Summary Background The relative safety of drug-eluting stents and bare-metal stents, especially with respect to stent thrombosis, continues to be debated. In view of the overall low frequency of ...stent thrombosis, large sample sizes are needed to accurately estimate treatment differences between stents. We compared the risk of thrombosis between bare-metal and drug-eluting stents. Methods For this network meta-analysis, randomised controlled trials comparing different drug-eluting stents or drug-eluting with bare-metal stents currently approved in the USA were identified through Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. Findings 49 trials including 50 844 patients randomly assigned to treatment groups were analysed. 1-year definite stent thrombosis was significantly lower with cobalt-chromium everolimus eluting stents (CoCr-EES) than with bare-metal stents (odds ratio OR 0·23, 95% CI 0·13–0·41). The significant difference in stent thrombosis between CoCr-EES and bare-metal stents was evident as early as 30 days (OR 0·21, 95% CI 0·11–0·42) and was also significant between 31 days and 1 year (OR 0·27, 95% CI 0·08–0·74). CoCr-EES were also associated with significantly lower rates of 1-year definite stent thrombosis compared with paclitaxel-eluting stents (OR 0·28, 95% CI 0·16–0·48), permanent polymer-based sirolimus-eluting stents (OR 0·41, 95% CI 0·24–0·70), phosphorylcholine-based zotarolimus-eluting stents (OR 0·21, 95% CI 0·10–0·44), and Resolute zotarolimus-eluting stents (OR 0·14, 95% CI 0·03–0·47). At 2-year follow-up, CoCr-EES were still associated with significantly lower rates of definite stent thrombosis than were bare-metal (OR 0·35, 95% CI 0·17–0·69) and paclitaxel-eluting stents (OR 0·34, 95% CI 0·19–0·62). No other drug-eluting stent had lower definite thrombosis rates compared with bare-metal stents at 2-year follow-up. Interpretation In randomised studies completed to date, CoCr-EES has the lowest rate of stent thrombosis within 2 years of implantation. The finding that CoCr-EES also reduced stent thrombosis compared with bare-metal stents, if confirmed in future randomised trials, represents a paradigm shift. Funding The Cardiovascular Research Foundation.
Abstract Background The incidence, predictors, and prognostic impact of post-discharge bleeding (PDB) after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation are ...unclear. Objectives This study sought to characterize the determinants and consequences of PDB after PCI. Methods The prospective ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) study was used to determine the incidence and predictors of clinically relevant bleeding events occurring within 2 years after hospital discharge. The effect of PDB on subsequent 2-year all-cause mortality was estimated by time-adjusted Cox proportional hazards regression. Results Among 8,582 “all-comers” who underwent successful PCI with DES in the ADAPT-DES study, PDB occurred in 535 of 8,577 hospital survivors (6.2%) at a median time of 300 days (interquartile range: 130 to 509 days) post-discharge. Gastrointestinal bleeding (61.7%) was the most frequent source of PDB. Predictors of PDB included older age, lower baseline hemoglobin, lower platelet reactivity on clopidogrel, and use of chronic oral anticoagulation therapy. PDB was associated with higher crude rates of all-cause mortality (13.0% vs. 3.2%; p < 0.0001). Following multivariable adjustment, PDB was strongly associated with 2-year mortality (hazard ratio HR: 5.03; p < 0.0001), with an effect size greater than that of post-discharge myocardial infarction (PDMI) (HR: 1.92; p = 0.009). Conclusions After successful PCI with DES in an unrestricted patient population, PDB is not uncommon and has a strong relationship with subsequent all-cause mortality, greater that that associated with PDMI. Efforts to reduce PDB may further improve prognosis after successful DES implantation. (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents ADAPT-DES; NCT00638794 )
Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, ...myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
Dual-antiplatelet therapy with aspirin and clopidogrel after percutaneous coronary intervention reduces the risk for coronary thrombotic events (CTEs) at the expense of increasing risk for major ...bleeding (MB). Metrics to accurately predict the occurrence of each respective event and inform clinical decision making are lacking.
The aim of this study was to develop and validate separate models to predict risks for out-of-hospital thrombotic and bleeding events after percutaneous coronary intervention with drug-eluting stents.
Using data from 4,190 patients treated with drug-eluting stents and enrolled in the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimen in Stented Patients) registry, separate risk scores were developed to predict CTE (defined as the composite of stent thrombosis or myocardial infarction) and MB (defined as the occurrence of a Bleeding Academic Research Consortium type 3 or 5 bleed). External validation was performed in the ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) registry.
