BACKGROUND: Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI). RESULTS: We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle ACEI + BB + MRA in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (-8.05 mL/m 2 , 95% CI: -14.88 to -1.23 mL/m 2 ) and ACEI + BB + SGLT-2i (-18.94 mL/m 2 , 95% CI: -36.97 to -0.61 mL/m 2 ) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (-3254.21 pg/mL, 95% CI: -6242.19 to -560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP. CONCLUSIONS: Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI + BB + MRA + SGLT-2i" is superior to the golden triangle "ACEI + BB + MRA" in improving LVEF. REGISTRATION PROSPERO; No. CRD42022354792.
Humans ; Heart Failure/physiopathology* ; Stroke Volume/physiology* ; Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Randomized Controlled Trials as Topic ; Mineralocorticoid Receptor Antagonists/therapeutic use* ; Adrenergic beta-Antagonists/therapeutic use*

Humans ; Stroke Volume ; Valsartan/therapeutic use* ; Heart Failure/drug therapy* ; Hypotension/drug therapy* ; Aminobutyrates/therapeutic use* ; Drug Combinations ; Angiotensin Receptor Antagonists/therapeutic use* ; Tetrazoles/therapeutic use* ; Treatment Outcome ; Ventricular Function, Left

Humans ; Stroke Volume ; Valsartan/therapeutic use* ; Heart Failure/drug therapy* ; Hypotension/drug therapy* ; Aminobutyrates/therapeutic use* ; Drug Combinations ; Angiotensin Receptor Antagonists/therapeutic use* ; Tetrazoles/therapeutic use* ; Treatment Outcome ; Ventricular Function, Left

Based on Guidelines for the Management of Clinical Comprehensive Evaluation of Drugs(trial version 2021), this study aims to sort out the clinical evidence of Huangkui Capsules(HC) in the treatment of chronic kidney diseases in aspects of safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine( "6+1" dimensions) from real-world data, secondary literature evaluations, questionnaires, and public data, with the methods in evidence-based medicine, epidemiology, pharmacoeconomics, and health technology. Furthermore, with multi-criteria decision analysis(MCDA) model and CSC v2.0, the clinical value of the medicine is comprehensively assessed. All the above are to highlight the advantages and characteristics of HC and lay a basis for scientific decision-making by the medical management department. The dimensions are graded A, B, C, or D. According to the conclusions from phase Ⅳ clinical trial, spontaneous reporting system(SRS), systematic review and Meta-analysis, acute toxicity and long-term toxicity tests, it mainly results in the adverse reactions of nausea, abdominal distension, vomiting, pruritus, rash, and good prognosis in patients. According to the available research, the safety evidence is sufficient and the risk is controllable, so the safety of this medicine is grade B. According to Meta-analysis, HC in combination with conventional drugs in the treatment of chronic kidney disease is superior to conventional drugs alone in reducing urinary protein, serum creatinine concentration, and blood urea nitrogen. In addition, HC combined angiotensin receptor blocker(ARB) or angiotensin converting enzyme inhibitor(ACEI) is outstanding in improving total clinical effective rate, reducing 24 h urinary protein quantity, urinary albumin excretion rate, serum creatinine concentration, triglyceride, and total cholesterol in the treatment of diabetic nephropathy as compared with ARB or ACEI alone. As for chronic nephritis, the application together with ARB or ACEI can raise the total effective rate, reduce 24 h urinary protein content, serum creatinine concentration, and blood urea nitrogen, and delay the progress of the disease. HC boasts high-quality evidence in treating chronic kidney disease, diabetic nephropathy, and chronic nephritis. It has obvious clinical significance in treating chronic kidney disease and thus its efficacy in this aspect is grade B. It has outstanding clinical significance for diabetic nephropathy and chronic nephritis and corresponding and the effectiveness is grade A. As for the pharmacoeconomic value, HC combined with ARB or ACEI is more economical in the treatment of chronic kidney disease than Bailing Capsules combined with ARB or ACEI, with high-quality evidence, and thus the economy of the formula is grade B. HC is a key solution to the high urinary protein in patients with hypotension and chronic kidney disease. The innovation is evidenced by the methods to ensuring drug supply, community-level supply, drug safety, effectiveness, and reasonable price, as wells as the aspects of enterprise philosophy, equipment management, research and development in process and technology, enterprise management and marketing. Thus, the prescription is grade A in innovation. The suitability, as evidenced in drug administration, technical management, drug storage, information service, and medication, is grade B. The course of the medicine is affordable, and it is accessible in a wide range of areas and hospitals. Thus, the accessibility is grade A. HC was developed from an in-hospital preparation, with application in numerous patients and thus large-scale real-world data. As a result, HC is grade B in terms of characteristics of traditional Chinese medicine. After comprehensive evaluation, the clinical value of HC in treating chronic kidney disease is class B, and that for diabetic nephropathy and chronic nephritis is class A. The result is of great reference value for the basic clinical medication management.
Angiotensin Receptor Antagonists/adverse effects* ; Angiotensin-Converting Enzyme Inhibitors ; Capsules ; Diabetic Nephropathies/drug therapy* ; Humans ; Renal Insufficiency, Chronic/drug therapy*

