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This study evaluated the efficacy of intravenous (IV) calcium pretreatment for preventing diltiazem-induced hypotension and assessed its safety in adult patients with atrial fibrillation (AF)/atrial flutter (AFL) with rapid ventricular response (RVR). This randomized, double-blind, placebo-controlled trial included 217 adults with AF/AFL and a ventricular rate > 120 beats per minute, who were randomized into three groups: those who received an IV NaCl 0.9 % placebo pretreatment prior to IV diltiazem (PD; 73 patients) and those who received 90 mg (C90D; 71 patients) and 180 mg (C180D; 73 patients) IV calcium chloride pretreatment before IV diltiazem. We compared participants' systolic blood pressure (SBP) and heart rate (HR) at baseline and at 5, 10, and 15 min post-treatment, as well as the incidence of adverse events (e.g., hypotension, urticaria, nausea) among the groups. The PD and C90D pretreatment groups had significantly lower HR measurements at 10 and 15 min compared to the C180D group. In addition, at 5 min, the mean SBP in the PD group was significantly lower compared to the C90D and C180D groups. At 10 min, the mean SBP was significantly higher in the C180D group than in the other groups. Furthermore, at 15 min, the mean SBP was significantly higher in both the C90D and C180D groups than in the PD group. There were no significant differences between the calcium pretreatment and placebo groups in terms of the need for additional diltiazem doses or the incidence of adverse events. IV calcium pretreatment effectively prevents diltiazem-induced hypotension in patients with AF/AFL with RVR without compromising the efficacy of diltiazem in achieving and maintaining ventricular rate control. Trial registry: National Library of Medicine Clinical Trial Registry; No.: NCT06494007; URL: https://clinicaltrials.gov/study/NCT06494007

Intravenous diltiazem has experienced numerous supply shortages over the past few years. The purpose of this study was to compare the safety and efficacy of a traditional diltiazem intravenous bolus and continuous infusion protocol to a diltiazem intravenous bolus and oral maintenance protocol for acute rate control in the emergency department. Patients who received intravenous diltiazem in the emergency department between January 1, 2018 and May 31, 2019 were screened. Patients were included if they received the diltiazem intravenous bolus and continuous infusion protocol (IV + infusion group) or the hybrid diltiazem intravenous bolus and oral maintenance protocol (IV + PO group). The primary outcome was the proportion of patients with rate control, without need for additional rate control agents or additional boluses during the maintenance phase. A total of 106 patients were matched with 53 patients in each group. For the primary outcome of rate control at four hours, 62.3% of patients in the intravenous bolus + infusion group versus 75.5% of patients in the IV bolus + PO group (p = 0.142) achieved rate control. There was no difference in rates of hypotension or bradycardia between groups. Results of this study demonstrated no difference in acute rate control when using a hybrid IV and oral diltiazem protocol, compared to a traditional IV bolus and infusion strategy. This information supports the further use of a hybrid diltiazem IV and oral protocol, which provides increased flexibility during shortages of either medication.

Objective This study aims to compare the short- and long-term outcomes of botulinum toxin (BT) alone versus BT combined with topical diltiazem (TD) in the treatment of chronic anal fissures (CAF). Design The study is designed as a retrospective analysis, reviewing data from 1296 patients diagnosed with anal fissures who presented to our clinic between 2017 and 2022. Setting Single center (University hospital). Patients A total of 217 patients who met the inclusion criteria were analyzed, with 143 receiving BT alone and 74 receiving the combination of BT + TD. Interventions BT was administered as 100 IU injected into four quadrants. TD was applied twice daily for 10 days immediately following the BT injection. Main outcome measures Primary outcome measures were fissure healing at 2 months and days to pain-free defecation. Secondary outcome measures were complete healing and recurrence rates at 24 months. Results There were no significant differences in demographic characteristics and symptom duration between the BT and BT + TD groups. The median time to pain-free defecation was 7 days across the entire series, with no statistical difference between groups. At 2 months, complete healing was observed in 74.4% of patients, with no significant difference between groups: 74.8% for BT and 74.3% for BT + TD. During a median follow-up of 53 (22–101) months, a recurrence rate of 26.3% was observed, and TD showed no effect on complete healing and recurrence rates. Limitations The most significant limitation of our study is its retrospective design and the absence of a placebo control for TD. Conclusion The study demonstrates that BT is an effective and safe treatment for CAF, with or without the addition of TD. The combination therapy did not show superior outcomes.

