In this trial, patients with patent foramen ovale and cryptogenic embolism were assigned to undergo closure with the use of a percutaneous device or to receive medical therapy. There was no ...significant difference in the rates of recurrent embolic events or death.
Paradoxical embolism by means of a patent foramen ovale has been blamed as a cause of stroke and other systemic ischemic events since the 19th century.
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The actual passage of a venous clot through a patent foramen ovale has been documented in a few cases and resulted in systemic embolic events such as ischemic stroke, transient ischemic attack (TIA),
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or myocardial infarction.
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Catheter-based closure of patent foramen ovale was introduced in 1992.
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Observational long-term data suggest that closure of patent foramen ovale in patients with a history of ischemic stroke may reduce the risk of recurrent stroke as compared . . .
Summary Stable coronary artery disease is the most common clinical manifestation of ischaemic heart disease and a leading cause of mortality worldwide. Myocardial revascularisation is a mainstay in ...the treatment of symptomatic patients or those with ischaemia-producing coronary lesions, and reduces ischaemia to a greater extent than medical treatment. Documentation of ischaemia and plaque burden is fundamental in the risk stratification of patients with stable coronary artery disease, and several invasive and non-invasive techniques are available (eg, fractional flow reserve or intravascular ultrasound) or being validated (eg, instantaneous wave-free ratio and optical coherence tomography). The use of new-generation drug-eluting stents and arterial conduits greatly improve clinical outcome in patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). PCI is feasible, safe, and effective in many patients with stable coronary artery disease who remain symptomatic despite medical treatment. In patients with multivessel and left main coronary artery disease, the decision between PCI or CABG is guided by the local Heart Team (team of different cardiovascular specialists, including non-invasive and invasive cardiologists, and cardiac surgeons), who carefully judge the possible benefits and risks inherent to PCI and CABG. In specific subsets, such as patients with diabetes and advanced, multivessel coronary artery disease, CABG remains the standard of care in view of improved protection against recurrent ischaemic adverse events.
Summary Background Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting ...bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. Methods A total of 14 963 patients treated with DAPT after coronary stenting—largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation—were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12–24 months) or short (3–6 months) treatment in relation to baseline bleeding risk. Findings The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61–0·85) in the derivation cohort, and 0·70 (0·65–0·74) in the PLATO trial validation cohort and 0·66 (0·61–0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (pinteraction =0·007), and exerted a significant ischaemic benefit only in this latter group. Interpretation The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration. Funding None.
Abstract
Aims
Owing to new evidence from randomized controlled trials (RCTs) in low-risk patients with severe aortic stenosis, we compared the collective safety and efficacy of transcatheter aortic ...valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the entire spectrum of surgical risk patients.
Methods and results
The meta-analysis is registered with PROSPERO (CRD42016037273). We identified RCTs comparing TAVI with SAVR in patients with severe aortic stenosis reporting at different follow-up periods. We extracted trial, patient, intervention, and outcome characteristics following predefined criteria. The primary outcome was all-cause mortality up to 2 years for the main analysis. Seven trials that randomly assigned 8020 participants to TAVI (4014 patients) and SAVR (4006 patients) were included. The combined mean STS score in the TAVI arm was 9.4%, 5.1%, and 2.0% for high-, intermediate-, and low surgical risk trials, respectively. Transcatheter aortic valve implantation was associated with a significant reduction of all-cause mortality compared to SAVR {hazard ratio HR 0.88 95% confidence interval (CI) 0.78–0.99, P = 0.030}; an effect that was consistent across the entire spectrum of surgical risk (P-for-interaction = 0.410) and irrespective of type of transcatheter heart valve (THV) system (P-for-interaction = 0.674). Transcatheter aortic valve implantation resulted in lower risk of strokes HR 0.81 (95% CI 0.68–0.98), P = 0.028. Surgical aortic valve replacement was associated with a lower risk of major vascular complications HR 1.99 (95% CI 1.34–2.93), P = 0.001 and permanent pacemaker implantations HR 2.27 (95% CI 1.47–3.64), P < 0.001 compared to TAVI.
