<div><h4>Effects of Renin-Angiotensin system blockers on outcomes from COVID-19: A systematic review and meta-analysis of randomised controlled trials.</h4><i>Lee MMY, Kondo T, Campbell RT, Petrie MC, ... Jhund PS, McMurray JJV</i><br /><b>Background:</b><br/>and aims</b><br />Randomised controlled trials (RCTs) have assessed the effects of renin-angiotensin system (RAS) blockers in adults with COVID-19. This meta-analysis provides estimates of the safety and efficacy of treatment with (versus without) RAS blockers from these trials.<br /><b>Methods</b><br />PubMed, Web of Science, and ClinicalTrials.gov were searched (March 1-April 12, 2023). Event/patient numbers were extracted, comparing ACE inhibitor/ARB treatment, to no treatment, for the outcomes: intensive care unit (ICU) admission, mechanical ventilation, vasopressor use, acute kidney injury (AKI), renal replacement therapy (RRT), acute myocardial infarction, stroke/transient ischaemic attack, heart failure, thromboembolic events, and all-cause death. Fixed-effects meta-analysis estimates were pooled.<br /><b>Results</b><br />Sixteen RCTs including 3492 patients were analysed. Compared with discontinuation of RAS blockers, continuation was not associated with increased risk of ICU (RR 0.96, 0.66-1.41), ventilation (RR 0.77, 0.55-1.09), vasopressors (RR 0.92, 0.58-1.44), AKI (RR 1.01, 0.40-2.56), RRT (RR 1.01, 0.46-2.21), or thromboembolic events (RR 1.07, 0.36-3.19). RAS blocker initiation was not associated with increased risk of ICU (RR 0.71, 0.47-1.08), ventilation (RR 1.12, 0.91-1.38), AKI (RR 1.28, 0.89-1.86), RRT (RR 1.66, 0.89-3.12), or thromboembolic events (RR 1.20, 0.06-23.70), although vasopressor use increased (RR 1.27, 1.02-1.57). The RR for all-cause death in the continuation/discontinuation trials was 1.24 (0.80-1.92), and 1.22 (0.96-1.55) in the initiation trials. In patients with severe/critical COVID-19, RAS blocker initiation increased the risk of all-cause death (RR 1.31, 1.01-1.72).<br /><b>Conclusion</b><br />ACE inhibitors and ARBs may be continued in non-severe COVID-19 infection, where indicated. Conversely, initiation of RAS blockers may be harmful in critically ill patients. PROSPERO registration number: CRD42023408926.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 22 Sep 2023; epub ahead of print</small></div>

<div><h4>Characteristics and outcomes in patients with a prior myocardial infarction treated with extended dual antiplatelet therapy with ticagrelor 60 mg: findings from ALETHEIA, a multi-country observational study.</h4><i>Bonaca M, Lesén E, Giannitsis E, Hedberg J, ... Ten Berg J, Storey RF</i><br /><b>Background</b><br />Guidelines recommend extended dual antiplatelet therapy (DAPT), including ticagrelor 60 mg twice daily, in high-risk post myocardial infarction (MI) patients who have tolerated 12 months and are not at high bleeding risk. The real-world utilization and bleeding and ischemic outcomes associated with long-term ticagrelor 60 mg in routine clinical practice have not been well described.<br /><b>Methods</b><br />Register and claims data from US (Optum Clinformatics, IBM MarketScan, Medicare) and Europe (Sweden, Italy, UK, Germany) were extracted. Patients initiating ticagrelor 60 mg ≥ 12 months after MI, meeting eligibility criteria for PEGASUS-TIMI 54 trial, were included. The cumulative incidence of the composite of MI, stroke, or all-cause mortality, and of bleeding requiring hospitalization were calculated. Meta-analyses were performed to combine estimates from each source.<br /><b>Results</b><br />7 035 patients treated with ticagrelor 60 mg met eligibility criteria. Median age was 67 years and 29% were females; 12% had a history of multiple MIs. The majority (95%) had been treated with ticagrelor 90 mg prior to initiating ticagrelor 60 mg. At 12 months from initiation of ticagrelor 60 mg, the cumulative incidence (95% CI) of MI, stroke or mortality was 3.33% (2.73-4.04) and was approximately three-fold the risk of bleeding (0.96%; 0.69-1.33).<br /><b>Conclusions</b><br />This study provides insights into the use of ticagrelor 60 mg in patients with prior MI in clinical practice. Observed event rates for ischemic events and bleeding generally align with those in the pivotal trials, support the established safety profile of ticagrelor, and highlight the significant residual ischemic risk in this population.Clinical Trials.gov Registration NCT04568083.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 31 Aug 2023; epub ahead of print</small></div>

