Complementary evidence on the performance of coronary stents generated by a randomized controlled trial and a worldwide registry.

BACKGROUND: Large-scale registries can provide valuable complementary data to randomized controlled trials (RCT) for the postmarketing evaluation of coronary stents, but their scientific relevance remains debated. METHODS: We sought to compare the evidence on the performance of a single coronary stent platform generated by the RCT for its regulatory approval and a well-conducted international registry. Patients treated with the Ultimaster coronary stent in the CENTURY II (CII-UM) trial (n = 551) were compared to patients in the real-world e-ULTIMASTER (e-UM) registry (n = 35,389). All major events were adjudicated by an independent clinical event committee in both studies. Propensity weighted analysis was used to balance baseline and procedural differences between the 2 populations. RESULTS: Coronary artery disease was more complex in e-UM compared to CII-UM, including more acute coronary syndromes, multivessel disease, left main, arterial, or venous grafts, and chronic total occlusions (P < .005 for all). At one-year follow-up and after excluding periprocedural myocardial infarction (MI) there was no statistically significant difference between CII-UM and e-UM regarding all-cause death (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.26-1.20, P = .14), cardiac death (HR 0.71, 95% CI 0.29-1.72, P = .45), target lesion failure (HR 1.18, 95% CI 0.78-1.78, P = .44), and target vessel MI (HR 0.76, 95% CI 0.24-2.38, P = .63). However, target vessel revascularization rate was significantly higher in CII-UM than in e-UM, HR 1.78, 95% CI 1.23-2.56, P = .002. CONCLUSIONS: A well-conducted large-scale registry can provide valuable complementary evidence to RCTs on the postmarket performance of new coronary stents, across a wider range of uses and various geographic areas.

Outcomes and regional differences in practice in a worldwide coronary stent registry.

OBJECTIVE: The primary objective was to assess the performance of a new generation thin-strut sirolimus-eluting coronary stent with abluminal biodegradable polymer in an all comer population. The secondary objective was to detail differences in contemporary percutaneous coronary intervention (PCI) practice worldwide. METHODS: e-Ultimaster was an all-comer, prospective, global registry (NCT02188355) with independent event adjudication enrolling patients undergoing PCI with the study stent. The primary outcome measure was target lesion failure (TLF) at 1 year, defined as the composite of cardiac death, target vessel myocardial infarction and clinically driven target lesion revascularisation. Data were stratified according to 4 geographical regions. RESULTS: A total of 37 198 patients were enrolled (Europe 69.2%, Asia 17.8%, Africa/Middle East 6.6% and South America/Mexico 6.5%) and 1-year follow-up was available for 35 389 patients (95.1%). One-year TLF occurred in 3.2% of the patients, ranging from 2% (Africa/Middle East) to 4.1% (South America/Mexico). In patients with acute coronary syndrome, potent P2Y12 inhibitors were prescribed in 48% of patients at discharge, while at 1 year 72% were on any dual antiplatelet therapy. Lipid-lowering treatment was administered in 80.9% and 75.5% of patients at discharge and 1 year, respectively. Regional differences in the profile of the treated patients as well as in PCI practice were reported. CONCLUSIONS: In this investigation with worldwide representation, contemporary PCI using a new generation thin-strut sirolimus-eluting coronary stent with abluminal biodegradable polymer was associated with low 1-year TLF across clinical presentations and continents. Suboptimal adherence to current recommendations around antiplatelet and lipid lowering treatments was detected.

Comparative Methodological Assessment of the Randomized GLOBAL LEADERS Trial Using Total Ischemic and Bleeding Events.