Consecutively hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) in Wuhan, China were retrospectively enrolled from January 2020 to March 2020 to investigate the association between the use of renin-angiotensin system inhibitor (RAS-I) and the outcome of this disease. Associations between the use of RAS-I (angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)), ACEI, and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status. A total of 2771 patients with COVID-19 were included, with moderate and severe cases accounting for 45.0% and 36.5%, respectively. A total of 195 (7.0%) patients died. RAS-I (hazard ratio (HR)= 0.499, 95% confidence interval (CI) 0.325-0.767) and ARB (HR = 0.410, 95% CI 0.240-0.700) use was associated with a reduced risk of all-cause mortality among patients with COVID-19. For patients with hypertension, RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352 (95% CI 0.162-0.764) and 0.279 (95% CI 0.115-0.677), respectively. RAS-I exhibited protective effects on the survival outcome of COVID-19. ARB use was associated with a reduced risk of all-cause mortality among patients with COVID-19.
Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; COVID-19 ; Humans ; Hypertension/drug therapy* ; Renin-Angiotensin System ; Retrospective Studies

Objective: To evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOAC) in patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM). Methods: This study was a prospective cohort study. The data of this study were based on the Chinese Atrial Fibrillation Registry (CAFR) Study, which was a prospective, multicenter registry study. The CAFR Study enrolled inpatients and outpatients with AF from 31 hospitals. Patients with AF and HCM were selected from August 2011 to December 2018. The patients were divided into NOAC-treated group and warfarin-treated group. General clinical data, echocardiographic results and treatment options were collected and compared between the two groups. Patients were followed up every 6 months; outcome events included effective endpoint events(thromboembolism)and safety endpoint events(major bleeding). The incidence of endpoint events in both groups was calculated and compared. Cox proportional hazards regression models and Kaplan-Meier survival analysis were performed to determine the association between NOAC use and endpoint events. Results: A total of 393 patients were included (average age: (60.5±11.8) years, 252 men (64.1%)). There were 133 (34.0%) patients in the NOAC-treated group and 260 (66.0%) patients in the warfarin-treated group. Compared with the warfarin-treated group, the patients in the NOAC-treated group had a higher proportion of paroxysmal AF, catheter ablation of AF, a lower proportion of hypertension, ischemic stroke/transient ischemic attack (TIA), lower heart rate, lower usage rate of angiotensin-converting enzyme inhibitors(ACEI)/angiotensin receptor blockers(ARB), β-blockers, non-dihydropyridine calcium channel blockers(NDH-CCB)(P<0.05). There were no significant differences on the echocardiographic results, including interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic diameter, left atrial diameter, left ventricular ejection fraction(P>0.05). After a follow-up of 42 (24, 60)months, the incidence rates of thromboembolism were 1.63 and 2.10 events per 100 person-years for NOAC-and warfarin-treated group, and those of major bleeding were 0.66 and 1.03 events per 100 person-years. Kaplan-Meier survival analysis showed survival rates free from endpoint events were similar between NOAC-treated group and warfarin-treated group(thromboembolism-free survival comparison, P=0.476; major bleeding-free survival comparison, P=0.855). Cox multivariate regression analysis revealed that there was no significant difference on risk of thromboembolism(HR=1.21, 95%CI: 0.42-3.50, P=0.720) and major bleeding(HR=1.50, 95%CI: 0.27-8.41, P=0.642) between NOAC-treated and warfarin-treated group. Conclusion: Patients with AF and HCM can be safely and effectively treated with NOAC.
Administration, Oral ; Aged ; Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Anticoagulants/therapeutic use* ; Atrial Fibrillation/drug therapy* ; Cardiomyopathy, Hypertrophic/drug therapy* ; Humans ; Male ; Middle Aged ; Prospective Studies ; Stroke ; Stroke Volume ; Treatment Outcome ; Ventricular Function, Left

