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JACC. Cardiovascular Imaging Feb 2015Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular... (Review)
Review
Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50% to 65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively-defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve or myocardial perfusion reserve <2.5 by positron emission tomography, cardiac magnetic resonance imaging, dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 papers met the strict inclusion criteria. The papers were heterogeneous, using different treatments, endpoints, and definitions of CMD. The small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded published data. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD.
Topics: Coronary Angiography; Coronary Circulation; Diagnosis, Differential; Humans; Magnetic Resonance Imaging, Cine; Microcirculation; Microvascular Angina; Myocardial Revascularization; Positron-Emission Tomography; Practice Guidelines as Topic; Regional Blood Flow
PubMed: 25677893
DOI: 10.1016/j.jcmg.2014.12.008 -
Hypertension in Pregnancy Dec 2024Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality.
METHODS
This network meta-analysis was registered with PROSPERO. We searched the PubMed, ClinicalTrials.gov. and Embase databases for studies published from inception to the 31 of March 2023. RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis (DMA) statistical analysis. Funnel maps, network meta-analysis (NMA), the surface under the cumulative ranking curve (SUCRA) to rank the different interventions and publication bias were generated by STATA 17.0 software.
RESULTS
We included eight randomized controlled trials (RCTs) involving a total of 1192 women with PE; two studies were of high quality and six were of moderate quality. Eight interventions were addressed in the NMA. In the DMA, we found that blood pressure in the Ketanserin group were significantly higher than those in the Nicardipine group. NMA showed that blood pressure in the Dihydralazine group was significantly higher than that in the Methyldopa, Labetalol, Nicardipine and Diltiazem groups. And the blood pressure in the Labetalol group was significantly lower than that in the Nicardipine group. SUCRA values showed that Diltiazem was more effective in lowering blood pressure than other drugs looked at in this study.
CONCLUSION
According to the eight RCTs included in this study, Diltiazem was the most effective in reducing blood pressure in PE patients; Labetalol and Nicardipine also had good effects. Diltiazem is preferred for the treatment of patients with severe PE and high blood pressure.
Topics: Pregnancy; Female; Humans; Antihypertensive Agents; Labetalol; Pre-Eclampsia; Diltiazem; Nicardipine; Network Meta-Analysis
PubMed: 38488570
DOI: 10.1080/10641955.2024.2329068 -
Emergency Medicine International 2023Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in the emergency department (ED) and when patients present in acute AF with rapid ventricular... (Review)
Review
Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in the emergency department (ED) and when patients present in acute AF with rapid ventricular rate (RVR), it can result in significant morbidity and mortality. Primary treatment modalities are aimed at rate control with the two most common agents being intravenous metoprolol and diltiazem. Some evidence suggests that diltiazem may be more effective at controlling rate in these patients; however, the dosing strategies, pharmacologic differences, and study designs may play a role in the observation of these differences. The purpose of this article is to review the evidence for using weight-based metoprolol in the treatment of AF with RVR. The vast majority of studies comparing metoprolol and diltiazem for the treatment of acute AF with RVR compare a flat dose of metoprolol to a weight-based dose of diltiazem. Following a comprehensive review, only two studies have compared a weight-based dosing strategy of intravenous (IV) metoprolol versus IV diltiazem for this disease state. Overall, the two studies only contained 94 patients and failed to meet power. Beyond differing dosing strategies, differences in pharmacokinetics between the two medications (like the onset of action and metabolism) could have played a role in the differences observed in the studies. Further studies are warranted to provide better guidance on which agent should be used in the treatment of acute AF with RVR.
PubMed: 37096182
DOI: 10.1155/2023/3138064 -
World Journal of Surgery Feb 2023Haemorrhoidectomy is often complicated by significant post-operative pain, to which spasm of the internal anal sphincter is thought to be a contributing factor. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Haemorrhoidectomy is often complicated by significant post-operative pain, to which spasm of the internal anal sphincter is thought to be a contributing factor. This study appraises the evidence behind interventions aimed at lowering sphincter spasm to relieve post-haemorrhoidectomy pain.
METHODS
A Preferred Reporting Items for Systematic Reviews and Meta-analyses compliant systematic review was conducted. Medline, EMBASE, and CENTRAL databases were systematically searched. All RCTs which compared interventions targeting the internal anal sphincter to relieve pain post excisional haemorrhoidectomy were included. The primary outcome measure was pain on the visual analogue scale.
