Association Between Calcium Supplementation and the Risk of Cardiovascular Disease and Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Some observational studies and randomised controlled trials (RCTs) have reported an association between calcium supplementation and increased risk of cardiovascular disease. Previous meta-analyses on the topic, based on data from RCTs and observational studies, have contradictory findings. This meta-analysis was conducted to determine the difference in associated risks of calcium supplementation with cardiovascular disease and stroke in RCTs. METHODS: Relevant studies published from database inception to 6 August 2021 were sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Any RCTs focusing on the relationship between calcium supplementation and incidence of cardiovascular disease or stroke were included. Articles were screened independently by two authors, according to the PICO criteria, with disagreements resolved by a third author. RESULTS: Twelve RCTs were included in the meta-analysis. Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and all-cause/cardiovascular mortality. Subgroup analysis focusing on calcium monotherapy/calcium co-therapy with vitamin D, female sex, follow-up duration, and geographical region did not affect the findings. CONCLUSION: Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and cardiovascular/all-cause mortality. Further studies are required to examine and understand these associations.

Association Between Breast Arterial Calcifications and Cardiovascular Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Recent studies have shown that breast arterial calcification (BAC) detected on screening mammography is linked to cardiovascular diseases via medial calcification. However, its effect on cardiovascular outcomes remains unclear. Therefore, we conducted a meta-analysis to determine the effect of BAC on cardiovascular outcomes in patients. METHODS: Three electronic databases (Pubmed, Embase, and Scopus) were searched on May 1, 2022, for studies examining the relationship between BAC and cardiovascular outcomes including cardiac death, acute myocardial infarction, ischemic heart disease, stroke, peripheral artery disease, and heart failure. A random-effects meta-analysis model was used to summarise the studies. RESULTS: A total of 5 longitudinal studies were included with a combined cohort of 87,865 patients. Significantly, the pooled risk ratio (RR) of the association between BAC and cardiac death was 2.06 (P < 0.00001). BAC was associated with a significantly increased risk of developing other cardiovascular diseases, such as ischemic/hemorrhagic stroke (RR 1.51; P = 0.003), ischemic stroke (RR 1.82; P < 0.00001), peripheral vascular disease (RR 1.24; P = 0.003), and heart failure (RR 1.84; P < 0.00001). There was no significant relationship for developing myocardial infarction or for total cardiovascular diseases. CONCLUSIONS: Our findings suggest that BAC was associated with an increased risk of cardiovascular mortality, and certain cardiovascular outcomes. There is thus a potential to use BAC as a sex-specific cardiovascular risk assessment tool. Furthermore, there is a need for more widespread reporting of BAC to better understand the pathophysiologic mechanisms behind its correlation with cardiovascular disease and to apply it in clinical practice.

Ischaemic events in hypertrophic cardiomyopathy patients with and without atrial fibrillation: a systematic review and meta-analysis.

Hypertrophic cardiomyopathy predisposes to acute cerebrovascular events including ischaemic stroke, transient ischaemic attack and systemic thromboembolism. Atrial fibrillation confers even higher risk. We aim to report the incidence of these complications and to investigate the impact of atrial fibrillation on the ischaemic risk in patients with hypertrophic cardiomyopathy. A literature search was performed on PubMed, Scopus, Embase/Ovid and Cochrane library from inception to 20th March 2021. We compared the incidence of ischaemic strokes, transient ischaemic attack, non-specified thromboembolism events and systemic thromboembolism in hypertrophic cardiomyopathy patients with or without atrial fibrillation. Non-specified thromboembolism events in our paper referred to thromboembolic events whereby types were not specified in the studies. Meta-analysis was performed using StataSE 16 software, and heterogeneity was assessed using I2 test. A total of 713 studies were identified. Thirty-five articles with 42,570 patients were included. The pooled incidence of stroke/ transient ischaemic attack was 7.45% (95% confidence interval [CI] 5.80-9.52, p < 0.001) across 24 studies with a total of 37,643 hypertrophic cardiomyopathy patients. Atrial fibrillation significantly increased the risk of total stroke/ transient ischaemic attack (Risk Ratio 3.26, 95% CI 1.75-6.08, p < 0.001, I2 = 76.0). The incidence of stroke/ transient ischaemic attack was 9.30% (95% CI 6.64-12.87, p = 0.316) in the apical hypertrophic cardiomyopathy subgroup. Concomitant atrial fibrillation in hypertrophic cardiomyopathy increases the risk of thromboembolic events including ischaemic stroke and transient ischaemic attack. The apical subgroup shows a similar risk of acute cerebrovascular events as the overall hypertrophic cardiomyopathy population.

