Comparing a strategy of sirolimus-eluting balloon treatment to drug-eluting stent implantation in de novo coronary lesions in all-comers: Design and rationale of the SELUTION DeNovo Trial.

BACKGROUND: Drug eluting stents (DES) are associated with a 2% to 4% annual rate of target lesion failure through 5-to-10-year follow-up. The presence of a metallic protheses is a trigger for neo-atherosclerosis and very late stent thrombosis. A "leave nothing behind" strategy using Drug Coated Balloons has been suggested; however, paclitaxel coated balloons are only recommended in selected indications. Recently a novel sirolimus eluting balloon, the SELUTION SLR TM 014 PTCA balloon (SEB) (M.A. MedAlliance SA, Nyon, Switzerland) has been developed. HYPOTHESIS: A strategy of percutaneous coronary intervention (PCI) with SEB and provisional DES is non-inferior to a strategy of systematic DES on target vessel failure (TVF) at one and five years. If non-inferiority is met at 5 years, superiority will be tested. DESIGN: SELUTION DeNovo is a multi-center international open-label randomized trial. Subjects meeting eligibility criteria are randomized 1:1 to treatment of all lesions with either SEB and provisional DES or systematic DES. Major inclusion criteria are PCI indicated for ≥1 lesion considered suitable for treatment by either SEB or DES and clinical presentation with chronic coronary syndrome, unstable angina or non-ST segment elevation myocardial infarction (NSTEMI). There is no limitation in the number of lesions to be treated. Target lesions diameters are between 2 and 5 mm. Major exclusion criteria are lesions in the left main artery, chronic total occlusions, ST segment elevation myocardial infarction and unstable non-ST segment elevation myocardial infarction. Three thousand three hundred twenty six patients will be included in 50 sites in Europe and Asia. TVF rates and their components will be determined at 30 days, 6 months and annually up to 5 years post-intervention. Among secondary endpoints, bleeding events, cost-effectiveness data and net clinical benefits will be assessed. SUMMARY: SELUTION DeNovo trial is an open-label, multi-center international randomized trial comparing a strategy of PCI with SEB and provisional DES to a strategy of PCI with systematic DES on TVF at one and five years. Non-inferiority will be tested at one and five years. If non-inferiority is met at five years, superiority will be tested.

Polymer-free Biolimus-A9 coated thin strut stents for patients at high bleeding risk 1-year results from the LEADERS FREE III study.

BACKGROUND: In patients at high bleeding risk (HBR), the LEADERS FREE (LF) trial established the safety and efficacy of a polymer-free drug coated (Biolimus-A9) stainless steel stent (SS-DCS) with 30 days of dual antiplatelet treatment (DAPT). In LEADERS FREE III, we studied a new cobalt-chromium thin-strut stent (CoCr-DCS) in HBR patients. METHODS: The CoCr-DCS shares all of the design features of the SS-DCS but has a CoCr stent platform with strut thickness of 84-88 µm. The primary safety endpoint was a composite of cardiac death, myocardial infarction (MI), and definite/probable stent thrombosis. The primary efficacy endpoint was clinically indicated target lesion revascularization. Outcomes were compared to those of LF (non-inferiority to SS-DCS for safety and superiority to SS-BMS for efficacy). Additional propensity-matched comparisons were performed to account for baseline differences. RESULTS: We recruited 401 HBR patients using identical criteria to the LF trial. At 1 year, the primary safety endpoint was reached by 31/401 (8.0%) of patients treated with the CoCr-DCS versus 35/401 (8.9%) for the propensity-matched cohort (HR: 0.89, [0.55-1.44], p < 0.001 for non-inferiority, 0.62 for superiority). The efficacy endpoint was reached by 16/401 (4.2%) of CoCr-DCS patients versus 41/401 (10.6%) in the propensity-matched cohort (HR: 0.4 [0.2:0.7]) (p = 0.007 for superiority). There was no statistical difference between CoCr-DCS and SS-DCS in terms of efficacy (HR: 1.46 [0.68-3.15], p = 0.33). CONCLUSIONS: The new thin-strut CoCr-DCS proved non-inferior to the SS-DCS for safety, and superior to the BMS for efficacy in HBR patients treated with 30 days of DAPT.

