Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Background: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. Methods: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Findings: Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. Interpretation: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Funding: Novo Nordisk

Alternative therapy interaction with warfarin: what doctors should know

Warfarin effectiveness and safety is substantially affected by concurrent therapy. This paper reviews the main mechanisms of warfarin interactions with other agents, which underlie adverse effect development: platelet dysfunction, gastro-intestinal effects, suppressed intestinal synthesis of vitamin K, disturbed warfarin metabolism, or disrupted vitamin K cycle. The main medication groups, affecting warfarin effectiveness and safety, are presented. The effects of foods, supplements, and herbal medications on anticoagulant effect of warfarin are discussed

Myocardial infarction caused by non-atherothrombotic lesion of carotid arteries

Atherothrombosis is not the sole cause of myocardial infarction (MI). The clinical picture of MI of different origin is similar to the classical one. At the same time, coronaroangiography reveals changes in coronary arteries of patients with MI without atherosclerotic obstruction varying from totally intact vessels to atherosclerosis responsible for their 50% narrowing. MI without atherosclerotic obstruction is rarely encountered in clinical practice but regularly occurs in patients with acute coronary syndrome. Atherosclerotic obstruction was absent in 9-10% of the women and 7-8% of men with IM and ST segment elevation. Coronaroangiography demonstrated similar changes in women having MI without ST segment elevation. Men with the same condition exhibited atherosclerotic obstruction only in 4-7% of the cases. Unstable angina was associated with an enhanced frequency of unaffected coronary arteries which increased the difference between the two sexes. MI without atherosclerotic obstruction may be caused by a spasm of coronary arteries, eccentrically located plaques, Takotsubo syndrome, microvascular spasm, myocarditis caused by PVB19 virus, coronary embolism, thrombophilia, spontaneous dissection of coronary arteries, and their abnormalities. Patients having MI without atherosclerotic obstruction require evaluation of the risk of therapy on an individual basis.</jats:p

Antiplatelet therapy in cardiology

Platelets are important components of hemostasis and play a key role in the formation of atherothrombosis. Rupture or erosion of atherosclerotic plaque gives rise to a thrombus with the involvement of platelets. Antiplatelet agents are instrumental in preventing the development of atherothrombosis of different localization, including coronary arteries.</jats:p

Recommendations on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation (Based on 2018 European Heart Rhythm Association Practical Guide)

Non-vitamin K antagonist oral anticoagulants (NOACs) – direct oral anticoagulants – are getting the ever-broadening use in clinical practice. However, many problems related to optimal use of NOACs in specific clinical situations remain unresolved. European Heart Rhythm Association in April 2018 issued the renovated recommendations on the use of NOACs in patients with atrial fibrillation. The authors of recommendations presented some specific clinical variants for which they formulated practical advices based on the evidence obtained in randomized clinical trials. They also outlined the indications for use of NOACs, formulated practical start-program and scheme of subsequent follow-up management of patients taking NOACs. Recommendations contain information on pharmacokinetics of NOACs and their interactions with other drugs, consideration of feasibility of NOACs use in patients with chronic renal insufficiency or advanced liver disease. Many other practical problems are covered as well.  </jats:p

Model for calculating the risk of venous thrombosis

Aim. To develop a model for calculating the risk of venous thrombosis, taking into account the presence of known risk factors, comorbidity and congenital thrombophilia.Material and methods. During the study (2015 to 2017), 79 patients with venous thrombosis were examined (36 men and 43 women, mean age — 56,76±15,570). The control group consisted of 83 patients and healthy volunteers without thrombosis at the moment and in history (35 men and 48 women, average age — 43,95±18,136). All individuals included in the study were analyzed for the presence of G1691A mutations in the factor V gene, G20210A in the prothrombin gene, C677T polymorphism in the 5,10-methylenetetrahydrofolate reductase gene, and polymorphism in the SERPINE1 gene of plasminogen activator inhibitor. Real-time polymerase chain reaction was used to identify mutations. To create a risk calculation model, a linear regression analysis was performed.Results. We have developed a model for calculating the risk of venous thrombosis. The resulting formula showed high prognostic accuracy (the area under the ROC curve is 95,9%). For patients who do not have data on the presence of these mutations, a short version of the risk calculation model was developed (the area under the ROC curve is 94,6%).Conclusion. We have developed a risk calculation model taking into account the presence of known risk factors, congenital thrombophilia and comorbidities. Thromboprophylaxis is necessary in &gt;0,45 individual risk, which corresponds to a high risk of developing venous thrombosis. Patients who have not previously been diagnosed with thrombophilia and are in the middle risk group for venous thrombosis, according to a short version of the model, must be screened for congenital thrombophilia to clarify the risk

Impact of thrombophilia and waist circumference on the risk of venousthromboembolism

Abstract Background Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE) represents a major health problem. In the general population, the absolute risk of any kind of VTE is 0.1%–0.2% per year, and it increases with age. VTE is an important and preventable cause of morbidity and mortality, with almost a third of survivors experiencing long term effects. Obesity is well-known risk factor of VTE. The extent of the effects of obesity on VTE depends not only on total body fat, but also on the distribution of adipose tissue (e.g., central obesity) and the interplay among risk factors for VTE, such as genetic mutations, and other risk factors. Thrombophilia, venous thromboembolism, obesity, waist circumference Purpose The aim of this study is to investigate the impact of waist circumference on the risk of venous thromboembolism Methodology The study involved 68 patients with VTE (33 females and 34 males, mean age 56.8 years ±15.3) and 84 patients without VTE (38 males and 46 females, 44.4 years±18.6). From 2015 to 2017, data have been collected from records of patients admitted to department of internal medicine. All subjects were recruited to the study during their stay in the hospital. The reasons for hospitalization were: acute event of DVT or PE for the main group, the absence of acute event or history of VTE for the control group. DVT was diagnosed by ultrasonic Doppler examination, and PE was confirmed by intravenous radiocontrast computed tomography. Anthropometric measures were performed with subjects wearing short-sleeved garments and no shoes; waist circumference was measured in centimeters at the umbilical line. For all patients genetic testing for inherited thrombophilia – Factor V Leiden G1691A, Prothrombin G20210A, MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism – was performed by real-time PCR technique. Results Factor V Leiden G1691A increase the risk of VTE in 2.11 (CI: 1.79–2.48), p=0.049, prothrombin G20210A in 3.21 (CI: 1.66–6.211), p=0.049. MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism also increase the risk of VTE, but it was no significant. Study have shown that waist circumference &amp;gt;80 cm increase the risk of VTE in 3.19 (CI: 1.35–7.58), p=0.019. Combination of inherited thrombophilia (Factor V Leiden G1691A, Prothrombin G20210A, MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism) and waist circumference &amp;gt;80 cm increase the risk of VTE in 3.51 (CI: 1.76–7.04), p&amp;lt;0.001. Conclusion Previous results of our work indicate influence of waist circumference &amp;gt;80 cm on the risk of VTE, especially risk of thrombosis is higher in patients with combination inherited thrombophilia and waist circumference &amp;gt;80 cm. Funding Acknowledgement Type of funding sources: None. </jats:sec