BACKGROUND: Time-to-first-event analysis considers only the first event irrespective of its severity. There are several methods to assess trial outcomes beyond time-to-first-event analysis, such as analyzing total events and ranking outcomes. In the GLOBAL LEADERS study, time-to-first-event analysis did not show superiority of ticagrelor monotherapy following one-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention to conventional 12-month DAPT followed by aspirin monotherapy in the reduction of the primary composite end point of all-cause mortality or new Q-wave myocardial infarction. This study sought to explore various analytical approaches in assessing total ischemic and bleeding events after percutaneous coronary intervention in the GLOBAL LEADERS study. METHODS AND RESULTS: Total ischemic and bleeding events were defined as all-cause mortality, any stroke, any myocardial infarction, any revascularization, or Bleeding Academic Research Consortium grade 2 or 3 bleeding. We used various analytical approaches to analyze the benefit of ticagrelor monotherapy over conventional DAPT. For ischemic and bleeding events at 2 years after percutaneous coronary intervention, ticagrelor monotherapy demonstrated a 6% risk reduction, compared with conventional 12-month DAPT in time-to-first-event analysis (hazard ratio, 0.94 [95% CI, 0.88-1.01]; log-rank P=0.10). In win ratio analysis, win ratio was 1.05 (95% CI, 0.97-1.13; P=0.20). Negative binomial regression and Andersen-Gill analyses which include repeated events showed statistically significant advantage for ticagrelor monotherapy (rate ratio, 0.92 [95% CI, 0.85-0.99; P=0.020] and hazard ratio, 0.92 [95% CI, 0.85-0.99; P=0.028], respectively), although in weighted composite end point analysis, the hazard ratio was 0.93 (95% CI, 0.84-1.04; log-rank P=0.22). CONCLUSIONS: Statistical analyses considering repeated events or event severity showed that ticagrelor monotherapy consistently reduced ischemic and bleeding events by 5% to 8%, compared with conventional 1-year DAPT. Applying multiple statistical methods could emphasize the multiple facets of a trial and result in accurate and more appropriate analyses. Considering the recurrence of ischemic and bleeding events, ticagrelor monotherapy appeared to be beneficial after percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

Impact of coronary lesion complexity in percutaneous coronary intervention: one-year outcomes from the large, multicentre e-Ultimaster registry.

AIMS: The present study sought to examine the prevalence, clinical characteristics and one-year outcomes of patients undergoing percutaneous coronary intervention (PCI) to complex lesions (multivessel PCI, ≥3 stents, ≥3 lesions, bifurcation with ≥2 stents, total stent length >60 mm or chronic total occlusion [CTO]) in a prospective multicentre registry. METHODS AND RESULTS: Using the e-Ultimaster multicentre registry, a post hoc subgroup analysis was performed on 35,839 patients undergoing PCI, stratified by procedure complexity, and further by number and type of complex features. Overall, complex PCI patients (n=9,793, 27.3%) were older, more comorbid and were associated with an increased hazard ratio (HR) of the composite endpoint at one year (target lesion failure [TLF]: 1.41 [1.25; 1.59]), driven by an increased hazard of cardiac death (1.28 [1.05; 1.55]), target vessel myocardial infarction (1.48 [1.18; 1.86]) and clinically driven target lesion revascularisation. The hazard of complications increased with the rising number of complex features (3-6 vs 1-2 vs none) for all outcomes. All individual complex features were associated with an increased hazard of composite complications (except CTO) and definite/probable stent thrombosis. CONCLUSIONS: Overall, complex PCI is associated with an increased risk of mortality and complications at one year. The number and types of complex features have differing impacts on long-term outcomes.

Transcarotid transcatheter aortic valve implantation.

Transcatheter aortic valve implantation is a well-recognized treatment option for high-risk patients with aortic stenosis. The femoral approach is possible in 80% of cases. Initially, only the transcarotid and subclavian approaches were performed as alternative routes. Both approaches have advantages and disadvantages. The carotid approach is a new approach that offers direct vascular access to the aortic valve. The technique of access is very simple and well known to all cardiovascular surgeons, and the morbidity is minimal. It avoids a thoracotomy with all its complications. We present here our technique and results of our initial experience.

Mid-term results of 150 TAVI comparing apical versus femoral approaches.