Prevalence and incidence of stroke, white matter hyperintensities, and silent brain infarcts in patients with chronic heart failure: A systematic review, meta-analysis, and meta-regression.

Introduction: Heart failure (HF) is associated with ischemic stroke (IS). However, there are limited studies on the prevalence of IS, white matter hyperintensities (WMHs), and silent brain infarcts (SBIs). Furthermore, interaction with ejection fraction (EF) is unclear. Methods: We searched three databases (viz., PubMed, Embase, and Cochrane) for studies reporting the incidence or prevalence of IS, WMHs, and SBIs in HF. A total of two authors independently selected included studies. We used random-effects models, and heterogeneity was evaluated with I2 statistic. Meta-regression was used for subgroup analysis. Results: In total, 41 articles involving 870,002 patients were retrieved from 15,267 records. Among patients with HF, the pooled proportion of IS was 4.06% (95% CI: 2.94-5.59), and that of WMHs and SBIs was higher at 15.67% (95% CI: 4.11-44.63) and 23.45% (95% CI: 14.53-35.58), respectively. Subgroup analysis of HFpEF and HFrEF revealed a pooled prevalence of 2.97% (95% CI: 2.01-4.39) and 3.69% (95% CI: 2.34-5.77), respectively. Subgroup analysis of WMH Fazekas scores 1, 2, and 3 revealed a decreasing trend from 60.57 % (95% CI: 35.13-81.33) to 11.57% (95% CI: 10.40-12.85) to 3.07% (95% CI: 0.95-9.47). The relative risk and hazard ratio of patients with HF developing IS were 2.29 (95% CI: 1.43-3.68) and 1.63 (95% CI: 1.22-2.18), respectively. Meta-regression showed IS prevalence was positively correlated with decreasing anticoagulant usage. Conclusion: We obtained estimates for the prevalence of IS, WMH, and SBI in HF from systematic review of the literature. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=255126, PROSPERO [CRD42021255126].

Prevalence and Risk Factors of Cardiac Amyloidosis in Heart Failure: A Systematic Review and Meta-Analysis.

AIMS: Heart failure (HF) is one of the leading causes of mortality worldwide. Heart failure is also one of the most common presentations of cardiac amyloidosis (CA). Contemporary epidemiological data of CA in HF patients is lacking. Hence, this systematic review and meta-analysis was conducted to determine the prevalence of amyloidosis in HF patients, and to clarify the risk factors of concomitant CA and HF. METHODS: A systematic review and meta-analysis was performed. Studies were retrieved from Medline, EMBASE, Scopus and Cochrane library. The search was not restricted in time, type or language of publication. The prevalence of CA in HF grouped according to diagnostic techniques and risk factors of CA with HF was analysed. RESULTS: Eleven (11) studies were included, involving 3,303 patients. The pooled prevalence of CA in HF was 13.7%. The overall prevalence of CA in HF with preserved ejection fraction was 15.1%, and that of HF with reduced ejection fraction was 11.3%. The main factors associated with the diagnosis of CA in HF included older age, males, raised NT pro-BNP, increased interventricular septal thickness in diastole, apical sparing, and reduced left ventricular systolic function. CONCLUSION: A high index of clinical suspicion is required to identify HF patients with CA. Supportive investigations may be helpful when clinically correlated. A considerable proportion of HF patients have CA and certain risk factors may be helpful in increasing suspicion of CA in HF.

The impact of sodium-glucose cotransporter inhibitors on blood pressure: a meta-analysis and metaregression of 111 randomized-controlled trials.

