Safety and efficacy of bempedoic acid: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND AND AIMS: Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia. METHODS: PubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867). RESULTS: Study search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79-0.95), myocardial infarction (OR 0.76, 95% CI 0.64-0.88) and unstable angina (OR 0.69, 95% CI 0.54-0.88) compared to control, over a median follow up of 87 (15-162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]-22.42,95% CI - 24.02% to - 20.82%), total cholesterol (- 16.50%,95% - 19.21% to - 13.79%), Apo-B lipoprotein (- 19.55%, - 22.68% to - 16.42%) and high-sensitivity CRP (- 27.83%, - 31.71% to - 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27-1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy. CONCLUSIONS: The improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout.

SCAI stage reclassification at 24 h predicts outcome of cardiogenic shock: Insights from the Altshock-2 registry.

BACKGROUND: Cardiogenic shock (CS) includes several phenotypes with heterogenous hemodynamic features. Timely prognostication is warranted to identify patients requiring treatment escalation. We explored the association of the updated Society for Cardiovascular Angiography and Interventions (SCAI) stages classification with in-hospital mortality using a prospective national registry. METHODS: Between March 2020 and February 2022 the Altshock-2 Registry has included 237 patients with CS of all etiologies at 11 Italian Centers. Patients were classified according to their admission SCAI stage (assigned prospectively and independently updated according to the recently released version). In-hospital mortality was evaluated for association with both admission and 24-h SCAI stages. RESULTS: The overall in-hospital mortality was 38%. Of the 237 patients included and staged according to the updated SCAI classification, 20 (8%) had SCAI shock stage B, 131 (55%) SCAI stage C, 61 (26%) SCAI stage D and 25 (11%) SCAI stage E. In-hospital mortality stratified according to the SCAI classification at 24 h was 18% for patients in SCAI stage B, 27% for SCAI stage C, 63% for SCAI stage D and 100% for SCAI stage E. Both the revised SCAI stages on admission and at 24 h were associated with in-hospital mortality, but the classification potential slightly increased at 24-h. After adjusting for age, sex, lactate level, eGFR, CVP, inotropic score and mechanical circulatory support [MCS], SCAI classification at 24 h was an independent predictor of in-hospital mortality. CONCLUSIONS: In the Altshock-2 registry the utility of SCAI shock stages to identify risk of in-hospital mortality increased at 24 h after admission. Escalation of treatment (either pharmacological or with MCS) should be tailored to achieve prompt clinical improvement within the first 24 h after admission. Registration: http://www. CLINICALTRIALS: gov; Unique identifier: NCT04295252.

Non-invasive ventilation for SARS-CoV-2 acute respiratory failure: a subanalysis from the HOPE COVID-19 registry.

BACKGROUND: The COVID-19 pandemic has seriously challenged worldwide healthcare systems and limited intensive care facilities, leading to physicians considering the use of non-invasive ventilation (NIV) for managing SARS-CoV-2-related acute respiratory failure (ARF). METHODS: We conducted an interim analysis of the international, multicentre HOPE COVID-19 registry including patients admitted for a confirmed or highly suspected SARS-CoV-2 infection until 18 April 2020. Those treated with NIV were considered. The primary endpoint was a composite of death or need for intubation. The components of the composite endpoint were the secondary outcomes. Unadjusted and adjusted predictors of the primary endpoint within those initially treated with NIV were investigated. RESULTS: 1933 patients who were included in the registry during the study period had data on oxygen support type. Among them, 390 patients (20%) were treated with NIV. Compared with those receiving other non-invasive oxygen strategy, patients receiving NIV showed significantly worse clinical and laboratory signs of ARF at presentation. Of the 390 patients treated with NIV, 173 patients (44.4%) met the composite endpoint. In-hospital death was the main determinant (147, 37.7%), while 62 patients (15.9%) needed invasive ventilation. Those requiring invasive ventilation had the lowest survival rate (41.9%). After adjustment, age (adjusted OR (adj(OR)) for 5-year increase: 1.37, 95% CI 1.15 to 1.63, p<0.001), hypertension (adj(OR) 2.95, 95% CI 1.14 to 7.61, p=0.03), room air O2 saturation <92% at presentation (adj(OR) 3.05, 95% CI 1.28 to 7.28, p=0.01), lymphocytopenia (adj(OR) 3.55, 95% CI 1.16 to 10.85, p=0.03) and in-hospital use of antibiotic therapy (adj(OR) 4.91, 95% CI 1.69 to 14.26, p=0.003) were independently associated with the composite endpoint. CONCLUSION: NIV was used in a significant proportion of patients within our cohort, and more than half of these patients survived without the need for intubation. NIV may represent a viable strategy particularly in case of overcrowded and limited intensive care resources, but prompt identification of failure is mandatory to avoid harm. Further studies are required to better clarify our hypothesis. TRIAL REGISTRATION NUMBERS: NCT04334291/EUPAS34399.