BACKGROUND: Transcatheter aortic-valve implantation (TAVI) is a new therapeutic choice for treating aortic stenosis in patients considered high risk for surgery. This blooming therapeutic technique still requires evaluation of medium and long term outcome. METHOD: We hereby report our results of the first 150 consecutive patients to receive TAVI implants in our population recruited from July 2009 to March 2013 in a retrospective and monocentric study. We analyzed long term morbidity and mortality criteria. We compared the apical and femoral approach results and researched predictors of cardiac mortality. RESULTS: The mean monitoring period was 387.62 days, mean Euroscore was 21.8, and mean Society of Thoracic Surgeons (STS) risk score was 9.2. The success rate for the procedure was 94.6 %. A total of 39 patients died. The mortality rates at the immediate perioperative point, 30 days, 1 year, and 2 years, were 4 %, 11.3 %, 22.7 %, and 26 %, respectively. As regards complications, there were 10 hemodynamic complications (6.6 %) and 20 vascular (13.3 %), 11 cardiac tamponades (7.4 %), eight mechanical (5.3 %), ten major hemorrhagic (6.7 %), 14 pulmonary (9.3 %), and 18 infectious complications (12 %). When comparing the rates of reported complications in terms of different approaches, we observed significantly more hemodynamic complications in the apical group (p = 0.049). Pulmonary complications were also significantly more common in cases of apical approach (p = 0.029). The majority of the patients reported clear functional improvement throughout their follow-up. CONCLUSION: The results of the first 150 patients to receive the implant at the Nancy University Teaching Hospital (CHU Nancy) were consistent with findings in the literature. TAVI proved a credible and effective alternative to surgical valve replacement for patients at high risk during surgery.

Transcatheter aortic valve implantation via right carotid artery route for severe aortic regurgitation management in a patient with chronic operated type A aortic dissection.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) technique is now widely accepted as an alternative for the treatment of very high-risk patients in cases of aortic stenosis. However, use of this technique in cases of pure native aortic regurgitation (AR) remains discussed. CASE REPORT: We report the case of a 68-year-old patient with severe AR referred to our hospital 10 years after a supracoronary ascending aorta replacement surgery for acute type A aortic dissection. Because of respiratory contraindication to redo sternotomy, we treated this patient with the implantation of a CoreValve prosthesis inserted via right carotid access. We discuss the TAVI strategy in the case of severe AR and the possibility to use alternative vascular access. CONCLUSION: In very high-risk patients, TAVI can be discussed and considered as an alternative treatment for severe AR, with right carotid access proven as feasible.

Does optical coherence tomography optimize results of stenting? Rationale and study design.

BACKGROUND: To date, no randomized study has investigated the value of optical coherence tomography (OCT) in optimizing the results of coronary angioplasty for non-ST-segment elevation acute coronary syndromes. METHODS: DOCTORS is a randomized, prospective, multicenter, open-label clinical trial to evaluate the utility of OCT to optimize results of angioplasty of a lesion responsible for non-ST-elevation acute coronary syndromes. Patients (n = 250) will be randomized to undergo OCT-guided angioplasty (use of OCT to optimize procedural result, including change to strategy with the possibility of additional interventions) or angioplasty under fluoroscopy alone. The primary end point is the functional result of the angioplasty procedure as assessed by fractional flow reserve (FFR) measured at the end of the procedure. Secondary end points include safety of OCT in the context of angioplasty for ACS, percentage of patients in whom OCT reveals suboptimal result of stenting, percentage of patients in whom a change in procedural strategy is decided based on OCT data, correlation between quantitative measures by OCT and FFR, determination of a threshold for quantitative OCT measure that best predicts FFR ≥ 0.90, and identification of OCT variables that predict postprocedure FFR. Adverse cardiac events (death, recurrent myocardial infarction, stent thrombosis, and repeat target lesion revascularization) at 6 months will be recorded. CONCLUSION: The DOCTORS randomized trial (ClinicalTrials.gov NCT01743274) is designed to investigate whether use of OCT yields useful additional information beyond that obtained by angiography alone and, if so, whether this information changes physician strategy and impacts on the functional result of angioplasty as assessed by FFR.

Heart failure with systolic dysfunction complicating acute myocardial infarction - differential outcomes but similar eplerenone efficacy by ST-segment or non-ST-segment elevation: A post hoc substudy of the EPHESUS trial.