Validation of high bleeding risk criteria and definition as proposed by the academic research consortium for high bleeding risk.

AIMS: To validate the set of clinical and biochemical criteria proposed by consensus by the Academic Research Consortium (ARC) for High Bleeding Risk (HBR) for the identification of HBR patients. These criteria were categorized into major and minor, if expected to carry in isolation, respectively, ≥4% and <4% Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding risk within 1-year after percutaneous coronary intervention (PCI). High bleeding risk patients are those meeting at least 1 major or 2 minor criteria. METHODS AND RESULTS: All patients undergoing PCI at Bern University Hospital, between February 2009 and September 2018 were prospectively entered into the Bern PCI Registry (NCT02241291). Age, haemoglobin, platelet count, creatinine, and use of oral anticoagulation were prospectively collected, while the remaining HBR criteria except for planned surgery were retrospectively adjudicated. A total of 16 580 participants with complete ARC-HBR criteria were included. After assigning 1 point to each major and 0.5 point to each minor criterion, we observed for every 0.5 score increase a step-wise augmentation of BARC 3 or 5 bleeding rates at 1 year ranging from 1.90% among patients fulfilling no criterion, through 4.01%, 5.98%, 7.42%, 8.60%, 12.21%, 12.29%, and 17.64%. All major and five out of six minor criteria, conferred in isolation a risk for BARC 3 or 5 bleeding at 1 year exceeding 4% at the upper limit of the 95% confidence intervals. CONCLUSION: All major and the majority of minor ARC-HBR criteria identify in isolation patients at HBR.

Defining High Bleeding Risk in Patients Undergoing Percutaneous Coronary Intervention.

Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.

Drug-eluting or bare-metal stents for percutaneous coronary intervention: a systematic review and individual patient data meta-analysis of randomised clinical trials.

BACKGROUND: New-generation drug-eluting stents (DES) have mostly been investigated in head-to-head non-inferiority trials against early-generation DES and have typically shown similar efficacy and superior safety. How the safety profile of new-generation DES compares with that of bare-metal stents (BMS) is less clear. METHODS: We did an individual patient data meta-analysis of randomised clinical trials to compare outcomes after implantation of new-generation DES or BMS among patients undergoing percutaneous coronary intervention. The primary outcome was the composite of cardiac death or myocardial infarction. Data were pooled in a one-stage random-effects meta-analysis and examined at maximum follow-up and a 1-year landmark. Risk estimates are reported as hazard ratios (HRs) with 95% CIs. This study is registered in PROSPERO, number CRD42017060520. FINDINGS: We obtained individual data for 26 616 patients in 20 randomised trials. Mean follow-up was 3·2 (SD 1·8) years. The risk of the primary outcome was reduced in DES recipients compared with BMS recipients (HR 0·84, 95% CI 0·78-0·90, p<0·001) owing to a reduced risk of myocardial infarction (0·79, 0·71-0·88, p<0·001) and a possible slight but non-significant cardiac mortality benefit (0·89, 0·78-1·01, p=0·075). All-cause death was unaffected (HR with DES 0·96, 95% CI 0·88-1·05, p=0·358), but risk was lowered for definite stent thrombosis (0·63, 0·50-0·80, p<0·001) and target-vessel revascularisation (0·55, 0·50-0·60, p<0·001). We saw a time-dependent treatment effect, with DES being associated with lower risk of the primary outcome than BMS up to 1 year after placement. While the effect was maintained in the longer term, there was no further divergence from BMS after 1 year. INTERPRETATION: The performance of new-generation DES in the first year after implantation means that BMS should no longer be considered the gold standard for safety. Further development of DES technology should target improvements in clinical outcomes beyond 1 year. FUNDING: Bern University Hospital.

Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk.

Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.

Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk.