Objective: To summarize the clinical characteristics of patients with Takotsubo syndrome (TTS) from China and compare these features with patients from Europe/North America. Methods: We reviewed case reports published between 1990 and 2020 with the key words of "Takotsubo syndrome" "stress cardiomyopathy" "apical balloon syndrome" and "broken heart syndrome", in Wanfang, CNKI, Pubmed and Web of Science databases, and 1 294 articles were identified, including 128 articles reporting 163 cases in China and 1 166 articles reporting 1 256 cases in Europe/North America. The characteristics of demographics, triggers, symptoms, electrocardiogram, echocardiography, left ventriculogram,coronary angiography, treatment and prognosis were analyzed and compared between Chinese and European/North American cases. Results: A total of 1 294 articles (1 419 cases: 163 from China, 1 256 from Europe/North America) were included in the final analysis. The characteristics of Chinese cases included: (1) demographic:the age was (59.6±16.9) years, which was similar with that of European/North American ((59.7±17.4) years, P=0.90), and female accounting for 78.5% (128/163), which was lower than that of European/North American (85.4% (1 073/1 256), P=0.02). (2) Triggers:mental triggers accounted for 48.5% (79/163), physical triggers accounted for 43.6% (71/163), and no triggers accounted for 7.9% (13/163), respectively. Compared with Europe/North America, the ratio of patients with mental triggers was higher in China, while the ratio of patients with physical triggers and no triggers was lower (P<0.05). (3) Symptoms: chest pain (52.8% (86/163)), chest tightness (35.0% (57/163)), shortness of breath (33.1% (54/163)), dizziness (16.0% (26/163)), sweating (15.3% (25/163)), palpitations (12.3% (20/163)), syncope (9.2% (15/163)) abdominal pain/diarrhea (8.6% (14/163)), hypotension (7.4% (12/163)), and fatigue (1.2% (2/163)) were illustrated in sequence. Compared with patients in Europe/North America, the ratio of patients with chest tightness, dizziness, sweating, palpitations, abdominal pain/diarrhea was higher in Chinese patients, while the ratio of patients with hypotension was lower in Chinese patients (P<0.05). (4) Electrocardiogram: main manifestations were myocardial ischemia symptoms, such as ST-segment elevation (63.8% (104/163)), T wave inversion (46.0% (75/163)), ST-segment depression (8.6% (14/163)). Compared with European/North American, the ratio of patients with ST-segment elevation, T wave inversion, and atrioventricular block was higher in Chinese patients (P<0.05). (5) Echocardiography and imaging:apical dyskinesia (59.5% (97/163)) and apical/left ventricular bulbar dilation (36.2%(59/163)) dominated the echocardiography findings. Compared with European/North American, the ratio of patients with apical dyskinesia, apical/left ventricular bulbar dilation, and mitral regurgitation was higher in Chinese patients, while the ratio of patients with dyskinesia in other parts and left ventricular ejection fraction<50% was lower in Chinese patients (P<0.05). Left ventricular angiography showed 36.2% (59/163) of apical dyskinesia in Chinese patients, which was higher than that reported in European/North American patients, and 38.7% (63/163) of apical/left ventricular bulbar dilation was reported in Chinese patients, which was similar to that reported in European/North American patients. Coronary angiography showed percent of no stenosis or stenosis less than 50% was 87.1% (142/163), which was similar to that reported in European/North American patients (P>0.05). The typical type of TTS accounted for 96.3% (157/163), which was significantly higher than that reported in European/ American patients, while the ratio of basal type and midventricular type was lower (P<0.01). (6) Treatment and prognosis:the applied drugs in China were listed in order as following, β-blockers (41.1% (67/163)), antiplatelet agents (37.4%(61/163)), ACEI/ARB (36.2%(59/163)), anticoagulants (27.0%(44/163)), diuretics (19.6% (32/163)), etc. Compared with Europe/North America, the ratio of antiplatelet agents, anticoagulants, statins, diuretics, and nitrates use was higher in China (P<0.05), while the use of oxygen therapy and IABP was similar (P>0.05). The hospital mortality in China was 5.5% (9/163), during 1-year follow-up the recurrence rate was 3.7% (6/163) and the mortality was 0. The prognosis was similar with that in Europe/North America. Conclusions: Compared with TTS cases in Europe/North America, TTS cases in China also occur usually in middle-aged and elderly women, most of whom have mental/physical triggers and typical imaging manifestations, followed by a low hospital mortality rate and recurrence rate.
Abdominal Pain/complications* ; Adult ; Aged ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Anticoagulants ; Arrhythmias, Cardiac/complications* ; China/epidemiology* ; Diuretics ; Dizziness/complications* ; Dyskinesias/complications* ; Electrocardiography ; Europe/epidemiology* ; Female ; Humans ; Hypotension/complications* ; Middle Aged ; Platelet Aggregation Inhibitors ; Stroke Volume ; Takotsubo Cardiomyopathy/etiology* ; Ventricular Function, Left

