Efficacy of diltiazem 2% rectal gel in the treatment of chronic anal fissure: a retrospective observational study.

OBJECTIVE: The aim of this study is to describe the effectiveness and safety of a magistral formulation of diltiazem 2% rectal gel as a treatment for chronic anal fissure. MATERIAL AND METHODS: A retrospective observational study of all patients that began treatment with diltiazem 2% gel during 2019. The primary endpoint of the study was anal fissure healing. We also looked for differences in effectiveness between those initiating treatment and those who had been previously treated, long-term effectiveness through a 2-year follow-up and frequency of adverse effects. RESULTS: Of the 166 patients included in the study, anal fissure healed in 72.9%. We detected adverse effects in 12 patients, the most common was local irritation. After 2 years of follow-up, 88% of patients did not relapse. CONCLUSION: In this study, use of topical diltiazem 2% has been shown to be effective and safe in the treatment of anal fissure and should be considered as the first line of therapy.

OBJETIVO: El objetivo de este estudio es describir la efectividad y la seguridad de una fórmula magistral de diltiazem 2% gel rectal, como tratamiento de la fisura anal crónica. MATERIAL Y MÉTODOS: Un studio observacional retrospectivo de todos los pacientes que comenzaron a ser tratados con diltiazem 2% gel durante el año 2019. La variable principal del estudio fue la cicatrización de la fisura anal. También se buscaron diferencias de efectividad entre aquellos que iniciaban el tratamiento y los que ya habían sido tratados previamente, efectividad a largo plazo mediante un seguimiento de 2 años y frecuencia de aparición de efectos adversos. RESULTADOS: De los 166 pacientes incluidos en el estudio, el 72,9% cicatrizaron la fisura anal. No detectamos diferencias estadísticamente significativas de efectividad entre los pacientes naive y aquellos que ya habían sido tratados. Detectamos efectos adversos en 12 pacientes, siendo el más frecuente la irritación local. Tras 2 años de seguimiento, el 88% de los pacientes no presentaron ninguna recaída. CONCLUSIÓN: En este estudio, el uso de diltiazem 2% tópico ha mostrado ser efectivo y seguro en el tratamiento de la fisura anal y debería considerarse como primera línea terapéutica.

Intravenous Diltiazem Versus Metoprolol in Acute Rate Control of Atrial Fibrillation/Flutter and Rapid Ventricular Response: A Meta-Analysis of Randomized and Observational Studies.

BACKGROUND: Atrial fibrillation (AF) and/or atrial flutter (AFL) with rapid ventricular response (RVR) is a condition that often requires urgent treatment. Although guidelines have recommendations regarding chronic rate control therapy, recommendations on the best choice for acute heart rate (HR) control in RVR are unclear. METHODS: A systematic search across multiple databases was performed for studies evaluating the outcome of HR control (defined as HR less than 110 bpm and/or 20% decrease from baseline HR). Included studies evaluated AF and/or AFL with RVR in a hospital setting, with direct comparison between intravenous (IV) diltiazem and metoprolol and excluded cardiac surgery and catheter ablation patients. Hypotension (defined as systolic blood pressure less than 90 mmHg) was measured as a secondary outcome. Two authors performed full-text article review and extracted data, with a third author mediating disagreements. Random effects models utilizing inverse variance weighting were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using the I2 test. RESULTS: A total of 563 unique titles were identified through the systematic search, of which 16 studies (7 randomized and 9 observational) were included. In our primary analysis of HR control by study type, IV diltiazem was found to be more effective than IV metoprolol for HR control in randomized trials (OR 4.75, 95% CI 2.50-9.04 with I2 = 14%); however, this was not found for observational studies (OR 1.26, 95% CI 0.89-1.80 with I2 = 55%). In an analysis of observational studies, there were no significant differences between the two drugs in odds of hypotension (OR 1.12, 95% CI 0.51-2.45 with I2 = 18%). CONCLUSION: While there was a trend toward improved HR control with IV diltiazem compared with IV metoprolol in randomized trials, this was not seen in observational studies, and there was no observed difference in hypotension between the two drugs.