Impact of design of coronary stents and length of dual antiplatelet therapies on ischaemic and bleeding events: a network meta-analysis of 64 randomized controlled trials and 102 735 patients.

AIMS: The differential impact on ischaemic and bleeding events of the type of drug-eluting stent [durable polymer stents [DES] vs. biodegradable polymer stents vs. bioresorbable scaffolds (BRS)] and length of dual antiplatelet therapy (DAPT) remains to be defined. METHODS AND RESULTS: Randomized controlled trials comparing different types of DES and/or DAPT durations were selected. The primary endpoint was Major Adverse Cardiovascular Events (MACE) [a composite of death, myocardial infarction (MI), and target vessel revascularization]. Definite stent thrombosis (ST) and single components of MACE were secondary endpoints. The arms of interest were: BRS with 12 months of DAPT (12mDAPT), biodegradable polymer stent with 12mDAPT, durable polymer stent [everolimus-eluting (EES), zotarolimus-eluting (ZES)] with 12mDAPT, EES/ZES with <12 months of DAPT, and EES/ZES with >12 months of DAPT (DAPT > 12 m). Sixty-four studies with 150 arms and 102 735 patients were included. After a median follow-up of 20 months, MACE rates were similar in the different arms of interest. EES/ZES with DAPT > 12 m reported a lower incidence of MI than the other groups, while BRS showed a higher rate of ST when compared to EES/ZES, irrespective of DAPT length. A higher risk of major bleedings was observed for DAPT > 12 m as compared to shorter DAPT. CONCLUSION: Durable and biodegradable polymer stents along with BRS report a similar rate of MACE irrespective of DAPT length. Fewer MI are observed with EES/ZES with DAPT > 12 m, while a higher rate of ST is reported for BRS when compared to EES/ZES, independently from DAPT length. Stent type may partially affect the outcome together with DAPT length.

Impact of an optical coherence tomography guided approach in acute coronary syndromes: A propensity matched analysis from the international FORMIDABLE-CARDIOGROUP IV and USZ registry.

AIM: To determine the potential clinical impact of OCT (Optical Coherence Tomography) during primary percutaneous coronary intervention in patients presenting with ACS (Acute Coronary Syndrome). METHODS AND RESULTS: FORMIDABLE is a multicentre retrospective registry enrolling all patients presenting with ACS and treated with an OCT-guided approach, while the USZ registry enrolled patients treated with a standard angiography guided approach. Multivariate adjustment was performed via a propensity score matching. The number stents useds was the primary outcome, while the incidence of MACE (a composite of death, myocardial infarction, target vessel revascularization, and stent thrombosis) was the secondary endpoint. A total of 285 patients OCT-guided and 1,547 angiography guided patients were enrolled, resulting in 270 for each cohort after propensity score with matching. Two stents were used in 12% versus 34%; 3 stents in 8% versus 38% of the patients (P < 0.001). After a follow up of 700 days (450-890), there was no difference in myocardial infarction (6% vs. 6%, P = 0.86), while MACE (11% vs. 16%, P = 0.06), target vessel revascularization (2% vs. 4%, P = 0.15) and stent thrombosis rates (0% vs. 2.7%, P = 0.26) were numerically lower for the OCT-guided cohort but none of these endpoints did reach statistical significance. CONCLUSIONS: An OCT-guided approach reduced the number of stents used, number of patients treated with more than one stent, while there was no statistically significant difference in clinical endpoints while most of them were numerically lower, including stent thrombosis rates. © 2016 Wiley Periodicals, Inc.