Over 2 years, CTEs occurred in 151 patients (3.8%) and MB in 133 (3.3%). Independent predictors of CTEs included acute coronary syndrome, prior revascularization, diabetes mellitus, renal dysfunction, and current smoking. Independent predictors of MB included older age, body mass index, triple therapy at discharge, anemia, current smoking, and renal dysfunction. Each model displayed moderate levels of discrimination and adequate calibration.
Simple risk scores of baseline clinical variables may be useful to predict risks for ischemic and bleeding events after PCI with DES, thereby facilitating clinical decisions surrounding the optimal duration of DAPT. (Patterns of Non-Adherence to Anti-Platelet Regimen in Stented Patients PARIS; NCT00998127).
Fractional flow reserve (FFR) is an invasive procedure used during coronary angiography to determine the functional significance of coronary stenoses. Its use is particularly helpful in intermediate ...or angiographically ambiguous lesions in the absence of noninvasive functional studies. Randomized clinical trials have reported improved clinical outcomes with the use of FFR to guide coronary revascularization, including a reduction in cardiac death or myocardial infarction, as well as costs, with an FFR-based strategy compared with a conventional angiography-based approach. Current societal guidelines provide a Class II, Level of Evidence: A recommendation to perform FFR in angiographically intermediate stenoses in the absence of stress testing or in the presence of discordant stress test results and angiographic findings. However, despite the relative ease of use of FFR, multiple technical factors can impair its accuracy, and attention to detail is critical when performing the test. This review focuses on the fundamental basics of FFR testing, clinical evidence, and limitations.
Compared with visual angiographic assessment, pressure wire-based physiological measurement more accurately identifies flow-limiting lesions in patients with coronary artery disease. Nonetheless, ...angiography remains the most widely used method to guide percutaneous coronary intervention (PCI). In FAVOR III China, we aimed to establish whether clinical outcomes might be improved by lesion selection for PCI using the quantitative flow ratio (QFR), a novel angiography-based approach to estimate the fractional flow reserve.
FAVOR III China is a multicentre, blinded, randomised, sham-controlled trial done at 26 hospitals in China. Patients aged 18 years or older, with stable or unstable angina pectoris or patients who had a myocardial infarction at least 72 h before screening, who had at least one lesion with a diameter stenosis of 50–90% in a coronary artery with a reference vessel of at least 2·5 mm diameter by visual assessment were eligible. Patients were randomly assigned to a QFR-guided strategy (PCI performed only if QFR ≤0·80) or an angiography-guided strategy (PCI based on standard visual angiographic assessment). Participants and clinical assessors were masked to treatment allocation. The primary endpoint was the 1-year rate of major adverse cardiac events, a composite of death from any cause, myocardial infarction, or ischaemia-driven revascularisation. The primary analysis was done in the intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT03656848).
Between Dec 25, 2018, and Jan 19, 2020, 3847 patients were enrolled. After exclusion of 22 patients who elected not to undergo PCI or who were withdrawn by their physicians, 3825 participants were included in the intention-to-treat population (1913 in the QFR-guided group and 1912 in the angiography-guided group). The mean age was 62·7 years (SD 10·1), 2699 (70·6%) were men and 1126 (29·4%) were women, 1295 (33·9%) had diabetes, and 2428 (63·5%) presented with an acute coronary syndrome. The 1-year primary endpoint occurred in 110 (Kaplan-Meier estimated rate 5·8%) participants in the QFR-guided group and in 167 (8·8%) participants in the angiography-guided group (difference, –3·0% 95% CI –4·7 to –1·4; hazard ratio 0·65 95% CI 0·51 to 0·83; p=0·0004), driven by fewer myocardial infarctions and ischaemia-driven revascularisations in the QFR-guided group than in the angiography-guided group.
In FAVOR III China, among patients undergoing PCI, a QFR-guided strategy of lesion selection improved 1-year clinical outcomes compared with standard angiography guidance.
Beijing Municipal Science and Technology Commission, Chinese Academy of Medical Sciences, and the National Clinical Research Centre for Cardiovascular Diseases, Fuwai Hospital.
The majority of stent-related major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) are believed to occur within the first year. Very-late (>1-year) stent-related ...MACE have not been well described.
The purpose of this study was to assess the frequency and predictors of very-late stent-related events or MACE by stent type.
Individual patient data from 19 prospective, randomized metallic stent trials maintained at a leading academic research organization were pooled. Very-late MACE (a composite of cardiac death, myocardial infarction MI, or ischemia-driven target lesion revascularization ID-TLR), and target lesion failure (cardiac death, target-vessel MI, or ID-TLR) were assessed within year 1 and between 1 and 5 years after PCI with bare-metal stents (BMS), first-generation drug-eluting stents (DES1) and second-generation drug-eluting stents (DES2). A network meta-analysis was performed to evaluate direct and indirect comparisons.