Role of magnesium alone or in combination with diltiazem and/or amiodarone in prevention of atrial fibrillation following off-pump coronary artery bypass grafting.

Objectives: In this study the authors have tried to examine the role of magnesium alone or in combination with diltiazem and / or amiodarone in prevention of atrial fibrillation (AF) following off-pump coronary artery bypass grafting (CABG). Background: AF after CABG is common and contributes to morbidity and mortality. Various pharmacological preventive measures including magnesium, amiodarone, diltiazem, and combination therapy among others have been tried to lower the incidence of AF. Most of the studies have been performed in patients undergoing conventional on-pump CABG. In this uncontrolled trial, efficacy of magnesium alone or in combination with amiodarone and / or diltiazem has been studied in patients undergoing off-pump CABG. Methods: One hundred and fifty patients undergoing off-pump CABG were divided into 3 groups, Group M (n=21) received intraoperative magnesium infusion at 30mg/ kg over 1 hour after midline sternotomy; Group MD (n=78) received magnesium infusion in similar manner with diltiazem infusion at 0.05 µg/kg/hr throughout the intraoperative period; Group AMD (n=51) received preoperative oral amiodarone at a dose of 200 mg three times a day for 3 days followed by 200 mg twice daily for another 3 days followed by 200 mg once daily till the day of surgery along with magnesium and diltiazem infusion as in other groups. AF lasting more than 10 min or requiring medical intervention was considered as AF. Results: The overall incidence of postoperative AF was 12.6% with 11.7% in group AMD, 19% in group M, and 11.5% in group MD, which was not statistically significant. Conclusions: It is concluded that the use of amiodarone and/or diltiazem in addition to magnesium did not result in additional benefit of lowering the incidence of AF.

Impact of posaconazole and diltiazem on pharmacokinetics of encorafenib, a BRAF V600 kinase inhibitor for melanoma and colorectal cancer with BRAF mutations.

Encorafenib is a potent and selective ATP competitive inhibitor of BRAF V600-mutant kinase approved for patients with BRAF-mutant melanoma and colorectal cancer. Encorafenib is mainly metabolized by cytochrome P450 (CYP) 3A4 in vitro and may be susceptible to drug-drug interactions when co-administered with CYP3A inhibitors or inducers. The primary objective was to assess the impact of the strong CYP3A inhibitor posaconazole (part 1) and the moderate CYP3A and P-gp inhibitor diltiazem (part 2) on encorafenib pharmacokinetics in healthy volunteers following a single 50-mg dose. A total of 32 participants were enrolled (16 each in parts 1 and 2). The area under the curve extrapolated to infinity (AUCinf ) and maximum plasma concentration (Cmax ) geometric mean for encorafenib increased by 183% and 68.4%, respectively, when co-administered with posaconazole. Apparent encorafenib clearance decreased from 26.0 to 9.2 L/h when coadministered with posaconazole, and plasma terminal half-life (t½ ) of encorafenib increased from 4.3 to 7.3 h. The AUCinf and Cmax geometric mean for encorafenib increased by 83.0% and 44.7%, respectively, when co-administered with diltiazem. Similarly, the apparent encorafenib clearance decreased from 29.0 to 16.0 L/h when co-administered with diltiazem, and plasma t½ of encorafenib increased from 6.6 to 7.9 h. There were no deaths, serious adverse events (AEs), or patient discontinuations due to AEs in parts 1 or 2. The most frequently reported treatment-related AEs were erythema (n = 14; 88%) and headache (n = 11; 69%) in part 1 and headache (n = 7; 44%) in part 2. The results of this study indicate that co-administration of encorafenib with strong or moderate CYP3A4 inhibitors should be avoided.

Failure of diltiazem to prevent 1:1 conduction of atrial flutter: a case report.