<div><h4>External validity of the PRECISE-DAPT score in patients undergoing PCI: a systematic review and meta-analysis.</h4><i>Munafò AR, Montalto C, Franzino M, Pistelli L, ... Micari A, Costa F</i><br /><b>Aims</b><br />To summarise the totality of evidence validating the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score, ascertaining its aggregate discrimination and validation power in multiple population subsets.<br /><b>Methods and results</b><br />We searched electronic databases from 2017 (PRECISE-DAPT proposal) up to March 2023 for studies that reported the occurrence of out-of-hospital bleedings according to the PRECISE-DAPT score in patients receiving DAPT following percutaneous coronary intervention (PCI). Pooled odds ratio (OR) with 95% confidence interval (CI) were used as summary statistics and were calculated using a random-effects model. Primary and secondary endpoints were the occurrence of any and major bleeding, respectively. A total of twenty-one studies and 67 283 patients were included; 24.7% of patients (N = 16 603) were at high-bleeding risk (PRECISE-DAPT ≥ 25) and when compared to those at low-bleeding risk, they experienced a significantly higher rate of any out-of-hospital bleeding (OR: 2.71; 95% CI: 2.24-3.29; p-value < 0.001) and major bleedings (OR: 3.51; 95% CI: 2.71-4.55; p-value < 0.001). Pooling data on c-stat whenever available, the PRECISE-DAPT score showed a moderate discriminative power in predicting major bleeding events at 1-year (pooled c-stat: 0.71; 95% CI: 0.64-0.77).<br /><b>Conclusion</b><br />This systematic review and meta-analysis confirms the external validity of the PRECISE-DAPT score in predicting out-of-hospital bleeding outcomes in patients on DAPT following PCI. The moderate discriminative ability highlights the need for future improved risk prediction tools in the field.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 26 Aug 2023; epub ahead of print</small></div>

<div><h4>Impact of transfusion strategy on platelet aggregation and biomarkers in myocardial infarction patients with anemia.</h4><i>Silvain J, Lattuca B, Puymirat E, Ducrocq G, ... Simon T, Steg PG</i><br /><b>Background</b><br />Higher rates of thrombotic events have been reported in myocardial infarction (MI) patients requiring blood transfusion. The impact of blood transfusion strategy on thrombosis and inflammation is still unknown.<br /><b>Objective</b><br />To compare the impact of a liberal vs. a restrictive transfusion strategy on P2Y12 platelet reactivity and biomarkers in the multicentric randomized REALITY trial.<br /><b>Methods</b><br />Patients randomized to a liberal (hemoglobin ≤10 g/dL) or a restrictive (hemoglobin ≤8 g/dL) transfusion strategy had VASP-PRI platelet reactivity measured centrally in a blinded fashion and platelet reactivity unit (PRU) measured locally using encrypted VerifyNow; at baseline and after randomization. Biomarkers of thrombosis (P-selectin, PAI-1, vWF) and inflammation (TNF-α) were also measured. The primary endpoint was the change in the VASP-PRI (difference from baseline and post randomization) between the randomized groups.<br /><b>Results</b><br />A total of 100 patients randomized were included in this study (n = 50 in each group). Transfused patients received on average 2.4 ± 1.6 units of blood. We found no differences in change of the VASP PRI (difference 1.2% 95% CI (-10.3-12.7%)) or by the PRU (difference 13.0 95% CI (-21.8-47.8)) before and after randomization in both randomized groups. Similar results were found in transfused patients (n = 71) regardless of the randomized group, VASP PRI (difference 1.7%; 95% CI (-9.5-1.7%)) or PRU (difference 27.0; 95% CI (-45.0-0.0)). We did not find an impact of transfusion strategy or transfusion itself in the levels of P-selectin, PAI-1, vWF, and TNF-α.<br /><b>Conclusion</b><br />In this study, we found no impact of a liberal vs. a restrictive transfusion strategy on platelet reactivity and biomarkers in MI patients with anemia. A conclusion that should be tempered due to missing patients with exploitable biological data that has affected our power to show a difference.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 23 Aug 2023; epub ahead of print</small></div>

