scholarly journals Safety of Perioperative Anticoagulant Discontinuation in Cardiovascular Patients Undergoing Periodontal Therapy

2018 ◽  
Vol 2 (9) ◽  
pp. 207-212
Author(s):  
Ritesh Vatsa ◽  
Priyanka Priyadarshini
Keyword(s):  
Anticoagulant Therapy ◽  
Dual Therapy ◽  
Thromboembolic Events ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Anticoagulant Drug ◽  
Drug Regimens ◽  
History Of ◽  
Meta Analyses ◽  
Treatment Procedures

Periodontists are encountering increasing number of cases in their practices where patients present with cardiovascular diseases. Patients with a history of myocardial infarction, ischaemic stroke, acute coronary syndrome or peripheral vascular disease are prescribed anticoagulant medications by cardiologists, such as aspirin, warfarin, clopidogrel, ticlopidine, prasugrel, dipyridamole, cilostazol or dabigatran- either as monotherapy or dual therapy, for prevention of further thromboembolic events during lifetime. As because these agents act by inhibiting platelet aggregation, they tend to prolong bleeding time. Concerns regarding excessive periprocedural bleeding in patients receiving such drugs have led to some clinicians recommending periprocedural discontinuation of anticoagulant therapy. However, several studies, including systematic reviews and meta-analyses, have proved that there is no significantly increased risk of bleeding associated with continuing anticoagulant therapy when compared with discontinuation or modification of the anticoagulant regimen. In fact, without the anticoagulant medication, these patients have been found to be at increased risk of thromboembolic events with potentially serious consequences. The accepted recommendation, therefore, is that the anticoagulant drug regimens should not be altered or discontinued prior to periodontal treatment procedures, as the risks associated with such discontinuation far outweigh the consequences of prolonged bleeding, which can be well controlled with local measures.

scholarly journals Current Anticoagulation Recommendation for COVID-19 Patients

2021 ◽  
Vol 2 (4) ◽  
pp. 1-3
Author(s):  
Indra Prasetya
Keyword(s):  
Disease Severity ◽  
Anticoagulant Therapy ◽  
Essential Role ◽  
Thromboembolic Events ◽  
Severe Hypoxemia ◽  
Health Organizations ◽  
The World ◽  
Anticoagulant Drug ◽  
Drug Regimens

Thromboembolic events in COVID-19 patients can be one of the factors that aggravate the disease and increase mortality. When severe hypoxemia and hypotension occur in COVID-19 patients, the possibility of embolism should be considered. As a result, anticoagulant therapy in COVID-19 patients has an essential role in lowering disease severity and mortality. Many studies report that giving anticoagulants to COVID-19 patients can reduce mortality. Therefore, it is important to understand the role and use of anticoagulant therapy in cases of COVID-19. Several guidelines that have been issued by several health organizations in the world and Indonesia can be used as guidelines for clinicians to start anticoagulant therapy in cases of COVID-19. Various anticoagulant drug regimens have also been recommended to be used both as prophylaxis and as therapy for thromboembolism that can occur after COVID-19 cases.

684 Cardiac troponins and adverse outcomes in European patients with atrial fibrillation: a report from the ESC-EHRA EORP atrial fibrillation general long-term registry

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Marrco Vitolo ◽  
Vincenzo Livio Malavasi ◽  
Marco Proietti ◽  
Igor Diemberger ◽  
Laurent Fauchier ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Regression Analysis ◽  
Cox Regression ◽  
Adverse Outcomes ◽  
Cox Regression Analysis ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
History Of ◽  
Cardiac Troponins