BACKGROUND: Patients at high risk for bleeding who undergo percutaneous coronary intervention (PCI) often receive bare-metal stents followed by 1 month of dual antiplatelet therapy. We studied a polymer-free and carrier-free drug-coated stent that transfers umirolimus (also known as biolimus A9), a highly lipophilic sirolimus analogue, into the vessel wall over a period of 1 month. METHODS: In a randomized, double-blind trial, we compared the drug-coated stent with a very similar bare-metal stent in patients with a high risk of bleeding who underwent PCI. All patients received 1 month of dual antiplatelet therapy. The primary safety end point, tested for both noninferiority and superiority, was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy end point was clinically driven target-lesion revascularization. RESULTS: We enrolled 2466 patients. At 390 days, the primary safety end point had occurred in 112 patients (9.4%) in the drug-coated-stent group and in 154 patients (12.9%) in the bare-metal-stent group (risk difference, -3.6 percentage points; 95% confidence interval [CI], -6.1 to -1.0; hazard ratio, 0.71; 95% CI, 0.56 to 0.91; P<0.001 for noninferiority and P=0.005 for superiority). During the same time period, clinically driven target-lesion revascularization was needed in 59 patients (5.1%) in the drug-coated-stent group and in 113 patients (9.8%) in the bare-metal-stent group (risk difference, -4.8 percentage points; 95% CI, -6.9 to -2.6; hazard ratio, 0.50; 95% CI, 0.37 to 0.69; P<0.001). CONCLUSIONS: Among patients at high risk for bleeding who underwent PCI, a polymer-free umirolimus-coated stent was superior to a bare-metal stent with respect to the primary safety and efficacy end points when used with a 1-month course of dual antiplatelet therapy. (Funded by Biosensors Europe; LEADERS FREE ClinicalTrials.gov number, NCT01623180.).

Biolimus-A9 polymer-free coated stent in high bleeding risk patients with acute coronary syndrome: a Leaders Free ACS sub-study.

Aims: Although a true clinical challenge, high bleeding risk patients with an acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) have never been specifically studied. Leaders Free ACS, a pre-specified Leaders Free sub-study, determined efficacy, and safety of a combination of 1-month dual anti-platelet therapy (DAPT) with implantation of either a polymer-free Biolimus-A9-coated stent (BA9-DCS) or a bare-metal stent (BMS) in these patients. Methods and results: Leaders Free included 2466 patients undergoing PCI who had at least 1 of 13 pre-defined factors for an increased bleeding risk. Of these, 659 ACS patients were included in this analysis (BA9-DCS 330, BMS 329). At 12-month follow-up, treatment with the BA9-DCS was more effective (clinically driven target-lesion revascularization 3.9 vs. 9.0%, P = 0.009) and safer (cumulative incidence of cardiac death, myocardial infarction, or definite or probable stent thrombosis 9.3 vs. 18.5%, P = 0.001), driven by significantly lower rates of cardiac mortality (3.4 vs. 6.9%, P = 0.049) and myocardial infarction (6.9 vs. 13.8%, P = 0.005). Conclusion: We believe that the results of this sub-analysis from the Leaders Free trial are likely to significantly impact clinical practice for high bleeding risk patients presenting with an ACS: the use of a BMS can, in our view, no longer be recommended, and, given the paucity of available data for second-generation DES with shortened DAPT in these patients, the BA9-DCS should currently be considered as the device with the strongest evidence to support its use for this indication.

Left bundle-branch block in patients with acute myocardial infarction: Presentation, treatment, and trends in outcome from 1997 to 2016 in routine clinical practice.

BACKGROUND: Whether patients with acute myocardial infarction presenting with new or presumed new left bundle-branch block (LBBB) should be treated in the same way as those presenting with ST-elevation (STE) is still a matter of debate. METHODS: Data from 28,358 patients enrolled in AMIS Plus from 1997 to 2016 were analyzed to evaluate differences in treatment and outcome of patients presenting with LBBB (n=2295) or STE (n=26,090) on their initial electrocardiogram using descriptive statistics and multivariate logistic regression. RESULTS: LBBB patients were older (75.0 vs 64.3 years, P<.001) with a greater burden of risk factors and comorbidities. They were admitted 80 minutes later and more frequently in Killip III/IV (20% vs 7%, P<.001). Even after adjustment for age and gender, LBBB patients were less likely to receive aspirin (odds ratio [OR] 0.40, 95% CI 0.34-0.47), P2Y12 inhibitors (OR 0.50, 95% CI 0.45-0.54), ß-blockers (OR 0.81, 95% CI 0.76-0.89), and statins (OR 0.70, 95% CI 0.63-0.76) or undergo percutaneous coronary interventions (OR 0.38, 95% CI 0.35-0.42). Crude in-hospital mortality of patients with LBBB was 16.2% versus 6.5% for patients with STE, but adjusted OR was 1.07 (95% CI 0.93-1.24). Mortality of LBBB patients decreased from 22.6% in 1997-2001 to 11.9% in 2012-2016. CONCLUSIONS: Acute myocardial infarction patients with new or presumed new LBBB presence are at high risk of morbidity and mortality. They were treated less aggressively, and although mortality has halved during the last 20 years, there may be room for further improvement. Additional studies are needed to better identify those patients with LBBB who may maximally benefit from an early invasive treatment strategy.

