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Current guidelines recommend potent platelet inhibition with ticagrelor or prasugrel in patients after an acute coronary syndrome. However, data about optimal platelet inhibition in older patients are scarce. We aimed to investigate the safety and efficacy of clopidogrel compared with ticagrelor or prasugrel in older patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). We did the open-label, randomised controlled POPular AGE trial in 12 sites (ten hospitals and two university hospitals) in the Netherlands. Patients aged 70 years or older with NSTE-ACS were enrolled and randomly assigned in a 1:1 ratio using an internet-based randomisation procedure with block sizes of six to receive a loading dose of clopidogrel 300 mg or 600 mg, or ticagrelor 180 mg or prasugrel 60 mg, and then a maintenance dose for the duration of 12 months (clopidogrel 75 mg once daily, ticagrelor 90 mg twice daily, or prasugrel 10 mg once daily) on top of standard care. Patient and treating physicians were aware of the allocated treatment strategy, but the outcome assessors were masked to treatment allocation. Primary bleeding outcome consisted of PLATelet inhibition and patient Outcomes (PLATO; major or minor bleeding [superiority hypothesis]). Co-primary net clinical benefit outcome consisted of all-cause death, myocardial infarction, stroke, PLATO major and minor bleeding (non-inferiority hypothesis, margin of 2%). Follow-up duration was 12 months. Analyses were done on intention-to-treat basis. This trial is registered with the Netherlands Trial Register (NL3804), ClinicalTrials.gov (NCT02317198), and EudraCT (2013–001403–37). Between June 10, 2013, and Oct 17, 2018, 1002 patients were randomly assigned to clopidogrel (n=500) or ticagrelor or prasugrel (n=502). Because 475 (95%) patients received ticagrelor in the ticagrelor or prasugrel group, we will refer to this group as the ticagrelor group. Premature discontinuation of the study drug occurred in 238 (47%) of 502 ticagrelor group patients randomly assigned to ticagrelor, and in 112 (22%) of 500 patients randomly assigned to clopidogrel. Primary bleeding outcome was significantly lower in the clopidogrel group (88 [18%] of 500 patients) than in the ticagrelor group (118 [24%] of 502; hazard ratio 0·71, 95% CI 0·54 to 0·94; p=0·02 for superiority). Co-primary net clinical benefit outcome was non-inferior for the use of clopidogrel (139 [28%]) versus ticagrelor (161 [32%]; absolute risk difference −4%, 95% CI −10·0 to 1·4; p=0·03 for non-inferiority). The most important reasons for discontinuation were occurrence of bleeding (n=38), dyspnoea (n=40), and the need for treatment with oral anticoagulation (n=35). In patients aged 70 years or older presenting with NSTE-ACS, clopidogrel is a favourable alternative to ticagrelor, because it leads to fewer bleeding events without an increase in the combined endpoint of all-cause death, myocardial infarction, stroke, and bleeding. Clopidogrel could be an alternative P2Y12 inhibitor especially for elderly patients with a higher bleeding risk. ZonMw.

The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with second-generation drug eluting stents (DESs) is unclear. Because prolonged DAPT is associated with higher bleeding risk and health care costs, establishing optimal DAPT duration is of paramount importance. No other randomized controlled trials have evaluated the safety of shorter DAPT duration in ST-elevation myocardial infarction (STEMI) patients treated with second-generation DESs and latest P2Y12 platelet receptor inhibitors. Six months of DAPT after Resolute Integrity stent implantation in STEMI patients is not inferior to 12 months of DAPT in clinical outcomes. The Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation In ST-elevation Myocardial Infarction (DAPT-STEMI) trial is a randomized, multicenter, international, open-label trial designed to examine the safety (noninferiority) of 6-month DAPT after Resolute Integrity stent implantation in STEMI patients compared with 12-month DAPT. Event-free patients on DAPT at 6month will be randomized (1:1 fashion) between single (aspirin only) versus DAPT for an additional 6 months and followed until 2 years after primary percutaneous coronary intervention. The primary end point is a patient-oriented composite endpoint of all-cause mortality, any myocardial infarction, any revascularization, stroke, and major bleeding (net adverse clinical events [NACE]) at 18 months after randomization. To achieve a power of 85% for a noninferiority limit of 1.66, a total of 1100 enrolled patients are required. The DAPT-STEMI trial aims to assess in STEMI patients treated with second-generation DESs whether discontinuation of DAPT after 6 months of event-free survival is noninferior to routine 12-month DAPT.