<div><h4>Platelet inhibition with orodispersible ticagrelor in acute coronary syndromes according to morphine use: the TASTER study final results.</h4><i>Parodi G, Dossi F, Raccis M, Talanas G, ... Sanna GD, Canonico ME</i><br /><b>Aim</b><br />To date, it is still unknown whether orodispersible tablet (ODT) ticagrelor might represent a suitable way to reach a proper antiaggregation in acute coronary syndrome (ACS) patients receiving morphine. Aim of the present study was to evaluate platelet inhibition with 180 mg ticagrelor loading dose (LD) administered as ODT compared with standard coated tablet ticagrelor formulation in ACS patients undergoing percutaneous coronary intervention (PCI) according to morphine use.<br /><b>Methods & results</b><br />One-hundred and 30 patients presenting with STEMI or very high-risk NSTE-ACS were randomly assigned to receive ODT or standard ticagrelor LD. Potential morphine-ticagrelor interaction was assessed by stratified randomization according to morphine use. Platelet reactivity was evaluated by Platelet Reactivity Units (PRU) VerifyNow™ฏ 1, 2, 4 and 6 hours after ticagrelor LD. The primary endpoint was residual platelet reactivity 1 hour after LD across the two ticagrelor formulation and according to morphine use. Safety endpoints were major bleedings and other in-hospital ticagrelor administration-related adverse events. One hour after LD, PRU median value was higher in morphine-treated patients (N=32) as compared with patients not receiving morphine (N=98; PRU= 187 [70-217]) vs 73 [7-187]; p=0.012). In patients with morphine, 1-hour PRU values were similar between study groups (192 [114-236] vs 173 [16-215] in ODT and standard tablet ticagrelor, respectively). Similarly, in patients without morphine, 1-hour PRU values were not significantly different between study groups (69 [8-152] vs 110 [6 - 193] in ODT and standard tablet ticagrelor, respectively). Platelet reactivity appeared similar in the 2 study arms at 2, 4 and 6 hours after LD. No significant difference was observed among patients with or without morphine regarding in-hospital adverse events or drug side-effects, even if a reinfarction due to acute stent thrombosis was observed in a patient treated with morphine.<br /><b>Conclusions</b><br />There was no difference between ODT and standard ticagrelor tablets in terms of post-LD residual platelet reactivity, percentage of platelet inhibition or safety regardless to morphine use.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 17 Aug 2023; epub ahead of print</small></div>

<div><h4>Clinical Outcomes in Elderly Atrial Fibrillation Patients at Increased Bleeding Risk Treated with Very-Low-Dose versus Regular-Dose Non-Vitamin K Antagonist Oral Anticoagulants: a Nationwide Cohort Study.</h4><i>Chan YH, Chao TF, Chen SW, Lee HF, ... See LC, Lip GYH</i><br /><b>Aims</b><br />The ELDERCARE-AF trial showed that edoxaban at a very-low-dosage (VLD) of 15 mg/day was more effective than a placebo at preventing stroke/systemic embolism without significantly increasing the risk of serious bleeding. We aimed to compare the effectiveness and safety for VLD non-vitamin K antagonist oral anticoagulants (NOACs) (edoxaban 15 mg once daily, dabigatran 110 or 150 once daily, apixaban 2.5 mg once daily, or rivaroxaban 10 mg (without the diagnosis of chronic kidney disease) or less than 10 mg once daily) versus regular-dosage (RD) NOACs (edoxaban 60/30 mg once daily or other labeling-dosage NOACs) among a real-world cohort of elderly AF population similar to the ELDERCARE-AF cohort.