One-year clinical outcomes after sirolimus-eluting coronary stent implantation in diabetics enrolled in the worldwide e-SELECT registry.

BACKGROUND: Diabetes mellitus has worse outcome after percutaneous coronary intervention. AIM: We assessed stent thrombosis (ST), major adverse cardiac events (MACE), and major bleeding rates at 1 year after implantation of sirolimus-eluting stents (SES) in patients with diabetes mellitus in a large multicenter registry. METHODS: From May 2006 to April 2008, 15,147 unselected consecutive patients were enrolled at 320 centers in 56 countries in a prospective, observational registry after implantation of ≥ 1 SES. Source data were verified in 20% randomly chosen patients at > 100 sites. Adverse events were adjudicated by an independent Clinical Event Committee. RESULTS: Complete follow-up at 1 year was obtained in 13,693 (92%) patients, 4,577 (30%) of whom were diabetics. Within diabetics, 1,238 (9%) were insulin-treated diabetics (ITD). Diabetics were older (64 vs. 62 years, P < 0.001), with higher incidence of major coronary risk factors, co-morbidities, and triple-vessel coronary artery disease. Coronary lesions had smaller reference vessel diameter (2.88 ± 0.46 vs. 2.93 ± 0.45 mm, P < 0.001) and were more often heavily calcified (26.1% vs. 22.6%, P < 0.001). At 1 year, diabetics had higher MACE rate (6.8% vs. 3.9%, P < 0.001) driven by ITD (10.6% vs. 5.5%, P < 0.001). Finally, diabetics had significant increase in ST (1.7% vs. 0.7%, P < 0.001), principally owing to ITD (3.4% vs. 1.1%, P < 0.001). There was an overall low risk of major bleeding during follow-up, without significant difference among subgroups. CONCLUSIONS: In the e-SELECT registry, diabetics represented 30% of patients undergoing SES implantation and had significantly more co-morbidities and complex coronary lesions. Although 1-year follow-up documented good overall outcome in diabetics, higher ST and MACE rates were observed, mainly driven by ITD. © 2015 Wiley Periodicals, Inc.

Outcomes following implantation of the Biolimus A9-eluting BioMatrix coronary stent: Primary analysis of the e-BioMatrix registry.

OBJECTIVES: To assess the safety and efficacy of Biolimus A9-eluting stents (BES, BioMatrix™ and BioMatrix Flex™) in routine clinical practice. BACKGROUND: The LEADERS randomized trial has documented equivalent efficacy and superior safety of the BES when compared to a first generation Sirolimus-eluting Cypher(TM) stent. METHODS: 5,472 patients from 57 centers, treated with BES, were enrolled in an international multicenter registry and followed clinically up to 2 years. RESULTS: Mean patient age was 63.2 ± 11 years, 24% of patients had diabetes, and 49.8% presented with an acute coronary syndrome. 99.3% of patients were discharged on dual antiplatelet therapy (DAPT), 83.3% remained on DAPT at 1 year and 30.6% at 2 years. The incidence of the composite primary end point [major adverse cardiac events (MACE) at 12 months] was 4.5% [cardiac death 0.9%, myocardial infarction 1.7%, clinically indicated target vessel revascularization (ci-TVR) 2.8%]. MACE incidence was 6.8% at 24 months (cardiac death 1.5%, myocardial infarction 2.4%, ci-TVR 4.3%). At 12 months, 32 patients (0.6%) had suffered at least one definite or probable stent thrombosis (ST), and 91 patients (1.7%) a major bleed (MB). Nine patients with ST (27.3%) and 7 patients with a MB (7.7%) died during the first year after the index procedure. Between 12 and 24 months after implantation, there were 18 (0.4%) additional MB and 8 (0.2%) additional ST. CONCLUSIONS: This large international cohort documents a low 12 and 24 months MACE incidence and a very low ST incidence in an unselected patient population undergoing BES implantation. The results are in keeping with those of the randomized controlled LEADERS trial. Even though ST with this stent was a rare event, it was still associated with significant mortality. MB remains a problem, and warrants improved tailoring of DAPT in recipients of drug eluting stents.