THE STORM (acute coronary Syndrome in paTients end Of life and Risk assesMent) study.

INTRODUCTION: Elderly patients with coexisting frailty and multiple comorbidities frequently present to the emergency department (ED). Because non-cardiovascular comorbidities and declining health status may affect their life expectancy, management of these patients should start in the ED. This study evaluated the role of Gold Standards Framework (GSF) criteria for identifying patients with acute coronary syndromes (ACS) approaching end of life. METHODS: All consecutive patients admitted to the ED and hospitalised with a diagnosis of ACS between May 2012 and July 2012 were included. According to GSF criteria, patients were labelled as positive GSF status when they met at least one general criterion and two heart disease criteria; furthermore, traditional cardiovascular risk scores (the Global Registry for Acute Coronary Events (GRACE) score and the Age, Creatinine and Ejection Fraction (ACEF) score) were calculated and WHOQOL-BREF was assessed. Mortality and repeat hospitalisation due to cardiovascular and non-cardiovascular causes were evaluated at 3-month and 12-month follow-up. RESULTS: From a total of 156 patients with ACS enrolled, 22 (14%) had a positive GSF. A positive GSF was associated with higher rate of non-cardiovascular events (22.7% vs 6.7%; p=0.03) at 3 months and higher rates of both cardiovascular and non-cardiovascular events (36% vs 16.4%; p=0.04 and 27.3% vs 6.7%; p=0.009, respectively) at 12 months. In multivariate analysis, an in-hospital GRACE score was a predictor of cardiovascular events, while a positive GSF independently predicted non-cardiovascular events. CONCLUSIONS: The GSF score independently predicts non-cardiovascular events in patients presenting with ACS and may be used along with traditional cardiovascular risk scores in choosing wisely the most appropriate treatment. The present results need to be externally validated on larger samples.

Impact on prognosis of periprocedural myocardial infarction after percutaneous coronary intervention.

INTRODUCTION: Different definitions of periprocedural myocardial infarction (MI) after percutaneous coronary intervention (PCI) have been provided, but their impact on prognosis remains to be determined. METHODS: Procedural data from consecutive patients undergoing PCI from 2009 to 2011 were revised to adjudicate diagnosis of periprocedural MI according to CK-MB increase (>3 × URL and >5 × URL), to troponin increase (>3 × 99th percentile URL and >5 × 99th percentile URL) and to recent 2012 Task Force and Society for Cardiovascular Angiography and Interventions (SCAI) definitions. Major adverse cardiovascular events (MACE) was the primary end-point. RESULTS: Seven hundred twelve patients were enrolled; after 771 days, 115 (16.7%) patients experienced MACE. One hundred ninety patients were diagnosed with a periprocedural MI defined as elevation of troponin >5 × 99th percentile of URL. When adjudicating 2012 Task Force definition on these patients, 46 were excluded and 1.4% of them experienced a MACE and 0.3% died, while among 144 with periprocedural MI, 2.9% reported a MACE and 1.3% died. After appraisal of SCAI definition, 176 patients were excluded, 3.8% of them with a MACE and 1.4% died, and for those with periprocedural MI, 0.5% experienced a MACE and 0.1% died. Similar low performance was appraised after reclassification of patients from more than 3 of upper limit of CK-MB and of troponin. At multivariate analysis, none of these definitions related to adverse events. CONCLUSION: Periprocedural MI represents a frequent complication for patients undergoing PCI. All present definitions share a still not satisfactory discrimination between patients with and without adverse events at follow-up, stressing the need for more accurate definitions.

Transitioning to Palliative Care in an Italian Cardiac Intensive Care Unit Network.