Aminobutyrates ; Angiotensin Receptor Antagonists ; China ; Consensus ; Drug Combinations ; Heart Failure/drug therapy* ; Humans ; Neprilysin ; Stroke Volume ; Tetrazoles ; Valsartan

INTRODUCTION: There are concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may worsen the outcomes of patients with COVID-19. This systematic review and meta-analysis aimed to study the in-hospital mortality among COVID-19 patients who were on ACEIs/ARBs as compared to those not on ACEIs/ARBs. METHODS: We searched PubMed, EMBASE, clinicaltrials.gov and Google Scholar between 1 January 2020 and 30 May 2020 to identify all studies that evaluated the use of ACEIs/ARBs and reported the in-hospital mortality outcomes of COVID-19 patients. Nine non-randomised studies were eligible for inclusion in the analysis. The primary outcome studied was the in-hospital mortality of COVID-19 patients who were on ACEIs/ARBs compared with those not on ACEIs/ARBs. RESULTS: Of the 8,313 patients in the nine studies, 7,622 (91.7%) were from studies with all-comers, while 691 (8.3%) were from studies involving only patients with hypertension. 577 (14.6%) in-hospital deaths were observed out of a total of 3,949 patients with an outcome in the nine studies. Overall, no significant difference was observed in the in-hospital mortality between patients on ACEIs/ARBs and those not on ACEIs/ARBs (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.75-1.50; p = 0.73). Further sensitivity analysis in the hypertension group and the all-comers group showed similar results (OR 0.88, 95% CI 0.58-1.32; p = 0.53 and OR 1.85, 95% CI 1.00-3.43; p = 0.05, respectively). CONCLUSION We observed that ACEIs/ARBs had no significant impact on the in-hospital mortality of COVID-19 patients and can be used safely in patients with indications.
Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; COVID-19 ; Hospital Mortality ; Humans ; Hypertension/drug therapy* ; SARS-CoV-2

OBJECTIVE: Cardiovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk. The effects of drugs on individual usage are also often unknown. This review aimed to examine the correlation between depression and common cardiovascular drugs, develop more potent interventions for depression in cardiovascular patients, and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression. DATA SOURCES: The data in this review were obtained from articles included in PubMed, EMBASE, and Web of Science. STUDY SELECTION: Clinical trials, observational studies, review literature, and guidelines about depression and cardiovascular drugs were selected for the article. RESULTS: We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review. Statins have been proven to have antidepressant effects. Some studies believe angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARB) can exert an antidepressant influence by acting on the renin-angiotensin system, but further clinical trials are needed to confirm this. Beta-blockers have previously been associated with depression, but the current study found no significant association between beta blockers and the risk of depression. Aspirin may have antidepressant effects by suppressing the immune response, but its role as an antidepressant remains controversial. calcium channel blockers (CCBs) can regulate nerve signal transduction by adjusting calcium channels, but whether this effect is beneficial or harmful to depression remains unclear. Finally, some cases have reported that nitrates and diuretics are associated with depression, but the current clinical evidence is insufficient. CONCLUSIONS Statins have been proven to have antidepressant effect, and the antidepressant effects of ACEIs/ARB and aspirin are still controversial. CCBs are associated with depression, but it is unclear whether it is beneficial or harmful. No association has been found with β-blockers, diuretics, and nitrates.
Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Antihypertensive Agents/therapeutic use* ; Calcium Channel Blockers/therapeutic use* ; Cardiovascular Agents/therapeutic use* ; Cardiovascular Diseases/drug therapy* ; Depression/drug therapy* ; Humans ; Hypertension/drug therapy* ; Renin-Angiotensin System