Abstract Aims Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear. To assess the factors associated with cTn testing in routine clinical practice and to evaluate the association of elevated levels of cTn with adverse outcomes in a large contemporary cohort of European AF patients. Methods and results Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into three groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), and (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism/any acute coronary syndrome (ACS)/cardiovascular (CV) death, defined as major adverse cardiovascular events (MACE) and all-cause death were the main endpoints. 10 445 (94.1%) AF patients were included in this analysis [median age 71 years, interquartile range (IQR): 63–77; males 59.7%]. cTn were tested in 2834 (27.1%). Overall, cTn was elevated in 904 (8.7%) and in-range in 1930 (18.5%) patients. Patients in whom cTn was tested tended to be younger (P < 0.001) and more frequently presenting with first detected AF and atypical AF-related symptoms (i.e. chest pain, dyspnoea, or syncope) (P < 0.001). On multivariable logistic regression analysis, female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease (CAD), and atypical AF symptoms were independently associated with cTn testing. After a median follow-up of 730 days (IQR: 692–749), 957 (9.7%) composite endpoints occurred while all-cause death was 9.5%. Kaplan–Meier analysis showed a higher cumulative risk for both outcomes in patients with elevated cTn levels (Figure) (Log Rank tests, P < 0.001). On adjusted Cox regression analysis, elevated levels of cTn were independently associated with a higher risk for MACE [hazard ratio (HR): 1.74, 95% confidence interval (CI): 1.40–2.16] and all-cause death (HR 1.45, 95% CI: 1.21–1.74). Elevated levels of cTn were independently associated with a higher occurrence of MACE, all-cause death, any ACS, CV death and hospital readmission even after the exclusion of patients with history of CAD, diagnosis of ACS at discharge, those who underwent coronary revascularization during the admission and/or who were treated with oral anticoagulants plus antiplatelet therapy. Conclusions Elevated cTn levels were independently associated with an increased risk of all-cause mortality and adverse CV events, even after exclusion of CAD patients. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

scholarly journals CIRURGIAS ORAIS EM PACIENTES EM USO DE VARFARINA: REVISÃO DE LITERATURA

2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Marlus Da Silva Pedrosa ◽  
Jézlia Chris Da Silva Galdino ◽  
Flávia Ennes Dourado Ferro ◽  
José Guilherme Férrer Pompeu ◽  
Marcia Socorro da Costa Borba
Keyword(s):  
Drug Therapy ◽  
Anticoagulant Therapy ◽  
Dental Treatment ◽  
Oral Surgery ◽  
Thromboembolic Events ◽  
Risk Of Bleeding ◽  
Dental Procedures ◽  
Therapy Interruption ◽  
Anticoagulant Drug ◽  
Dental Offices

Introduction: Dental treatment performed in patients on anticoagulant drug therapy is becoming increasingly common in dental offices. Thus, questions concerning thromboembolic and bleeding risks relative to invasive dental procedures, are frequently raised. Aim: To review the scientific evidences regarding anticoagulant therapy interruption in patients taking warfarin undergoing oral surgeries. Methods: It was carried out a literature review in the electronic SciELO, PubMed, Lilacs and Oviatt Library databases from January to March of 2016, using as descriptors: Anticoagulants, Warfarin, Oral Surgery, and Oral Hemorrhage. Results and Discussion: Anticoagulant therapy is extremely important in patients at high risk for development of thromboembolic events. Most studies show that the risk of bleeding oral surgery in patients taking warfarin is relatively insignificant and it can be controlled by simple measures such as hemostasis. Conclusion: It is highly recommended to not interrupt anticoagulant in minor oral surgeries.

Hormone replacement therapy in women with breast cancer. Do the risks outweigh the benefits?

1996 ◽  
Vol 14 (3) ◽  
pp. 997-1006 ◽  
Author(s):  
J A Roy ◽  
C A Sawka ◽  
K I Pritchard
Keyword(s):  
Breast Cancer ◽  
Replacement Therapy ◽  
Postmenopausal Women ◽  
Hormone Replacement ◽  
Risks And Benefits ◽  
Previous Diagnosis ◽  
Increased Risk ◽  
History Of ◽  
Expected Benefits ◽  
Meta Analyses

PURPOSE To review critically the literature regarding effects of estrogen replacement therapy (ERT)/combined estrogen and progesterone replacement therapy (HRT) on the risk of breast cancer and on other health risks and benefits in postmenopausal women, with a focus on risks and benefits in women with a previous diagnosis of breast cancer. METHOD A literature search was conducted using Medline, Cancerline, and the bibliographies of reports published as of March 1995. All five published meta-analyses that examined the risk of breast cancer in relation to ERT/HRT in otherwise healthy women were critically reviewed. All known reports of women with a history of breast cancer given ERT/HRT subsequent to diagnosis and additional reports regarding the benefits of ERT/HRT were also reviewed. RESULTS None of the five meta-analyses demonstrated a significantly increased risk of developing breast cancer in ever users compared with never users of ERT/HRT. Current use may be associated with a small increased risk. This increased risk should be balanced by the expected benefits of ERT/HRT on quality of life, bone metabolism, and cardiovascular function. Preliminary information does not suggest a major detrimental effect of ERT/HRT in women with a previous diagnosis of breast cancer, but these reports include few women with limited follow-up data. There are no randomized trials in women with a previous diagnosis of breast cancer. CONCLUSION In healthy postmenopausal women, the benefits associated with ERT/HRT outweigh the risks. In women with a previous diagnosis of breast cancer, the balance of risks and benefits should be explored in randomized controlled trials.

