Empagliflozin Effects in Patients with ST-Elevation Myocardial Infarction Undergoing Primary PCI: The EMI-STEMI Randomized Clinical Trial.

INTRODUCTION: Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, improves cardiovascular outcomes in heart failure patients, but data regarding the efficacy of empagliflozin in the setting of acute myocardial infarction (AMI) is still unclear. The current study aimed to evaluate whether treatment with empagliflozin before primary percutaneous coronary intervention (PCI) improves parameters associated with patients' outcomes. METHODS: We randomly assigned 101 non-diabetic and non-heart failure patients with ST-elevation myocardial infarction (STEMI) who underwent primary PCI to receive either empagliflozin (10 mg before PCI and once daily for 40 days) or placebo, in addition to the standard treatment. The primary outcomes were changes in left ventricular ejection fraction (LVEF) 40 days after PCI, changes in cardiac troponin I (cTnI) and estimates of its area under the curve (AUC) and the peak level, and resolution of ST-segment in > 50% of leads 90 min after PCI. RESULTS: No significant difference was observed in terms of the occurrence of ST-segment resolution > 50% (46.0% versus 45.0%; p = 0.92) and the mean level of cTnI at each time point between the two groups. The estimated mean [standard deviation (SD)] AUC of cTnI was 955.0 (595.7) ng h/ml in the intervention and 999.7 (474.7) ng h/ml in the control groups (p = 0.85) without any significant difference in peak cTnI level. The mean (SD) LVEF 40 days after primary PCI was significantly higher in empagliflozin-treated patients than the placebo group [43.2% (5.8%) versus 39.2% (6.7%); p = 0.002]. CONCLUSION: In this study, no significant differences were observed across the groups in terms of cTnI levels and ST-segment resolution in patients with STEMI undergoing primary PCI. However, it shed light on the potential benefits of empagliflozin in improving LVEF following STEMI. REGISTRATION: Iranian Registry of Clinical Trials Platform ( https://irct.behdasht.gov.ir/ ) identifier number IRCT20111206008307N42.

Sodium-glucose cotransporter-2 inhibitors in individuals with ischemia reperfusion injury: A systematic review.

Background: The effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on ischemia reperfusion injury (IRI) is a novel concept and only limited number of animals studies have yet been investigated. We aimed to perform a systematic review of literature to explore the clinical studies which investigated the effects of SGLT-2 inhibitors on myocardial IRI setting.Methods: We searched MEDLINE, Embase, and Cochrane Library from inception until December 7th, 2023. ClinicalTrials.gov was also explored for ongoing studies. Two authors independently conducted the literature search, examined the studies, and evaluated the eligibility criteria. Any disagreements or uncertainties were resolved by the corresponding author. The search strategy followed the PICO process (Population, Intervention, Comparison, and Outcome) and Emtree was used to select relevant keywords.Results: Of 220 articles identified from the literature research, five articles were included in the study, of which three studies lately were retracted. The remaining studies included 1229 participants, with 209 receiving SGLT-2 inhibitors and 1090 not receiving them. All of the participants were diabetic patients admitted with acute myocardial infarction (AMI), undergoing percutaneous coronary intervention (PCI). The results demonstrated that the use of SGLT-2 inhibitors is associated with lower troponin levels, and higher rates of ST resolution. The results of the studies also showed smaller infarct sizes, lower inflammatory biomarkers and improved left ventricular function at discharge among SGLT-2 inhibitor users.Conclusion: In line with in vivo and ex vivo findings, the results of this systematic review supported benefits of SGLT-2 inhibitors in IRI through reducing infarct size and inflammatory biomarkers. However, further clinical trials are warranted to provide robust evidence.

Effects of citalopram on blood pressure control in depressive patients with hypertension: A randomized clinical trial.