BACKGROUND: Differential outcomes in patients with acute systolic heart failure (HF) complicating acute myocardial infarction (AMI) and the efficacy of mineralocorticoid receptor antagonists according to non-ST-segment and ST-segment elevation myocardial infarction (NSTEMI, STEMI) status has not been specifically investigated. METHODS: In the EPHESUS study, 6632 patients with acute HF and left ventricular ejection fraction<40% were randomized 3-14 days post-AMI (median 7.3 ± 3.0 days) to receive eplerenone (n=3319) or placebo (n=3313). Among them, 6392 patients with available data on baseline ST-segment status (4634 STEMI; 1758 NSTEMI) were compared using a Cox model analysis stratified according to quintiles of propensity score (PS), taking into account major baseline risk factors, including revascularization. RESULTS: STEMI and NSTEMI patients differed significantly across a large variety of baseline characteristics. During 30 months of follow-up, all-cause death occurred in 19% and 13% (P<0.0001), cardiovascular death in 16% and 12% (P<0.0001), cardiovascular death and hospitalization in 33% and 26% (P<0.0001) and death from progression of HF in 5% and 3% (P<0.0001) of unadjusted NSTEMI and STEMI patients, respectively. After Cox model PS adjustment without revascularization, NSTEMI status still proved to be a risk factor for all-cause death, cardiovascular death and death from progression of HF. After Cox model PS adjustment including revascularization, none of the outcomes differed between STEMI and NSTEMI patients. Eplerenone morbidity and mortality benefits were consistent in the STEMI and NSTEMI subgroups. CONCLUSION: In patients with acute systolic HF complicating AMI, eplerenone improves outcomes equally in STEMI and NSTEMI patients. Worse outcomes associated with NSTEMI could be explained by more co-morbidities, less aggressive therapies and, mainly, less frequent revascularization.

A direct comparison of intravenous enoxaparin with unfractionated heparin in primary percutaneous coronary intervention (from the ATOLL trial).

Intravenous enoxaparin did not reduce significantly the primary end point (p = 0.06) compared with unfractionated heparin (UFH) in the randomized Acute Myocardial Infarction Treated with primary angioplasty and intravenous enoxaparin Or unfractionated heparin to Lower ischemic and bleeding events at short- and Long-term follow-up (ATOLL) trial. We present the results of the prespecified per-protocol analysis excluding patients who did not receive the treatment allocated by randomization or received both enoxaparin and UFH. We evaluated all-cause mortality, complication of myocardial infarction, procedural failure, or major bleeding (primary end point) and all-cause mortality, recurrent acute coronary syndrome, or urgent revascularization (main secondary end point). Baseline and procedural characteristics were well balanced between the 2 treatment groups. Of 910 randomized patients, 795 patients (87.4%) were treated according to the protocol with consistent anticoagulation using intravenous enoxaparin (n = 400) or UFH (n = 395). Enoxaparin reduced significantly the rates of the primary end point (relative risk [RR] 0.76, 95% confidence interval [CI] 0.62 to 0.94, p = 0.012) and the main secondary end point (RR 0.37, 95% CI 0.22 to 0.63, p <0.0001). There was less major bleeding with enoxaparin (RR 0.46, 95% CI 0.21 to 1.01, p = 0.050) contributing to the significant improvement of the net clinical benefit (RR 0.46, 95% CI 0.3 to 0.74, p = 0.0002). All-cause mortality was also reduced with enoxaparin (RR 0.36, 95% CI 0.18 to 0.74, p = 0.003). In conclusion, in the per-protocol analysis of the ATOLL trial, pertinent to >87% of the study population, enoxaparin was superior to UFH in reducing ischemic end points and mortality.

Residual viability is a predictor of the perfusion enhancement obtained with the cell therapy of chronic myocardial infarction: a pilot multimodal imaging study.