<br /><b>Methods and results</b><br />In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database (NHIRD), we identified a total of 7 294 and 4 151 consecutive AF patients aged 80 years or older with a CHADS2 score ≥ 2 who met the enrollment criteria (generally similar to ELDERCARE-AF) taking VLD and RD NOACs from June 1, 2012, to December 31, 2019, respectively. Propensity-score stabilized weighting (PSSW) was used to balance covariates across study groups. Patients were followed up from the first date of prescription for NOACs until the first occurrence of any study outcome, death, or until the end date of the study period (December 31, 2020). After PSSW, VLD NOAC was associated with a comparable risk of ischemic stroke/systemic embolism and major bleeding but a higher risk of major adverse limb events (MALEs) requiring lower limb revascularization or amputation (Hazard ratio [HR]:1.54, 95% confidential interval [CI]:1.09-2.18; p = 0.014), venous thrombosis (HR:3.75,95%CI:1.56-8.97; p = 0.003), and all-cause mortality (HR:1.21,95%CI:1.15-1.29; p < 0.001) compared to RD NOACs. VLD NOACs showed worse outcomes in most net clinical benefits (NCOs). The main result was consistent based on on-treatment analysis or accounting for death as a competing risk. In general, the advantage of NCOs for the RD NOACs over VLD NOACs persisted in most high-risk subgroups, consistent with the main analysis (P for interaction > 0.05).<br /><b>Conclusions</b><br />Use of VLD NOACs was associated with a greater risk of arterial and venous thrombosis, death as well as the composite outcomes, when compared to that of RD NOAC in high-risk elderly AF patients at increased bleeding risk. Thromboprophylaxis with RD NOAC is still preferable over VLD NOAC for the majority of elderly AF patients at increased bleeding risk.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 14 Aug 2023; epub ahead of print</small></div>

<div><h4>Bioinformatic platforms for clinical stratification of natural history of atherosclerotic cardiovascular diseases.</h4><i>Benincasa G, Suades R, Padrò T, Badimon L, Napoli C</i><br /><AbstractText>Although bioinformatic methods gained a lot of attention in the latest years, their use in real-world studies for primary and secondary prevention of atherosclerotic cardiovascular diseases (ASCVD) is still lacking. Bioinformatic resources have been applied to thousands of individuals from the Framingham Heart Study as well as health care-associated biobanks such as the UK Biobank, the Million Veteran Program, and the CARDIoGRAMplusC4D Consortium and randomized controlled trials (i.e. ODYSSEY, FOURIER, ASPREE, PREDIMED). These studies contributed to the development of polygenic risk scores (PRS) which emerged as novel potent genetic-oriented tools able to calculate the individual risk of ASCVD and to predict the individual response to therapies such as statins and PCSK9i. ASCVD are the first cause of death around the world including coronary heart disease (CHD), peripheral artery disease, and stroke. To achieve the goal of precision medicine and personalized therapy, advanced bioinformatic platforms are set to link clinically useful indices to heterogeneous molecular data, mainly epigenomics, transcriptomics, metabolomics and proteomics. The DIANA study found that differential methylation of ABCA1, TCF7, PDGFA, and PRKCZ significantly discriminated patients with acute coronary syndrome from healthy subjects and their expression levels positively associated with CK-MB serum concentrations. The ARIC Study revealed several plasma proteins, acting or not in lipid metabolism, with a potential role in determining the different pleiotropic effects of statins in each subject. The implementation of molecular high-throughput studies and bioinformatic techniques into traditional cardiovascular risk prediction scores is emerging as a more accurate practice to stratify patients earlier in life and to favour timely and tailored risk reduction strategies. Of note, radiogenomics aims to combine imaging features extracted for instance by coronary computed tomography angiography and molecular biomarkers to create CHD diagnostic algorithms useful to characterize atherosclerotic lesions and myocardial abnormalities. The current view is that such platforms could be of clinical value for prevention, risk stratification, and treatment of ASCVD.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 10 Aug 2023; epub ahead of print</small></div>