BACKGROUND: Recent data indicate that end-of-life management for patients affected by acute decompensated heart failure in cardiac intensive care units is aggressive, with late or no engagement of palliative care teams. OBJECTIVE: To assess current palliative care and end-of-life practices in a contemporary Italian multicenter registry of patients with cardiogenic shock due to acute decompensated heart failure. METHODS: A survey-based approach was used to collect data on palliative care and end-of-life management practices. The AltShock-2 registry enrolled patients with cardiogenic shock from 12 participating centers. A subset of 153 patients with cardiogenic shock due to acute decompensated heart failure enrolled between March 2020 and March 2023 was analyzed, with a focus on early engagement of palliative care teams and deactivation of implantable cardioverter-defibrillators (ICDs). RESULTS: "Do not resuscitate" orders were documented in patient records in only 5 of 12 centers (42%). Palliative care teams were engaged for 21 of 153 enrolled patients (13.7%). Among the 51 patients with ICDs, 6 of 17 patients who died (35%) had defibrillator deactivation. Of the 17 patients who died, 13 died in the hospital and 4 died within 6 months after discharge; 1 patient had ICD deactivation supported by palliative care services at home. CONCLUSIONS: Therapy-limiting practices, including ICD deactivation, are not routine in the Italian centers participating in this study. The results emphasize the importance of integrating palliative care as a simultaneous process with intensive care to address the unmet needs of these patients and their families.

Differences between cardiogenic shock related to acute decompensated heart failure and acute myocardial infarction.

AIMS: The present analysis from the multicentre prospective Altshock-2 registry aims to better define clinical features, in-hospital course, and management of cardiogenic shock complicating acutely decompensated heart failure (ADHF-CS) as compared with that complicating acute myocardial infarction (AMI-CS). METHODS AND RESULTS: All patients with AMI-CS or ADHF-CS enrolled in the Altshock-2 registry between March 2020 and February 2022 were selected. The primary objective was the characterization of ADHF-CS patients as compared with AMI-CS. In-hospital length of stay and mortality were secondary endpoints. One-hundred-ninety of the 238 CS patients enrolled in the aforementioned period were considered for the present analysis: 101 AMI-CS (80% ST-elevated myocardial infarction and 20% non-ST-elevated myocardial infarction) and 89 ADHF-CS. As compared with AMI-CS, ADHF-CS patients were younger [63 (IQR 59-76) vs. 67 (IQR 54-73) years, P = 0.01], but presented with higher creatinine [1.6 (IQR 1.0-2.6) vs. 1.2 (IQR 1.0-1.4) mg/dL, P < 0.001], bilirubin [1.3 (IQR 0.9-2.3) vs. 0.6 (IQR 0.4-1.1) mg/dL, P = 0.01], and central venous pressure values [14 mmHg (IQR 8-12) vs. 10 mmHg (IQR 7-14),P = 0.01]. Norepinephrine was the most common catecholamine used in AMI-CS (79.3%), whereas epinephrine was used more commonly in ADHF-CS (65.5%); 75.8% vs. 46.6% received a temporary mechanical support in AMI-CS and ADHF-CS, respectively (P < 0.001). Length of hospital stay was longer in the latter [28 (IQR 13-48) vs. 17 (IQR 9-29) days, P = 0.001]. Heart replacement therapies were more frequently used in the ADHF-CS group (heart transplantation 13.5% vs. 0% and left ventricular assist device 11% vs. 2%, P < 0.01 and 0.01, respectively). In-hospital mortality was 41.1% (38.6% AMI-CS vs. 43.8% ADHF-CS, P = 0.5). CONCLUSIONS: ADHF-CS is characterized by a higher prevalence of end-organ and biventricular dysfunction at presentation, a longer hospital length of stay, and higher need of heart replacement therapies when compared with AMI-CS. In-hospital mortality was similar between the two aetiologies. Our data warrant development of new management protocols focused on CS aetiology.

Pulmonary Artery Catheter Monitoring in Patients with Cardiogenic Shock: Time for a Reappraisal?