BACKGROUND: Atrial flutter with 1:1 conduction to the ventricles is a dangerous cardiac arrhythmia. Contemporary guidelines recommend atrioventricular nodal blocking agents should be co-administered with class 1C anti-arrhythmics, as prophylaxis against 1:1 flutter. No guidance is provided on the type or strength of atrioventricular nodal blockade required, and in practice, these agents are frequently prescribed at low dose, or even omitted, due to their side effect profile. CASE PRESENTATION: A 62 year old Caucasian man with a history of paroxysmal atrial fibrillation treated with flecainide, presented with atrial flutter with 1:1 conduction to the ventricles and was cardioverted. Diltiazem was added to prevent this complication and he again presented with atrial flutter with 1:1 conduction to the ventricles, despite prophylaxis with coadministration of diltiazem. CONCLUSIONS: This case report demonstrates failure of diltiazem to prevent 1:1 flutter in a patient chronically treated with flecainide for paroxysmal atrial fibrillation.

Effect of Nicorandil, Diltiazem, or Isosorbide Mononitrate for Oral Antispastic Therapy After Coronary Artery Bypass Grafting Using Radial Artery Grafts-A Pilot Randomized Controlled Trial (ASRAB-Pilot): Rationale and Study Protocol.

INTRODUCTION: The current evidence for chronic oral antispastic medication use after coronary artery bypass grafting using radial artery grafts (RA-CABG) is controversial. Calcium channel blockers, such as diltiazem, are the most commonly used antispastic medications after RA-CABG; other options include nitrates and nicorandil, but to date no sufficiently powered randomized controlled trials have been conducted to compare their efficacy. METHODS: This is a single-center, open-label, parallel three-arm, pilot randomized controlled trial. Patients without contraindications to any study medications and who successfully underwent RA-CABG surgery will be consecutively screened. Eligible patients will be randomized in a ratio of 1:1:1 (a total of 150 patients, 50 per arm) to receive nicorandil 5 mg orally thrice daily, diltiazem 180 mg orally once daily, or isosorbide mononitrate 50 mg orally once daily for 24 weeks. The primary outcomes are RA graft failure at week 1 and week 24. The secondary outcomes include major adverse cardiovascular event (MACE, a composite of all-cause death, myocardial infarction, stroke, and unplanned revascularization) and angina recurrence. The safety outcomes include hypotension occurrence, withdrawal of renin angiotensin aldosterone system inhibitors, serious adverse events, and other concerned adverse events within 24 weeks. CONCLUSION: This pilot trial will compare the preliminary effects of nicorandil, diltiazem, and isosorbide mononitrate on angiographic and clinical outcomes in patients who have undergone RA-CABG. Recruitment began in June 2020, and the estimated primary completion date is early 2023. Results of this study will provide much needed information for design of large confirmatory trials on the effectiveness of oral antispastic medications after RA-CABG.

Atrial fibrillation induced by gabapentin: a case report.

BACKGROUND: Gabapentin is commonly prescribed for the treatment of neuropathic pain, restless leg syndrome, and partial-onset seizures. Although the most frequent side effects of gabapentin are associated with the central nervous system, gabapentin can also affect the cardiovascular system. Case reports and observational studies have showed that gabapentin can be associated with increased risk of atrial fibrillation. However, all the evidence is concentrated in patients older than 65 years old with comorbidities that predispose them to the development of arrhythmias. CASE PRESENTATION: We describe a case of an African American male in his 20s that presented to our chronic pain clinic with lumbar radiculitis and developed atrial fibrillation 4 days after being started on gabapentin. Laboratory workup did not show significant abnormalities, including normal complete blood count, comprehensive metabolic panel, toxicology screen, and thyroid-stimulating hormone. Transthoracic and transesophageal echocardiography showed a patent foramen ovale with right-to-left shunt. The patient was initially treated with diltiazem for heart rate control and apixaban. Direct current cardioversion with successful conversion to sinus rhythm was performed 24 hours after admission. The patient was then discharged on apixaban and diltiazem. Apixaban was changed to low-dose aspirin 1 month after discharge. CONCLUSION: With rapidly increasing usage of gabapentin for approved and off-label indications, it is important to identify unintended adverse effects of this drug as they are considered safe alternatives to opioids. New-onset atrial fibrillation could be induced by gabapentin in young individuals.