<div><h4>Post-Diagnostic Statin Use and its Association with Cancer Recurrence and Mortality in Breast Cancer Patients: A Systematic Review and Meta-analysis.</h4><i>Jaiswal V, Agrawal V, Ang SP, Saleeb M, ... Kalra K, Jaiswal A</i><br /><b>Background</b><br />Statins are widely acknowledged for their application in patients with hypercholesterolemia to reduce cardiovascular morbidity and mortality. More recently, their potential to exert pleiotropic effects, particularly in impeding the proliferation of neoplastic cells, has attracted considerable attention. Prior studies have demonstrated that statins may mitigate cancer progression and micrometastasis. However, the benefits of statins in breast cancer have been inconclusive.<br /><b>Objective</b><br />The aim of this meta-analysis was to evaluate the impact of statin use following a breast cancer diagnosis on breast cancer recurrence and mortality.<br /><b>Methods</b><br />We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 30th May 2023. Hazard ratios (HR) were pooled using a random-effect model. The primary outcome of interest was the risk of breast cancer recurrence. The secondary outcomes included breast cancer-specific mortality and all-cause mortality.<br /><b>Results</b><br />A total of 15 studies with 156,448 patients were included in the final analysis. The mean age of patients between statin users and non-users was 64.59 and 59.15 years, respectively. Statin use was associated with a reduction in the recurrence of breast cancer (HR 0.76, 95%CI: 0.67-0.87) compared with non-statin users. This trend was similar among lipophilic statin users (HR 0.73, 95%CI: 0.63-0.85) but not for hydrophilic statin users (HR 1.17, 95%CI: 0.82-1.68). Furthermore, all-cause mortality (HR 0.82, 95%CI: 0.66-1.02) and breast cancer mortality (HR 0.87, 95% CI: 0.69-1.10) were comparable between statin and non-statin users. However, lipophilic statins demonstrated a reduction in both all-cause mortality (HR 0.84, 95%CI: 0.75-0.93) and breast cancer mortality (HR 0.85, 95%CI: 0.74-0.99) compared to non-statin users.<br /><b>Conclusion</b><br />Among patients with breast cancer, statin use post-diagnosis decreases the risk of breast cancer recurrence. Furthermore, lipophilic statins exhibit an additional advantage of reducing both all-cause and breast cancer-specific mortality.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 10 Aug 2023; epub ahead of print</small></div>

<div><h4>The Effect of SGLT2 Inhibitors on the Endothelium and the Microcirculation: From Bench to Bedside and Beyond.</h4><i>Dimitriadis K, Adamopoulou E, Pyrpyris N, Sakalidis A, ... Aggeli K, Tsioufis K</i><br /><AbstractText>The beneficial cardiovascular effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors irrespective of the presence of diabetes mellitus are nowadays well established and they already constitute a significant pillar for the management of heart failure, irrespective of the ejection fraction. The exact underlying mechanisms accountable for these effects, however, remain largely unknown. The direct effect on endothelial function and microcirculation is one of the most well-studied. Preclinical data suggest that SGLT2 inhibitors directly affect endothelial function independently of glucose and specifically via several interplaying molecular pathways, resulting in improved vasodilation, increased NO production, enhanced mitochondrial homeostasis, endothelial cell viability and angiogenesis as well as attenuation of oxidative stress and inflammation. Clinical data systematically confirm this beneficial effect on the endothelium, whereas the evidence concerning the effect on the microcirculation is conflicting. The broad range of studies presented in this review aims to link all available data from the bench to bedside and highlight the existing gaps as well as the future directions in the investigations concerning the effects of SGLT2 inhibitors on the endothelium and the microcirculation.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 27 Jul 2023; epub ahead of print</small></div>