PURPOSE: Up to now, there has been limited investigation into cell therapy in the chronic phase of severe myocardial infarction (MI), and many questions remain concerning the contribution of the engrafted cells and especially their impact on the reperfusion of MI areas, when assessed by objective quantitative imaging techniques. This randomized pilot SPECT, PET, and MRI study was aimed at assessing the effects of bone marrow mononuclear cells (BMNCs) when implanted in areas of severe and chronic MI. MATERIALS AND METHODS: Fourteen patients, who were referred for coronary artery bypass grafting (CABG) and in whom a screening MIBI-SPECT revealed severely damaged myocardium (<50% uptake under nitrate), were randomized between a cell therapy group (n = 7; CABG and injection of BMNCs within MI areas) and a control group (n = 7; CABG alone). RESULTS: The MI areas exhibited a posttherapeutic enhancement in the rest-uptake of MIBI in the cell therapy group [difference between 6-month control and baseline: +6.8% (5.4%), P = 0.03] but not in the control group [+1.0% (4.3%)]. However, in a per-patient analysis, this improvement was significant (> +9%) in only 3 cell therapy patients, whose MI areas before therapy had a higher FDG uptake [59% (9%) vs 38% (8%), P = 0.03] and a lower transmural extent at MRI [40% (6%) vs 73% (18%), P = 0.03] when compared with the other cell therapy patients. CONCLUSIONS: Perfusion enhancement, obtained with BMNCs in areas of chronic MI, might require an intermediate level of viability documented with FDG-PET and MRI and that totally necrotic MI seems refractory to this cell therapy technique.

French Ministry of Health prospective multicentre study using bio-active stents coated with titanium nitride oxide: the EVIDENCE registry.

BACKGROUND: Coronary stents have evolved over time, from bare-metal stents to drug-eluting stents, and now to bioactive stents. AIMS: We sought to explore the immediate outcome of the titanium-nitride-oxide-coated bioactive stent, Titan2(®), in real-world practice, and the incidence of major cardiac events at follow-up. METHODS: Consecutive patients admitted for percutaneous intervention for at least one significant (≥50%) lesion in a native coronary artery were treated with Titan2(®) stent implantation. The primary endpoint was total major adverse cardiac events at 12-month follow-up. Secondary endpoints included target lesion revascularization at 12-month follow-up and the duration of dual antiplatelet therapy. RESULTS: Among 356 patients (mean age 67.4 ± 12.1 years), 77.2% were male and 39.3% were treated for myocardial infarction (MI). A total of 546 Titan2(®) stents were implanted in 420 lesions. Angiographic and clinical procedural success was achieved in all cases. No cases of in-hospital major adverse cardiac events or acute stent thrombosis were reported. Of 335 patients (94.1%) with 12-month clinical follow-up, four (1.2%) died, MI occurred in five (1.5%), target lesion revascularization was performed in 17 (5.1%) and major adverse cardiac events occurred in 24 (7.2%). One patient (0.3%) suffered late stent thrombosis during follow-up, but no cases of acute or subacute stent thrombosis occurred. Dual antiplatelet therapy continued beyond 6 months in 64.5% of patients. CONCLUSIONS: In real-world practice, Titan2(®) stent implantation achieves an excellent immediate outcome, with a low incidence of major adverse cardiac events at 12-month follow-up.

Prehospital abciximab in ST-segment elevation myocardial infarction: results of the randomized, double-blind MISTRAL study.

BACKGROUND: The value of prehospital initiation of glycoprotein IIb/IIIa inhibitors remains a controversial issue. We sought to investigate whether in-ambulance initiation of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) improves ST-segment elevation resolution (STR) after primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: MISTRAL (Myocardial Infarction with ST-elevation Treated by Primary Percutaneous Intervention Facilitated by Early Reopro Administration in Alsace) is a prospective, randomized, double-blind study. Two hundred and fifty-six patients with acute STEMI were allocated to receive abciximab either in the ambulance (ambulance group, n=127) or in the catheterization laboratory (hospital group, n=129). The primary end point was complete (>70%) STR after PCI. Complete STR was not significantly different between the 2 groups (before PCI, 21.6% versus 15.5%, P=0.28; after PCI, 70.3% versus 65.8%, P=0.49). Thrombolysis In Myocardial Infarction (TIMI) 2 to 3 flow rates before PCI tended to be higher in the ambulance group (46.8% versus 35%, P=0.08) but not after PCI (70.3% versus 65.8%, P=0.49). Slow flow tended to be lower (5.6% versus 13.4%, P=0.07), and distal embolization occurred significantly less often in the ambulance group (8.1% versus 21.1%, P=0.008). One- and 6-month major adverse cardiac event rates were low and similar in both groups. CONCLUSIONS: Early ambulance administration of abciximab in STEMI did not improve either STR or TIMI flow rate after PCI. However, it tended to improve TIMI flow pre-PCI and decreased distal embolization during procedure. Larger studies are needed to confirm these results.