Association of Nondihydropyridine Calcium Channel Blockers Versus ß-Adrenergic Receptor Blockers With Risk of Heart Failure Hospitalization.

Heart failure (HF) with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are interrelated and often coexisting conditions in older adults. Although equally recommended, nondihydropyridine calcium channel blockers (non-DHP CCBs), such as diltiazem and verapamil, are less often used than ß blockers. Because recent studies suggested that ß-blocker use in both HFpEF and AF may increase the risk for HF, we tested whether non-DHP CCBs were associated with lower HF hospitalization risk than ß blockers. We examined fee-for-service Medicare beneficiaries who were aged ≥66 years, had HFpEF or AF, and newly initiated a ß blocker (n = 83,458) or non-DHP CCB (n = 18,924) from 2014 to 2018. The outcomes of HF hospitalization and all-cause mortality were analyzed using multivariable-adjusted Cox regression in the full cohort and, separately, in the subset without a recent hospital or skilled nursing discharge. Follow-up was analyzed using 2 frameworks: intention-to-treat and censored-at-drug-switch-or-discontinuation. There was a modestly protective association of non-DHP CCBs for the risk of HF hospitalization. Before drug switch or discontinuation, the use of diltiazem or verapamil was associated with decreased risk of HF hospitalization in the full cohort (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.81 to 1.00, p = 0.05) and in the subgroup (HR 0.70, 95% CI 0.56 to 0.89, p = 0.003). However, the association with all-cause mortality tended to favor ß blockers, including in the intention-to-treat analysis (HR 1.21, 95% CI 1.17 to 1.25, p <0.001). In conclusion, compared with ß blockers, the initiation of diltiazem or verapamil in patients with HFpEF or AF may be associated with fewer HF hospitalization events but also with more all-cause deaths.

Topical Lidocaine or Lidocaine/Diltiazem Ointment Following Rubber Band Ligation of Hemorrhoids: A Prospective 3-Armed Randomized Controlled Trial.

