Impact of the number of modifiable risk factors on clinical outcomes after percutaneous coronary intervention: An analysis from the e-Ultimaster registry

Aims: A substantial proportion of the patients undergoing percutaneous coronary intervention (PCI) have none of the of standard modifiable cardiovascular risk factors (SMuRFs): hypertension, diabetes, hypercholesterolaemia and smoking. The aim of this analysis was to compare clinical outcomes after PCI according to the number of SMuRFs. Methods: Patients with an indication for a PCI were stratified based upon the number of SMuRFs: 0, 1, 2 or 3–4. The primary outcome was target lesion failure (TLF), a composite of cardiac death, target vessel-related myocardial infarction or clinically driven target lesion revascularization at 1-year. Inverse weighted propensity score (IWPS) adjustment was performed to adjust for differences in baseline characteristics. Results: The prevalence of SMuRFs was: 0 SMuRF 16.4 %; 1 SMuRF 27.8 %; 2 SMuRFs 34.7 % and 3–4 SMuRFs 21.1 %. Patients without SMuRFs were younger, more likely to be male and had less complex coronary artery disease. The incidence of TLF increased with the number of SMuRFs: 2.65 %, 2.75 %, 3.23 %, and 4.24 %, P trend &lt; 0.001. The relative risk (RR) for a TLF was 60 % higher (95 % confidence interval 1.32–1.93, p &lt; 0.01) for patients with 3–4 SMuRFs compared to patients without SMuRFs. The trend remained (P trend &lt; 0.01) after IWPS with TLF rates of 2.88 %, 2.64 %, 2.88 % and 3.65 %. The RR for a TLF was 27 % higher (95 % CI 1.05–1.53, p &lt; 0.01). Conclusion: The incidence of clinical events at 1-year increased with the number of SMuRFs. While patients without SMuRFs have a relatively favourable risk profile, more research is needed to optimize therapeutic management in the majority of patients.</p

Distal Versus Conventional Radial Access for Coronary Angiography and Intervention The DISCO RADIAL Trial

BACKGROUND Currently, transradial access (TRA) is the recommended access for coronary procedures because of increased safety, with radial artery occlusion (RAO) being its most frequent complication, which will increasingly affect patients undergoing multiple procedures during their lifetimes. Recently, distal radial access (DRA) has emerged as a promising alternative access to minimize RAO risk. A large-scale, international, randomized trial comparing RAO with TRA and DRA is lacking. OBJECTIVES The aim of this study was to assess the superiority of DRA compared with conventional TRA with respect to forearm RAO. METHODS DISCO RADIAL (Distal vs Conventional Radial Access) was an international, multicenter, randomized controlled trial in which patients with indications for percutaneous coronary procedure using a 6-F Slender sheath were randomized to DRA or TRA with systematic implementation of best practices to reduce RAO. The primary endpoint was the incidence of forearm RAO assessed by vascular ultrasound at discharge. Secondary endpoints include crossover, hemostasis time, and access site-related complications. RESULTS Overall, 657 patients underwent TRA, and 650 patients underwent DRA. Forearm RAO did not differ between groups (0.91% vs 0.31%; P = 0.29). Patent hemostasis was achieved in 94.4% of TRA patients. Crossover rates were higher with DRA (3.5% vs 7.4%; P = 0.002), and median hemostasis time was shorter (180 vs 153 minutes; P < 0.001). Radial artery spasm occurred more with DRA (2.7% vs 5.4%; P = 0.015). Overall bleeding events and vascular complications did not differ between groups. CONCLUSIONS With the implementation of a rigorous hemostasis protocol, DRA and TRA have equally low RAO rates. DRA is associated with a higher crossover rate but a shorter hemostasis time. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

ULTrasound-guided TRAnsfemoral puncture in COmplex Large bORe PCI: study protocol of the UltraCOLOR trial