Introduction: Since there is a bi-directional interaction between hypertension and depression, we aimed to evaluate the effects of citalopram administration in the management of hypertension. Methods: A randomized clinical trial was conducted on 72 patients with concomitant depression and hypertension. The intervention group (n=41) received citalopram 20 mg daily plus anti-hypertensive standard treatment, while the control group (n=31) received only the standard treatment. The study's primary endpoint was in-office blood pressure (BP) measurement at baseline and home BP monitoring in the first and second months after entering the study. Results: There were no significant differences in baseline systolic BP (163.3±19.6 vs.164.2±20.3 mm Hg; P=0.910) and diastolic BP (94.5±13.8 vs. 88.2±14.4; P=0.071). After one month, diastolic BP (82.7±11.7 vs. 77.09±12.2; P=0.023) was significantly higher in the control group compared to the intervention group. Two months after the intervention, systolic BP (133.8±16.5 vs. 124.5±12.4; P=0.009) and diastolic BP (80.7±10.3 vs. 73.7±9.7; P=0.002) were significantly decreased in the intervention group compared to the control group. Conclusion: This study supported the beneficial effects of citalopram in lowering BP in patients with concomitant depression and hypertension.

Comparison between proactive and retroactive models of medication reconciliation in patients hospitalized for acute decompensated heart failure.

BACKGROUND: Most research on the impact of medication reconciliation on patient safety focused on the retroactive model, with limited attention given to the proactive model. OBJECTIVE: This study was conducted to compare the proactive and retroactive models in patients hospitalized for acute decompensated heart failure. METHODS: This prospective, quasi-experimental study was conducted over six months, from June to November 2022, at the cardiology unit of an academic hospital in Iran. Eligible patients were those hospitalized for acute decompensated heart failure using a minimum of five regular medications before admission. Medication reconciliation was performed in 81 cases using the proactive model and in 81 using the retroactive model. RESULTS: 556 medications were reconciled using the retroactive model, and 581 were reconciled using the proactive model. In the retroactive cases, 341 discrepancies (both intentional and unintentional) were identified, compared to 231 in the proactive cases. The proportion of patients with at least one unintentional discrepancy was significantly lower in the proactive cases than in the retroactive cases (23.80% versus 74.03%). Moreover, the number of unintentional discrepancies was significantly lower in the proactive cases compared to the retroactive cases (22 out of 231 discrepancies versus 150 out of 341 discrepancies). In the retroactive cases, medication omission was the most frequent type of unintentional discrepancy (44.00). About, 42.70% of reconciliation errors detected in the retroactive cases were judged to have the potential to cause moderate to severe harm. While the average time spent obtaining medication history was similar in both models (00:27 [h: min] versus 00:30), the average time needed to complete the entire process was significantly shorter in the proactive model compared to the retroactive model (00:41 min versus 00:51). CONCLUSION: This study highlighted that the proactive model is a timely and effective method of medication reconciliation, particularly in improving medication safety for high-risk patients.

Impact of Clinical Pharmacist-conducted Medication Reconciliation at Admission and Discharge on Medication Safety in Patients Hospitalized with Acute Decompensated Heart Failure.

BACKGROUND: Most studies have focused on the impact of medication reconciliation on one of the points of hospital admission or discharge. In this study, we aimed to investigate the impact of medication reconciliation at both admission and discharge on medication safety in patients hospitalized with acute decompensated heart failure. METHODS: This was a prospective, single-center, cohort study conducted in a tertiary care cardiovascular hospital from October 2022 to March 2023 on patients hospitalized with acute decompensated heart failure. Patients were considered eligible if they were taking at least five chronic medications prior to hospital admission. Medication reconciliation was carried out for the study patients by a clinical pharmacy team both at admission and discharge. Further, the study patients also received comprehensive discharge counseling as well as post-discharge follow-up and monitoring. RESULTS: Medication reconciliation was applied for 129 patients at admission and 118 of them at discharge. The mean time needed for medication reconciliation presses was 32 min per patient on admission and 22min per patient on discharge. Unintentional medication discrepancies were relatively common both at admission and discharge in the study participants, but compared to admission, discrepancies were less frequent at discharge (178 versus 72). Based on the consensus review, about 30% of identified errors detected at both admission and discharge were judged to have the potential to cause moderate to severe harm to the patient, and most of the clinical pharmacists' recommendations on unintended discrepancies were accepted by physicians and resulted in changes in medication orders (more than 80%). Further, the majority of the participants were 'very satisfied' or 'satisfied' with the clinical pharmacy services provided to them during hospitalization and after hospital discharge (89.90%). CONCLUSIONS: Our results demonstrated that heart failure patients are vulnerable to medication discrepancies both at admission and discharge and implementing a comprehensive medication reconciliation by clinical pharmacists could be helpful in improving medication safety in these patients.