Anal fissure is a common proctologic condition that causes significant pain and anguish to patients, significantly impacting their quality of life and well-being. There are various treatment options for anal fissure, ranging from pharmacological agents that reduce anal sphincter tone to surgical interventions for cases resistant to medical management. Ayurvedic treatments have shown potential for the therapeutic management of anal fissure. This clinical study aims to analyze the efficacy and safety of murivenna anal infiltration compared to diltiazem topical application in chronic anal fissure. This is an open-labeled, randomized, controlled parallel group clinical trial with a sample size of 66 participants to be randomized and allocated in a 1:1 ratio to 2 groups. The intervention group will be treated with murivenna anal infiltration, and the control group will be treated with topical application of diltiazem for a period of 4 weeks. The primary outcome will be the proportion of participants demonstrating complete healing after 4 weeks of treatment. The secondary outcomes will be the proportion of participants demonstrating complete healing after 7 days and 14 days of treatment, change in pain at or after defecation, cessation of bleeding, and any recurrence during the study period. Any adverse events will also be recorded during the trial period. The project was funded in July 2023, and the study period is 24 months. Participant recruitment started in December 2023. As of August 2024, we have enrolled 50 participants. The data analysis will be complete by June 2025, and the results are expected to be published by August 2025. High recurrence rates, adverse effects, incomplete healing, and the negative impact on patients' daily activities and quality of life underscore the need for alternative therapeutic options. Ayurveda offers potential for more sustainable relief with fewer adverse effects. Murivenna oil is a time-tested medicated oil effectively used by Ayurvedic physicians for various ulcers of traumatic and pathological origin. This study will provide scientific evidence on the efficacy and safety of murivenna anal infiltration; further, it can be incorporated into the cost-effective management of chronic anal fissure. Clinical Trials Registry India CTRI/2023/09/057330; https://tinyurl.com/y4ut9e8p. DERR1-10.2196/63063.

Background High-sensitive (hs-) cardiac troponin assays provide prognostic information in atrial fibrillation (AF) patients. Few studies have explored the impact of long-term rate control therapy on levels of troponin in AF patients without coronary heart disease and heart failure. This substudy of the RATe control in Atrial Fibrillation (RATAF) II study aimed to compare the effects of six months’ treatment with diltiazem and metoprolol on hs-troponin I (TnI) levels both at rest and during exercise testing in patients with permanent AF. Methods This was a parallel-group, randomized, investigator-blinded clinical trial. The cohort consisted of 93 patients (28 women, mean age 71 ± 7 years) with symptomatic, permanent AF with preserved left ventricular systolic function and no coronary heart disease. Participants were randomized in a 1:1 ratio to receive either diltiazem 360 mg ( n  = 49) or metoprolol 100 mg ( n  = 44) once daily for six months. Blood tests were drawn at rest and during peak exercise testing at baseline, one month and six months’ treatment. This research has been supported by grants from the South-Eastern Norway Regional Health Authority and Vestre Viken Hospital Trust. Results Six months’ treatment with diltiazem and metoprolol significantly lowered the heart rate at rest and peak exercise. Both treatment groups exhibited a decrease in hs-TnI levels at rest (diltiazem p  = 0.008, metoprolol p  = 0.03) and peak exercise (diltiazem p  < 0.001, metoprolol p  = 0.004) at six months compared to baseline levels, with no significant differences observed between the groups. Conclusions In patients with permanent AF, six months of rate control therapy with diltiazem or metoprolol lowered levels of hs-TnI. Further research is warranted to determine whether this reduction translates into an improved prognosis. Trial registration NCT02695992. Registration date: 2015–04-28.