<div><h4>Platelet activation and endothelial dysfunction biomarkers in acute coronary syndrome: the impact of PCSK9 inhibition.</h4><i>Ziogos E, Chelko SP, Harb T, Engel M, ... Gerstenblith G, Leucker TM</i><br /><b>Aims</b><br />Platelet activation and endothelial dysfunction contribute to adverse outcomes in patients with acute coronary syndromes (ACS). The goals of this study were to assess the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on markers of platelet activation and endothelial dysfunction in ACS patients and the interaction among PCSK9, platelets, and endothelial cells (ECs) on left internal mammary artery (LIMA) vascular endothelium using specimens obtained during coronary artery bypass surgery (CABG).<br /><b>Methods and results</b><br />ACS patients enrolled in the Evolocumab in Acute Coronary Syndrome trials were randomized to placebo or a single dose of 420 mg evolocumab within 24 hours of hospitalization. Serum samples for analysis of platelet factor 4 (PF4) and P-selectin, markers of platelet activation, and von Willebrand factor (vWF), a marker of endothelial dysfunction, were obtained at baseline and 30 days. Additionally, LIMA segments obtained during CABG from patients who were and were not receiving evolocumab were immunostained with PCSK9; CD61, a platelet-specific marker; and CD31, an endothelial cell-specific marker. Forty-six participants were randomized to placebo or to evolocumab. Controlling for baseline levels, PF4 and vWF were significantly lower in the evolocumab, than in the placebo, group at 30 days. Immunostaining of LIMA specimens from twelve participants undergoing CABG revealed colocalization of PCSK9, CD61, and CD31 at the vascular endothelium. Administration of evolocumab was associated with decreased overlap of PCSK9, CD61, and CD31.<br /><b>Conclusions</b><br />PCSK9 inhibition decreases markers of platelet activation and endothelial dysfunction in ACS patients. PCSK9 is associated with platelets and vascular ECs in LIMA segments and PCSK9 inhibition decreases that interaction.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 19 Jul 2023; epub ahead of print</small></div>

<div><h4>Cardiovascular events in patients treated with bempedoic acid versus placebo: systematic review and meta-analysis.</h4><i>Mutschlechner D, Tscharre M, Huber K, Gremmel T</i><br /><b>Aims</b><br />Reduction of low-density lipoprotein cholesterol (LDL-C) decreases cardiovascular mortality and morbidity. Bempedoic acid represents a promising novel lipid modifying agent for patients who cannot reach guideline recommended LDL-C goals or statin-intolerant patients, but data on safety and cardiovascular outcomes are limited. We therefore aimed to systematically review randomized controlled trials investigating bempedoic acid versus placebo in patients with hyperlipidemia.<br /><b>Methods</b><br />A systematic search on the databases PubMed, Web of Science, and Embase until 20 March 2023 was performed. All randomized trials comparing bempedoic acid (180 mg daily) with placebo in patients with an indication for lipid-lowering therapy were included. As primary endpoint we analysed three-point major adverse cardiovascular events (MACE) consisting of cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke. The analysis was carried out using the odds ratio as the outcome measure. Due to the expected heterogeneity across studies a random-effects model was fitted to the data.<br /><b>Results</b><br />Out of 258 manuscripts, 10 manuscripts fulfilled the inclusion criteria. In total, these trials included 18,200 patients (9,765 on bempedoic acid, 8,435 on placebo). Bempedoic acid significantly reduced MACE compared to placebo (OR 0.84 [95% CI 0.76-0.96]; p<0.001; I2=0%). The endpoint reduction was driven by a lower rate of non-fatal MI, whereas bempedoic acid had no significant effect on stroke (OR 0.86 [95% CI 0.69-1.08]; p=0.20, I2=0%) and all-cause mortality (OR 1.19 [95% CI 0.73-1.93]; p=0.49; I2=18%).<br /><b>Conclusion</b><br />Bempedoic acid reduced non-fatal MI in patients with hyperlipidemia, whereas it had no significant effect on stroke and all-cause mortality.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 18 Jul 2023; epub ahead of print</small></div>