Empagliflozin and colchicine in patients with reduced left ventricular ejection fraction following ST-elevation myocardial infarction: a randomized, double-blinded, three-arm parallel-group, controlled trial.

PURPOSE: There is accumulating evidence regarding the potential benefits of empagliflozin in individuals with acute myocardial infarction (MI). Based on the literature, colchicine could also reduce the risk of MI and death in individuals with cardiovascular disease (CVD). However, trials investigating the effects of the combination of empagliflozin with colchicine and high-dose empagliflozin monotherapy in this setting are lacking. METHODS: In this trial, 106 non-diabetic participants with reduced left ventricular ejection fraction (LVEF) following recent ST-elevation MI were randomly assigned to empagliflozin 10 mg/day, empagliflozin 10 mg/day plus colchicine 0.5 mg twice daily, or empagliflozin 25 mg/day groups within 72 h after primary percutaneous coronary intervention (PCI). The study's primary outcomes were the changes in New York Heart Association (NYHA) functional class and high-sensitivity C-reactive protein (hs-CRP) over 12 weeks. RESULTS: The baseline characteristics of individuals were statistically similar between the study groups. Changes in NYHA functional class over 12 weeks were not significantly different between the study groups. hs-CRP was significantly reduced in all groups (all P < 0.001); however, there was no significant change between the groups over the study period. Changes in tumor necrosis factor-alpha (TNF-α), LVEF, and left ventricular end-diastolic dimension (LVEDD) during the research period did not differ significantly between groups. CONCLUSION: This study showed that neither the combination treatment of empagliflozin 10 mg/day with colchicine nor the monotherapy of empagliflozin 25 mg/day was superior to empagliflozin 10 mg/day in terms of changes in clinical, inflammatory, and echocardiographic outcome parameters in patients with recent MI with reduced LVEF over 3 months. Further studies are warranted to confirm the findings. TRIAL REGISTRATION: Clinical trial ID: IRCT20111206008307N39. Registration date: 27 October 2022. https://www.irct.ir/trial/66216.

Clinical considerations on monkeypox antiviral medications: An overview.

Monkeypox (mpox), a virus belonging to the orthopoxvirus family, can cause a zoonotic infectious disease with morbidity and cosmetic complications. Therefore, effective antiviral drugs with appropriate safety profiles are important for the treatment of patients with mpox. To date, there is no FDA-approved drug for the treatment of mpox. However, tecovirimat, brincidofovir, and cidofovir are the candidate therapies for the management of mpox. Given the safety concerns following the use of these medications, we aimed to review evidence on the clinical considerations of mpox antiviral medications that will be useful to guide clinicians in the treatment approach. Based on the current evidence, tecovirimat has favorable clinical efficacy, safety, and side effect profile and it can be considered as first-line treatment for mpox.

Empagliflozin and colchicine in patients with reduced left ventricular ejection fraction following ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: a study protocol for a randomized, double-blinded, three-arm parallel-group, controlled trial.

