Statin Therapy in Post-Operative Atrial Fibrillation: Focus on the Anti-Inflammatory Effects.

BACKGROUND: Atrial fibrillation (AF) occurring after cardiac surgery, post-operative AF (POAF), is a serious and common complication of this treatment. POAF may be life-threatening and the available preventive strategies are insufficient or are associated with significantly increased risk of adverse effects, especially in long-term use. Therefore, more appropriate treatment strategies are needed. METHODS: In this paper, the efficacy, safety, and other aspects of using statins in the prevention of POAF focusing on their anti-inflammatory effects are reviewed. RESULTS: Recent studies have suggested that inflammation has a significant role in POAF, from the first AF episode to its serious complications including stroke and peripheral embolism. On the other hand, statins, the most widely used medications in cardiovascular patients, have pleiotropic effects, including anti-inflammatory properties. Therefore, they may potentially be effective in POAF prevention. Statins, especially atorvastatin, appear to be an effective option for primary prevention of POAF, especially in patients who had coronary artery bypass grafting (CABG), a cardiac surgery treatment associated with inflammation in the heart muscle. However, several large studies, particularly with rosuvastatin, did not confirm the beneficial effect of statins on POAF. One large clinical trial reported higher risk of acute kidney injury (AKI) following high-dose rosuvastatin in Chinese population. In this study, rosuvastatin reduced the level of C-reactive protein (CRP) but did not reduce the rate of POAF. CONCLUSION: Further studies are required to find the most effective statin regimen for POAF prevention with the least safety concern and the highest health benefits.

The Efficacy of Anti-inflammatory Agents in the Prevention of Atrial Fibrillation Recurrences.

Several studies have indicated an association between inflammation and the recurrence of Atrial Fibrillation (AF), especially after ablation, which is a therapeutic option leading to local inflammation. On the other hand, each AF can lead to another AF, as a general rule. Thus, preventing recurrences of AF is extremely important for patient outcomes. In this paper, we attempted to review the effect of medicinal agents with anti-inflammatory properties on the prevention of AF recurrence. There are several randomized controlled trials (RCTs) and meta-analyses on the prevention of AF recurrence using agents with anti-inflammatory properties, which include steroids, colchicine, statins, and n-3 fatty acids (n-3 FA). Clinical trials evaluating the efficacy of anti-inflammatory drugs in preventing the recurrence of AF led to inconsistent results for corticosteroids, statins and n-3 FAs. These results may be related to the fact that inflammation is not the only factor responsible for triggering recurrences of AF. For example, the presence of structural, mechanical and electrical remodeling could potentially be the most important factors that trigger recurrences of AF but these factors have not been addressed in most of the reported studies. Therefore, future clinical trials are needed to compare the efficacy of anti-inflammatory drugs in AF patients with, or without other factors. For colchicine, a potent anti-inflammatory drug, there are limited studies. However, all the studies investigating colchicine in the context of AF were consistent and promising, especially when colchicine was used on a short-term basis following ablation in patients with paroxysmal AF. Therefore, colchicine could be a promising candidate for further clinical studies involving recurrent AF.

Antipsychotic Drugs and Risk of Developing Venous Thromboembolism and Pulmonary Embolism: A Systematic Review and Meta-Analysis.

BACKGROUND: Antipsychotic (AP) medications are the cornerstone treatment for schizophrenia and some other psychiatric diseases. However, some observational studies suggest that these medications might increase the risk of venous thromboembolism (VTE) and pulmonary embolism (PE). OBJECTIVES: The aim of this study was to assess whether AP medications are associated with the development of VTE or PE, and to assess the risk based on any type of AP drugs, quality of studies and after adjustment of risk factors. DATA SOURCES: To identify relevant studies, we searched PubMed and EMBASE databases up to February 2019. We also searched the reference lists of relevant articles for related studies. STUDY SELECTION: Twenty studies fulfilled the eligibility criteria and were included in our meta-analysis after screening relevant observational cohort and case-control studies. PRIMARY OUTCOME: The primary outcome of our meta-analysis was the occurrence of all VTE or PE only attributed to exposure to AP medications compared with non-exposure to AP medications. RESULTS: Exposure to AP drugs was associated with a significant increase in the risk of VTE (RR 1.53, 95% CI 1.30-1.80, I2 = 85%) and PE (RR 3.69, 95% CI 1.23-11.07, I2 = 90%). In the subgroup metaanalysis, the use of low-potency AP drugs was associated with a higher risk of VTE, (RR 1.90, 95% CI 1.04-3.47, I2 = 78%). CONCLUSION: AP exposure was associated with a 1.5-fold increase in the risk of VTE and a 3.7-fold increase in the risk of PE. Low-potency AP drugs were associated with a higher risk of VTE. However, high heterogeneity among studies limits the generalizability of the results.