<div><h4>Bleeding risk and P2Y12-inhibitors in all-comer patients with ST-segment elevation myocardial infarction treated with percutaneous coronary intervention: a single-center cohort study.</h4><i>Jacobsen MR, Jabbari R, Engstrøm T, Grove EL, ... Kelbæk H, Sørensen R</i><br /><b>Aims</b><br />To characterise and follow patients with ST-segment elevation myocardial infarction (STEMI) at HBR (high bleeding risk) according to the PRECISE-DAPT score (predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy), and to examine the use of P2Y12-inhibitors and subsequent risk of major adverse cardiovascular events (MACE) and bleeding.<br /><b>Methods and results</b><br />This single-center cohort study included 6 179 consecutive STEMI patients who underwent percutaneous coronary intervention (PCI) at Copenhagen University Hospital, Rigshospitalet, between 2009-2016. Individual linkage to nationwide registries was conducted to obtain information on diagnoses, claimed drugs, and vital status. Of the 5 532 (89.5%) patients with available PRECISE-DAPT scores, 33.0% were at HBR and more often elderly and female with more comorbidities than non-HBR patients. One-year cumulative incidence rates per 100 person-years were 8.7 and 2.1 for major bleeding and 36.8 and 8.3 for MACE in HBR and non-HBR patients, respectively. Among the 4 749 (85.8%) patients who survived and collected a P2Y12-inhibitor ≤ 7 days from discharge, 68.2% of HBR patients were treated with ticagrelor or prasugrel and 31.8% with clopidogrel, while 18.2% non-HBR patients were treated with clopidogrel. Adherence was high for all (>75% days coverage). The risk of MACE was lower in ticagrelor and prasugrel than clopidogrel-treated patients without differences in major bleeding.<br /><b>Conclusion</b><br />One-third of PCI-treated all-comer patients with STEMI were at HBR according to the PRECISE-DAPT score and more often treated with potent P2Y12-inhibitors instead of clopidogrel. Thus, ischaemic risk may be weighted over bleeding risk in STEMI patients at HBR.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 04 Jul 2023; epub ahead of print</small></div>

<div><h4>The effect of discontinuing beta-blockers after different treatment durations following acute myocardial infarction in optimally treated, stable patients without heart failure - a Danish, nationwide cohort study.</h4><i>Halili A, Holt A, Eroglu TE, Haxha S, ... Torp-Pedersen C, Bang CN</i><br /><b>Aims</b><br />We studied the effect of discontinuing beta-blockers following myocardial infarction in comparison to continuous beta-blocker use in optimally treated, stable patients without heart failure.<br /><b>Methods and results</b><br />Using nationwide registers, we identified first-time myocardial infarction patients treated with beta-blockers following percutaneous coronary intervention or coronary angiography. The analysis was based on landmarks selected as 1, 2, 3, 4, and 5 years after the first redeemed beta-blocker prescription date. The outcomes included all-cause death, cardiovascular death, recurrent myocardial infarction, and a composite outcome of cardiovascular events and procedures. We used logistic regression and reported standardized absolute 5-year risks and risk differences at each landmark year. Among 21 220 first-time myocardial infarction patients, beta-blocker discontinuation was not associated with an increased risk of all-cause death, cardiovascular death, or recurrent myocardial infarction compared with patients continuing beta-blockers (landmark year 5; absolute risk difference [95% confidence interval]), correspondingly; -4.19% [-8.95%; 0.57%], -1.18% [-4.11%; 1.75%], and -0.37% [-4.56%; 3.82%]). Further, beta-blocker discontinuation within two years after myocardial infarction was associated with an increased risk of the composite outcome (landmark year 2; absolute risk [95% confidence interval] 19.87% [17.29%; 22.46%]) compared with continued beta-blocker use (landmark year 2; absolute risk [95% confidence interval] 17.10% [16.34%; 17.87%]), which yielded an absolute risk difference [95% confidence interval] at -2.8% [-5.4%; -0.1%], however, there was no risk difference associated with discontinuation hereafter.<br /><b>Conclusion</b><br />Discontinuation of beta-blockers one year or later after a myocardial infarction without heart failure was not associated with increased serious adverse events.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 30 Jun 2023; epub ahead of print</small></div>