BACKGROUND: Patients with acute myocardial infarction are at greater risk for chronic heart failure and mortality. Currently, there is limited evidence supporting the beneficial effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular outcomes in non-diabetic patients with reduced left ventricular ejection fraction following acute myocardial infarction. Furthermore, the clinical effects of the combination of standard-dose sodium-glucose cotransporter-2 inhibitors with colchicine and high-dose sodium-glucose cotransporter-2 inhibitors in this setting have not been evaluated yet. METHODS: A prospective, double-blinded, parallel-group, placebo control randomized trial will be carried out at Shahid Madani Heart Center, the largest teaching referral hospital for cardiovascular diseases, affiliated with Tabriz University of Medical Sciences. A total of 105 patients with reduced left ventricular ejection fraction (≤ 40%) following the first episode of ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention with stent insertion will be randomized 1:1:1 to receive empagliflozin 10 mg daily, a combination of empagliflozin 10 mg daily and colchicine 0.5 mg twice daily, or empagliflozin 25 mg daily for 12 weeks. The primary outcomes are changes in the New York Heart Association functional classification and high-sensitivity C-reactive protein from the randomization through week 4 and week 12. DISCUSSION: The present study will be the first trial to evaluate the efficacy and safety of early treatment with the combination of standard-dose empagliflozin and colchicine as well as high-dose empagliflozin in non-diabetic patients with reduced left ventricular ejection fraction following ST-elevation myocardial infarction. The results of this research will represent a significant step forward in the treatment of patients with acute myocardial infarction. TRIAL REGISTRATION: Clinical trial ID: IRCT20111206008307N39. Registration date: 27 October 2022.

SARS-CoV-2-associated organs failure and inflammation: a focus on the role of cellular and viral microRNAs.

SARS-CoV-2 has been responsible for the recent pandemic all over the world, which has caused many complications. One of the hallmarks of SARS-CoV-2 infection is an induced immune dysregulation, in some cases resulting in cytokine storm syndrome, acute respiratory distress syndrome and many organs such as lungs, brain, and heart that are affected during the SARS-CoV-2 infection. Several physiological parameters are altered as a result of infection and cytokine storm. Among them, microRNAs (miRNAs) might reflect this poor condition since they play a significant role in immune cellular performance including inflammatory responses. Both host and viral-encoded miRNAs are crucial for the successful infection of SARS-CoV-2. For instance, dysregulation of miRNAs that modulate multiple genes expressed in COVID-19 patients with comorbidities (e.g., type 2 diabetes, and cerebrovascular disorders) could affect the severity of the disease. Therefore, altered expression levels of circulating miRNAs might be helpful to diagnose this illness and forecast whether a COVID-19 patient could develop a severe state of the disease. Moreover, a number of miRNAs could inhibit the expression of proteins, such as ACE2, TMPRSS2, spike, and Nsp12, involved in the life cycle of SARS-CoV-2. Accordingly, miRNAs represent potential biomarkers and therapeutic targets for this devastating viral disease. In the current study, we investigated modifications in miRNA expression and their influence on COVID-19 disease recovery, which may be employed as a therapy strategy to minimize COVID-19-related disorders.

SGLT2 Inhibitors' Cardiovascular Benefits in Individuals Without Diabetes, Heart Failure, and/or Chronic Kidney Disease: A Systematic Review.

Despite the growing body of evidence regarding the beneficial cardiovascular effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors, clinical data in individuals without diabetes, heart failure (HF), and/or chronic kidney disease (CKD) is limited. A systematic review of the literature was conducted in PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar, from database inception until May 4, 2023, to explore new evidence of SGLT2 inhibitors' cardiovascular benefits in individuals without diabetes, HF, and/or CKD. A total of 1156 individuals from 14 studies (13 randomized controlled trials and 1 nonrandomized study) were included. The results showed the benefits of SGLT2 inhibitors on blood pressure, weight, and body mass index in this population with an acceptable safety profile. The current evidence supports the potential role of SGLT2 inhibitors as primary prevention in individuals without diabetes, HF, and/or CKD. This review may shed light on the use of SGLT2 inhibitors in conditions such as stage A HF and metabolic syndrome. The literature trend is going toward uncovering SGLT2 inhibitors' role in stage B HF, different types of myocardial infarction, and cardiac arrhythmias.

