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Arterial hypertension.
Brouwers, S, Sudano, I, Kokubo, Y, Sulaica, EM
Lancet (London, England). 2021;(10296):249-261
Abstract
Arterial hypertension is the most important contributor to the global burden of disease; however, disease control remains poor. Although the diagnosis of hypertension is still based on office blood pressure, confirmation with out-of-office blood pressure measurements (ie, ambulatory or home monitoring) is strongly recommended. The definition of hypertension differs throughout various guidelines, but the indications for antihypertensive therapy are relatively similar. Lifestyle adaptation is absolutely key in non-pharmacological treatment. Pharmacologically, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, and diuretics are the first-line agents, with advice for the use of single-pill combination therapy by most guidelines. As a fourth-line agent, spironolactone should be considered. The rapidly evolving field of device-based therapy, especially renal denervation, will further broaden therapeutic options. Despite being a largely controllable condition, the actual rates of awareness, treatment, and control of hypertension are disappointingly low. Further improvements throughout the process of patient screening, diagnosis, treatment, and follow-up need to be urgently addressed.
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Angiotensin Receptor Blocker and Calcium Channel Blocker Preventing Atrial Fibrillation Recurrence in Patients with Hypertension and Atrial Fibrillation: A Meta-analysis.
Ma, H, Jiang, H, Feng, J, Gan, Y
Cardiovascular therapeutics. 2021;:6628469
Abstract
BACKGROUND Atrial fibrillation (AF) is the most common serious cardiac rhythm disturbances and is responsible for substantial morbidity and mortality in general population. Hypertension is the most prevalent and potentially modifiable risk factor for AF. This study is aimed at evaluating the effect of angiotensin receptor blocker (ARB) or calcium channel blocker (CCB) on AF recurrence among patients with hypertension and AF. METHODS The PubMed, EMBASE, Medline, and Cochrane Collaboration of Controlled Clinical Trials registry databases were searched from their inception to September 2020. RESULTS A total of 7 randomized controlled trials (RCTs) enrolling 1495 patients were included in our study. This finding showed that ARB had a statistically significant superiority in preventing AF recurrence (OR: 0.43, 95% CI: 0.30-0.72, P = 0.0006) and persistent AF (OR: 0.41, 95% CI: 0.24-0.71, P = 0.001) compared to CCB. Subgroup analysis showed that there was a significant difference in telmisartan subgroup (OR: 0.54, 95% CI: 0.23-1.29, P = 0.17) and nontelmisartan subgroup (OR: 0.42, 95% CI: 0.23-0.77, P = 0.005). Subgroup analysis indicated that nifedipine subgroup did not show a statistically significant difference on AF recurrence between ARB and CCB (OR: 0.88, 95% CI: 0.46-1.68, P = 0.69), but amlodipine subgroup showed that ARB had a significant superiority in prevention of AF recurrence (OR: 0.39, 95% CI: 0.27-0.56, P < 0.0001) compared with CCB. CONCLUSIONS This study suggests that ARB is superior to CCB for preventing the AF recurrence and persistent AF among patients with hypertension and AF.
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Association of calcium channel blocker use with clinical outcome of COVID-19: A meta-analysis.
Alsagaff, MY, Mulia, EPB, Maghfirah, I, Luke, K, Nugraha, D, Rachmi, DA, Septianda, I, A'yun, MQ
Diabetes & metabolic syndrome. 2021;(5):102210
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Abstract
AIMS: This meta-analysis aims to analyze the association of calcium channel blocker (CCB) use with COVID-19 clinical outcomes. METHODS PubMed, ProQuest, Science Direct, Scopus, and medRxiv databases were searched systematically in a limited period. The primary outcome was mortality. RESULTS A total of 119,298 patients from 31 eligible studies were included. Pooled analysis of the random-effect model revealed CCB was not associated with reduced mortality (OR = 1.21 [95%CI: 0.98-1.49], p = 0.08). Interestingly, subgroup analysis in hypertensive patients revealed significantly reduced mortality (OR = 0.69 [95%CI: 0.52-0.91], p = 0.009). CONCLUSION CCB usage was not associated with the outcome of COVID-19. However, CCB was associated with a decreased mortality rate in hypertensive COVID-19 patients.
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Electrophysiological and ECG Effects of Perhexiline, a Mixed Cardiac Ion Channel Inhibitor, Evaluated in Nonclinical Assays and in Healthy Subjects.