Atrial fibrillation is the most commonly encountered sustained cardiac arrhythmia. Restoration and maintenance of sinus rhythm is believed by many physicians to be superior to rate control only. However, there are no prospective data that compare both therapeutic strategies. The Pharmacological Intervention in Atrial Fibrillation (PIAF) trial was a randomised trial in 252 patients with atrial fibrillation of between 7 days and 360 days duration, which compared rate (group A, 125 patients) with rhythm control (group B, 127 patients). In group A, diltiazem was used as first-line therapy and amiodarone was used in group B. The primary study endpoint was improvement in symptoms related to atrial fibrillation. Over the entire observation period of 1 year, a similar proportion of patients reported improvement in symptoms in both groups (76 responders at 12 months in group A vs 70 responders in group B, p=0·317). Amiodarone administration resulted in pharmacological restoration of sinus rhythm in 23% of patients. Walking distance in a 6 min walk test was better in group B compared with group A, but assessment of quality of life showed no differences between groups. The incidence of hospital admission was higher in group B (87 [69%] out of 127 vs 30 [24%] out of 125 in group A, p=0·001). Adverse drug effects more frequently led to a change in therapy in group B (31 [25%] patients compared with 17 [14%] in group A, p=0·036. With respect to symptomatic improvement in patients with atrial fibrillation, the therapeutic strategies of rate versus rhythm control yielded similar clinical results overall. However, exercise tolerance is better with rhythm control, although hospital admission is more frequent. These data may serve as a basis to select therapy in individual patients.

Intravenous diltiazem and metoprolol are both commonly used to treat atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED), but the advantages and disadvantages of these drugs cannot be verified. This meta-analysis aimed to assess the efficacy and safety of intravenous diltiazem versus metoprolol for AF with RVR. We systematically searched PubMed, Web of Science, Embase, Cochrane library, the China National Knowledge Infrastructure (CNKI), Wanfang, China Biology Medicine disc (CBM) and the WeiPu (VIP). Meta-analysis was performed using weighted mean difference (WMD), relative risk (RR) and 95% confidence interval (CI). Statistical analysis was performed using Review Manager 5.4.1. Seventeen studies involving 1214 patients in nine randomized controlled trials (RCTs) and eight cohort studies were included in meta-analysis, including 643 patients in the intravenous diltiazem group and 571 patients group in the intravenous metoprolol. The results of the meta-analysis showed that compared with intravenous metoprolol, intravenous diltiazem was found higher efficacy (RR =1.11; 95% CI = 1.06 to 1.16, p < 0.00001), shorter average onset time (RR = −1.13; 95% CI = −1.97 to −0.28, p = 0.009), lower ventricular rate (RR = −9.48; 95% CI = −12.13 to −6.82, p<0.00001), less impact on systolic blood pressure (WMD = 3.76; 95% CI: 0.20 to 7.33, P = 0.04), and no significant difference in adverse events (RR = 0.80, 95% CI = 0.55 to 1.14, P = 0.22) and diastolic blood pressure (WMD = −1.20; 95% CI: −3.43 to 1.04, P = 0.29) was found between intravenous diltiazem and metoprolol. Intravenous diltiazem has higher efficacy, shorter average onset time, lower ventricular rate, less impact on blood pressure, and with no increase in adverse events compared to intravenous metoprolol.