Anti-inflammatory drugs in the prevention of post-operative atrial fibrillation: a literature review.

Atrial fibrillation (AF) is a serious and common complication following heart surgery. Cardiac surgery triggers inflammation in the heart and makes it susceptible to the incidence of AF. Therefore, anti-inflammatory drugs may reduce the rate of AF incidence in the post-surgery conditions. Immunosuppressant agents, steroidal anti-inflammatory drugs (corticosteroids), non-aspirin non-steroid anti-inflammatory drugs (NSAIDs), colchicine and omega-3 unsaturated fatty acids (n-3 UFA) are drugs with well-known anti-inflammatory properties. The efficacy, safety and other aspects of using these drugs in the prevention of post-operative AF (POAF) have been reviewed here. Studies evaluating the efficacy of colchicine have shown that it could be effective in the prevention of POAF. However, there is a need for additional studies to find a colchicine regimen with optimal efficacy and higher tolerability. The use of corticosteroids may also be of value based on the most of meta-analyses. In the case of n-3 polyunsaturated fatty acids and NSAIDs, current data fail to support their efficacy in POAF prevention. Moreover, perioperative administration of NSAIDs may be associated with some severe safety considerations. Immunosuppressant agents have not been used for the prevention of POAF. Further studies are needed to find the most effective strategy for POAF prevention with the least safety considerations and the highest health benefits.

Anti-Androgen Drugs in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review.

OBJECTIVE: This study aimed to systematically investigate whether anti-androgens could significantly reduce Obsessive-Compulsive Disorder (OCD) symptoms compared to placebo or usual care in OCD patients. METHODS: PubMed, EMBASE, CENTRAL and International Clinical Trials Registry Platform (ICTRP) databases were searched up to October 2018 using relevant keywords. All randomized and if not available non-randomized studies conducted on a population including OCD patients who were administered with anti-androgen, which reported changes in their symptoms, were included. The studies on compulsive hypersexuality were excluded. Required data were extracted from full-text of the included articles by two independent authors. One randomized and four non-randomized trials were found. RESULTS: The only randomized trial showed that flutamide, an anti-androgen agent, was effective in reducing compulsion scores in male OCD patients with comorbid Tourette syndrome, compared to placebo. Three out of four non-randomized trials showed that different anti-androgens including finasteride, cyproterone acetate and triptorelin were effective in reducing OCD symptoms. The only study, which failed to show the efficacy of an anti-androgen agent, administered OCD patients with flutamide. Despite the positive results, available studies provide the evidence with low quality based on the Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) approach. CONCLUSION: Available studies are not sufficient for a precise answer to our study question. There is still a need for further large randomized blinded clinical trials to evaluate the effectiveness of antiandrogens in OCD patients. It is recommended that gender, comorbidities and subscales of Yale- Brown Obsessive-Compulsive Score (Y-BOCS) should be considered in designing the studies and interpreting their results.

The effect of diabetes mellitus on pharmacokinetics, pharmacodynamics and adverse drug reactions of anticancer drugs.

Diabetes mellitus (DM) and cancer are global problems carrying huge human, social, and economic impact. Type 2 diabetes (T2DM) is associated with an increased risk for a number of cancers, including breast, pancreatic, and liver cancer. Moreover, adverse drug reactions are higher in paitents with cancer with T2DM compared to cancer patients without T2DM. Cellular mechanisms of hyperglycemia and chemotherapy efficacy may be different depending upon the particular cancer type and the condition of the patient. This review evaluates the effect of DM on the pharmacokinetic, pharmacodynamic, and adverse drug reactions of commonly used anticancer drugs such as cisplatin, methotrexate, paclitaxel, doxorubicin, and adriamycin in both clinical and animal models. A literature search was conducted in scientific databases including Web of Science, PubMed, Scopus, and Google Scholar including the relevant keywords. The results of the effectiveness of anticancer therapies in patients with DM are, however, inconsistent because DM can negatively impact multiple diverse entities including nerves and vascular structures, insulin-like growth factor 1, the function of the innate immune system, drug pharmacokinetics, the expression levels of hepatic CYP450 , Mdr 1b and enzymes that then lead to drug toxicity. However, in a few circumstances, DM led to attenuation of the toxicity of anticancer drugs secondary to attenuation of the energy-dependent renal uptake process. Overall, the impact of DM on patients with cancer is variable because of the diverse types of cancers and the spectrum of anticancer drugs. With respect to the evidence for cancer involvement in DM pathophysiology and the response to anticancer treatment in patients with DM, many questions still remain and further clinical trials are needed.