Among 25,032 total patients, 3,718, 7,934, and 13,380 were treated with BMS, DES1, and DES2, respectively. MACE rates within 1 year after PCI were progressively lower after treatment with BMS versus DES1 versus DES2 (17.9% vs. 8.2% vs. 5.1%, respectively, p < 0.0001). Between years 1 and 5, very-late MACE occurred in 9.4% of patients (including 2.9% cardiac death, 3.1% MI, and 5.1% ID-TLR). Very-late MACE occurred in 9.7%, 11.0%, and 8.3% of patients treated with BMS, DES1, and DES2, respectively (p < 0.0001), linearly increasing between 1 and 5 years. Similar findings were observed for target lesion failure in 19,578 patients from 12 trials. Findings were confirmed in the network meta-analysis.
In this large-scale, individual patient data pooled study, very-late stent-related events occurred between 1 and 5 years after PCI at a rate of ∼2%/year with all stent types, with no plateau evident. New approaches are required to improve long-term outcomes after PCI.
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Objectives The aim of this study was to develop a practical risk score to predict the risk and implications of major bleeding in acute coronary syndromes (ACS). Background Hemorrhagic complications ...have been strongly linked with subsequent mortality in patients with ACS. Methods A total of 17,421 patients with ACS (including non–ST-segment elevation myocardial infarction MI, ST-segment elevation MI, and biomarker negative ACS) were studied in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) and the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trials. An integer risk score for major bleeding within 30 days was developed from a multivariable logistic regression model. Results Non-coronary artery bypass graft surgery (CABG)-related major bleeding within 30 days occurred in 744 patients (7.3%) and had 6 independent baseline predictors (female sex, advanced age, elevated serum creatinine and white blood cell count, anemia, non–ST-segment elevation MI, or ST-segment elevation MI) and 1 treatment-related variable (use of heparin + a glycoprotein IIb/IIIa inhibitor rather than bivalirudin alone) (model c -statistic = 0.74). The integer risk score differentiated patients with a 30-day rate of non–CABG-related major bleeding ranging from 1% to over 40%. In a time-updated covariate-adjusted Cox proportional hazards regression model, major bleeding was an independent predictor of a 3.2-fold increase in mortality. The link to mortality risk was strongest for non–CABG-related Thrombolysis In Myocardial Infarction (TIMI)-defined major bleeding followed by non-TIMI major bleeding with or without blood transfusions, whereas isolated large hematomas and CABG-related bleeding were not significantly associated with subsequent mortality. Conclusions Patients with ACS have marked variation in their risk of major bleeding. A simple risk score based on 6 baseline measures plus anticoagulation regimen identifies patients at increased risk for non–CABG-related bleeding and subsequent 1-year mortality, for whom appropriate treatment strategies can be implemented.
The risk of recurrent ischemic and bleeding events after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) may not be uniform over time, which ...may affect the benefit-to-risk ratio of guideline-recommended antithrombotic therapies in different intervals.
This study sought to characterize the average daily ischemic rates (ADIRs) and average daily bleeding rates (ADBRs) within the first year after primary PCI for STEMI.
Among 3,602 patients with STEMI who were enrolled in the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial, all ischemic and bleeding events, including recurrent events, were classified according to the timing of their occurrence as acute (≤24 h after PCI), subacute (1 day to 30 days), and late (30 days to 1 year). Patients were treated with aspirin and clopidogrel for the entire year. ADIRs included cardiac death, reinfarction, and definite stent thrombosis. ADBRs included non–coronary artery bypass graft–related Thrombolysis In Myocardial Infarction major and minor bleeding. ADIRs and ADBRs were calculated as the total number of events divided by the number of patient-days of follow-up in each interval assuming a Poisson distribution. Generalized estimating equations were used to test the absolute least square mean differences (LSMD) between ADIRs and ADBRs.
The ADIR and ADBR both exponentially decreased from the acute to the late periods (p < 0.0001). Although there were no significant differences in ADIR and ADBR in the acute phase (LSMD: +0.11%; 95% confidence interval CI: −0.35% to 0.58%; p = 0.63), the ADBR was greater than the ADIR in the subacute phase (LSMD: −0.39%; 95% CI: −0.58% to −0.20%; p < 0.0001). In the late phase, the ADIR exceeded the ADBR (LSMD: +1.51%; 95% CI: 1.04% to 1.98%; p < 0.0001).
After primary PCI, the ADIR and ADBR both markedly decreased over time. Although the rates for bleeding exceeded those for ischemia within 30 days, the daily risk of ischemia significantly exceeded the daily risk of bleeding beyond 30 days, supporting the use of intensified platelet inhibition during the first year after STEMI.
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