Cardiogenic shock represents one of the most dramatic scenarios to deal with in intensive cardiology care and is burdened by substantial short-term mortality. An integrated approach, including timely diagnosis and phenotyping, along with a well-established shock team and management protocol, may improve survival. The use of the Swan-Ganz catheter could play a pivotal role in various phases of cardiogenic shock management, encompassing diagnosis and haemodynamic characterisation to treatment selection, titration and weaning. Moreover, it is essential in the evaluation of patients who might be candidates for long-term heart-replacement strategies. This review provides a historical background on the use of the Swan-Ganz catheter in the intensive care unit and an analysis of the available evidence in terms of potential prognostic implications in this setting.

Prognostic implications of pulmonary artery catheter monitoring in patients with cardiogenic shock: A systematic review and meta-analysis of observational studies.

PURPOSE: To investigate the impact of pulmonary artery catheter (PAC) monitoring on survival of cardiogenic shock(CS), in the light of the controversies in available evidence. MATERIALS AND METHODS: MEDLINE, EMBASE, Cochrane library and Web of Science were systematically screened to identify most relevant studies on patients with CS comparing PAC use to non-use during hospital stay. Short-term mortality was the primary endpoint and the use of Mechanical Circulatory Support (MCS) devices was the secondary one. RESULTS: Six observational studies including 1,166,762 patients were selected. The most frequent etiology of CS was post-myocardial infarction (75% [95% CI 55-89%] in PAC-group and 81%[95% CI 47-95%] in non-PAC group). Overall, PAC was used in 33%(95% CI 24-44%) of cases. Pooling data adjusted for confounders, a significant association between the PAC-group and a reduction in short-term mortality emerged when compared to the non-PAC group (36%[95% CI 27-45%] vs 47%[95% CI 35-59%];AdjustedOR 0.71, 95% CI 0.59-0.87, p < 0.01). MCS use was significantly higher in PAC vs non-PAC group (59% [95% CI 54-65%]) vs 48% [95% CI 43-53%]);OR 1.60 [95% CI 1.27-2.02, p < 0.01]). CONCLUSIONS: PAC was associated with lower incidence of short-term mortality in CS pooling adjusted observational studies. Prospective studies are needed to confirm our hypothesis and better clarify the mechanisms of this potential prognostic benefit.

Comparison of ECMO vs ECpella in Patients With Non-Post-Pericardiotomy Cardiogenic Shock: An Updated Meta-Analysis.

INTRODUCTION: The impact of Impella and ECMO (ECPELLA) in cardiogenic shock (CS) remains to be defined. The aim of this meta-analysis is to evaluate the benefit of ECPELLA compared to VA-ECMO in patients with non post-pericardiotomy CS. METHODS: All studies reporting short term outcomes of ECpella or VA ECMO in non post-pericardiotomy CS were included. The primary endpoint was 30-day mortality. Vascular and bleeding complications and LVAD implantation/heart transplant within 30-days were assessed as secondary outcomes. RESULTS: Of 407 studies identified, 13 observational studies (13,682 patients, 13,270 with ECMO and 412 with ECpella) were included in this analysis. 30-day mortality was 55.8% (51.6-59.9) in the VA-ECMO group and 58.3% (53.5-63.0) in the ECpella group. At meta-regression analysis the implantation of IABP did not affect mortality in the ECMO group. The rate of major bleeding in patients on VA-ECMO and ECpella support were 21.3% (16.9-26.5) and 33.1% (25.9-41.2) respectively, while the rates of the composite outcome of LVAD implantation and heart transplantation within 30-days in patients on VA-ECMO and ECpella support were 14.4% (9.0-22.2) and 10.8%. When directly compared in 3 studies, ECpella showed a positive effect on 30-day mortality compared to ECMO (OR: 1.81: 1.039-3.159). CONCLUSION: Our data suggest that ECpella may reduce 30-day mortality and increase left ventricle recovery, despite increased of bleeding rates.