OBJECTIVE: Multiple trials on sodium-glucose cotransporter (SGLT) inhibitors have been performed recently demonstrating blood pressure (BP) reduction benefits in both diabetic and nondiabetic patients. Hence, we conducted a systematic review and meta-analysis to determine the effect of different SGLT inhibitors on BP in both patients with and without diabetes mellitus. METHODS: Four electronic databases (PubMed, Embase, Cochrane, and SCOPUS) were searched on 4 November 2021 for articles published from 1 January 2000 up to 21 November 2021, for studies evaluating the BP effects of SGLT inhibitors. Pair-wise meta-analysis and random effects metaregression models were utilized. RESULTS: In total, 111 studies examining SBP (108 studies, 104 304 patients) and/or DBP (82 studies, 74 719 patients) were included. In patients with diabetes, the random effects model demonstrated SGLT inhibitor produced a mean reduction in SBPs of -3.46 mmHg (95% confidence interval: -3.83, -3.09) compared with placebo. There were no statistically significant changes in BP among patients without diabetes. Drug response relationship was not observed in SGLT inhibitors and BP, except for Canagliflozin and DBP. CONCLUSION: Sodium-glucose cotransporter 2 inhibitors and combined sodium-glucose cotransporter 1/2 inhibitors produced small reductions in BP in patients with diabetes.

Evaluating the Initiation of Sodium/Glucose Cotransporter 2 Inhibitors within 2 Weeks of an Acute Hospital Admission: A Systematic Review and Meta-Analysis of Nine Clinical Trials.

OBJECTIVE: Recent studies have increasingly shown the benefits of using sodium/glucose cotransporter 2 inhibitor (SGLT2i). However, there are concerns regarding the initiation of SGLT2i during acute hospital admissions due to the potential increased risk of complications. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of SGLT2i initiation within 2 weeks of an acute hospital admission. METHODS: Four electronic databases (PubMed, Embase, Cochrane, and Scopus) were searched for articles published from inception up to 27 March 2021 that evaluated the efficacy and/or safety of SGLT2i initiation within 2 weeks of an acute hospital admission. Random-effects pair-wise meta-analysis models were utilized to summarize the studies. The protocol was registered with PROSPERO (CRD42021245492). RESULTS: Nine clinical trials were included with a combined cohort of 1,758 patients. Patients receiving SGLT2i had a mean increase in 24-h urine volume of +487.55 mL (95% CI 126.86-848.25; p = 0.008) compared to those not started on SGLT2i. Patients with heart failure treated with SGLT2i had a 27% relative risk reduction in rehospitalizations for heart failure, compared to controls (risk ratio 0.73; p = 0.005). There were no differences in other efficacy and safety outcomes examined. CONCLUSION: There was no increased harm with initiation of SGLT2i within 2 weeks of an acute hospital admission, and its use reduced the relative risk of rehospitalizations for heart failure in patients with heart failure. It was also associated with increased urine output. However, current evidence pool is limited, especially in specific population subtypes.

Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors and Combined SGLT1/2 Inhibitors on Cardiovascular, Metabolic, Renal, and Safety Outcomes in Patients with Diabetes: A Network Meta-Analysis of 111 Randomized Controlled Trials.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of anti-hyperglycemic drugs that has been steadily increasing in popularity due to its cardiovascular and renal benefits. Dual SGLT1/SGLT2 (SGLT1/2) inhibitors have potentially augmented anti-hyperglycemic action due to additional SGLT1 inhibition. This network meta-analysis aimed to compare the treatment effect across various outcomes between pure SGLT2 inhibitors and combined SGLT1/2 inhibitors in patients with diabetes. METHODOLOGY: Four electronic databases (PubMed, Embase, Cochrane, and Scopus) were searched for randomized controlled trials published from inception to 15th January 2022. Frequentist network meta-analysis was conducted to summarize the treatment effects reported in individual trials, stratified by type 1 (T1DM) and type 2 diabetes mellitus (T2DM). This meta-analysis was registered on PROSPERO (CRD42020222031). RESULTS: Our meta-analysis included 111 articles, comprising a combined cohort of 103,922 patients. SGLT2 inhibitors (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin, and luseogliflozin) and SGLT1/2 inhibitors (licogliflozin and sotagliflozin) were compared. Frequentist network meta-analysis demonstrated that in T2DM patients, SGLT1/2 inhibitors led to a decreased hazard rate of myocardial infarction (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.56-0.98) and stroke (HR 0.65, 95% CI 0.47-0.92) compared with SGLT2 inhibitors. SGLT2 inhibitors achieved a greater hemoglobin A1c (HbA1c) reduction than SGLT1/2 inhibitors (0.16%, 95% CI 0.06-0.26). In patients with T2DM, the risk of diarrhea (risk ratio [RR] 1.42, 95% CI 1.07-1.88) and severe hypoglycemia (RR 5.89, 95% CI 1.41-24.57) were found to be higher with SGLT1/2 inhibitor use compared with SGLT2 inhibitor use. No differences were observed for cardiovascular, metabolic, and safety outcomes between SGLT1/2 inhibitors and SGLT2 inhibitors in patients with T1DM. CONCLUSIONS: In patients with T2DM, compared with pure SGLT2 inhibitors, combined SGLT1/2 inhibitors demonstrated a lower risk of myocardial infarction and of stroke, but were associated with a higher risk of diarrhea and severe hypoglycemia.

Effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on serum urate levels in patients with and without diabetes: a systematic review and meta-regression of 43 randomized controlled trials.

Objectives: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to reduce serum urate in patients with type 2 diabetes mellitus. To evaluate if this effect applies to both patients with and without diabetes, we conducted a systematic review and meta-analysis of SGLT2 inhibitors on serum urate levels in this population. Methods: Four electronic databases (PubMed, Embase, Cochrane and SCOPUS) were searched on 25 September 2021 for articles published from 1 January 2000 up to 25 September 2021, for studies that examined the effect of SGLT2 inhibitors on serum urate in study subjects. Random-effects meta-analysis was performed, with subgroup analyses on the type of SGLT2 inhibitor agent administered, presence of type 2 diabetes mellitus, presence of chronic kidney disease and drug dose. Results: A total of 43 randomized controlled trials, with a combined cohort of 31,921 patients, were included. Both patients with [-31.48 µmol/L; 95% confidence interval (CI): -37.35 to -25.60] and without diabetes (-91.38 µmol/L; 95% CI: -126.53 to -56.24) on SGLT2 inhibitors had significantly lower urate levels when compared with placebo. This treatment effect was similarly observed across different types of SGLT2 inhibitors. However, in type 2 diabetes mellitus (T2DM) patients with chronic kidney disease, the reduction in serum urate with SGLT2 inhibitors became insignificant (95% CI: -22.17 to 5.94, p < 0.01). Conclusion: This study demonstrated that SGLT2 inhibitors are beneficial in reducing serum urate in patients with and without diabetes. SGLT2 inhibitors could therefore contribute to the general treatment of hyperuricaemia.

Comparison of the Efficacy and Safety of Non-vitamin K Antagonist Oral Anticoagulants with Warfarin in Atrial Fibrillation Patients with a History of Bleeding: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with atrial fibrillation (AF) require oral anticoagulation to prevent ischemic stroke. However, oral anticoagulation may cause bleeding, and patients with AF and a history of bleeding were excluded from pivotal trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. We therefore aimed to assess the efficacy and safety of NOACs compared with warfarin in patients with AF and a history of bleeding. METHODS: We conducted a systematic review of retrospective studies and clinical trials using the PubMed, EMBASE, SCOPUS, Cochrane Library, and Web of Science databases to May 2021. RESULTS: Overall, 56,697 patients from six studies were included. NOACs significantly reduced the risk of ischemic stroke (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.59-0.91; p = 0.005), fatal ischemic stroke (HR 0.49, 95% CI 0.39-0.61; p < 0.001), all-cause mortality (HR 0.70, 95% CI 0.50-0.98; p = 0.04), major bleeding events (HR 0.75, 95% CI 0.67-0.84; p < 0.001), intracranial hemorrhage (ICH; HR 0.63, 95% CI 0.48-0.82; p < 0.001), fatal ICH (HR 0.33, 95% CI 0.20-0.56, p < 0.001), and gastrointestinal bleeding (HR 0.83, 95% CI 0.72-0.96; p = 0.01). CONCLUSIONS: NOACs showed better efficacy and safety profile compared with warfarin in patients with AF and a history of bleeding. Randomized controlled trials are warranted to validate these findings.