Myocardial infarction in a 45-year-old man following an anaphylactic reaction to a wasp sting.

We present the case of a 45-year-old man with clinical features of acute coronary syndrome with persistent ST segment elevation following an anaphylactic reaction to a wasp sting treated with adrenaline. A thrombolysis is performed with no effect on clinical signs, leading to an emergency cardiac catheterization which reveals a non-occlusive thrombosis of the right coronary artery. The pathophysiology and clinical implications of this association are discussed.

Femoral pseudoaneurysms and current cardiac catheterization: evaluation of risk factors and treatment.

OBJECTIVES: We sought to determine the incidence of femoral pseudoaneurysm (FPA) following cardiac catheterization, identify the risk factors for FPA and factors influencing therapeutic strategy. METHODS: 11,992 consecutive patients who underwent cardiac catheterization via femoral artery were studied over a period of four years in one University Hospital. Our prospective case control group analysis registered patients who developed FPA after the procedure. Patient-related factors, procedure related factors and peri-procedure treatment were compared between the two groups. RESULTS: 76 FPA were diagnosed over the study period accounting for a global incidence of 0.6% procedures. By univariate analysis, interventional procedure (p<0.01), rhythmologic procedure (p=0.03), sheath>or=6F (p=0.04) and left groin puncture (p<0.001) were FPA risk factors. By multivariate analysis, interventional procedure (adjusted odds ratio [OR]=1.99; 95% confidence interval [CI]1.14-3.44 p=0.01) and left groin puncture (OR=4.65; 95% CI, 1.78-12.1 p=0.001) are independent predictive factors of FPA. FPA thrombosis was obtained by ultrasound guided compression (UGC) in 71% of the cases. By univariate analysis, PFA diameter larger than 4 cm (p<0.001), the use of anticoagulation (p<0.01) or GPIIbIIIa inhibitors (p=0.001) and UGC under anticoagulation (p=0.01) are predictive factors of need for FPA surgical repair. By multivariate analysis, FPA diameter>4 cm and use of GPIIbIIIa inhibitors are independent predictive factors of FPA's surgical treatment. Superficial femoral puncture was predictive of successful UGC both by uni and multivariate analysis. CONCLUSIONS: Our study shows that FPA occurrence is mainly due to by procedure-related factors. FPA size, level of puncture and the use of GPIIbIIIa inhibitors are independent predictive factors of need for surgical therapy.

Comparison of two-year outcomes in patients undergoing isolated coronary artery bypass grafting with and without peripheral artery disease.

We aimed to evaluate the long-term clinical outcomes among patients with peripheral arterial disease (PAD) after coronary artery bypass grafting. We studied 589 consecutive patients who had undergone isolated coronary artery bypass grafting from January 2003 to June 2005 at our university hospital. The effect of PAD was assessed by comparing the 2-year follow-up data from 2 groups of patients: 243 patients with and 346 without PAD. A large systematic atherosclerosis screening was performed, including cerebrovascular disease, lower extremity artery disease, and abdominal aorta disease and its branches. PAD was defined as a history of treated atherosclerotic disease and significant atherosclerotic stenosis on screening. Patients with PAD were significantly older (70 +/- 9 vs 64 +/- 11 years, p <0.001) and were more often men (p = 0.04) than those without PAD. They had a greater incidence of hypertension (p = 0.002), chronic renal dysfunction (p <0.01), chronic pulmonary disease (p = 0.005), and a history of coronary artery disease (p = 0.03). No significant difference was noted between the 2 groups with regard to the left ventricular ejection fraction. The 2-year cumulative survival rate was 76.6% for patients with PAD and 94.1% for those with isolated coronary disease (p <0.001). In conclusion, after adjusting all significant variables, the presence of PAD appeared as an independent predictive factor for all-cause mortality (adjusted hazard ratio 3.2, 95% confidence interval 1.8 to 5.7, p = 0.001).

Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial.

