The Smokers Health Multiple ACtions (SMAC-1) Trial: Study Design and Results of the Baseline Round.

BACKGROUND: Lung cancer screening with low-dose helical computed tomography (LDCT) reduces mortality in high-risk subjects. Cigarette smoking is linked to up to 90% of lung cancer deaths. Even more so, it is a key risk factor for many other cancers and cardiovascular and pulmonary diseases. The Smokers health Multiple ACtions (SMAC-1) trial aimed to demonstrate the feasibility and effectiveness of an integrated program based on the early detection of smoking-related thoraco-cardiovascular diseases in high-risk subjects, combined with primary prevention. A new multi-component screening design was utilized to strengthen the framework on conventional lung cancer screening programs. We report here the study design and the results from our baseline round, focusing on oncological findings. METHODS: High-risk subjects were defined as being >55 years of age and active smokers or formers who had quit within 15 years (>30 pack/y). A PLCOm2012 threshold >2% was chosen. Subject outreach was streamlined through media campaign and general practitioners' engagement. Eligible subjects, upon written informed consent, underwent a psychology consultation, blood sample collection, self-evaluation questionnaire, spirometry, and LDCT scan. Blood samples were analyzed for pentraxin-3 protein levels, interleukins, microRNA, and circulating tumor cells. Cardiovascular risk assessment and coronary artery calcium (CAC) scoring were performed. Direct and indirect costs were analyzed focusing on the incremental cost-effectiveness ratio per quality-adjusted life years gained in different scenarios. Personalized screening time-intervals were determined using the "Maisonneuve risk re-calculation model", and a threshold <0.6% was chosen for the biennial round. RESULTS: In total, 3228 subjects were willing to be enrolled. Out of 1654 eligible subjects, 1112 participated. The mean age was 64 years (M/F 62/38%), with a mean PLCOm2012 of 5.6%. Former and active smokers represented 23% and 77% of the subjects, respectively. At least one nodule was identified in 348 subjects. LDCTs showed no clinically significant findings in 762 subjects (69%); thus, they were referred for annual/biennial LDCTs based on the Maisonneuve risk (mean value = 0.44%). Lung nodule active surveillance was indicated for 122 subjects (11%). Forty-four subjects with baseline suspicious nodules underwent a PET-FDG and twenty-seven a CT-guided lung biopsy. Finally, a total of 32 cancers were diagnosed, of which 30 were lung cancers (2.7%) and 2 were extrapulmonary cancers (malignant pleural mesothelioma and thymoma). Finally, 25 subjects underwent lung surgery (2.25%). Importantly, there were zero false positives and two false negatives with CT-guided biopsy, of which the patients were operated on with no stage shift. The final pathology included lung adenocarcinomas (69%), squamous cell carcinomas (10%), and others (21%). Pathological staging showed 14 stage I (47%) and 16 stage II-IV (53%) cancers. CONCLUSIONS: LDCTs continue to confirm their efficacy in safely detecting early-stage lung cancer in high-risk subjects, with a negligible risk of false-positive results. Re-calculating the risk of developing lung cancer after baseline LDCTs with the Maisonneuve model allows us to optimize time intervals to subsequent screening. The Smokers health Multiple ACtions (SMAC-1) trial offers solid support for policy assessments by policymakers. We trust that this will help in developing guidelines for the large-scale implementation of lung cancer screening, paving the way for better outcomes for lung cancer patients.

GLP-1-ra and heart failure-related outcomes in patients with and without history of heart failure: an updated systematic review and meta-analysis.