Introduction Although recently published evidence favours transradial access (TRA) when using large-bore guiding catheters for percutaneous coronary intervention (PCI) of complex coronary lesions, the femoral artery will still be used in a considerate proportion of patients undergoing complex PCI, especially in PCI of chronic total occlusions (CTO). Ultrasound-guided puncture of the femoral artery may reduce clinically relevant access site complications, but robust evidence is lacking up to date. Methods and analysis A total of 542 patients undergoing complex PCI, defined as PCI of CTO, complex bifurcation, heavy calcified lesion or left main, in which the 7-F or 8-F transfemoral access is required, will be randomised to ultrasound-guided puncture or fluoroscopy-guided puncture. The primary outcome is the incidence of the composite end-point of clinically relevant access site related bleeding and/or vascular complications requiring intervention. Access site complications and major adverse cardiovascular events up to 1 month will also be compared between both groups. Ethics and dissemination Ethical approval for the study was granted by the local Ethics Committee ('Medisch Ethische Toetsing Commissie Isala Zwolle') for all Dutch sites, 'Comité Medische Ethiek Ziekenhuis Oost-Limburg' for Hospital Oost-Limburg, 'Comité d'éthique CHU-Charleroi - ISPPC' for Centre Hospilatier Universitaire de Charleroi and 'Ethik Kommission de Arztekammer Nordrhein' for Elisabeth-Krankenhaus). The trial outcomes will be published in peer-reviewed journals of the concerned literature. The ultrasound guided transfemoral access in complex large bore PCI trial has been administered in the ClinicalTrials.gov database, reference number: NCT03846752. Registration details ClinicalTrials.gov identifier: NCT03846752

Influence of Bleeding Risk on Outcomes of Radial and Femoral Access for Percutaneous Coronary Intervention: An Analysis From the GLOBAL LEADERS Trial

Background: Radial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding. Methods: Patients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days. Results: In the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; Pinteraction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; Pinteraction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant. Conclusions: Our findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because thisContexte : Il a et e d emontr e que l ’accès par l’artère radiale reduit la mortalite et les h emorragies, en particulier chez les patients presentant un syndrome coronarien aigu. Malgr e cela, les cardiologues interventionnels qui ont acquis de l’experience en matière d ’accès par l’artère femorale pr efèrent encore utiliser cette voie lorsqu ’ils doivent pratiquer une intervention coronarienne percutanee. On connaît mal l’interêt de chacune de ces techniques d ’accès vasculaire au regard du risque d’hemorragie. Methodologie : Les patients de l’essai GLOBAL LEADERS ont et e repartis en deux groupes, selon qu ’ils presentaient un risque d’hemorragie faible ou elev e d ’après le score PRECISE-DAPT median, puis les resultats cliniques ont et e compar es à 30 jours. Resultats : Dans l’ensemble de la population, aucune difference sta- tistiquement significative n’a et e observ ee entre l ’accès radial et l’accès femoral quant au critère d ’evaluation principal, compos e de la mortalite toutes causes confondues et d ’un nouvel infarctus du myocarde (IM) avec onde Q (rapport des risques instantanes [RRI] de 0,70; intervalle de confiance [IC] à 95 % : 0,42-1,15). L’accès radial a et e associe à un taux signi ficativement plus faible de survenue du critère secondaire d’evaluation de l ’innocuite, c ’est-à-dire une hemorragie de type 3 ou 5 selon la classification du BARC (Bleeding Academic Research Consortium) (RRI de 0,55; IC à 95 % : 0,36-0,84). Lorsqu’on compare les sujets en fonction du risque d’hemorragie, les critères d’evaluation de l ’innocuite principal (RRI de 0,47; IC à 95 % : 0,26- 0,85; p ¼ 0,012; pinteraction ¼ 0,019) et secondaire (RRI de 0,57; IC à 95 % : 0,35-0,95; p ¼ 0,030; pinteraction ¼ 0,631) sont favorables à l’accès radial au sein de la population presentant un risque d ’hemor- ragie elev e. Dans la population pr esentant un risque d ’hemorragie faible, les differences entre l ’accès radial et l’accès femoral quant aux critères d’evaluation de l ’innocuite principal et secondaire ne sont toutefois plus statistiquement significatives. Conclusions : Selon ces observations, les resultats concernant la mortalite ou la survenue d ’un nouvel IM avec onde Q et le risque d’hemorragie de type 3 ou 5 selon la classi fication du BARC indiquent que l’accès radial serait à privilegier lorsque le risque d ’hemorragie est elev e, mais pas lorsqu ’il est faible. Comme il ne s’agissait pas d’une analyse principale, il convient de considerer ces observations comme etant g en eratrices d ’hypothèses

Polymer-based or polymer-free stents in patients at high bleeding risk

Background: polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. Methods: in an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. Results: a total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drug-coated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P = 0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P = 0.007 for noninferiority). Conclusions: among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.)