AIMS: To test the hypothesis that an earlier post-acute myocardial infarction (AMI) eplerenone initiation in patients with left ventricular systolic dysfunction (LVSD) and heart failure (HF) is associated with better long-term outcomes. METHODS AND RESULTS: The 6632 patients of the EPHESUS study were randomized from day 3 to 14 after the index AMI (median = 7 days), of these 3319 were assigned to eplerenone. We analysed the differential effects of time-to-eplerenone initiation vs. placebo, based on the median time to initiation of treatment (<7 days-'earlier', > or =7days-'later'). Effects on outcomes were evaluated over a mean 16-month follow-up, using Cox proportional hazards regression analysis. The earlier eplerenone initiation (<7 days) reduced the risk of all-cause mortality by 31% (P = 0.001) when compared with the 'earlier' placebo' and also reduced the risks of cardiovascular (CV) hospitalization/CV mortality by 24% (P < 0.0001) and sudden cardiac death (SCD) by 34% (P < 0.0001). In contrast, later eplerenone initiation (> or =7 days) had no significant effect on outcomes. Interactions between time-to-randomization and treatment were significant. These associations remained substantially unchanged after risk adjustment in multivariable models. CONCLUSION: An earlier eplerenone administration (3-7days) post-AMI improved outcomes in patients with LVSD and HF. This benefit was not observed when eplerenone was initiated later (> or =7days).

Extracellular cardiac matrix biomarkers in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study.

BACKGROUND: Aldosterone stimulates cardiac collagen synthesis. Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac remodeling in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction. METHODS AND RESULTS: In a substudy of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), which evaluated the effects of the selective aldosterone receptor antagonist eplerenone versus placebo, serum levels of collagen biomarkers were measured in 476 patients with congestive heart failure after acute myocardial infarction complicated with left ventricular systolic dysfunction. The combination of the type I collagen telopeptide and brain natriuretic peptide levels above median at baseline was associated with all-cause mortality and the composite end point of cardiovascular death or heart failure hospitalization, with hazard ratios of 2.49 (P=0.039) and 3.03 (P=0.002), respectively. During follow-up, levels of aminoterminal propeptide of type I and type III procollagen were found to be consistently lower in the eplerenone group and significantly lower beginning at 6 months. CONCLUSIONS: Changes in biomarkers of collagen synthesis and degradation suggest that extracellular matrix remodeling is an active process in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction. High type I collagen telopeptide and high brain natriuretic peptide serum levels are associated with the highest event rate. Eplerenone suppresses post-acute myocardial infarction collagen turnover changes.

Comparison of thrombolysis followed by broad use of percutaneous coronary intervention with primary percutaneous coronary intervention for ST-segment-elevation acute myocardial infarction: data from the french registry on acute ST-elevation myocardial infarction (FAST-MI).

BACKGROUND: Intravenous thrombolysis remains a widely used treatment for ST-elevation myocardial infarction; however, it carries a higher risk of reinfarction than primary PCI (PPCI). There are few data comparing PPCI with thrombolysis followed by routine angiography and PCI. The purpose of the present study was to assess contemporary outcomes in ST-elevation myocardial infarction patients, with specific emphasis on comparing a pharmacoinvasive strategy (thrombolysis followed by routine angiography) with PPCI. METHODS AND RESULTS: This nationwide registry in France included 223 centers and 1714 patients over a 1-month period at the end of 2005, with 1-year follow-up. Sixty percent of the patients underwent reperfusion therapy, 33% with PPCI and 29% with intravenous thrombolysis (18% prehospital). At baseline, the Global Registry of Acute Coronary Events score was similar in thrombolysis and PPCI patients. Time to initiation of reperfusion therapy was significantly shorter in thrombolysis than in PPCI (median 130 versus 300 minutes). After thrombolysis, 96% of patients had coronary angiography, and 84% had subsequent PCI (58% within 24 hours). In-hospital mortality was 4.3% for thrombolysis and 5.0% for PPCI. In patients with thrombolysis, 30-day mortality was 9.2% when PCI was not used and 3.9% when PCI was subsequently performed (4.0% if PCI was performed in the same hospital and 3.3% if performed after transfer to another facility). One-year survival was 94% for thrombolysis and 92% for PPCI (P=0.31). After propensity score matching, 1-year survival was 94% and 93%, respectively. CONCLUSIONS: When used early after the onset of symptoms, a pharmacoinvasive strategy that combines thrombolysis with a liberal use of PCI yields early and 1-year survival rates that are comparable to those of PPCI.