Impact of lipid-lowering therapies on cardiovascular outcomes according to coronary artery calcium score. A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Coronary artery calcium (CAC) score improves the accuracy of risk stratification for atherosclerotic cardiovascular disease (ASCVD) events compared with traditional cardiovascular risk factors. We evaluated the interaction of coronary atherosclerotic burden as determined by the CAC score with the prognostic benefit of lipid-lowering therapies in the primary prevention setting. METHODS: We reviewed the MEDLINE, EMBASE, and Cochrane databases for studies including individuals without a previous ASCVD event who underwent CAC score assessment and for whom lipid-lowering therapy status stratified by CAC values was available. The primary outcome was ASCVD. The pooled effect of lipid-lowering therapy on outcomes stratified by CAC groups (0, 1-100,> 100) was evaluated using a random effects model. RESULTS: Five studies (1 randomized, 2 prospective cohort, 2 retrospective) were included encompassing 35 640 individuals (female 38.1%) with a median age of 62.2 [range, 49.6-68.9] years, low-density lipoprotein cholesterol level of 128 (114-146) mg/dL, and follow-up of 4.3 (2.3-11.1) years. ASCVD occurrence increased steadily across growing CAC strata, both in patients with and without lipid-lowering therapy. Comparing patients with (34.9%) and without (65.1%) treatment exposure, lipid-lowering therapy was associated with reduced occurrence of ASCVD in patients with CAC> 100 (OR, 0.70; 95%CI, 0.53-0.92), but not in patients with CAC 1-100 or CAC 0. Results were consistent when only adjusted data were pooled. CONCLUSIONS: Among individuals without a previous ASCVD, a CAC score> 100 identifies individuals most likely to benefit from lipid-lowering therapy, while undetectable CAC suggests no treatment benefit.

Underlying heart diseases and acute COVID-19 outcomes.

BACKGROUND: The presence of any underlying heart condition could influence outcomes during the coronavirus disease 2019 (COVID-19). METHODS: The registry HOPE-COVID-19 (Health Outcome Predictive Evaluation for COVID-19, NCT04334291) is an international ambispective study, enrolling COVID-19 patients discharged from hospital, dead or alive. RESULTS: HOPE enrolled 2798 patients from 35 centers in 7 countries. Median age was 67 years (IQR: 53.0-78.0), and most were male (59.5%). A relevant heart disease was present in 682 (24%) cases. These were older, more frequently male, with higher overall burden of cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, smoking habit, obesity) and other comorbidities such renal failure, lung, cerebrovascular disease and oncologic antecedents (p < 0.01, for all). The heart cohort received more corticoids (28.9% vs. 20.4%, p < 0.001), antibiotics, but less hydroxychloroquine, antivirals or tocilizumab. Considering the epidemiologic profile, a previous heart condition was independently related with shortterm mortality in the Cox multivariate analysis (1.62; 95% CI 1.29-2.03; p < 0.001). Moreover, heart patients needed more respiratory, circulatory support, and presented more in-hospital events, such heart failure, renal failure, respiratory insufficiency, sepsis, systemic infammatory response syndrome and clinically relevant bleedings (all, p < 0.001), and mortality (39.7% vs. 15.5%; p < 0.001). CONCLUSIONS: An underlying heart disease is an adverse prognostic factor for patients suffering COVID-19. Its presence could be related with different clinical drug management and would benefit from maintaining treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers during in-hospital stay.

Long versus short dual antiplatelet therapy in acute coronary syndrome patients treated with prasugrel or ticagrelor and coronary revascularization: Insights from the RENAMI registry.