Clinical, echocardiographic and prognostic outcomes of patients with concordant and discordant high-gradient aortic stenosis in an Asian cohort.

Literature of patients with severe high-gradient aortic stenosis (HG AS) (mean pressure gradient [MPG] ≥ 40 mmHg and aortic valve area [AVA] ≥ 1.0 cm2) remains limited. This study seeks to compare the prognostic outcomes of patients with high-gradient concordant (HGCON-AS) and discordant AS (HGDIS-AS) in an Asian cohort. From 2010 to 2015, patients with moderate-to-severe AS with preserved left ventricular ejection fraction (LVEF ≥ 50%) were recruited and stratified into 3 groups based on index echocardiogram-(1) HGDIS-AS, (2) HGCON-AS and (3) moderate AS (MOD-AS). The primary study endpoints was all-cause mortality, with secondary endpoints of congestive heart failure (CHF) admissions and aortic valve replacement (AVR). Multivariable Cox regression was used and Kaplan-Meier curves were constructed to evaluate associations between HGDIS-AS, HGCON-AS and MOD-AS, and the study outcomes. A total of 467 patients were studied, comprising of 6.2% HGDIS-AS, 13.9% HGCON-AS and 79.9% MOD-AS patients. There was significantly higher AVR rates in the HGCON-AS group (58.5%), followed by HGDIS-AS (31.0%) and MOD-AS (4.6%), p < 0.001) groups. After adjusting for confounders, HGCON-AS was significantly associated with all-cause mortality (HR 3.082, 95% CI 1.479-6.420, p = 0.003) and CHF admissions (HR 12.728, 95% CI 2.922-55.440 p = 0.001) but not HGDIS-AS, with MOD-AS as the reference group. Both HGDIS-AS (HR 7.715, 95% CI 2.927-20.338; p < 0.001) and HGCON-AS (HR 21.960, 95% CI 10.833-44.515, p < 0.001) were independent predictors of AVR. After exclusion of reversible high-flow states, HGDIS-AS patients appear to have a more favourable prognostic profile compared to HGCON-AS patients. Large prospective interventional studies examining the prognostic differences between the two groups will be the next important step.

Cognitive Impairment in Heart Failure-A Review.

Cognitive impairment (CI) is common in heart failure (HF). Patients with HF demonstrate reduced global cognition as well as deficits in multiple cognitive domains compared to controls. Degree of CI may be related to HF severity. HF has also been associated with an increased risk of dementia. Anatomical brain changes have been observed in patients with HF, including grey matter atrophy and increased white matter lesions. Patients with HF and CI have poorer functional independence and self-care, more frequent rehospitalisations as well as increased mortality. Pathophysiological pathways linking HF and CI have been proposed, including cerebral hypoperfusion and impaired cerebrovascular autoregulation, systemic inflammation, proteotoxicity and thromboembolic disease. However, these mechanisms are poorly understood. We conducted a search on MEDLINE, Embase and Scopus for original research exploring the connection between HF and CI. We then reviewed the relevant literature and discuss the associations between HF and CI, the patterns of brain injury in HF and their potential mechanisms, as well as the recognition and management of CI in patients with HF.

Myocardial infarction, stroke and cardiovascular mortality among migraine patients: a systematic review and meta-analysis.