AIMS: Glucagon-like peptide-1 receptor agonists (GLP1-ra) have shown to reduce cardiovascular (CV) events in patients with diabetes, including heart failure (HF) hospitalizations. However, whether such benefit consistently occurs in patients with history of HF remains uncertain. We performed a systematic review and meta-analysis to assess the impact of GLP1-ra on CV outcomes in patients with and without HF history. METHODS AND RESULTS: All randomized, placebo-controlled trials evaluating GLP1-ra and reporting CV outcomes stratified by HF history were searched in Pubmed from inception to November 12th, 2023. The primary outcome was HF hospitalizations. Secondary outcomes included CV death, the composite of CV death and hospitalizations for HF, and major adverse cardiovascular events (MACE). Hazard ratio (HR) and 95% confidence interval (CIs) were used as effect estimates and calculated with a random-effects model. 68,653 patients (GLP1-ra = 34,301, placebo = 34,352) from 10 trials were included. GLP1-ra reduced HF hospitalization (no HF: HR = 0.79, 95% CI 0.63-0.98; HF: HR = 1.00, 95% CI 0.82-1.24, pinteraction = 0.12), CV death (no HF: HR = 0.81, 95% CI 0.71-0.92; HF: HR = 0.97, 95% CI 0.81-1.15, pinteraction = 0.11), and the composite of HF hospitalizations and CV death (no HF: HR = 0.80, 95% CI 0.72-0.89; HF: HR = 1.00 95% CI 0.88-1.15, pinteraction = 0.010) only in patients without history of HF, despite a significant interaction between HF history and treatment effect was detected only for the latter. MACE were reduced in both subgroups without significant interaction between HF history and treatment effect (no HF: HR = 0.86, 95% CI 0.78-0.96; HF: HR = 0.83, 95% CI 0.72-0.95, pinteraction = 0.69). CONCLUSION: GLP1-ra do not decrease HF-hospitalization risk, despite a potential benefit in patients without history of HF, but are effective in reducing ischemic events irrespective of the presence of HF. PROSPERO-registered (CRD42022371264).

Validation of a Contemporary Acute Kidney Injury Risk Score in Patients With Acute Coronary Syndrome.

BACKGROUND: A simple, contemporary risk score for the prediction of contrast-associated acute kidney injury (CA-AKI) after percutaneous coronary intervention (PCI) was recently updated, although its external validation is lacking. OBJECTIVES: The aim of this study was to validate the updated CA-AKI risk score in a large cohort of acute coronary syndrome patients from the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of angioX) trial. METHODS: The risk score identifies 4 risk categories for CA-AKI. The primary endpoint was to appraise the receiver-operating characteristics of an 8-component and a 12-component CA-AKI model. Independent predictors of Kidney Disease Improving Global Outcomes-based acute kidney injury and the impact of CA-AKI on 1-year mortality and bleeding were also investigated. RESULTS: The MATRIX trial included 8,201 patients with complete creatinine values and no end-stage renal disease. CA-AKI occurred in 5.5% of the patients, with a stepwise increase of CA-AKI rates from the lowest to the highest of the 4 risk categories. The receiver-operating characteristic area under the curve was 0.67 (95% CI: 0.64-0.70) with model 1 and 0.71 (95% CI: 0.68-0.74) with model 2. CA-AKI risk was systematically overestimated with both models (Hosmer-Lemeshow goodness-of-fit test: P < 0.05). The 1-year risks of all-cause mortality and bleeding were higher in CA-AKI patients (HR: 7.03 [95% CI: 5.47-9.05] and HR: 3.20 [95% CI: 2.56-3.99]; respectively). There was a gradual risk increase for mortality and bleeding as a function of the CA-AKI risk category for both models. CONCLUSIONS: The updated CA-AKI risk score identifies patients at incremental risks of acute kidney injury, bleeding, and mortality. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627).

Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.

INTRODUCTION: Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. METHODS AND ANALYSIS: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. ETHICS AND DISSEMINATION: This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings. TRIAL REGISTRATION NUMBER: NCT05339841.

Nebivolol versus placebo in patients undergoing anthracyclines (CONTROL Trial): rationale and study design.

AIMS: Anthracyclines are the chemotherapeutic agents most frequently associated with cardiotoxicity, while remaining widely used. Different neurohormonal blockers have been tested as a primary prevention strategy to prevent or attenuate the onset of cardiotoxicity, with mixed results. However, prior studies were often limited by a nonblinded design and an assessment of cardiac function based only on echocardiographic imaging. Moreover, on the basis of an improved mechanistic understanding of anthracycline cardiotoxicity mechanisms, new therapeutic strategies have been proposed. Among cardioprotective drugs, nebivolol might be able to prevent the cardiotoxic effects of anthracyclines, through its protective properties towards the myocardium, endothelium, and cardiac mitochondria. This study aims to evaluate the cardioprotective effects of the beta blocker nebivolol in a prospective, placebo-controlled, superiority randomized trial in patients with breast cancer or diffuse large B cell lymphoma (DLBCL) who have a normal cardiac function and will receive anthracyclines as part of their first-line chemotherapy programme. METHODS: The CONTROL trial is a randomized, placebo-controlled, double-blinded, superiority trial. Patients with breast cancer or a DLBCL, with a normal cardiac function as assessed by echocardiography, scheduled for treatment with anthracyclines as part of their first-line chemotherapy programme will be randomized 1 : 1 to nebivolol 5 mg once daily (o.d.) or placebo. Patients will be examined with cardiological assessment, echocardiography and cardiac biomarkers at baseline, 1 month, 6 months and 12 months. A cardiac magnetic resonance (CMR) assessment will be performed at baseline and at 12 months. The primary end point is defined as left ventricular ejection fraction reduction assessed by CMR at 12 months of follow-up. CONCLUSION: The CONTROL trial is designed to provide evidence to assess the cardioprotective role of nebivolol in patients undergoing chemotherapy with anthracyclines. CLINICAL TRIAL REGISTRATION: The study is registered in the EudraCT registry (number: 2017-004618-24) and in the ClinicalTrials.gov registry (identifier: NCT05728632).