INTRODUCTION: The benefits of short versus long-term dual antiplatelet therapy (DAPT) based on the third generation P2Y12 antagonists prasugrel or ticagrelor, in patients with acute coronary syndromes treated with percutaneous coronary intervention remain to be clearly defined due to current evidences limited to patients treated with clopidogrel. METHODS: All acute coronary syndrome patients from the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) undergoing percutaneous coronary intervention and treated with aspirin, prasugrel or ticagrelor were stratified according to DAPT duration, that is, shorter than 12 months (D1 group), 12 months (D2 group) and longer than 12 months (D3 group). The three groups were compared before and after propensity score matching. Net adverse clinical events (NACEs), defined as a combination of major adverse cardiac events (MACEs) and major bleedings (including therefore all cause death, myocardial infarction and Bleeding Academic Research Consortium (BARC) 3-5 bleeding), were the primary end points, MACEs (a composite of all cause death and myocardial infarction) the secondary one. Single components of NACEs were co-secondary end points, along with BARC 2-5 bleeding, cardiovascular death and stent thrombosis. RESULTS: A total of 4424 patients from the RENAMI registry with available data on DAPT duration were included in the model. After propensity score matching, 628 patients from each group were selected. After 20 months of follow up, DAPT for 12 months and DAPT for longer than 12 months significantly reduced the risk of NACE (D1 11.6% vs. D2 6.7% vs. D3 7.2%, p = 0.003) and MACE (10% vs. 6.2% vs. 2.4%, p < 0.001) compared with DAPT for less than 12 months. These differences were driven by a reduced risk of all cause death (7.8% vs. 1.3% vs. 1.6%, p < 0.001), cardiovascular death (5.1% vs. 1.0% vs. 1.2%, p < 0.0001) and recurrent myocardial infarction (8.3% vs. 5.2% vs. 3.5%, p = 0.002). NACEs were lower with longer DAPT despite a higher risk of BARC 2-5 bleedings (4.6% vs. 5.7% vs. 6.2%, p = 0.04) and a trend towards a higher risk of BARC 3-5 bleedings (2.4% vs. 3.3% vs. 3.9%, p = 0.06). These results were not consistent for female patients and those older than 75 years old, due to an increased risk of bleedings which exceeded the reduction in myocardial infarction. CONCLUSION: In unselected real world acute coronary syndrome patients treated with percutaneous coronary intervention, DAPT with prasugrel or ticagrelor prolonged beyond 12 months markedly reduces fatal and non-fatal ischaemic events, offsetting the increased risk deriving from the higher bleeding risk. On the contrary, patients >75 years old and female ones showed a less favourable risk-benefit ratio for longer DAPT due to excess of bleedings.

Impact of aspirin on takotsubo syndrome: a propensity score-based analysis of the InterTAK Registry.

AIMS: The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS). METHODS AND RESULTS: Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50-3.04, P = 0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78-1.58, P = 0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting. CONCLUSION: In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621.

Prognostic impact of MitraClip in patients with left ventricular dysfunction and functional mitral valve regurgitation: A comprehensive meta-analysis of RCTs and adjusted observational studies.

The real prognostic impact of MitraClip in patients with significant functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction remains to be elucidated. Two randomized controlled trials (RCTs) with conflicting results have been recently published. We conducted a comprehensive meta-analysis of all RCTs and adjusted observational studies to evaluate the clinical impact of percutaneous mitral valve repair when compared with optimal medical therapy (OMT) alone, in patients with symptomatic FMR and LV dysfunction. Death from any cause and heart failure rehospitalizations at the longest available follow-up were the primary endpoints. Cardiac death, one year and short-term death were the secondary ones. 2255 patients (1207 for MitraClip and 1048 for OMT-only) from 8 studies (2 RCTs and 6 observational studies) were included. At a median (mid-term) follow-up of 438 days (IQR 360-625) MitraClip was associated with a significant reduction of all-cause death (odds Ratio [OR] 0.55, 95%CI 0.41-0.73, p < 0.001; [ORadj] 0.66, 95%CI 0.49-0.90, p = 0.009) and rehospitalization (OR 0.49, 95%CI 0.24-1.00, p = 0.05 and ORadj 0.63, 95%CI 0.43-0.94, p = 0.02). At one year, adjusted analysis demonstrated a trend favoring the experimental cohort (ORadj 0.73, 95%CI 0.53-1.02, p = 0.07). Meta-regression suggested that benefit of MitraClip on mid-term survival persists even after accounting for the prevalence of implanted CRT, burden of comorbidities, NYHA class, cardiomyopathy etiology and LV function and dimensions. In conclusion, MitraClip for FMR in patients with LV dysfunction is associated with a considerable reduction of death and HF hospitalization at mid-term follow-up. Further ongoing RCTs are needed to strengthen present results.