Risk Burden of Cancer in Patients Treated With Abbreviated Dual Antiplatelet Therapy After PCI: Analysis of Multicenter Controlled High-Bleeding Risk Trials.

BACKGROUND: Oncological patients with coronary artery disease face an elevated risk of hemorrhagic and ischemic events following percutaneous coronary intervention. Despite medical guidelines recommending minimal dual antiplatelet therapy (DAPT) duration for patients with cancer, dedicated data on abbreviated DAPT in this population is lacking. This study aims to evaluate the occurrence of ischemic and hemorrhagic events in patients with cancer compared with other high-bleeding risk individuals. METHODS: Patient-level data from 4 high-bleeding risk coronary drug-eluting stent studies (ONYX One, LEADERS FREE, LEADERS FREE II, and SENIOR trials) treated with short DAPT were analyzed. The comparison focused on patients with high-bleeding risk with and without cancer, assessing 1-year rates of net adverse clinical events (all-cause death, myocardial infarction, stroke, revascularization, and Bleeding Academic Research Consortium [BARC] types 3 to 5 bleeding) and major adverse clinical events (all-cause death, myocardial infarction, stroke). RESULTS: A total of 5232 patients were included, of whom 574 individuals had cancer, and 4658 were at high-bleeding risk without previous cancer. Despite being younger with fewer risk factors, patients with cancer had higher net adverse clinical event (HR, 1.25; P=0.01) and major adverse clinical event (HR, 1.26; P=0.02), primarily driven by all-cause mortality and major bleeding (BARC 3-5), but not myocardial infarction, stroke, stent thrombosis, or repeat revascularization. Cancer was an independent predictor of net adverse clinical event (P=0.005), major adverse clinical event (P=0.01), and major bleeding (P=0.03). CONCLUSIONS: The present work is the first report on abbreviated DAPT dedicated to patients with cancer. Cancer is a major marker of adverse outcomes and these events had high lethality. Despite short DAPT, patients with cancer experienced higher rates of major bleeding compared with patients without cancer with high-bleeding risk, which occurred mainly after DAPT discontinuation. These findings reinforce the need for a more detailed and individualized stratification of those patients. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03344653, NCT01623180, NCT02843633, NCT0284.

Clinical outcomes with thin versus thick strut polymer-free biolimus-coated stents at 3 years.

BACKGROUND: For high bleeding-risk patients (HBR) undergoing percutaneous coronary intervention (PCI), the LEADERS FREE (LF) and LEADERS FREE II (LF II) trials established the safety and efficacy of a stainless steel polymer-free biolimus-coated stent (SS-BCS) with 30 days of dual antiplatelet treatment (DAPT). The LEADERS FREE III (LF III) trial investigated clinical outcomes after PCI with the next-generation cobalt-chromium thin-strut polymer-free biolimus-coated stent (CoCr-BCS) in HBR patients. AIMS: To report the final 3-year results of the LF III trial and compare them to LF II. METHODS: LF III was a prospective, multicentre, open-label single-arm study to evaluate the safety and efficacy of the CoCr-BCS stent. The primary safety endpoint was the composite of cardiac death (CD), myocardial infarction(MI) or definite/probable stent thrombosis (ST). The primary efficacy endpoint was clinically driven target lesion revascularisation (cd-TLR). We performed a propensity-matched comparison to the 3-year outcomes of LF II. RESULTS: After 3 years, CD/MI/ST had occurred in 57 patients (15%, 95% CI 11.8% to 19%) and cd-TLR in 23 (6.2%, 95% CI 4.1% to 9.2%) patients. In a propensity-matched comparison of patients treated with the CoCr-BCS versus the SS-BCS, there were similar rates of CD (6.6% vs 7.8%, p=0.50), MI (7.1% vs 8.3%, p=0.47) and definite/probable ST (1.1% vs 2%, HR 0.56, 95% CI 0.16 to 1.93, p=0.35). The rates of cd-TLR were 5.3% with CoCr-BCS versus 9.8% with SS-BCS (HR 0.54, 95% CI 0.31 to 0.96, p=0.03). CONCLUSION: LF III confirms the long-term safety and efficacy of the CoCr-BCS in HBR patients treated with 1 month of DAPT. TRIAL REGISTRATION NUMBER: NCT02843633, NCT03118895.