Midei, MG, Darpo, B, Ayers, G, Brown, R, Couderc, JP, Daly, W, Ferber, G, Sager, PT, Camm, AJ
Journal of clinical pharmacology. 2021;(12):1606-1617
Abstract
Perhexiline has been used to treat hypertrophic cardiomyopathy. In addition to its effect on carnitine-palmitoyltransferase-1, it has mixed ion channel effects through inhibition of several cardiac ion currents. Effects on cardiac ion channels expressed in mammalian cells were assayed using a manual patch-clamp technique, action potential duration (APD) was measured in ventricular trabeculae of human donor hearts, and electrocardiogram effects were evaluated in healthy subjects in a thorough QT (TQT) study. Perhexiline blocked several cardiac ion currents at concentrations within the therapeutic range (150-600 ng/mL) with IC50 for hCav1.2 ∼ hERG < late hNav1.5. A significant APD shortening was observed in perhexiline-treated cardiomyocytes. The TQT study was conducted with a pilot part in 9 subjects to evaluate a dosing schedule that would achieve therapeutic and supratherapeutic perhexiline plasma concentrations on days 4 and 6, respectively. Guided by the results from the pilot, 104 subjects were enrolled in a parallel-designed part with a nested crossover comparison for the positive control. Perhexiline caused QTc prolongation, with the largest effect on ΔΔQTcF, 14.7 milliseconds at therapeutic concentrations and 25.6 milliseconds at supratherapeutic concentrations and a positive and statistically significant slope of the concentration-ΔΔQTcF relationship (0.018 milliseconds per ng/mL; 90%CI, 0.0119-0.0237 milliseconds per ng/mL). In contrast, the JTpeak interval was shortened with a negative concentration-JTpeak relationship, a pattern consistent with multichannel block. Further studies are needed to evaluate whether this results in a low proarrhythmic risk.
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Inhibitory effect of calcium channel blockers on the deterioration of lung function in adult-onset asthma.
Tsuzuki, R, To, M, Yamawaki, S, Kono, Y, To, Y
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2021;(6):731-733
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Cardiovascular Benefits of Combination Angiotensin-Converting Enzyme Inhibition Plus Calcium Channel Blockade in Black Hypertensive Patients.
Brook, RD, Kaciroti, N, Jamerson, T, Jamerson, KA
Hypertension (Dallas, Tex. : 1979). 2021;(4):1150-1152
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Dihydropyridine Calcium Channel Blockers and the Risk of Severe COVID-19.
Mendez, SR, Frank, RC, Stevenson, EK, Chung, M, Silverman, MG
Chest. 2021;(1):89-93
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Dantrolene repurposed to treat sepsis or septic shock and COVID-19 patients.
Wei, H, Liang, G, Vera, RM
European review for medical and pharmacological sciences. 2021;(7):3136-3144
Abstract
Disruption of intracellular Ca2+ homeostasis via excessive and pathological Ca2+ release from the endoplasmic reticulum (ER) and/or sarcoplasmic reticulum (SR) through ryanodine receptor (RyRs) Ca2+ channels play a critical role in the pathology of systemic inflammatory response syndrome (SIRS) and associated multiple organ dysfunction syndrome (MODS) in sepsis or septic shock. Dantrolene, a potent inhibitor of RyRs, is expected to ameliorate SIRS and MODS and decrease mortality in sepsis or septic shock patients. This review summarized the potential mechanisms of therapeutic effects of dantrolene in sepsis or septic shock at molecular, cell, and organ levels and provided suggestions and strategies for future clinical studies.
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Diltiazem versus metoprolol for the management of atrial fibrillation: A systematic review and meta-analysis.
Jafri, SH, Xu, J, Warsi, I, Cerecedo-Lopez, CD
The American journal of emergency medicine. 2021;:323-327
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Pharmacological interventions for the prevention of renal injury in surgical patients: a systematic literature review and meta-analysis.
Pathak, S, Olivieri, G, Mohamed, W, Abbasciano, R, Roman, M, Tomassini, S, Lai, F, Wozniak, M, Murphy, GJ
British journal of anaesthesia. 2021;(1):131-138
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Abstract
BACKGROUND The aim of this systematic review was to summarise the results of randomised controlled trials (RCTs) that have evaluated pharmacological interventions for renoprotection in people undergoing surgery. METHODS Searches were conducted to update a previous review using the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE to August 23, 2019. RCTs evaluating the use of pharmacological interventions for renal protection in the perioperative period were included. The co-primary outcome measures were 30-day mortality and acute kidney injury (AKI). Pooled effect estimates were expressed as risk ratios (RRs) (95% confidence intervals). RESULTS We included 228 trials enrolling 56 047 patients. Twenty-three trials were considered to be at low risk of bias across all domains. Atrial natriuretic peptides (14 trials; n=2207) reduced 30-day mortality (RR: 0.63 [0.41, 0.97]) and AKI events (RR: 0.43 [0.33, 0.56]) without heterogeneity. These effects were consistent across cardiac surgery and vascular surgery subgroups, and in sensitivity analyses restricted to studies at low risk of bias. Inodilators (13 trials; n=2941) reduced mortality (RR: 0.71 [0.53, 0.94]) and AKI events (RR: 0.65 [0.50, 0.85]) in the primary analysis and in cardiac surgery cohorts. Vasopressors (4 trials; n=1047) reduced AKI (RR: 0.56 [0.36, 0.86]). Nitric oxide donors, alpha-2-agonists, and calcium channel blockers reduced AKI in primary analyses, but not after exclusion of studies at risk of bias. Overall, assessment of the certainty of the effect estimates was low. CONCLUSIONS There are multiple effective pharmacological renoprotective interventions for people undergoing surgery.