In 2014, based on new study results,3,4 European guidelines first recommended the use of new-generation drug-eluting stents rather than bare-metal stents in STEMI.5 Up to 30% of participants in recent allcomer trials assessing the new-generation biodegradable polymer sirolimus-eluting stent (Orsiro) were treated for STEMI.6–9 Within STEMI subgroups, only the BIOSCIENCE trial found a significant between-stent difference favouring biodegradable polymer sirolimus-eluting stents.7,10 In The Lancet, Juan Iglesias and colleagues11 report the 1-year outcomes of the BIOSTEMI trial, which is, to our knowledge, the first dedicated randomised trial to compare biodegradable polymer sirolimus-eluting stents with durable polymer everolimus-eluting stents (Xience) in patients with STEMI. In the BIOSCIENCE trial, the significantly lower target lesion failure rate in biodegradable polymer sirolimus-eluting stents (3% vs 9% in the durable polymer everolimus-eluting stent group) was mainly driven by numerical differences in the safety endpoints of cardiac death (2% in the biodegradable polymer sirolimus-eluting stent group vs 5% in the durable polymer everolimus-eluting stent group) and target vessel myocardial infarction (1% in the biodegradable polymer sirolimus-eluting stent group vs 3% in the durable polymer everolimus-eluting stent group).10 From a pathophysiological point of view, it makes sense to expect a lower target lesion revascularisation risk in culprit vessels of STEMI, as allcomer studies suggest.7,10,13 Myocardial scarring reduces the subtended myocardial volume. [...]the same degree of (recurrent) lumen narrowing that leads to angina in patients without previous STEMI might remain unnoticed after STEMI because of the smaller amount of viable myocardium. [...]showing superiority of biodegradable polymer sirolimus-eluting stents in reducing target lesion revascularisation is more difficult in a population with STEMI.

AbstractObjectiveTo show that limiting dual antiplatelet therapy (DAPT) to six months in patients with event-free ST-elevation myocardial infarction (STEMI) results in a non-inferior clinical outcome versus DAPT for 12 months.DesignProspective, randomised, multicentre, non-inferiority trial.SettingPatients with STEMI treated with primary percutaneous coronary intervention (PCI) and second generation zotarolimus-eluting stent.ParticipantsPatients with STEMI aged 18 to 85 that underwent a primary PCI with the implantation of second generation drug-eluting stents were enrolled in the trial. Patients that were event-free at six months after primary PCI were randomised at this time point.InterventionsPatients that were taking DAPT and were event-free at six months were randomised 1:1 to single antiplatelet therapy (SAPT) (ie, aspirin only) or to DAPT for an additional six months. All patients that were randomised were then followed for another 18 months (ie, 24 months after the primary PCI).Main outcome measuresThe primary endpoint was a composite of all cause mortality, any myocardial infarction, any revascularisation, stroke, and thrombolysis in myocardial infarction major bleeding at 18 months after randomisation.ResultsA total of 1100 patients were enrolled in the trial between 19 December 2011 and 30 June 2015. 870 were randomised: 432 to SAPT versus 438 to DAPT. The primary endpoint occurred in 4.8% of patients receiving SAPT versus 6.6% of patients receiving DAPT (hazard ratio 0.73, 95% confidence interval 0.41 to 1.27, P=0.26). Non-inferiority was met (P=0.004 for non-inferiority), as the upper 95% confidence interval of 1.27 was smaller than the prespecified non-inferiority margin of 1.66.ConclusionsDAPT to six months was non-inferior to DAPT for 12 months in patients with event-free STEMI at six months after primary PCI with second generation drug-eluting stents.Trial registrationClinicaltrials.gov NCT01459627.

Absorbable scaffolds were designed to overcome the limitations of conventional, non-absorbable metal-based drug-eluting stents. So far, only polymeric absorbable scaffolds are commercially available. We aimed to assess the safety and performance of a novel second-generation drug-eluting absorbable metal scaffold (DREAMS 2G) in patients with de-novo coronary artery lesions. We did this prospective, multicentre, non-randomised, first-in-man trial at 13 percutaneous coronary intervention centres in Belgium, Brazil, Denmark, Germany, Singapore, Spain, Switzerland, and the Netherlands. Eligible patients had stable or unstable angina or documented silent ischaemia, and a maximum of two de-novo lesions with a reference vessel diameter between 2·2 mm and 3·7 mm. Clinical follow-up was scheduled at months 1, 6, 12, 24, and 36. Patients were scheduled for angiographic follow-up at 6 months, and a subgroup of patients was scheduled for intravascular ultrasound, optical coherence tomography, and vasomotion assessment. All patients were recommended to take dual antiplatelet treatment for at least 6 months. The primary endpoint was in-segment late lumen loss at 6 months. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01960504. Between Oct 8, 2013, and May 22, 2015, we enrolled 123 patients with 123 coronary target lesions. At 6 months, mean in-segment late lumen loss was 0·27 mm (SD 0·37), and angiographically discernable vasomotion was documented in 20 (80%) of 25 patients. Intravascular ultrasound assessments showed a preservation of the scaffold area (mean 6·24 mm2 [SD 1·15] post-procedure vs 6·21 mm2 [1·22] at 6 months) with a low mean neointimal area (0·08 mm2 [0·09]), and optical coherence tomography did not detect any intraluminal mass. Target lesion failure occurred in four (3%) patients: one (<1%) patient died from cardiac death, one (<1%) patient had periprocedural myocardial infarction, and two (2%) patients needed clinically driven target lesion revascularisation. No definite or probable scaffold thrombosis was observed. Our findings show that implantation of the DREAMS 2G device in de-novo coronary lesions is feasible, with favourable safety and performance outcomes at 6 months. This novel absorbable metal scaffold could be an alternative to absorbable polymeric scaffolds for treatment of obstructive coronary disease. Biotronik AG.