BACKGROUND: Rubber band ligation of hemorrhoids causes less pain than excisional hemorrhoidectomy, but many patients still experience significant postprocedure discomfort. OBJECTIVE: This study aimed to determine whether topical lidocaine, with or without diltiazem, is more effective than placebo for analgesia after hemorrhoid banding. DESIGN: This is a prospective, randomized, double-blinded, placebo-controlled trial. Patients were randomly assigned to 2% lidocaine, 2% lidocaine with 2% diltiazem, or a placebo ointment. SETTINGS: This study was performed at 2 university public teaching hospitals and 2 private hospitals in Australia. PATIENTS: Consecutive patients aged ≥18 years undergoing hemorrhoid banding were selected. INTERVENTIONS: Topical ointments were applied postprocedure 3× daily for 5 days. MAIN OUTCOME MEASURES: Visual analog pain score, opiate analgesia usage, and patient satisfaction were the main outcome measures. RESULTS: Of 159 eligible patients, 99 were randomly assigned (33 in each group). Pain scores were reduced at 1 hour for the lidocaine (OR 4.15 [1.12-15.41]; p = 0.03) and lidocaine/diltiazem groups (OR 3.85 [1.05-14.11]; p = 0.04) compared with placebo. Patients in the lidocaine/diltiazem group had improved satisfaction (OR 3.82 [1.28-11.44]; p = 0.02) and were more likely to recommend the procedure to others (OR 9.33 [1.07-81.72]; p = 0.04). Patients in the lidocaine/diltiazem group required approximately 45% less total and in-hospital analgesia compared with the placebo. There was no difference in complications between any of the groups. LIMITATIONS: A cost/benefit analysis was not performed. Analgesic efficacy appeared to be short term and the procedures were performed only in the hospital/nonambulatory setting. CONCLUSIONS: Topical lidocaine reduced short-term analgesia use, whereas combination lidocaine/diltiazem was associated with both improved analgesia and patient satisfaction after hemorrhoid banding. LIDOCANA TPICA O UNGENTO DE LIDOCANA/DILTIAZEM DESPUS DE LA LIGADURA HEMORROIDAL CON BANDA ELSTICA UN ENSAYO PROSPECTIVO CONTROLADO Y ALEATORIZADO DE TRES BRAZOS: ANTECEDENTES:La ligadura de hemorroides con banda elástica causa menos dolor que la hemorroidectomía escisional, pero muchos pacientes siguen experimentando molestias significativas tras el procedimiento.OBJETIVO:Este estudio tiene como objetivo determinar si la lidocaína tópica, con o sin diltiazem, es más eficaz que el placebo para la analgesia tras la ligadura hemorroidal.DISEÑO:Este es un ensayo prospectivo, aleatorizado, doble ciego, controlado con placebo. Los pacientes fueron aleatorizados para recibir lidocaína al 2 %, lidocaína al 2 % con diltiazem al 2 % o ungüento de placebo.AJUSTES:Este estudio se realizó en dos hospitales públicos con docencia universitaria y dos hospitales privados en Australia.PACIENTES:Se seleccionaron pacientes consecutivos de ≥18 años sometidos a ligadura para hemorroides.INTERVENCIONES:Se aplicaron ungüentos tópicos tras el procedimiento tres veces al día durante 5 días.PRINCIPALES MEDIDAS DE RESULTADO:La puntuación analógica visual del dolor, el uso de analgésicos opiáceos y la satisfacción del paciente fueron las principales medidas de resultado.RESULTADOS:De 159 pacientes elegibles, 99 fueron aleatorizados (33 en cada grupo). Las puntuaciones de dolor se redujeron a la hora para los grupos de lidocaína (OR 4,15 (1,12-15,41); p = 0,03) y lidocaína/diltiazem (OR 3,85 (1,05-14,11), p = 0,04) en comparación con el placebo.Los pacientes del grupo de lidocaína/diltiazem mejoraron su satisfacción (OR 3,82 (1,28-11,44), p = 0,02) y eran más propensos de recomendar el procedimiento a otros (OR 9,33 (1,07-81,72), p = 0,04). Los pacientes del grupo de lidocaína/diltiazem requirieron aproximadamente un 45 % menos de analgesia total e intrahospitalaria en comparación con el grupo de placebo. No hubo diferencia en las complicaciones entre ninguno de los grupos.LIMITACIONES:No se realizó un análisis de costo/beneficio. La eficacia analgésica pareció ser a corto plazo y los procedimientos solo se realizaron en el hospital/entorno no ambulatorio.CONCLUSIÓN:La lidocaína tópica mejora la analgesia a corto plazo, mientras que la combinación de lidocaína/diltiazem se asocia tanto con una mejor analgesia como con la satisfacción del paciente tras la colocación de bandas para hemorroides. (Traducción-Dr Osvaldo Gauto ).

A Real-World Matched Cohort Study of the Effect of Concomitant Amiodarone or Diltiazem Administration on Apixaban Peak and Trough Concentrations.