Diagnostic accuracy of functional, imaging and biochemical tests for patients presenting with chest pain to the emergency department: A systematic review and meta-analysis.

BACKGROUND: Non-invasive ischaemia tests and biomarkers are widely adopted to rule out acute coronary syndrome in the emergency department. Their diagnostic accuracy has yet to be precisely defined. METHODS: Medline, Cochrane Library CENTRAL, EMBASE and Biomed Central were systematically screened (start date 1 September 2016, end date 1 December 2016). Prospective studies (observational or randomised controlled trial) comparing functional/imaging or biochemical tests for patients presenting with chest pain to the emergency department were included. RESULTS: Overall, 77 studies were included, for a total of 49,541 patients (mean age 59.9 years). Fast and six-hour highly sensitive troponin T protocols did not show significant differences in their ability to detect acute coronary syndromes, as they reported a sensitivity and specificity of 0.89 (95% confidence interval 0.79-0.94) and 0.84 (0.74-0.9) vs 0.89 (0.78-0.94) and 0.83 (0.70-0.92), respectively. The addition of copeptin to troponin increased sensitivity and reduced specificity, without improving diagnostic accuracy. The diagnostic value of non-invasive tests for patients without troponin increase was tested. Coronary computed tomography showed the highest level of diagnostic accuracy (sensitivity 0.93 (0.81-0.98) and specificity 0.90 (0.93-0.94)), along with myocardial perfusion scintigraphy (sensitivity 0.85 (0.77-0.91) and specificity 0.92 (0.83-0.96)). Stress echography was inferior to coronary computed tomography but non-inferior to myocardial perfusion scintigraphy, while exercise testing showed the lower level of diagnostic accuracy. CONCLUSIONS: Fast and six-hour highly sensitive troponin T protocols provide an overall similar level of diagnostic accuracy to detect acute coronary syndrome. Among the non-invasive ischaemia tests for patients without troponin increase, coronary computed tomography and myocardial perfusion scintigraphy showed the highest sensitivity and specificity.

Prasugrel or ticagrelor in patients with acute coronary syndrome and diabetes: a propensity matched substudy of RENAMI.

INTRODUCTION: The safety and efficacy of prasugrel and ticagrelor in patients with diabetes mellitus presenting with acute coronary syndrome and treated with percutaneous coronary intervention remain to be assessed. METHODS: All diabetes patients admitted for acute coronary syndrome and enrolled in the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) were compared before and after propensity score matching. Net adverse cardiovascular events (composite of death, stroke, myocardial infarction and BARC 3-5 bleedings) and major adverse cardiovascular events (composite of death, stroke and myocardial infarction) were the co-primary endpoints. Single components of primary endpoints were secondary endpoints. RESULTS: Among 4424 patients enrolled in RENAMI, 462 and 862 diabetes patients treated with prasugrel and ticagrelor, respectively, were considered. After propensity score matching, 386 patients from each group were selected. At 19±5 months, major adverse cardiovascular events and net adverse cardiovascular events were similar in the prasugrel and ticagrelor groups (5.4% vs. 3.4%, P=0.16 and 6.7% vs. 4.1%, P=0.11, respectively). Ticagrelor was associated with a lower risk of death and BARC 2-5 bleeding when compared to prasugrel (2.8% vs. 0.8%, P=0.031 and 6.0% vs. 2.6%, P=0.02, respectively) and a clear but not significant trend for a reduction of BARC 3-5 bleeding (2.3% vs. 0.8%, P=0.08). There were no significant differences in myocardial infarction recurrence and stent thrombosis. CONCLUSION: Diabetes patients admitted for acute coronary syndrome seem to benefit equally in terms of major adverse cardiovascular events from ticagrelor or prasugrel use. Ticagrelor was associated with a significant reduction in all-cause death and bleedings, without differences in recurrent ischaemic events, which should be confirmed in dedicated randomised controlled trials.