During the past decade, many patients had zotarolimus-eluting stents implanted, which had circular shape cobalt–chromium struts with limited radiographic visibility. The Resolute Onyx stent was developed to improve visibility while reducing strut thickness, which was achieved by using a novel composite wire with a dense platinum–iridium core and an outer cobalt–chromium layer. We did the first randomised clinical trial to assess the safety and efficacy of this often-used stent compared with the Orsiro stent, which consists of ultrathin cobalt–chromium struts. We did an investigator-initiated, assessor-blinded and patient-blinded, randomised non-inferiority trial in an allcomers population at seven independently monitored centres in Belgium, Israel, and the Netherlands. Eligible participants were aged 18 years or older and required percutaneous coronary intervention with drug-eluting stents. After guide wire passage with or without predilation, members of the catheterisation laboratory team used web-based computer-generated allocation sequences to randomly assign patients (1:1) to either the Resolute Onyx or the Orsiro stent. Randomisation was stratified by sex and diabetes status. Patients and assessors were masked to allocated stents, but treating clinicians were not. The primary endpoint was target vessel failure at 1 year, a composite of cardiac death, target-vessel-related myocardial infarction, and target vessel revascularisation, and was assessed by intention to treat (non-inferiority margin 2·5%) on the basis of outcomes adjudicated by an independent event committee. This trial is registered with ClinicalTrials.gov, number NCT02508714. Between Oct 7, 2015, and Dec 23, 2016, 2516 patients were enrolled, 2488 of whom were included in the intention-to-treat analysis (28 withdrawals or screening failures). 1243 participants were assigned to the Resolute Onyx group, and 1245 to the Orsiro group. Overall, 1765 (70·9%) participants presented with acute coronary syndromes and 1275 (51·2%) had myocardial infarctions. 1-year follow-up was available for 2478 (99·6%) patients. The primary endpoint was met by 55 (4·5%) patients in the Resolute Onyx group and 58 (4·7%) in the Orsiro group. Non-inferiority of Resolute Onyx to Orsiro was thus established (absolute risk difference −0·2% [95% CI −1·9 to 1·4]; upper limit of the one-sided 95% CI 1·1%; pnon-inferiority=0·0005). Definite or probable stent thrombosis occurred in one (0·1%) participant in the Resolute Onyx group and nine (0·7%) in the Orsiro group (hazard ratio 0·11 [95% CI 0·01–0·87]; p=0·0112). The Resolute Onyx stent was non-inferior to Orsiro for a combined safety and efficacy endpoint at 1-year follow-up in allcomers. The low event rate in both groups suggests that both stents are safe, and the very low rate of stent thrombosis in the Resolute Onyx group warrants further clinical investigation. Biotronik and Medtronic.

Millions of patients with obstructive coronary artery disease worldwide are treated with metallic stents each year. Since the first stent implantation in a human in 1986, stents have undergone substantial refinements that have involved numerous innovations and extensive clinical research.1 Over three decades, various problems were faced and solved or minimised. [...]these studies included many patients with complex clinical characteristics (eg, acute myocardial infarction, diabetes, or multivessel disease) and target lesions (eg, with a total occlusion or thrombi). [...]the incidence of all-cause death was the only one of 20 outcome parameters to differ significantly between stents (14·1% in the biodegradable-polymer group vs 10·3% in the durable-polymer group; RR 1·36, 95% CI 1·06–1·75; p=0·017), driven by a difference between groups in the incidence of death secondary to different types of cancer.