BACKGROUND: An increasing number of studies have shown an association between migraine and cardiovascular disease, in particular cardio- and cerebro-vascular events. METHODS: Three electronic databases (PubMed, Embase and Scopus) were searched from inception to May 22, 2021 for prospective cohort studies evaluating the risk of myocardial infarction, stroke and cardiovascular mortality in migraine patients. A random effects meta-analysis model was used to summarize the included studies. RESULTS: A total of 18 prospective cohort studies were included consisting of 370,050 migraine patients and 1,387,539 controls. Migraine was associated with myocardial infarction (hazard ratio, 1.36; 95% CI, 1.23-1.51; p = < 0.001), unspecified stroke (hazard ratio, 1.30; 95% CI, 1.07-1.60; p = 0.01), ischemic stroke (hazard ratio, 1.35; 95% CI, 1.03-1.78; p = 0.03) and hemorrhagic stroke (hazard ratio, 1.43; 95% CI, 1.07-1.92; p = 0.02). Subgroup analysis of migraine with aura found a further increase in risk of myocardial infarction and both ischemic and hemorrhagic stroke, as well as improved substantial statistical heterogeneity. Migraine with aura was also associated with an increased risk of cardiovascular mortality (hazard ratio, 1.27; 95% CI, 1.14-1.42; p = < 0.001). CONCLUSION: Migraine, especially migraine with aura, is associated with myocardial infarction and stroke. Migraine with aura increases the risk of overall cardiovascular mortality.

Inter-Ethnic Differences in Valvular Dysfunction, Aortopathy, and Progression of Disease of an Asian Bicuspid Aortic Valve Population.

BACKGROUND: There are differences in bicuspid aortic valve (BAV) characteristics between Asian and European populations, but little is known about the inter-ethnic differences in bicuspid valve function and aortic root dimensions within the diverse Asian population. METHODS: From 1992-2017, 562 patients with index echocardiographic diagnosis of BAV in a tertiary health care institution in Singapore were analysed according to their ethnic groups: Chinese, Malay, Indian, and Eurasian. Study outcomes included BAV complications (infective endocarditis, aortic dissection) and clinical outcomes (aortic valve surgery, aortic root surgery, all-cause mortality). Total events were defined as composite outcome of all BAV complications and outcomes. Aortic dimensions and aortic dilatation rates were also studied. RESULTS: There were 379 (67.5%) Chinese, 79 (14.0%) Malay, 73 (13.0%) Indian, and 31 (5.5%) Eurasian patients. Type 1 BAV (58.5%) was the most prevalent BAV morphology, with moderate-to-severe aortic stenosis (AS) (36.8%) being the most common complication in the overall population. There was a higher prevalence of type 0 BAV in Chinese and Indian groups, and type 1 BAV with fusion of left-right coronary cusp in Eurasian and Malay groups (p=0.082). There was no difference in significant AS among groups. The highest prevalence of moderate-to-severe aortic regurgitation was observed amongst the Eurasian group, followed by Chinese, Indian, and Malay groups (p=0.033). The Chinese group had the largest mean indexed diameters of the aortic root. Multivariable linear regression demonstrated that only the Chinese had significantly larger indexed diameters in the aortic annulus, sinotubular junction (STJ), and ascending aorta (AA), relative to the Eurasian group, after adjusting for age, sex, smoking, hypertension, hyperlipidaemia, diabetes, and aortic regurgitation. On follow-up echocardiography, there was a trend towards the highest dilatation rates of sinus of Valsalva and STJ amongst Indian, and AA amongst Malay groups. Kaplan-Meier curves showed the highest incidence of total events amongst Chinese, followed by Malay, Indian and Eurasian (log-rank=9.691; p=0.021) patients. CONCLUSION: There were differences in BAV morphology, valve dysfunction, aortopathy, and prognosis within the Asian population. Chinese patients had one of the highest prevalence of significant aortic regurgitation, with the largest aortic dimensions and worst outcomes compared with other Asian ethnicities. Closer surveillance is warranted in BAV patients within the Asian population.