The continuous emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2) variants and the increasing number of breakthrough infection cases among vaccinated people support the urgent need for research and development of antiviral drugs. Viral entry is an intriguing target for antiviral drug development. We found that diltiazem, a blocker of the L-type calcium channel Ca v 1.2 pore-forming subunit (Ca v 1.2 α 1c ) and an FDA-approved drug, inhibits the binding and internalization of SARS-CoV-2, and decreases SARS-CoV-2 infection in cells and mouse lung. Ca v 1.2 α 1c interacts with SARS-CoV-2 spike protein and ACE2, and affects the attachment and internalization of SARS-CoV-2. Our finding suggests that diltiazem has potential as a drug against SARS-CoV-2 infection and that Ca v 1.2 α 1c is a promising target for antiviral drug development for COVID-19.

Intravenous (IV) diltiazem and metoprolol are commonly used to achieve rate control for atrial fibrillation with RVR (Afib with RVR), and are both recommended as first-line by current guidelines. While prior studies investigated the efficacy of these medications, there is little evidence available regarding the risk of adverse events (AEs) with their use. We identified randomized controlled trials (RCT) and observational studies reporting rates of AEs following administration of IV diltiazem and metoprolol for Afib with RVR by searching PubMed, SCOPUS, EMBASE, and Cochrane Library. Our primary outcome was the incidence of AEs and specifically hypotension and bradycardia, which were examined individually as secondary outcomes. We performed random-effects meta-analysis to identify rates of each AE. We used moderator analysis and meta-regressions to evaluate risk factors. We used the Cochrane Risk-of-Bias 2 tool and the Newcastle-Ottawa Scale to assess study quality. We reviewed 13 studies and included 1660 patients, 888 (53 %) treated with metoprolol and 772 (47 %) with diltiazem. Metoprolol was associated with a 26 % lower risk of AE (total incidence 10 %) compared to diltiazem (total incidence 19 %), (RR 0.74, 95 % CI 0.56–0.98, p = 0.034) with a prediction interval of 0.50–1.10. Patients with higher initial heart rates faced higher rates of AEs (Correlation Coefficient 0.11, 95 % CI 0.03–0.19, p = 0.006). There was no difference with respect to rates of bradycardia (RR 0.44, 95 % CI 0.15–1.30, p = 0.14) or hypotension (RR 0.80, 95 % CI 0.61–1.04, p = 0.10). Afib with RVR treated with metoprolol had lower rates of AE (bradycardia and/or hypotension) compared to those treated with diltiazem. We found no difference in rates of hypotension or bradycardia when individually assessed. Existing data are limited by small sample sizes, variability in dosing, and limited representation of important patient subgroups.

No randomized trial has been conducted to compare different vasodilators for treating no-reflow during primary percutaneous coronary intervention (PCI) for ST-segment elevation acute myocardial infarction. The prospective, randomized, 2-center trial was designed to compare the effect of 3 different vasodilators on coronary no-reflow. A total of 102 patients with no-reflow in primary PCI were randomized to receive intracoronary infusion of diltiazem, verapamil, or nitroglycerin (n = 34 in each group) through selective microcatheter. The primary end point was coronary flow improvement in corrected thrombolysis in myocardial infarction frame count (CTFC) after administration of the drug. Compared with that of the nitroglycerin group, there was a significant improvement of CTFC after drug infusion in the diltiazem and verapamil groups (42.4 frames vs 28.1 and 28.4 frames, P < .001). The improvement in CTFC was similar between the diltiazem and verapamil groups (P = .9). Compared with the nitroglycerin group, the diltiazem and verapamil groups had more complete ST-segment resolution at 3 hours after PCI, lower peak troponin T level, and lower N-terminal pro–B-type natriuretic peptide levels at 1 and 30 days after PCI. After drug infusion, the drop of heart rate and systolic blood pressure in the verapamil group was greater than that in the diltiazem and nitroglycerin groups. Intracoronary infusion of diltiazem or verapamil can reverse no-reflow more effectively than nitroglycerin during primary PCI for acute myocardial infarction. The efficacy of diltiazem and verapamil is similar, and diltiazem seems safer.