RESULTS
Of the initial 10,221 search results, 39 articles were included in a qualitative synthesis, and 33 studies were included in a meta-analysis. Topical glyceryl trinitrate (GTN) reduced pain on day 7 (7 studies, 485 participants), with a mean difference and 95% confidence interval (MD, 95% CI) of -1.34 (-2.31; -0.37), I = 91%. Diltiazem reduced pain on day 3 on the VAS, and the MD was -2.75 (-398; -1.51) shown in five studies (n = 227). Botulinum toxin reduced pain on day 7, in four studies with 178 participants, MD -1.43 (-2.50; -0.35) I = 62%. The addition of Lateral Internal Sphincterotomy to haemorrhoidectomy reduced pain on day 2 in three studies with 275 participants, MD of -2.13 (-3.49; -0.77) I = 92%. The results were limited by high heterogeneity and risk of bias.
CONCLUSION
Evidence suggests that lateral sphincterotomy, administration of botulinum toxin and the application of topical diltiazem or GTN can reduce post-operative pain after haemorrhoidectomy. Lateral sphincterotomy should not be routinely used due to the risk of incontinence.
Topics: Humans; Hemorrhoidectomy; Diltiazem; Nitroglycerin; Pain, Postoperative; Spasm; Botulinum Toxins
PubMed: 36357803
DOI: 10.1007/s00268-022-06807-3 -
British Journal of Anaesthesia May 2022New onset atrial fibrillation (NOAF) is the most common arrhythmia affecting critically unwell patients. NOAF can lead to worsening haemodynamic compromise, heart... (Review)
Review
BACKGROUND
New onset atrial fibrillation (NOAF) is the most common arrhythmia affecting critically unwell patients. NOAF can lead to worsening haemodynamic compromise, heart failure, thromboembolic events, and increased mortality. The aim of this systematic review and narrative synthesis is to evaluate the non-pharmacological and pharmacological management strategies for NOAF in critically unwell patients.
METHODS
Of 1782 studies, 30 were eligible for inclusion, including 4 RCTs and 26 observational studies. Efficacy of direct current cardioversion, amiodarone, β-adrenergic receptor antagonists, calcium channel blockers, digoxin, magnesium, and less commonly used agents such as ibutilide are reported.
RESULTS
Cardioversion rates of 48% were reported for direct current cardioversion; however, re-initiation of NOAF was as high as 23.4%. Amiodarone was the most commonly reported intervention with cardioversion rates ranging from 18% to 96% followed by β-antagonists with cardioversion rates from 40% to 92%. Amiodarone was more effective than diltiazem (odds ratio [OR]=1.91, P=0.32) at cardioversion. Short-acting β-antagonists esmolol and landiolol were more effective compared with diltiazem for cardioversion (OR=3.55, P=0.04) and HR control (OR=3.2, P<0.001).
CONCLUSION
There was significant variation between studies with regard to the definition of successful cardioversion and heart rate control, making comparisons between studies and interventions difficult. Future RCTs comparing individual anti-arrhythmic agents, in particular magnesium, amiodarone, and β-antagonists, and studying the role of anticoagulation in critically unwell patients are required. There is also an urgent need for a core outcome dataset for studies of new onset atrial fibrillation to allow comparisons between different anti-arrhythmic strategies.
CLINICAL TRIAL REGISTRATION
PROSPERO CRD42019121739.
Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Diltiazem; Electric Countershock; Humans; Magnesium
PubMed: 34916053
DOI: 10.1016/j.bja.2021.11.016 -
Cureus Mar 2024This study aims to assess the association between intravenous diltiazem and metoprolol in rate control for atrial fibrillation (AF) patients with rapid ventricular rate,... (Review)
Review
This study aims to assess the association between intravenous diltiazem and metoprolol in rate control for atrial fibrillation (AF) patients with rapid ventricular rate, focusing on rate control efficacy and hemodynamic adverse events. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, electronic searches were conducted in Embase, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) until February 20, 2024. The primary outcome was achieving ventricular rate control < 110/min. Secondary outcomes included new hypotension (systolic blood pressure < 90 mm Hg) and bradycardia (heart rate < 60/min). Nineteen studies (three randomized controlled trials and 16 observational studies) were included in this meta-analysis. Pooled analysis showed intravenous metoprolol resulted in a 39% lower rate control attainment compared to diltiazem (OR: 0.61; 95% CI: 0.44 to 0.84; p = 0.002). There were no significant differences in bradycardia (OR: 0.51; 95% CI: 0.22 to 1.22; p = 0.13) or hypotension risk (OR: 1.08; 95% CI: 0.72 to 1.61; p = 0.72) between the two groups. Intravenous diltiazem demonstrated superior rate control efficacy compared to metoprolol in AF patients with rapid ventricular rate. However, no significant differences were observed in safety outcomes, namely, bradycardia and hypotension.