Comparison of the Efficacy and Safety of Direct Oral Anticoagulants and Vitamin K Antagonists in Patients with Atrial Fibrillation and Concomitant Liver Cirrhosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with atrial fibrillation (AF) have a higher risk of developing thromboembolic events. Current guidelines recommend the use of oral anticoagulants for stroke prevention in these patients. Several clinical trials demonstrated that direct oral anticoagulants (DOACs) have similar efficacy and are safer alternatives to traditional oral anticoagulants. However, patients with concomitant liver cirrhosis were excluded from these trials. OBJECTIVE: We aimed to systematically identify and review published clinical studies on the use of DOACs in patients with AF and liver cirrhosis and assess the efficacy and safety of DOACs in these patients. METHODS: A systematic review of clinical trials and retrospective studies was conducted by searching the PubMed, Cochrane Library, Embase, SCOPUS, and Web of Science databases up to September 2020. RESULTS: Three retrospective studies were included, involving 4011 patients with AF and liver cirrhosis. The use of DOACs was associated with a significant reduction in ischemic stroke (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.42-0.90; p = 0.01), major bleeding events (HR 0.64; 95% CI 0.57-0.72; p < 0.001), and intracranial hemorrhage (HR 0.49; 95% CI 0.40-0.59; p < 0.001). CONCLUSIONS: Compared with warfarin in patients with AF and liver cirrhosis, DOACs appear to be associated with improved efficacy and safety outcomes. Randomized controlled trials are warranted to confirm these findings.

Comparing Sacubitril/Valsartan Against Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure: A Systematic Review and Network Meta-analysis.

BACKGROUND AND OBJECTIVE: In recent trials, sodium-glucose cotransporter 2 (SGLT2) inhibitors proved effective as treatment for heart failure. However, the relative efficacy of sacubitril/valsartan against SGLT2 inhibitor in patients with heart failure remains unknown. Hence, we performed a network meta-analysis to compare the effects of sacubitril/valsartan against SGLT2 inhibitors on cardiovascular outcomes in patients with heart failure. METHODS: Four electronic databases (PubMed, Embase, Cochrane, SCOPUS) were searched for randomised-controlled trials (RCTs) published from 1st January 2000 to 25th September 2021. Two additional systematic reviews were conducted for RCTs of enalapril and valsartan to establish a common comparator arm. Frequentist network meta-analysis models were utilised to summarise the studies. RESULTS: Twenty-five RCTs were included, comprising a combined cohort of 47,275 patients. Network meta-analysis demonstrated that compared to SGLT2 inhibitors, sacubitril/valsartan achieved a larger hazard rate reduction in the composite of heart failure hospitalisation and cardiovascular death (hazard ratio [HR]: 0.86; 95% CI 0.75-0.98), cardiovascular death (HR: 0.78; 95% CI 0.65-0.94), and a larger mean change in systolic blood pressure at 8 or more months (weighted mean difference [WMD]: - 7.08 mmHg; 95% CI - 8.28 to - 5.89). There were no significant differences in treatment effects across heart failure hospitalisation, all-cause mortality, diastolic blood pressure at 12 weeks, and systolic blood pressure at 2-4 months. In patients with heart failure with reduced ejection fraction, sacubitril/valsartan achieved a 20% hazard rate reduction for cardiovascular death compared to SGLT2 inhibitors. CONCLUSIONS: In patients with heart failure, sacubitril/valsartan was demonstrated to be superior to SGLT2 inhibitors in the treatment effect for the composite of heart failure hospitalisation and cardiovascular death, cardiovascular death, and long-term blood pressure.

Effects of Sodium-Glucose Cotransporter 2 on Amputation Events: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are increasingly utilized in the treatment of diabetes mellitus as well as therapeutic extra-glycemic effects. However, there are still concerns over complications such as amputation events, given the results from the Canagliflozin Cardiovascular Assessment Study (CANVAS) trial. Hence, we conducted a systematic review and meta-analysis of randomized-controlled trials to investigate the effect of SGLT2 inhibitors on amputation events. METHODS: Four electronic databases (PubMed, Embase, Cochrane, and SCOPUS) were searched on November 21, 2020, for articles published from January 1, 2000, up to November 21, 2020, for studies that examined the effect of SGLT2 inhibitors on amputation events. Random-effect pair-wise meta-analysis for hazard ratios and fixed-effect Peto odds ratio meta-analysis were utilized to summarize the studies. RESULTS: A total of 15 randomized-controlled trials were included with a combined cohort of 63,716 patients. We demonstrated that there was no significant difference in amputation events across different types of SGLT2 inhibitors, different baseline populations, and different duration of SGLT2 inhibitor use. DISCUSSION/CONCLUSIONS: In this meta-analysis, SGLT2 inhibitors were not associated with a significant difference in amputation events.