<div><h4>Cardiovascular risks of continuing vs. initiating NSAIDs after first-time myocardial infarction or heart failure: a nationwide cohort study.</h4><i>Schmidt M, Hallas J, Ernst MT, Pottegård A</i><br /><b>Aims</b><br />It is unknown whether the cardiovascular risks associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) shortly after first-time myocardial infarction (MI) or heart failure (HF) differ between patients continuing and initiating use.<br /><b>Methods and results</b><br />Using nationwide health registries, we conducted a cohort study of all patients with first-time MI or HF during 1996-2018 (n = 273 682). NSAID users (n = 97 966) were categorized as continuing (17%) and initiating (83%) users according to prescription fillings < 60 days before index diagnosis. The primary outcome was a composite of new MI, HF admission, and all-cause death. Follow-up started 30 days after the index discharge date. We used Cox regression to compute hazard ratios (HRs) with 95% confidence intervals (CIs) comparing NSAID users vs. non-users. The most commonly filled NSAIDs were ibuprofen (50%), diclofenac (20%), etodolac (8.5%), and naproxen (4.3%). The composite outcome HR of 1.25 (CI: 1.23-1.27) was driven by initiators (HR = 1.39, 1.36-1.41) and not continuing users (HR = 1.03, 1.00-1.07). The lack of association among continuing users was also observed for individual NSAIDs (ibuprofen and naproxen), except diclofenac (HR = 1.11, 95% CI: 1.05-1.18). Among initiators, the HR was 1.63 (CI: 1.57-1.69) for diclofenac, 1.31 (CI: 1.27-1.35) for ibuprofen, and 1.19 (CI: 1.08-1.31) for naproxen. The results were consistent for both MI and HF patients, the individual components of the composite outcome, and various sensitivity analyses.<br /><b>Conclusions</b><br />NSAID initiators were more susceptible to adverse cardiovascular outcomes after first-time MI or HF than continuing users.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 29 Jun 2023; epub ahead of print</small></div>

<div><h4>Initiation of eplerenone or spironolactone, treatment adherence, and associated outcomes in patients with new-onset heart failure with reduced ejection fraction: a nationwide cohort study.</h4><i>Larsson JE, Denholt C, Thune JJ, Raja AA, ... Gustafsson F, Kristensen SL</i><br /><b>Background</b><br />The mineralocorticoid receptor antagonists (MRAs) eplerenone and spironolactone are beneficial in heart failure with reduced ejection fraction (HFrEF), but have not been prospectively compared. We compared clinical outcomes, daily dosages, and discontinuation rates for the two drugs in a nationwide cohort.<br /><b>Methods</b><br />We identified all patients with HFrEF in the period 2016-2020, who were alive and had initiated MRA treatment at study start, 180 days after HF diagnosis. We estimated the 2-year risk of a composite of death and HF hospitalization, as well as each component separately, using Kaplan-Meier, cumulative incidence functions, and Cox proportional hazards models adjusted for age, sex, and comorbidities. Secondly, we assessed treatment withdrawal, cross-over, and daily drug dosage.<br /><b>Results</b><br />We included 7 479 patients; 653 (9%) on eplerenone and 6 840 (91%) on spironolactone. Patients in the eplerenone group were younger (median age 65 vs. 69 years), and more often men (91% vs. 68%), both p < 0.001. In adjusted analyses, with spironolactone as reference, there were no differences in the risk of the composite of all-cause death and HF hospitalization (HR 1.02, 95% CI 0.82-1.27), all-cause death (HR 0.93, 95% CI 0.67-1.30) or HF hospitalization (HR 1.10, 95% CI 0.84-1.42). Treatment withdrawal occurred in 34% in the eplerenone group and 53% in the spironolactone group (p < 0.001), treatment cross-over in 3%, and 10%, respectively. Daily dose >25 mg at 12 months, was observed in 230 patients (37%) in the eplerenone group and 771 patients (12%) in the spironolactone (p < 0.001).<br /><b>Conclusions</b><br />In a contemporary nationwide cohort of patients with new-onset HFrEF who initiated MRA, we found no differences in clinical outcomes associated with initiation of eplerenone vs. spironolactone. Treatment was more frequently withdrawn, and daily drug dosage was lower among patients treated with spironolactone.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 24 Jun 2023; epub ahead of print</small></div>