P5341Predictive factors of atherosclerotic cardiovascular diseases events in HIV-HVC co-infected patients: results from hepavih ANRS co13 cohort

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F Boccara ◽  
B K Tan ◽  
M Chalouni ◽  
D Salmon Ceron ◽  
A Cinaud ◽  
...  
Keyword(s):  
Viral Load ◽  
Sustained Viral Response ◽  
Biological Data ◽  
Personal History ◽  
Hiv Viral Load ◽  
Factors Associated ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
History Of

Abstract Introduction Several studies highlighted an increased risk of cardiovascular disease (CVD) in HIV-HCV co-infected patients without clearly identifying specific virologic factors associated with atherosclerotic CVD (ASCVD) events. Purpose Hence, we analyzed data collection from the French nationwide ANRS CO13 HEPAVIH cohort to determine the incidence of ASCVD events in HIV-HCV co-infected patients and the predictive factors associated with its occurrence. Methods The French multicenter nationwide ANRS CO13 HEPAVIH clinic-based cohort collected prospective clinical and biological data from HIV-HCV co-infected patients followed-up in 28 different university hospitals between December 2005 to November 2016. Participants with at least one year of follow-up were included. Primary outcome was the occurrence of major ASCVD events (cardiovascular death, acute coronary syndrome, coronary revascularization and stroke). Secondary outcomes were total ASCVD events including major ASCVD events and minor ASCVD events (peripheral arterial disease [PAD]). Incidence rates were estimated using Aalen-Johansen method and factors associated with ASCVD identified with Cox proportional hazards models. Results A total of 1213 patients were included: median age 45.4 years [42.1–49.0], 70.3% men, current smoking 70.2%, overweight 19.5%, liver cirrhosis 18.9%, chronic alcohol consumption 7.8%, diabetes mellitus (5.9%), personal history of CVD 2.7%, and statins use 4.1%. After a median follow-up of 5.1 years [3.9–7.0], 44 participants experienced at least one ASCVD event (26 major ASCVD event, and 20 a minor event). Incidences for total, major and minor ASCVD events were of 6.98 [5.19; 9.38], 4.01 [2.78; 6.00], and 3.17 [2.05; 4.92] per 1000 person-years, respectively. Personal history of CVD (Hazard Ratio (HR)=13.94 [4.25–45.66]), high total cholesterol (HR=1.63 [1.24–2.15]), low HDL cholesterol (HR=0.08 [0.02–0.34]) and undetectable HIV viral load (HR=0.41 [0.18–0.96]) were identified as independent factors associated with major ASCVD events while cirrhosis status, liver fibrosis and HCV sustained viral response were not. Cumulative incidence of CV events Conclusion HIV-HCV co-infected patients experience a high incidence of ASCVD events both coronary and peripheral artery diseases. Traditional CV risk factors are the main determinants of ASCVD whereas undetectable HIV viral load seems to be protective. Management of cholesterol abnormalities and controlling viral load are essential to modify this high cardiovascular risk. Acknowledgement/Funding Agence Natoinale de Recherche sur le SIDA et les Hépatites virales

Management Of Pregnancy In Patients With Antithrombin Deficiency

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 216-216
Author(s):  
Mario von Depka ◽  
Stefanie Döpke ◽  
Anja Henkel-Klene ◽  
Cornelia Wermes ◽  
Mahnaz Ekhlasi-Hundrieser ◽  
...  
Keyword(s):  
High Risk ◽  
Pregnancy Loss ◽  
Conflicts Of Interest ◽  
Fetal Loss ◽  
Bleeding Complications ◽  
Thromboembolic Events ◽  
Increased Risk ◽  
History Of ◽  
At Deficiency ◽  
The Mean