SGLT inhibitors on weight and body mass: A meta-analysis of 116 randomized-controlled trials.

OBJECTIVE: Multiple trials have demonstrated the metabolic effects of sodium/glucose cotransporter 2 (SGLT2) inhibitors in patients regardless of diabetes status, and recent trials have been conducted on the combined sodium/glucose cotransporter 1 and sodium/glucose cotransporter 2 (SGLT1/SGLT2) inhibitors. Therefore, a meta-analysis was conducted to investigate the weight reduction effects and dose-response relationship of SGLT inhibitors and to assess the relative efficacy of SGLT1/SGLT2 inhibitors. METHODS: Four electronic databases (PubMed, Embase, Cochrane, and Scopus) were searched on November 21, 2020, for articles published from January 1, 2000, up to November 21, 2020. RESULTS: In total, 116 randomized-controlled trials were included, with a combined cohort of 98,497 patients. Overall, patients had a mean weight reduction of -1.79 kg (95% CI: -1.93 to -1.66, p < 0.001) compared with placebo. This effect was observed across diabetes status, duration of follow-up, various comorbidities, and all SGLT drug types. Mean BMI changes were -0.71 kg/m2 (95% CI: -0.94 to -0.47, p < 0.001) compared with placebo. Canagliflozin, empagliflozin, sotagliflozin, and licogliflozin showed a dose-response relationship for mean weight change. Compared with SGLT2 inhibitors, SGLT1/SGLT2 inhibitors had a significantly larger reduction in weight. CONCLUSIONS: SGLT inhibitors demonstrated weight reduction benefits in this meta-analysis. Further studies are needed to clarify their role in weight management.

Post-ST-Segment Elevation Myocardial Infarction Follow-Up Care During the COVID-19 Pandemic and the Possible Benefit of Telemedicine: An Observational Study.

Background: Infectious control measures during the COVID-19 pandemic have led to the propensity toward telemedicine. This study examined the impact of telemedicine during the pandemic on the long-term outcomes of ST-segment elevation myocardial infarction (STEMI) patients. Methods: This study included 288 patients admitted 1 year before the pandemic (October 2018-December 2018) and during the pandemic (January 2020-March 2020) eras, and survived their index STEMI admission. The follow-up period was 1 year. One-year primary safety endpoint was all-cause mortality. Secondary safety endpoints were cardiac readmissions for unplanned revascularisation, non-fatal myocardial infarction, heart failure, arrythmia, unstable angina. Major adverse cardiovascular events (MACE) was defined as the composite outcome of each individual safety endpoint. Results: Despite unfavorable in-hospital outcomes among patients admitted during the pandemic compared to pre-pandemic era, both groups had similar 1-year all-cause mortality (11.2 vs. 8.5%, respectively, p = 0.454) but higher cardiac-related (14.1 vs. 5.1%, p < 0.001) and heart failure readmissions in the pandemic vs. pre-pandemic groups (7.1 vs. 1.7%, p = 0.037). Follow-up was more frequently conducted via teleconsultations (1.2 vs. 0.2 per patient/year, p = 0.001), with reduction in physical consultations (2.1 vs. 2.6 per patient/year, p = 0.043), during the pandemic vs. pre-pandemic era. Majority achieved guideline-directed medical therapy (GDMT) during pandemic vs. pre-pandemic era (75.9 vs. 61.6%, p = 0.010). Multivariable Cox regression demonstrated achieving medication target doses (HR 0.387, 95% CI 0.164-0.915, p = 0.031) and GDMT (HR 0.271, 95% CI 0.134-0.548, p < 0.001) were independent predictors of lower 1-year MACE after adjustment. Conclusion: The pandemic has led to the wider application of teleconsultation, with increased adherence to GDMT, enhanced medication target dosing. Achieving GDMT was associated with favorable long-term prognosis.