Rationale and design of the LEADERS FREE trial: A randomized double-blind comparison of the BioFreedom drug-coated stent vs the Gazelle bare metal stent in patients at high bleeding risk using a short (1 month) course of dual antiplatelet therapy.

BACKGROUND AND RATIONALE: Major bleeding is a powerful predictor of morbidity and mortality after percutaneous coronary intervention (PCI). To avoid prolonged dual antiplatelet therapy (DAPT), current guidelines recommend using a bare metal stent when PCI is indicated to treat patients at high risk of bleeding. The Biolimus A9-coated BioFreedom is a new stainless steel drug-coated stent devoid of polymer and has been shown to be associated with a low median late-loss of 0.17 mm at 12 months of follow-up. In an animal model, 98% of the drug has diffused into the vessel wall at 1 month. It is therefore reasonable to consider that such a device may have a potential safety advantage, and a lesser dependence on prolonged DAPT than a polymer-coated drug-eluting stent. TRIAL DESIGN: A total of 2456 patients considered at high risk of bleeding will be randomized in a double-blind fashion to the BioFreedom drug-coated stent or to a control arm (Gazelle bare metal stent). Both groups will be treated with DAPT during 1 month only, followed by long-term aspirin alone. At 1-year follow-up, the primary safety endpoint (a composite of cardiac death, myocardial infarction and stent thrombosis) will be assessed by a non-inferiority analysis, and the primary efficacy endpoint (clinically driven target lesion revascularization) by a superiority analysis. CONCLUSIONS: This trial should help better characterize a neglected subset of PCI patients and quantify both their thrombotic and bleeding risks. It has the potential to decrease the need for target lesion revascularization in patients unable to tolerate a prolonged course of DAPT and will assess the shortest DAPT course ever used with an active stent.

One-year outcome of small-vessel disease treated with sirolimus-eluting stents: a subgroup analysis of the e-SELECT registry.

OBJECTIVES: To investigate the characteristics and one-year outcomes following sirolimus-eluting CYPHER Select Plus stent (SES) implantation in small (SmVD) and non-small vessel disease (NSmVD) in the international e-SELECT registry. BACKGROUND: Large-scale registry data are lacking on DES outcomes in SmVD treatment. METHODS: There were 4,700 SmVD (at least one vessel with estimated reference vessel diameter [RVD] < 2.5 mm, excluding 283 patients with unknown RVD vessels) and 10,139 NSmVD only patients. RESULTS: The SmVD population was older, with more women, diabetics, and vessels treated, higher mean Charlson Comorbidity Index score (CCI), shorter lesions, and less STEMI presentation. The 1-year stent thrombosis (ST) rate (primary end-point), was significantly higher (1.3% vs. 0.7%) in SmVD versus NSmVD, mainly driven by early events. One-year major adverse cardiac event (MACE), myocardial infarction (MI), and clinically indicated target-lesion revascularization (TLR) rates were significantly higher in SmVD although death and major bleeding rates were similar in both groups. Complication rates were similar between pure (3,188 patients; only RVD < 2.5 mm) and mixed (1,795 patients; some RVD < 2.5 mm or unknown RVD) SmVD. Multivariate predictors for 1-year MACE in SmVD included saphenous vein graft or bifurcation lesions, major bleeding, any antiplatelet therapy discontinuation within 1 month, age, number of stents implanted, CCI, acute coronary syndrome, and insulin-dependent diabetes mellitus. CONCLUSION: SES implantation for SmVD occurs more frequently in women, diabetics, and those with multivessel disease and comorbidities. One-year ST, MACE, MI, and clinically indicated TLR rates are higher, although low overall, in SmVD or mixed SmVD patients while death rates are similar to NSmVD.