Abstract Introduction During pregnancy women have a four- to five-fold increased risk of thromboembolism (TE) compared to women who are not pregnant. Among the most important risk factors for TE in pregnancy is the presence of thrombophilia. Multiple reports have described an association between antithrombin (AT) deficiency and an increased rate of thromboembolic events especially during pregnancy. As the placental development depends on well-balanced pro- and anticoagulant mechanisms, thrombophilia, e.g. AT deficiency may be associated with poor pregnancy outcome. Despite anticoagulation with low molecular weight heparin (LMH) during pregnancy and the postpartum period alone, women with AT deficiency are still at a high risk to develop TE, especially perinatal and during puerperium because of withheld anticoagulation to prevent bleeding complications. Therefore, several guidelines recommend the administration of antithrombin concentrates during high risk situations as pregnancy. Here, we present the results of our study on the usage of AT concentrates in pregnant women with AT deficiency who either suffered from fetal loss or thromboembolism prior inclusion. Methods In total, 22 pregnancies in 19 patients (age: 31.9±4.7; 22-41) with AT deficiency were included in this open-label, single-center study. Ten patients (53%) had a history of fetal loss, 9/19 (47%) patients hat a history of thromboembolism. During all pregnancies AT concentrate (AT-C) was administered, in 18/22 (81.8%) pregnancies LMH was given in addition. Prior pregnancy losses (21/30, 70%) occurred in all trimester (t1: n=11, t2: n=5, and in t3: n=5). Historical live birth rate (LBR) was 30%. Blood samples were collected in all trimesters and postpartum to analyze AT activity and antigen, endogenous thrombin potential (ETP), thrombin-antithrombin-complex (TAT), Fragment 1+2 (F1+2) and c-reactive protein test (CRP). A total of 114 uneventful pregnancies of 113 healthy women served as controls. Furthermore, the mean doses of AT concentrates/kg BW and the mean total number of infusions were calculated. Results In total, 21 pregnancies (95.5%) were successful. Mean total requirement of AT concentrate per pregnancy was 79.454 IU (range: 3.000-272.000 IU) during 27.8 treatment days per pregnancy (range: 1-88). Our data show an increase of F1+2 in the course of pregnancy. Mean levels of F1+2 at t1, t2 and t3 (t1= 255.9 ± 107.6, t2= 360.9 ± 117.4, t3= 545.3 ± 220.3 pmol/L) were significantly higher than in controls (t1= 82.2 ± 43, t2= 140 ± 100.2, t3= 183.5 ± 103.1, p<.001). Mean level of TAT was higher (3.1 ± 1.4 ng/mL) than in controls (1.7 ± 1.6 ng/mL, p=.001) in t1, whereas mean TAT in t2 and t3 was lower than in controls (3.8 ± 1.3 vs. 4.8 ± 1.9, p=.03; 5.0 ± 1.4 vs. 6.1 ± 3.0 ng/mL, n.s., resp.). No thromboembolic events occurred. In patients receiving AT-C, LBR increased from 30% to 95.5% (p<0.001) with a relative risk of 49.0 to develop pregnancy loss without anticoagulant treatment (5.7 – 421.8; 95% CI). Conclusion In patients with AT deficiency receiving AT concentrate and LMH we could demonstrate a significant increase of LBR from 30% to 95.5%. Furthermore, no thromboembolic events occurred, though almost half of the patients had a history of thromboembolism. There was no clear evidence of increased hypercoagulability. We conclude that combined AT concentrate and LMH are safe and efficacious for mother and child in preventing thromboembolism and pregnancy loss. Further studies to evaluate the exact mode of anticoagulation and benefit of combining AT concentrate and LMH are warranted. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Circulating miR-206 and Wnt-signaling are associated with cardiovascular complications and a history of preeclampsia in women

2020 ◽  
Vol 134 (2) ◽  
pp. 87-101 ◽  
Author(s):  
Kenny Schlosser ◽  
Amanpreet Kaur ◽  
Natalie Dayan ◽  
Duncan J. Stewart ◽  
Louise Pilote ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Wnt Signaling ◽  
Target Genes ◽  
Cardiovascular Complications ◽  
Biological Pathways ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Molecular Determinants ◽  
History Of

Abstract Women with a history of preeclampsia (PE) have increased risk of cardiovascular disease (CVD) later in life. However, the molecular determinants underlying this risk remain unclear. We sought to understand how circulating miRNA levels are affected by prior PE, and related to biological pathways underpinning cardiovascular disease. RNA sequencing was used to profile plasma levels of 2578 miRNAs in a retrospective study of women with a history of PE or normotensive pregnancy, in two independent cohorts with either acute coronary syndrome (ACS) (n = 17–18/group) or no ACS (n = 20/group). Differential miRNA alterations were assessed in relation to a history of PE (within each cohort) or ACS (across cohorts), and compared with miRNAs previously reported to be altered during PE. A history of PE was associated with altered levels of 30 and 20 miRNAs in the ACS and non-ACS cohorts, respectively, whereas ACS exposure was associated with alterations in 259 miRNAs. MiR-206 was identified at the intersection of all comparisons relating to past/current PE and ACS exposure, and has previously been implicated in atherogenic activities related to hepatocytes, vascular smooth muscle cells and macrophages. Integration of all differentially altered miRNAs with their predicted and experimentally validated targets in silico revealed a number of highly targeted genes with potential atherogenic functions (including NFAT5, CCND2 and SMAD2), and one significantly enriched KEGG biological pathway (Wnt signaling) that was shared between all exposure groups. The present study provides novel insights into miRNAs, target genes and biological pathways that may underlie the long-term cardiovascular sequelae of PE.