Safety of metformin continuation in diabetic patients undergoing invasive coronary angiography: the NO-STOP single arm trial.

BACKGROUND: Despite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels. METHODS: In this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality. RESULTS: 142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3-2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3-2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR - 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43-150), no patients required hemodialysis and 2 patients died due to non-cardiac causes. CONCLUSIONS: In diabetic patients undergoing invasive coronary angiography, metformin continuation throughout the periprocedural period does not increase lactate levels and was not associated with any decline in renal function. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov (NCT04766008).

Distal vs Conventional Radial Access for Coronary Angiography and/or Intervention: A Meta-Analysis of Randomized Trials.

BACKGROUND: Emerging evidence from randomized clinical trials (RCTs) comparing distal radial access (DRA) with conventional radial access (RA) is available. OBJECTIVES: The aim of this study was to provide a quantitative appraisal of the effects of DRA) vs conventional RA for coronary angiography with or without intervention. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for RCT comparing DRA vs conventional RA for coronary angiography and/or intervention. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was radial artery occlusion (RAO) at the longest available follow-up. RESULTS: Fourteen studies enrolling 6,208 participants were included. Compared with conventional RA, DRA was associated with a significant lower risk of RAO, either detected at latest follow-up (risk ratio [RR]: 0.36; 95% CI: 0.23-0.56; P < 0.001; number needed to treat [NNT] = 30) or in-hospital (RR: 0.32; 95% CI: 0.19-0.53; P < 0.001; NNT = 28), as well as EASY (Early Discharge After Transradial Stenting of Coronary Arteries) ≥II hematoma (RR: 0.51; 95% CI: 0.27-0.96; P = 0.04; NNT = 107). By contrast, DRA was associated with a higher risk of access site crossover (RR: 3.08; 95% CI: 1.88-5.06; P < 0.001; NNT = 12), a longer time for radial puncture (standardized mean difference [SMD]: 3.56; 95% CI: 0.96-6.16; P < 0.001), a longer time for sheath insertion (SMD: 0.37; 95% CI: 0.16-0.58; P < 0.001), and a higher number of puncture attempts (SMD: 0.59, 95% CI: 0.48-0.69; P < 0.001). CONCLUSIONS: Compared with conventional RA, DRA is associated with lower risks of RAO and EASY ≥II hematoma but requires longer time for radial artery cannulation and sheath insertion, more puncture attempts, and a higher access site crossover.

One-Month Dual Antiplatelet Therapy After Bioresorbable Polymer Everolimus-Eluting Stents in High Bleeding Risk Patients.

Background It is unknown whether contemporary drug-eluting stents have a similar safety profile in high bleeding risk patients treated with 1-month dual antiplatelet therapy following percutaneous coronary interventions. Methods and Results We performed an interventional, prospective, multicenter, single-arm trial, powered for noninferiority with respect to an objective performance criterion to evaluate the safety of percutaneous coronary interventions with Synergy bioresorbable-polymer everolimus-eluting stent followed by 1-month dual antiplatelet therapy in patients with high bleeding risk. In case of need for an oral anticoagulant, patients received an oral anticoagulant in addition to a P2Y12 inhibitor for 1 month, followed by an oral anticoagulant only. The primary end point was the composite of cardiac death, myocardial infarction, or definite or probable stent thrombosis at 1-year follow-up. The study was prematurely interrupted because of slow recruitment. From April 2017 to October 2019, 443 patients (age, 74.8±9.2 years; women, 29.1%) at 10 Italian centers were included. The 1-year primary outcome occurred in 4.82% (95% CI, 3.17%-7.31%) of patients, meeting the noninferiority compared with the predefined objective performance criterion of 9.4% and the noninferiority margin of 3.85% (Pnoninferiority<0.001) notwithstanding the lower-than-expected sample size. The rates of cardiac death, myocardial infarction, and definite or probable stent thrombosis were 1.88% (95% CI, 0.36%-2.50%), 3.42% (95% CI, 2.08%-5.62%), and 0.94% (95% CI, 0.35%-2.49%), respectively. Conclusions Among high bleeding risk patients undergoing percutaneous coronary interventions with the Synergy bioresorbable-polymer everolimus-eluting stent, a 1-month dual antiplatelet therapy regimen is safe, with low rates of ischemic and bleeding events. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03112707.