One-year clinical outcomes after sirolimus-eluting coronary stent implantation for acute myocardial infarction in the worldwide e-SELECT registry.

BACKGROUND: The aim was to ascertain the 1-year clinical outcomes of 1,234 patients who underwent implantations of sirolimus-eluting stents (SES) for acute myocardial infarction (MI) in the multinational e-SELECT registry. METHODS: Fifteen thousand and one hundred and forty-seven patients treated with SES were entered in the e-SELECT registry, of whom 1,234 presented within <24 hours of onset of acute MI. RESULTS: At 1 year, the rates of major adverse cardiac events (MACE) (5.5% vs. 4.8%; P = 0.28) were similarly low in the acute and no acute MI groups. The rates of definite/probable stent thrombosis (ST) were higher in the acute MI group (2.1%vs; 0.88%, P < 0.001). ST was a strong independent predictor of death at 1 year (HR 13.4; 95% CI 5.0, 36.0; P < 0.001) and MI (HR 58.9; 95% CI 26.9, 129.1; P < 0.001). Dual antiplatelet therapy (DAPT) compliance at 6 months was 96.0% in the acute MI versus 94.5% in the no acute MI group (P = 0.03). CONCLUSION: In selected patients presenting within <24 hours of acute MI onset and highly compliant with DAPT, SES implantation was associated with similar rates of MACE, though higher rates of ST, as compared to no acute MI patients.

Characteristics and Outcome in Acute Coronary Syndrome Patients with and without Established Modifiable Cardiovascular Risk Factors: Insights from the Nationwide AMIS Plus Registry 1997-2010.

OBJECTIVES: Little is known about patients without known modifiable risk factors presenting initially with acute coronary syndrome (ACS). This study assessed baseline characteristics and outcomes of ACS patients with and without the known modifiable risk factors arterial hypertension, dyslipidemia, obesity, smoking or diabetes. METHODS: All ACS patients enrolled in the AMIS Plus Registry between 1997 and 2010 were analyzed until hospital discharge; a subgroup was re-assessed at the 1-year follow-up. Outcome measures were in-hospital mortality and major adverse cardiac or cerebrovascular events (MACCE) defined as a composite outcome of mortality, re-infarction and cerebrovascular events. RESULTS: Of 33,306 patients, 2,125 (6.4%) had none of these modifiable risk factors. They were older (males), had less moderate or severe comorbidities and were more frequently in Killip class I on admission. Treatment of ACS patients with or without modifiable risk factors was similar with regard to interventional therapies and use of antiplatelet agents. In-hospital mortality was lower in patients without modifiable risk factors but in-hospital MACCE and 1-year survival was similar. CONCLUSION: Lack of modifiable risk factors was an independent predictor of lower in-hospital mortality but not of MACCE in patients who presented with ACS.

Stents and antiplatelet therapy.

Coronary stents are used during the majority of percutaneous coronary interventions. When compared to medical therapy, they have been shown to decrease mortality for patients with acute coronary syndromes, and to improve symptom control in patients with stable angina. Their use, however, may be complicated by stent thrombosis (ST), a potentially fatal event. Early ST, which occurs during the first month following device implantation, is usually linked to procedural factors, with similar frequencies for bare metal stents and drug-eluting stents (DES). Late and very late (between 1 month and 1 year, respectively, and >1 year after the procedure) ST, which appear to be more frequent with DES, are due to factors such as incomplete stent apposition, delayed or dysfunctional endothelialization, and chronic inflammation. Furthermore, discontinuation of antiplatelet therapy (which includes the association of aspirin and thienopyridines) or resistance to these molecules may also lead to ST. New stent designs as well as the use of more potent antiplatelet therapies should contribute to reducing the incidence of ST in the future.