Colchicine: An ancient drug with multiple benefits

2020 ◽  
Vol 26 ◽  
Author(s):  
Georges El Hasbani ◽  
Ali Jawad ◽  
Imad Uthman
Keyword(s):  
Hepatic Cirrhosis ◽  
Efficacy And Safety ◽  
Recurrent Pericarditis ◽  
Postpericardiotomy Syndrome ◽  
Coronary Syndrome ◽  
Treatment And Prevention ◽  
Pregnancy And Lactation ◽  
History Of ◽  
Mediterranean Fever ◽  
Meta Analyses

: The history of colchicine dates to ancient Egyptians when it was used for alleviation of swelling and pain. Although its popularity varied throughout the years, colchicine has been a mainstay for the treatment of several diseases, mainly rheumatic and cardiac ones. The mechanism of action of the drug involves several intracellular and extracellular targets, although interaction with tubulin is the most described. Based on several clinical trials and meta-analyses, colchicine is safely recommended as a monotherapy or as an add-on for the treatment and prevention of recurrent pericarditis, postpericardiotomy syndrome, gout, pseudogout, familial Mediterranean fever (FMF), and Behçet’s disease (BD). Notably, a drug safety has been noted during pregnancy and lactation. Besides its major indications, colchicine has shown efficacy and safety in the treatment of various conditions. Because the indications for using colchicine in the prevention of certain conditions such as acute coronary syndrome, stroke, and hepatic cirrhosis and treatment of others such as pneumonia and psoriasis are still debatable, further research works are needed.

Hereditary Deficiencies of Protein C or Protein S Confer Increased Risk of Arterial Thromboembolic Events at Young Age. Results from a Large Family Cohort Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 422-422
Author(s):  
Bakhtawar Khan Mahmoodi ◽  
Jan-Leendert P. Brouwer ◽  
Nic J.G.M. Veeger ◽  
Jan van der Meer
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Protein S ◽  
Thromboembolic Events ◽  
Antithrombin Deficiency ◽  
Increased Risk ◽  
Atherosclerosis Risk ◽  
History Of ◽  
Arterial Thromboembolic Events ◽  
Atherosclerosis Risk Factors

Abstract Introduction: Hereditary deficiencies of protein S, protein C or antithrombin are strong risk factors for venous thromboembolism (VTE). Whether these deficiencies are associated with arterial thromboembolism (ATE) and whether history of VTE in these subjects predisposes to subsequent ATE has yet to be determined. Methods: Based on pedigree analysis we enrolled a total 552 subjects (52% women; mean age, 46±17 years), belonging to 84 different kindreds, in this retrospective family-cohort study. Detailed information on previous episodes of VTE, ATE, anticoagulants use and atherosclerosis risk factors (i.e. diabetes, hypertension, hyperlipidemia, and smoking) were collected. In addition to the index deficiencies participants were also tested for other thrombophilic defects; including factor V Leiden, prothrombin G20210A, increased FVIII and lupus anticoagulants. Primary study outcome was objectively verified symptomatic ATE. As the assumption for proportional hazards for the final model was not met over the entire observation period, we opted for a piecewise Cox model with a cut off point set at 55 years of age. Results: Of 552 subjects (mean age±SD, 46±17 years; 52% women), 308 had either protein S (35%), protein C (39%) or antithrombin deficiency (26%). Age, atherosclerosis risk factors and other thrombophilic defects were similar (P&gt;0.23) between deficient and non-deficient subjects. A total of 44 arterial thromboembolic events had occurred, corresponding to an overall annual incidences of 0.34% (95% CI, 0.23–0.49) in deficient and 0.17% (0.09–0.28) in non-deficient subjects, hazard ratio 2.3 (1.2–4.5; P=0.01). However, the risk hazards varied over lifetime; while risk of ATE conferred by these deficiencies was 5.4 (1.6–18.4; P=0.006) before age 55 years, it was 1.3 (0.6–2.9; P=0.51) thereafter. After adjusting for atherosclerosis risk factors and clustering of ATE within families, deficient subjects had 4.7-fold (1.5–14.2; P=0.007) higher risk of ATE before age 55 years, versus 1.1 (0.5–2.6; P=0.84) thereafter, compared to non-deficient family members. For separate deficiencies these were 4.6 (1.1 – 18.3), 6.9 (2.1 – 22.2) and 1.1 (0.1 – 10.9) in protein S-, protein C- and antithrombin-deficient subjects, respectively, before age 55 years. History of VTE was not related to subsequent ATE, hazard ratio 1.1 (0.5 – 2.2). Conclusions: Compared to non-deficient family members, subjects with protein S or protein C deficiencies but not antithrombin deficiency have an increased risk for ATE before age 55 years, independent of prior VTE. After age 55 years conventional atherosclerosis risk factors accounted for ATE. In thrombophilic families, deficiencies of protein S and protein C should be considered in atherothrombotic risk assessment before age 55 years.

