10% in the clopidogrel group and 4.04% in the ticlopidine group. After adjustment for heterogeneity in the trials, the odds ratio (OR) of having an ischemic event with clopidogrel, as compared with ticlopidine, was 0.72 (95% confidence interval CI 0.59 to 0.89, p = 0.002). Mortality was also lower in the clopidogrel group compared with the ticlopidine group—0.48% versus 1.09% (OR 0.55, 95% CI 0.37 to 0.82; p = 0.003).
Based on all available evidence from randomized clinical trials or registries, clopidogrel, in addition to better tolerability and fewer side effects, is at least as efficacious as ticlopidine in reducing MACE. This finding may be due to the more rapid onset of an antiplatelet effect seen with the loading dose of clopidogrel, which was used in most of these studies, or to better patient compliance with clopidogrel therapy. Therefore, clopidogrel plus aspirin should replace ticlopidine plus aspirin as the standard antiplatelet regimen after stent deployment.
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