The Placebo Effect on Symptoms, Quality of Life, and Functional Outcomes in Patients With Angina Pectoris: A Meta-analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: The placebo effect is a well described phenomenon in blinded studies evaluating antianginal therapeutics, although its effect on clinical research metrics remains unknown. We conducted a systematic review and meta-analysis to quantify the effect of placebo on end points of symptoms, life quality, and functional outcomes in randomized placebo-controlled trials (RCTs) of symptomatic stable coronary artery disease. METHODS: We systematically reviewed MEDLINE, EMBASE, and the Cochrane database for double-blind RCTs of antiangina therapeutics. Patients randomized to the placebo arm were the study population. Main outcomes were the changes in exercise performance (exercise treadmill test [ETT] parameters), quality of life (Seattle Angina Questionnaire domains), symptoms (Canadian Cardiovascular Society angina class) and drug usage (nitroglycerin tablets per week) between baseline and after placebo treatment. The primary outcome was ETT total duration time. Data were pooled with a random effect model. RESULTS: Seventy-eight RCTs (83% drug-controlled, 17% procedure-controlled) were included encompassing 4925 patients randomized to placebo. ETT total duration time was significantly improved after placebo treatment compared with baseline (mean, 29.2; 95% confidence interval, 20.6-37.8] seconds) with evidence of high heterogeneity (I2 = 98%) At subgroup analysis, crossover design was associated with a smaller placebo effect on ETT performance than parallel study design (P for interaction = 0.001). A significant placebo effect was observed for all secondary outcomes with overall high heterogeneity. CONCLUSIONS: A substantial placebo effect was present in angina RCTs across a variety of functional and life quality metrics. High variability in placebo effect size was present, mostly unexplained by differences in study and patient characteristics.

Association Between Colchicine Treatment and Clinical Outcomes in Patients with Coronary Artery Disease: Systematic Review and Meta-analysis.

Background: The authors examined the association between colchicine treatment and clinical outcomes in patients with coronary artery disease. Methods: They performed a meta-analysis of randomised controlled trials (RCTs) involving patients with coronary artery disease receiving addon colchicine to standard treatment compared with standard treatment. They used a mixed-effects Poisson regression model with random intervention effects to estimate the pooled incidence rate ratios (IRR) with 95% CI. Results: Ten RCTs were identified, including 12,819 participants followed up for a median of 6 months. Colchicine was associated with a lower risk of major adverse cardiovascular events (IRR 0.69; 95% CI [0.60-0.79]; number needed to treat for an additional beneficial outcome [NNTB] = 28); MI (IRR 0.77; 95% CI [0.64-0.93]; NNTB = 95) and ischaemic stroke (IRR 0.48; 95% CI [0.30-0.76]; NNTB = 155) and with a higher risk of gastrointestinal adverse events (IRR 1.69; 95% CI [1.12-2.54]; number needed to treat for an additional harmful outcome [NNTH] = 10). Colchicine did not affect all-cause death (IRR 1.09; 95% CI [0.85-1.40]), or cardiovascular death (IRR 0.75; 95% CI [0.51-1.12]), while it was associated with a higher risk of non-cardiovascular death (IRR 1.45; 95% CI [1.04-2.02]; NNTH = 396). Conclusion: The meta-analysis showed that the relative and absolute beneficial treatment effects of colchicine on cardiovascular outcomes outweigh the potential harm for non-cardiovascular mortality. Registration: PROSPERO 2021 CRD42021248874.