PubMed: 38646329
DOI: 10.7759/cureus.56560 -
Molecular Psychiatry Oct 2016l-type calcium channel (LTCC) antagonists have been used in bipolar disorder for over 30 years, without becoming an established therapeutic approach. Interest in this... (Review)
Review
l-type calcium channel (LTCC) antagonists have been used in bipolar disorder for over 30 years, without becoming an established therapeutic approach. Interest in this class of drugs has been rekindled by the discovery that LTCC genes are part of the genetic aetiology of bipolar disorder and related phenotypes. We have therefore conducted a systematic review of LTCC antagonists in the treatment and prophylaxis of bipolar disorder. We identified 23 eligible studies, with six randomised, double-blind, controlled clinical trials, all of which investigated verapamil in acute mania, and finding no evidence that it is effective. Data for other LTCC antagonists (diltiazem, nimodipine, nifedipine, methyoxyverapamil and isradipine) and for other phases of the illness are limited to observational studies, and therefore no robust conclusions can be drawn. Given the increasingly strong evidence for calcium signalling dysfunction in bipolar disorder, the therapeutic candidacy of this class of drugs has become stronger, and hence we also discuss issues relevant to their future development and evaluation. In particular, we consider how genetic, molecular and pharmacological data can be used to improve the selectivity, efficacy and tolerability of LTCC antagonists. We suggest that a renewed focus on LTCCs as targets, and the development of 'brain-selective' LTCC ligands, could be one fruitful approach to innovative pharmacotherapy for bipolar disorder and related phenotypes.
Topics: Bipolar Disorder; Calcium Channel Blockers; Calcium Channels, L-Type; Double-Blind Method; Humans; Isradipine; Nimodipine; Verapamil
PubMed: 27240535
DOI: 10.1038/mp.2016.86 -
PloS One 2018Arterial graft spasm is a severe complication after coronary artery bypass graft (CABG). Among numerous potential antispasmodic agents, systemic application of diltiazem... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Arterial graft spasm is a severe complication after coronary artery bypass graft (CABG). Among numerous potential antispasmodic agents, systemic application of diltiazem and nitroglycerin had been investigated most frequently over the past three decades. However, it remains inconclusive if either or both agents could improve patient outcomes by preventing graft spasm when applied perioperatively, and, if so, which one would be a better choice. The current systematic review and network meta-analysis aims to summarize the data from all available randomized clinical trials of perioperative continuous intravenous infusion of diltiazem and/or nitroglycerin in patients undergoing on-pump CABG in order to define and compare their roles in graft spasm prevention and their impacts on perioperative outcomes.
METHODS
We searched Ovid Medline, PubMed, CINAHL, Google Scholar and Cochrane Center for randomized controlled trials that reported outcome effects of perioperative continuous intravenous infusion of diltiazem and/or nitroglycerin in patients undergoing elective on-pump CABG. Conventional meta-analyses were conducted to evaluate the pairwise comparisons (diltiazem vs. placebo; nitroglycerin vs. placebo; diltiazem vs. nitroglycerin) on perioperative outcomes. Network meta-analyses were implemented to compare the three regimens through direct and indirect comparison.
RESULTS
Twenty-seven studies involving 1,660 patients were included. Pairwise and network meta-analyses found no significant difference in mortality among the groups. There are four studies that reported blood flow measurements of internal mammary artery grafts intraoperatively after dissecting or immediately after distal anastomosis while patients were on continuous intravenous infusion of diltiazem and nitroglycerin. Although insufficient for data synthesis, the measured results from all four studies suggest that both diltiazem and nitroglycerin significantly increased blood flow of arterial grafts compared to placebo. For other perioperative outcomes, compared to diltiazem, patients that received nitroglycerin had higher odds of postoperative atrial fibrillation (OR = 2.67, 95% CI: 1.15 to 6.24) and higher peak serum cardiac enzymes. Patients that received placebo had higher odds of atrial fibrillation (OR = 3.00, 95% CI: 1.18 to 7.63) and lower odds of requiring inotrope support (OR = 0.19, 95% CI: 0.04 to 0.73) compared to diltiazem. Data from the network meta-analysis indicated that diltiazem had significantly lower odds of postoperative atrial fibrillation compared to nitroglycerin (OR = 0.39, 95% CI: 0.18 to 0.85). In fact, the rank from highest to lowest rates of postoperative atrial fibrillation was placebo>nitroglycerin>diltiazem. The rank from highest to lowest odds of requiring inotropic support is nitroglycerin> diltiazem>placebo. However, placebo had significantly higher odds of postoperative myocardial infarction than diltiazem (OR = 4.51, 95% CI: 1.34 to 15.25). The rank from highest to lowest odds of postoperative myocardial infarction, transient cardiac ischemic event and atrial fibrillation is placebo>nitroglycerin>diltiazem.