Benefit and Risks of Aspirin in Addition to Ticagrelor in Acute Coronary Syndromes:A Post Hoc Analysis of the Randomized GLOBAL LEADERS Trial

Key PointsQuestionWhat are the benefits and risks of continuing aspirin in addition to P2Y12 receptor inhibition with ticagrelor among patients with acute coronary syndrome between 1 month and 12 months after percutaneous coronary intervention? FindingsIn this nonprespecified, post hoc analysis of the GLOBAL LEADERS randomized clinical trial, beyond 1 month after percutaneous coronary intervention in acute coronary syndrome, aspirin was associated with increased bleeding risk and appeared not to add to the benefit of ticagrelor on ischemic events. MeaningThe findings of this hypothesis-generating analysis pave the way for further trials evaluating aspirin-free antiplatelet strategies after percutaneous coronary intervention. ImportanceThe role of aspirin as part of antiplatelet regimens in acute coronary syndromes (ACS) needs to be clarified in the context of newer potent P2Y12 antagonists. ObjectiveTo evaluate the benefit and risks of aspirin in addition to ticagrelor among patients with ACS beyond 1 month after percutaneous coronary intervention (PCI). Design, Setting, and ParticipantsThis is a nonprespecified, post hoc analysis of GLOBAL LEADERS, a randomized, open-label superiority trial comparing 2 antiplatelet treatment strategies after PCI. The trial included 130 secondary/tertiary care hospitals in different countries, with 15991 unselected patients with stable coronary artery disease or ACS undergoing PCI. Patients had outpatient visits at 1, 3, 6, 12, 18, and 24 months after index procedure. InterventionsThe experimental group received aspirin plus ticagrelor for 1 month followed by 23-month ticagrelor monotherapy; the reference group received aspirin plus either clopidogrel (stable coronary artery disease) or ticagrelor (ACS) for 12 months, followed by 12-month aspirin monotherapy. In this analysis, we examined the clinical outcomes occurring between 31 days and 365 days after randomization, specifically in patients with ACS who, within this time frame, were assigned to receive either ticagrelor alone or ticagrelor and aspirin. Main Outcomes and MeasuresThe primary outcome was the composite of all-cause death or new Q-wave myocardial infarction. ResultsOf 15968 participants, there were 7487 patients with ACS enrolled; 3750 patients were assigned to the experimental group and 3737 patients to the reference group. Between 31 and 365 days after randomization, the primary outcome occurred in 55 patients (1.5%) in the experimental group and in 75 patients (2.0%) in the reference group (hazard ratio [HR], 0.73; 95% CI, 0.51-1.03; P=.07); investigator-reported Bleeding Academic Research Consortium-defined bleeding type 3 or 5 occurred in 28 patients (0.8%) in the experimental group and in 54 patients (1.5%) in the reference arm (HR, 0.52; 95% CI, 0.33-0.81; P=.004). Conclusions and RelevanceBetween 1 month and 12 months after PCI in ACS, aspirin was associated with increased bleeding risk and appeared not to add to the benefit of ticagrelor on ischemic events. These findings should be interpreted as exploratory and hypothesis generating; however, they pave the way for further trials evaluating aspirin-free antiplatelet strategies after PCI. Trial RegistrationClinicalTrials.gov identifier: NCT01813435. This secondary analysis of the GLOBAL LEADERS randomized clinical trial evaluates the benefit and risks of aspirin in addition to ticagrelor among patients with acute coronary syndrome beyond 1 month after percutaneous coronary intervention

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Extremity Dysfunction After Large-Bore Radial and Femoral Arterial Access

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