Clinical Effects of Dual Antiplatelet Therapy or Aspirin Monotherapy after Acute Minor Ischemic Stroke or Transient Ischemic Attack, a Meta-Analysis.

BACKGROUND: Evidence about the use of dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitors in patients with acute minor ischemic stroke or transient ischemic attack (TIA) is emerging. The aim of our study was to provide an updated and comprehensive analysis about the risks and benefits of DAPT versus aspirin monotherapy in this setting. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov databases, main international conference proceedings were searched for randomized controlled trials comparing DAPT versus aspirin monotherapy in patients with acute ischemic stroke or TIA not eligible for thrombolysis or thrombectomy presenting in the first 24 hours after the acute event. Data were pooled by meta-analysis using a random-effects model. The primary efficacy endpoint was ischemic stroke recurrence, and the primary safety outcome was major bleeding. Secondary endpoints were intracranial hemorrhage, hemorrhagic stroke, and allcause death. RESULTS: A total of 4 studies enrolling 21,459 patients were included. DAPT with clopidogrel was used in 3 studies, DAPT with ticagrelor in one study. DAPT duration was 21 days in one study, 1 month in one study, and 3 months in the remaining studies. DAPT was associated with a significant reduction in the risk of ischemic stroke recurrence (relative risk (RR), 0.74; 95% confidence interval (CI), 0.67-0.82, P<0.001, number needed to treat 50 (95% CI 40-72), while it was associated with a significantly higher risk of major bleeding (RR, 2.59; 95% CI 1.49-4.53, P=0.001, number needed to harm 330 (95% CI 149-1111), of intracranial hemorrhage (RR 3.06, 95% CI 1.41-6.66, P=0.005), with a trend towards higher risk of hemorrhagic stroke (RR 1.83, 95% CI 0.83-4.05, P=0.14), and a slight tendency towards higher risk of all-cause death (RR 1.30, 95% CI 0.89-1.89, P=0.16). CONCLUSION: Among patients with acute minor ischemic stroke or TIA, DAPT, as compared with aspirin monotherapy, might offer better effectiveness in terms of ischemic stroke recurrence at the expense of a higher risk of major bleeding. The trade-off between ischemic benefits and bleeding risks should be assessed in tailoring the therapeutic strategies.

[Percutaneous mitral valve repair in acute mitral regurgitation]. / Plastica mitralica transcatetere per il trattamento dell'insufficienza mitralica acuta.

Acute mitral regurgitation is a life-threatening pathology. Nowadays, percutaneous mitral valve repair with the MitraClip device offers, in selected patients, a safe and effective therapeutic alternative to open surgery. Hereby, we report the case of an 82-year-old woman with lateral ST-elevation myocardial infarction determining severe acute mitral regurgitation, who was treated with an urgent MitraClip procedure. Moreover, we discuss echocardiographic assessment of acute mitral regurgitation and we review available literature and possible management of this complex scenario.

MitraClip Treatment for Severe Mitral Regurgitation Due to Chordae Rupture Following Impella CP Support in a Patient With Severe Aortic Stenosis.

We report the case of an 85-year-old man with severe aortic stenosis who underwent high-risk percutaneous coronary intervention with Impella CP support. Unfortunately, the device caused mitral chordae tendineae rupture leading to severe mitral regurgitation. The patient underwent a staged fully percutaneous treatment with transcatheter aortic valve replacement followed by elective Mitraclip therapy. Echocardiographic monitoring is of paramount importance during Impella insertion and removal in order to avoid and deal with mitral damage. Mitraclip therapy is a feasible rescue therapy for severe mitral regurgitation due to chordae rupture in patients at high risk for surgery.

Drug-Coated balloons vs drug-eluting stents for the treatment of small coronary artery disease: A meta-analysis of randomized trials.