Interleukin-2 and Oncolytic Virotherapy: A New Perspective in Cancer Therapy.

By triggering immune responses in malignancies that have generally been linked to poor outcomes, immunotherapy has recently shown effectiveness. On the other hand, tumors provide an environment for cells that influence the body's immunity against cancer. Malignant cells also express large amounts of soluble or membrane-bound ligands and immunosuppressive receptors. In this regard, the combination of oncolytic viruses with pro-inflammatory or inflammatory cytokines, including IL-2, can be a potential therapy for some malignancies. Indeed, oncolytic viruses cause the death of cancerous cells and destroy the tumor microenvironment. They result in the local release of threat signals and antigens associated with tumors. As a result, it causes lymphocyte activity and the accumulation of antigenpresenting cells which causes them to accumulate in the tumor environment and release cytokines and chemokines. In this study, we reviewed the functions of IL-2 as a crucial type of inflammatory cytokine in triggering immune responses, as well as the effect of its release and increased expression following combination therapy with oncolytic viruses in the process of malignant progression, as an essential therapeutic approach that should be taken into consideration going forward.

Effects of Triamterene in Hospitalized Patients with Heart Failure and Diuretic Resistance: A Randomized Clinical Trial.

Due to the potential benefits of triamterene in diuretic resistance, this study was performed to assess whether triamterene add-on to the standard treatment of heart failure (HF)-related diuretic resistance improves outcomes. A randomized clinical trial was performed on 45 hospitalized patients with HF with reduced ejection fraction who had diuretic resistance. Patients were randomized to receive either triamterene 50 mg plus hydrochlorothiazide 25 mg (n = 23) or hydrochlorothiazide 50 mg alone (n = 22) until hospital discharge. The primary outcomes were changes in weight and fluid input-to-output ratio. Secondary outcomes were respiratory rate, hospitalization duration, serum sodium and potassium, estimated glomerular filtration rate, creatinine, and blood urea nitrogen levels during the study period. The mean (standard deviation) of weight changes was not significantly different in the intervention and the control groups (-6.3 [4.8] vs -4.8 [2.4] kg, respectively; P = .1). No significant differences were shown in input-to-output changes between the 2 groups (208.0 [243.4] in the intervention and 600.2 [250.3] in the control group; P = .4). Although the respiratory rate of triamterene-treated patients decreased, the difference did not reach statistical significance (P = .2). Other secondary outcomes were also similar in both groups. This study did not support the use of triamterene as an add-on therapy for patients with HF-related diuretic resistance.

Effect of Caffeine Consumption on Cardiovascular Disease: An Updated Review.

The incidence of cardiovascular diseases has significantly increased with the expansion of the industrialization of societies, which is notably linked to lifestyle changes and an unhealthy diet. Hence, determining the healthiest diet habits and supplements seems to be an appropriate way to decrease the global burden of cardiovascular diseases. Currently, caffeine, one of the most widely consumed compounds in the world, has emerged with some promising results in the treatment of numerous pathophysiological conditions of cardiovascular diseases. A literature search was conducted in PubMed, Scopus, Science Direct, Google Scholar, and Web of Science databases for the relevant articles regarding the pharmacology, preclinical, and clinical studies on the potential effects of caffeine on cardiovascular diseases. While caffeine could improve cardiovascular outcomes through several mechanisms of action, the literature review revealed controversial clinical effects of caffeine on blood pressure, cardiac arrhythmias, acute coronary syndrome, stable angina, and heart failure. In the case of dyslipidemia, coffee consumption increased total cholesterol, triglyceride, and low-density lipoprotein. Taken together, the existence of multiple confounding factors in the caffeine studies has resulted in inconclusive data interpretation. Further well-designed studies with adequate control of the confounding factors are warranted to draw a clear conclusion on the cardiovascular efficacy and safety of caffeine.