Conclusion
Compared with SAVR, TAVI is associated with reduction in all-cause mortality and stroke up to 2 years irrespective of baseline surgical risk and type of THV system.
Summary Background Percutaneous coronary intervention (PCI) with drug-eluting stents is the standard of care for treatment of native coronary artery stenoses, but optimum treatment strategies for ...bare metal stent and drug-eluting stent in-stent restenosis (ISR) have not been established. We aimed to compare and rank percutaneous treatment strategies for ISR. Methods We did a network meta-analysis to synthesise both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library Central Register of Controlled Trials, and Embase for randomised controlled trials published up to Oct 31, 2014, of different PCI strategies for treatment of any type of coronary ISR. The primary outcome was percent diameter stenosis at angiographic follow-up. This study is registered with PROSPERO, number CRD42014014191. Findings We deemed 27 trials eligible, including 5923 patients, with follow-up ranging from 6 months to 60 months after the index intervention. Angiographic follow-up was available for 4975 (84%) of 5923 patients 6–12 months after the intervention. PCI with everolimus-eluting stents was the most effective treatment for percent diameter stenosis, with a difference of −9·0% (95% CI −15·8 to −2·2) versus drug-coated balloons (DCB), −9·4% (–17·4 to −1·4) versus sirolimus-eluting stents, −10·2% (–18·4 to −2·0) versus paclitaxel-eluting stents, −19·2% (–28·2 to −10·4) versus vascular brachytherapy, −23·4% (–36·2 to −10·8) versus bare metal stents, −24·2% (–32·2 to −16·4) versus balloon angioplasty, and −31·8% (–44·8 to −18·6) versus rotablation. DCB were ranked as the second most effective treatment, but without significant differences from sirolimus-eluting (–0·2% 95% CI −6·2 to 5·6) or paclitaxel-eluting (–1·2% –6·4 to 4·2) stents. Interpretation These findings suggest that two strategies should be considered for treatment of any type of coronary ISR: PCI with everolimus-eluting stents because of the best angiographic and clinical outcomes, and DCB because of its ability to provide favourable results without adding a new stent layer. Funding None.
In view of the currently available evidence from randomized trials, we aimed to compare the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve ...replacement (SAVR) across the spectrum of risk and in important subgroups.
Trials comparing TAVI vs. SAVR were identified through Medline, Embase, and Cochrane databases. The primary outcome was death from any cause at 2 years. We performed random-effects meta-analyses to combine the available evidence and to evaluate the effect in different subgroups. This systematic review and meta-analysis is registered with PROSPERO (CRD42016037273). We identified four eligible trials including 3806 participants, who were randomly assigned to undergo TAVI (n = 1898) or SAVR (n = 1908). For the primary outcome of death from any cause, TAVI when compared with SAVR was associated with a significant 13% relative risk reduction hazard ratio (95% CI): 0.87 (0.76-0.99); P = 0.038 with homogeneity across all trials irrespective of TAVI device (P
= 0.306) and baseline risk (P
= 0.610). In subgroup analyses, TAVI showed a robust survival benefit over SAVR for patients undergoing transfemoral access 0.80 (0.69-0.93); P = 0.004, but not transthoracic access 1.17 (0.88-1.56); P = 0.293 (P
= 0.024) and in female 0.68 (0.50-0.91); P = 0.010, but not male patients 0.99 (0.77-1.28); P = 0.952 (P
= 0.050). Secondary outcomes of kidney injury, new-onset atrial fibrillation, and major bleeding favoured TAVI, while major vascular complications, incidence of permanent pacemaker implantation, and paravalvular regurgitation favoured SAVR.
Compared with SAVR, TAVI is associated with a significant survival benefit throughout 2 years of follow-up. Importantly, this superiority is observed irrespective of the TAVI device across the spectrum of intermediate and high-risk patients, and is particularly pronounced among patients undergoing transfemoral TAVI and in females.
One month after the implantation of biodegradable-polymer sirolimus-eluting coronary stents, patients at high bleeding risk were randomly assigned to stop dual antiplatelet therapy or to continue it ...for at least 2 additional months. At 1 year, 1 month of DAPT was noninferior to the longer treatment for ischemic cardiovascular events and was superior for bleeding.
Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk ...(HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized.
This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT PREdicting bleeding Complications in patients undergoing stent Implantation and SubsequEnt Dual AntiPlatelet Therapy score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting.
Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT.
Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity.
Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT.
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The purpose of this study was to determine the effect of evolocumab on optical coherence tomography (OCT) measures of plaque composition.
The proprotein convertase subtilisin kexin type-9 inhibitor ...evolocumab produced coronary atheroma regression in statin-treated patients.
Patients with a non–ST-segment elevation myocardial infarction were treated with monthly evolocumab 420 mg (n = 80) or placebo (n = 81) for 52 weeks. Patients underwent serial OCT and intravascular ultrasound imaging within a matched arterial segment of a nonculprit vessel. The primary analysis determined the change in the minimum fibrous cap thickness and maximum lipid arc throughout the imaged arterial segment. Additional analyses determined changes in OCT features in lipid-rich plaque regions and plaque burden. Safety and tolerability were evaluated.
Among treated patients, (age 60.5 ± 9.6 years; 28.6% women; low-density lipoprotein cholesterol LDL-C, 141.3 ± 33.1 mg/dL), 135 had evaluable imaging at follow-up. The evolocumab group achieved lower LDL-C levels (28.1 vs 87.2 mg/dL; P < 0.001). The evolocumab group demonstrated a greater increase in minimum fibrous cap thickness (+42.7 vs +21.5 μm; P = 0.015) and decrease in maximum lipid arc (−57.5o vs. −31.4o; P = 0.04) and macrophage index (−3.17 vs −1.45 mm; P = 0.04) throughout the arterial segment. Similar benefits of evolocumab were observed in lipid-rich plaque regions. Greater regression of percent atheroma volume was observed with evolocumab compared with placebo (−2.29% ± 0.47% vs −0.61% ± 0.46%; P = 0.009). The groups did not differ regarding changes in microchannels or calcium.
The combination of statin and evolocumab after a non–ST-segment elevation myocardial infarction produces favorable changes in coronary atherosclerosis consistent with stabilization and regression. This demonstrates a potential mechanism for the improved clinical outcomes observed achieving very low LDL-C levels following an acute coronary syndrome. (Imaging of Coronary Plaques in Participants Treated With Evolocumab; NCT03570697)
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Abstract
Aims
Current evidence on dyslipidaemia management has expanded to novel treatments and very low achieved levels of low-density lipoprotein cholesterol (LDL-C). We sought to compare the ...clinical impact of more-intensive vs. less-intensive LDL-C lowering by means of statins and currently recommended non-statin medications in secondary prevention.
Methods and results
We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials of statins, ezetimibe, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, or bile acid sequestrants with >500 patients followed for ≥1 year. We employed random-effects models using risk ratios (RRs) with 95% confidence intervals (CIs) to compare outcomes. We included 19 trials (15 of statins, 3 of PCSK9 inhibitors, and 1 of ezetimibe) with 152 507 patients randomly assigned to more-intensive (n = 76 678) or less-intensive treatment (n = 75 829). More-intensive treatment was associated with 19% relative risk reduction for the primary outcome, major vascular events (MVEs; RR 0.81, 95% CI 0.77–0.86). Risk reduction was greater across higher baseline levels and greater achieved reductions of LDL-C. The clinical benefit was significant across varying types of more-intensive treatment and was consistent for statins (RR 0.81, 95% CI 0.76–0.86) and non-statin agents (PCSK9 inhibitors and ezetimibe; RR 0.85, 95% CI 0.77–0.94) as active (more-intensive) intervention (P-interaction = 0.38). Each 1.0 mmol/L reduction in LDL-C was associated with 19% relative decrease in MVE. Death, cardiovascular death, myocardial infarction, stroke, and coronary revascularization also favoured more-intensive treatment.
Conclusion
Reduction of MVE is proportional to the magnitude of LDL-C lowering across a broad spectrum of on-treatment levels in secondary prevention. Statin intensification and add-on treatment with PCSK9 inhibitors or ezetimibe are associated with significant reduction of cardiovascular morbidity in this very high-risk population.
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