OBJECTIVES AND BACKGROUND: There is conflicting evidence about the effects of drug-coated balloons (DCB) compared with drug-eluting stents (DES) in patients with native small vessel coronary artery disease (CAD). METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases and main international conference proceedings were searched for randomized controlled trials (RCT) comparing DCB versus DES in patients with native small vessel CAD. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was target vessel revascularization (TVR). Secondary clinical endpoints were: myocardial infarction (MI), target lesion revascularization (TLR), all-cause death, cardiac death, and stent thrombosis or target vessel thrombosis. Secondary angiographic outcomes were: in-segment restenosis, in-segment percentage-diameter stenosis, in-segment late lumen loss, in-segment net luminal gain, and in-segment minimal lumen diameter. RESULTS: Five trials enrolling 1,459 patients were included. Mean clinical follow-up was 10.2 months. The use of DCB, compared with DES, was associated with similar risk of TVR (odds ratio [OR]: 0.97; 95% confidence interval [CI] 0.56 to 1.68; p = .92), TLR (OR: 1.74; 95% CI: 0.57 to 5.28; p = .33), all-cause death (OR: 1.03; 95% CI: 0.14 to 7.48; p = .98), with a trend toward a lower risk of MI (OR: 0.49; 95% CI: 0.23 to 1.03; p = .06), and with significant lower risk of vessel thrombosis (OR: 0.12; 95% CI: 0.01 to 0.94; p = .04). DCB use was associated with similar risk of angiographic restenosis (OR: 1.12; 95% CI 0.69 to 1.84; p = .64), comparable late luminal loss (standardized mean difference (SMD): -0.18; 95% CI: -0.39 to 0.03; p = .09), while leading to significant higher percentage diameter stenosis (SMD: 0.27; 95% CI 0.12 to 0.41; p < .01) and smaller minimal luminal diameter (SMD: -0.52; 95% CI: -0.86 to -0.18; p = .003). CONCLUSION: Compared with DES, the use of DCB for the treatment of native small vessel CAD is associated with similar TVR and restenosis and reduces the risk of vessel thrombosis, although DES implantation yields slightly better angiographic surrogate endpoints.

Dual antiplatelet therapy duration after percutaneous coronary intervention with drug-eluting stents: how short can we go?

Current guidelines recommend a duration of dual antiplatelet therapy (DAPT) with aspirin and oral P2Y12 receptor inhibitors following percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DES) of 6 months for most patients with stable coronary disease and of 12 months for most patients with acute coronary syndromes. Large evidence from randomised clinical trials of shorter DAPT regimens after PCI with newer-generation DES is now emerging in heterogenous patient population not selected on the basis of high bleeding risk as well as in patients at high bleeding risk. The scope of this review is to provide an update on the benefits and harms of these short DAPT regimens and to discuss future directions in DAPT strategies after PCI with newer generation DES.

Early detection of elevated cardiac biomarkers to optimise risk stratification in patients with COVID-19.

OBJECTIVE: Risk stratification is crucial to optimise treatment strategies in patients with COVID-19. We aimed to evaluate the impact on mortality of an early assessment of cardiac biomarkers in patients with COVID-19. METHODS: Humanitas Clinical and Research Hospital (Rozzano-Milan, Lombardy, Italy) is a tertiary centre that has been converted to the management of COVID-19. Patients with confirmed COVID-19 were entered in a dedicated database for cohort observational analyses. Outcomes were stratified according to elevated levels (ie, above the upper level of normal) of high-sensitivity cardiac troponin I (hs-TnI), B-type natriuretic peptide (BNP) or both measured within 24 hours after hospital admission. The primary outcome was all-cause mortality. RESULTS: A total of 397 consecutive patients with COVID-19 were included up to 1 April 2020. At the time of hospital admission, 208 patients (52.4%) had normal values for cardiac biomarkers, 90 (22.7%) had elevated both hs-TnI and BNP, 59 (14.9%) had elevated only BNP and 40 (10.1%) had elevated only hs-TnI. The rate of mortality was higher in patients with elevated hs-TnI (22.5%, OR 4.35, 95% CI 1.72 to 11.04), BNP (33.9%, OR 7.37, 95% CI 3.53 to 16.75) or both (55.6%, OR 18.75, 95% CI 9.32 to 37.71) as compared with those without elevated cardiac biomarkers (6.25%). A multivariate analysis identified concomitant elevation of both hs-TnI and BNP as a strong independent predictor of all-cause mortality (OR 3.24, 95% CI 1.06 to 9.93). CONCLUSIONS: An early detection of elevated hs-TnI and BNP predicts mortality in patients with COVID-19. Cardiac biomarkers should be systematically assessed in patients with COVID-19 at the time of hospital admission in order to optimise risk stratification.

Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe.

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39-61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the "Initiative for European Lung Screening (IELS)"-a large international group of physicians and other experts concerned with lung cancer-agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and presented findings at a meeting held in Milan in November 2018. The present recommendations reflect that consensus was reached.