Background/Aim: Current guidelines recommend transthoracic echocardiography (TTE) and ambulatory rhythm monitoring following ischemic stroke or transient ischemic attack (TIA) of undetermined cause for identifying cardioembolic sources (CES). Due to ongoing controversies about this routine strategy, we evaluated its yield in a real-world setting. Methods: In a tertiary medical center, we retrospectively evaluated consecutive patients with ischemic stroke or TIA of undetermined cause, who (after standard work-up) underwent TTE, ambulatory rhythm monitoring, or both. CES were classified as major if probably related to ischemic events and warranting a change of therapy. Results: Between January 2014 and December 2017, 674 patients had ischemic stroke or TIA of undetermined cause. Of all 484 patients (71.8%) who underwent TTE, 9 (1.9%) had a major CES. However, 7 of them had already been identified for cardiac evaluation due to new major electrocardiographic abnormalities or cardiac symptoms. Thus, only 2 patients (0.4%) truly benefitted from unselected TTE screening. Ambulatory rhythm monitoring was performed in 411 patients (61.0%) and revealed AF in 10 patients (2.4%). Conclusion: Detecting a major CES is essential because appropriate treatment lowers the risk of recurrent stroke. Nonetheless, in this real-world study that aimed at routine use of TTE and ambulatory rhythm monitoring in patients with ischemic stroke or TIA of undetermined cause, the prevalence of major CES was low. Most patients with major CES on TTE already had an indication for referral to a cardiologist, suggesting that major CES might also have been identified with a much more selective use of TTE.

•A novel Angio-iFR software showed excellent feasibility with short analysis times.•The angio-iFR analysis was robust with high interobserver reproducibility.•Per-vessel diagnostic performance of Angio-iFR did not reach the performance goal.•Current angio-derived FFR software did not reach the diagnostic accuracy previously reported. Angiography-derived fractional flow reserve (FFR) software has been developed using pressure wire based FFR as the reference, however most software requires 2 angiographic views ≥25 degrees apart limiting their clinical utility. This study aims to validate in a prospective multi-center registry the diagnostic performance of a novel angiography derived instantaneous wave-free ratio (Angio-iFR, Royal Philips, Amsterdam) with pressure wire-based iFR as reference. Coronary angiograms were obtained from patients with coronary artery lesions of between 40% and 90% severity and both iFR and FFR measurements. The pressure wire's position was documented during contrast injection in 2 angiographic views. Angio-iFR/FFR was computed at this exact position by independent corelab analysts blinded to physiological data. The primary end point was the sensitivity and specificity of the Angio-iFR compared to the corresponding invasively measured iFR values. The study was powered to meet prespecified performance goals for sensitivity (75%) and specificity (80%). A total of 441 patients were enrolled in 32 centers in Europe, Japan, and the United States. Paired Angio-iFR and wire-iFR were available in 398 vessels. The mean iFR was 0.90 (standard deviation: 0.11) with 31.9% of vessels having an iFR≤0.89. Angio-iFR software showed excellent feasibility (97%), and a median analysis time of 55 s. The per-vessel sensitivity and specificity of Angio-iFR was 77% (95% confidence interval [CI]: 69%-84%) and 49% (95% CI: 41%-54%) respectively, which fell below the performance goals. Angio-iFR did not achieve prespecified diagnostic performance against pressure wire-based iFR. Further software refinements are warranted. Radiographic Imaging Validation and EvALuation for Angio iFR (ReVEAL iFR), NCT0385750, https://clinicaltrials.gov/study/NCT03857503.

Knowledge about the changes in endothelial function after ST-elevation myocardial infarction (STEMI) is of substantial interest, but serial data are scarce. The aim of the present study was to noninvasively evaluate whether endothelial function, as assessed shortly after primary percutaneous coronary intervention (PPCI) for STEMI, may improve until 12-month follow-up. This prospective observational cohort study was performed in patients in the RESPONSE randomized trial who participated in a substudy and underwent noninvasive assessment of endothelial function at 1 (baseline), 6, and 12-month follow-up after treatment of a STEMI by PPCI. The reactive hyperemia peripheral artery tonometry (RH-PAT) method was used to assess endothelial function (higher RH-PAT index signifies better function). Of the 70 study participants, who were 57.4 ± 9.7 years of age, 55 (78.6%) were male and 9 (13%) had diabetes. The endothelial function deteriorated significantly during follow-up: the RH-PAT index at baseline, 6, and 12-month follow-up was 1.90 ± 0.58, 1.81 ± 0.57, and 1.69 ± 0.49, respectively (p = 0.04). Although patients were carefully treated in outpatient clinics and adequate pharmacological therapy was prescribed, we noted an increase in total cholesterol (p = 0.001), LDL cholesterol (p = 0.002), HbA1C (p = 0.054), and diastolic blood pressure (p = 0.047) However, multivariate analysis revealed that this increase in cardiovascular risk factors could not explain the observed deterioration in endothelial function. In patients with STEMI, we observed a significant deterioration in endothelial function during 12 months after PPCI that could not be explained by changes in the traditional cardiovascular risk profile.