CONCLUSION
Compared to nitroglycerin and placebo, perioperative continuous intravenous infusion of diltiazem had stronger protective effects against postoperative ischemic cardiac injuries and atrial fibrillation although patients may need more inotropic support. The increased blood flow from diltiazem use in arterial grafts may potentially contribute to the drug's outcome benefits.
Topics: Administration, Intravenous; Cardiotonic Agents; Coronary Artery Bypass; Diltiazem; Humans; Nitroglycerin; Perioperative Care; Postoperative Complications; Randomized Controlled Trials as Topic
PubMed: 30161246
DOI: 10.1371/journal.pone.0203315 -
Digestive Diseases (Basel, Switzerland) 2023Topical treatments and botulinum toxin injections are valid options for the management of patients with chronic anal fissures (CAF), but little is known about the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Topical treatments and botulinum toxin injections are valid options for the management of patients with chronic anal fissures (CAF), but little is known about the efficacy of these techniques in long-term follow-up. The aim of this meta-analysis was to evaluate the effectiveness, given to clinical outcomes, of medical treatments with calcium antagonists, nitroglycerin, and botulinum toxin on CAF treatment in adults.
METHOD
A systemic review and meta-analysis developed according to PRISMA [PLoS Med. 2009 Jul 21;6(7):e1000100; BMJ. 2010 Mar 23;340:c332] and registered in PROSPERO (Registration number: CRD42020120386). A systematic literature search was conducted through MEDLINE, EMBASE, Web of Science, and Cochrane Library databases. Randomized control trials that compared medical treatment were identified; publications had to have a clinical definition of CAF with at least one of the following signs or symptoms: visible sphincter fibers at the base of the fissure, anal papillae, sentinel piles, and indurated margins. The symptoms had to be chronic for at least 4 weeks. Data were independently extracted for each study, and a meta-analysis was drawn using fixed- and random-effects models.
RESULTS
17 randomized trials met the inclusion criteria. Diltiazem showed a superior effect compared with glycerin (RR = 1.16 [95% CI = 1.05-1.30]; I2 = 18%) and with fewer adverse effects (RR = 0.13 [95% CI = 0.04-0.042]; I2 = 87%). Similar results were evidenced with the use of nifedipine compared with lidocaine (RR = 4.53 [95% CI = 2.99-6.86]; I2 = 28%). Botulinum toxin did not show statistically significant differences compared to glycerin (RR = 0.81 [95% CI = 0.02-29.36]; I2 = 93%) or isosorbide dinitrate (RR = 1.45 [95% CI = 0.32-6.54]; I2 = 85%). Regarding recurrence, nifedipine was superior to lidocaine (RR = 0.18 [95% CI = 0.08-0.44]; I2 = 31%).
CONCLUSIONS
Calcium channel blockers performed well regarding the healing of CAF when compared to others in long-term follow-up. The superiority of botulinum toxin was not evidenced compared to topical treatments. More studies are needed to better assess recurrence rates.
Topics: Adult; Humans; Fissure in Ano; Nifedipine; Glycerol; Treatment Outcome; Nitroglycerin; Chronic Disease
PubMed: 36646066
DOI: 10.1159/000528222 -
Journal of Cutaneous Medicine and... Sep 2021Idiopathic chilblains is a cold-induced inflammatory condition that causes significant morbidity. When preventative measures alone are inadequate, oral nifedipine is...
Idiopathic chilblains is a cold-induced inflammatory condition that causes significant morbidity. When preventative measures alone are inadequate, oral nifedipine is generally recommended as first-line pharmacologic therapy. Given the natural course of this spontaneously remitting/relapsing condition, controls are needed to critically appraise studies and determine the value of treatments. We report a systematic review of placebo-controlled or comparative therapeutic trials for the treatment of idiopathic chilblains. Our search of PubMed, Embase, and Cochrane databases, identified 11 studies that met our inclusion criteria for a combined study population = 576. Therapies included nifedipine, pentoxifylline, tadalafil, topical glyceryl trinitrate (GTN), topical minoxidil, diltiazem, corticosteroids, and vitamin D. There was moderate evidence to support the use of nifedipine and pentoxifylline in the treatment of severe or refractory cases of idiopathic chilblains, while other therapies had inadequate evidence or nonsignificant results compared to placebo.
Topics: Chilblains; Humans; Nifedipine; Pentoxifylline; Vasodilator Agents
PubMed: 33653127
DOI: 10.1177/1203475421995130