P4608BET-inhibition with Apabetalone in Post-ACS Patients with Diabetes: Design and Baseline Characteristics of the BETonMACE trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K K Ray ◽  
S J Nicholls ◽  
M Sweeney ◽  
J Johansson ◽  
N Wong ◽  
...  
Keyword(s):  
Renal Function ◽  
Major Adverse Cardiovascular Events ◽  
Dependent Manner ◽  
Double Blind ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Low Hdl ◽  
History Of ◽  
Baseline Characteristics

Abstract Background Diabetes (DM) is associated with increased risk of macro/microvascular disease and cognitive decline. Inflammation and vascular calcification may be contributing factors. Bromodomain and extraterminal (BET) proteins coordinate gene transcription and modify the transcriptional response to hyperglycemia, and inflammation. Apabetalone competitively and selectively inhibits binding between BET proteins and acetyl-lysine marks on histone tails: normalizing transcriptional profiles to physiological levels; reducing in vitro alkaline phosphatase (ALP) transcription and in vivo plasma ALP in a dose-dependent manner. Phase 2 trials with apabetalone show improved renal function in the chronic kidney disease (CKD) subgroups. Furthermore, treatment showed a 55% reduction in CVD events with more pronounced benefit among patients with DM, low HDL-cholesterol (HDL-C) and high sensitivity C-reactive protein (hsCRP). Methods The double-blind, placebo controlled phase 3 BETonMACE trial is testing the hypothesis that apabetalone 100 mg b.i.d., added to standard care, reduces major adverse cardiovascular events (MACE: CV death, non-fatal myocardial infarction or stroke) in patients with DM, acute coronary syndrome (ACS) within the preceding 7–90 days, low HDL-C (<40 mg/dL in men; <45 mg/dL in women), and estimated glomerular filtration rate (eGFR) >30 mL/min/1.7m2. The trial will continue until at least 250 MACE, providing 80% power to detect a 30% reduction. Secondary endpoints include changes in eGFR in patients with baseline eGFR 30 to <60 mL/min/1.7m2, inflammatory markers, lipids, and ALP. In addition the Montreal Cognition Assessment (MoCA) test was performed in patients ≥70 years of age at baseline and annually. Results Enrollment of 2425 patients across 13 countries and 195 centers is now complete. Baseline characteristics [median (IQR)] include LDL-C 65.0 (36) mg/dL, HDL-C 33.0 (7) mg/dL, HbA1c 7.3 (2.3) %, hsCRP 2.8 (4.9) mg/L, mean blood pressure 129/76 mmHg, and CKD in 266 patients (10.8%). Background care was based on guideline recommendations. Diabetes medications include metformin (79%), insulin (36%), sulfonylureas (28%), DPP4 inhibitors (11%), SGLT2 inhibitors (9.7%) and GLP1 receptor agonists (0.3%). The CKD subpopulation vs. total population differed significantly from the whole population with regard to age (71 vs. 62 y. o.), male sex (58% vs. 75%), history of hypertension (46% vs. 88%), history of stroke (1.5% vs. 7.5%), and current smokers (6.1% vs. 13%). In the 70 year and older (n=466, 19%) population 54% (n=243) showed a baseline MoCA score 25 and lower suggesting cognitive impairment. Summary The BETonMACE trial is testing the hypothesis that selective BET-inhibition with apabetalone, added to established, evidence-based treatment, reduces MACE in high-risk patients with DM, recent ACS, and low HDL-C. The study will also assess apabetalone's effect on renal function and cognition.

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