The change of immunosuppressive regimen from calcineurin inhibitors to mammalian target of rapamycin (mTOR) inhibitors and its effect on malignancy following heart transplantation.

Malignancy is a significant cause of mortality after organ transplantation. There is an increased rate of malignancy following heart transplantation (HTx) compared to the general population and other organ transplant recipients. Post-HTx patients with a history of malignancy are also at a higher risk of developing new malignancies or exacerbation of their existing malignancies. Mammalian target of Rapamycin inhibitors (mTORIs) are newly introduced immunosuppressive drugs with a unique mechanism of action. By changing the immunosuppressive regimen from classic drugs, especially calcineurin inhibitors (CNIs) to mTORIs, the rate of developing de novo malignancies and the relapse of former malignancies is significantly reduced. However, issues like allograft function, total surveillance of patients, and post-transplantation complications should be considered during the conversion of drug regimens utilizing CNIs to drug regimens employing mTORIs. We reviewed different post-heart transplant maintenance immunosuppressive regimens and their effect on post-HTx malignancies with a focus on mTORIs, compared safety against effectiveness, and gathered conclusions based on our review of the literature, which may lead clinicians to make a better evidence-based decision regarding post-HTx maintenance immunosuppressive drug regimens. Overall, CNI to mTORI conversion in post-HTx maintenance immunosuppressive drug regimens was associated with a reduced rate of developing malignancy in post-HTx patients. Furthermore, nephrotoxicity decreased significantly while using mTORIs in combination with lower doses of CNIs and the rejection rate was equivalent to CNI-only regimens. In conclusion, mTORI-based maintenance immunosuppressive drug regimens seem to be safe and beneficial when considering efficacy vs. adverse effects, and all-cause mortality rates are significantly lower in patients switched to mTORIs when compared to CNI recipients.

Drug interactions of cola-containing drinks.

Cola-containing drinks (CCDs) are among the most common drinks in the world. There are some reports on interactions between CCDs and some drugs. However, there is no review on reported and possible interactions of CCDs. Thus, this paper attempted to provide a comprehensive review on this subject. It is well-accepted that CCDs are acidic and contain caffeine. It has been suggested that these two properties potentiate interactions of CCDs with different drugs in the context of both pharmacodynamics and pharmacokinetic, which includes drug absorption, metabolism, and renal excretion of drugs. It has been shown that serum concentrations of MTX, clozapine, carbamazepine, phenytoin, and ibuprofen increased following CCD consumption; these interactions can be toxic. Additionally, it has been reported that serum levels of lithium and warfarin were decreased and their efficacy reduced when simultaneously administered with CCDs. Serum concentrations of erlotinib and different azoles, including itraconazol, posaconazole, and ketoconazole, have been shown to increase when these drugs were co-administered with a CCD. As proposed and discussed here, CCDs have the potential for interactions with numerous other drugs and thus clinicians should be aware of reported and potential interactions of CCDs with various medications in order to avoid adverse reactions and achieve expected clinical response.

Atrial fibrillation in ß-thalassemia patients with a focus on the role of iron-overload and oxidative stress: A review.

Cardiac complications including arrhythmia and especially atrial fibrillation (AF) are common causes of death in ß-thalassemia patients. The main factor in the etiopathogenesis of these complications is iron overload, which results in increased oxidative stress. Although there is a known association between cardiac complications and iron overload in ß-thalassemia patients, there is no comprehensive review on AF and excessive iron with a focus on oxidative stress in these patients. The aim of this article was to review the different aspects of AF in ß-thalassemia patients with a focus on the prevention and treatment of AF by using iron chelators and/or anti-oxidants. AF in ß-thalassemia patients is more common than in the general population. One of the most important causes of AF is cardiac iron overload and the harmful effects of increased oxidative stress. Iron-induced AF can be reversed by using an intensive iron chelation regimen. Based on a few experimental studies, the combination of iron chelators with some anti-oxidants, including NAC, vitamin C, and acetaminophen, can lead to improved cardiac protection. However, the effect of such combinations on cardiac arrhythmias should be further evaluated with animal and human studies.