BACKGROUND: Apixaban is a substrate for p-glycoprotein and is extensively metabolized by cytochrome P450 (CYP) 3A4. There are minimal published data regarding the effect of amiodarone and diltiazem on apixaban serum concentrations. OBJECTIVE: The aim of this study was to determine the degree of elevation of apixaban concentrations resulting from amiodarone or diltiazem. METHODS: This was a matched cohort study approved by the Institutional Review Board. Patients receiving apixaban 5 mg twice daily with concomitant diltiazem or amiodarone were enrolled. Control groups were enrolled via matching characteristics of sex, age, weight, creatinine clearance, and statin therapy. Exclusions were an inappropriate dosage of apixaban or concomitant dronedarone, verapamil, ranolazine, naproxen, or both amiodarone and diltiazem. Blood samples were collected 3-4 h after and 0.5-2 h before an apixaban dose, corresponding to peak and trough concentrations, respectively. Results were compared using a t test. RESULTS: Thirty patients were enrolled in each of the four groups. The mean peak apixaban concentration was 239 ± 82 ng/mL in the amiodarone group and 208 ± 66 ng/mL in the corresponding control group (p = 0.068). Trough concentrations were 142 ± 71 ng/mL and 117 ± 41 ng/mL, respectively (p = 0.055). The mean peak apixaban concentration was 243 ± 99 ng/mL in the diltiazem group and 213 ± 82 ng/mL in the control group (p = 0.11). Trough concentrations were 130 ± 65 ng/mL and 108 ± 54 ng/mL, respectively (p = 0.09). CONCLUSION: Coadministration of amiodarone and diltiazem resulted in a trend toward increased apixaban concentrations. The extent of elevation suggests that empiric dose changes are not necessary; however, individual patients may benefit from monitoring and dose adjustment.

Management of atrial flutter and atrial fibrillation with rapid ventricular response in patients with acute decompensated heart failure: A systematic review.

OBJECTIVE: The objective was to evaluate the comparative effectiveness and safety of pharmacological and nonpharmacological management options for atrial fibrillation/atrial flutter with rapid ventricular response (AFRVR) in patients with acute decompensated heart failure (ADHF) in the acute care setting. METHODS: This study was a systematic review of observational studies or randomized clinical trials (RCT) of adult patients with AFRVR and concomitant ADHF in the emergency department (ED), intensive care unit, or step-down unit. The primary effectiveness outcome was successful rate or rhythm control. Safety outcomes were adverse events, such as symptomatic hypotension and venous thromboembolism. RESULTS: A total of 6577 unique articles were identified. Five studies met inclusion criteria: one RCT in the inpatient setting and four retrospective studies, two in the ED and the other three in the inpatient setting. In the RCT of diltiazem versus placebo, 22 patients (100%) in the treatment group had a therapeutic response compared to 0/15 (0%) in the placebo group, with no significant safety differences between the two groups. For three of the observational studies, data were limited. One observation study showed no difference between metoprolol and diltiazem for successful rate control, but worsening heart failure symptoms occurred more frequently in those receiving diltiazem compared to metoprolol (19 patients [33%] vs. 10 patients [15%], p = 0.019). A single study included electrical cardioversion (one patient exposed with failure to convert to sinus rhythm) as nonpharmacological management. The overall risk of bias for included studies ranged from serious to critical. Missing data and heterogeneity of definitions for effectiveness and safety outcomes precluded the combination of results for quantitative meta-analysis. CONCLUSIONS: High-level evidence to inform clinical decision making regarding effective and safe management of AFRVR in patients with ADHF in the acute care setting is lacking.

Comparison of diltiazem and metoprolol for atrial fibrillation with rapid ventricular rate: Systematic review and meta-analysis.

BACKGROUND: Intravenous calcium channel blockers or beta-blockers are the preferred rate control medications for hemodynamically stable patients with atrial fibrillation with rapid ventricular rate (AF-RVR) in the emergency department. OBJECTIVES: To compare the efficacy of intravenous diltiazem and metoprolol for rate control and safety with respect to development of hypotension and bradycardia in patients with AF-RVR. METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane databases, and the clinicaltrials.gov registry between database inception and 30th May 2021. Articles were included if they compared efficacy and safety of diltiazem versus metoprolol in critically ill adult patients hospitalized with AF-RVR. Outcome measures were achievement of rate control, development of new hypotension, and bradycardia after drug administration. RESULTS: Of 86 records identified, 14 were eligible, all of which had a low to moderate risk of overall bias. The meta-analysis (Mantel-Haenszel, random-effects model) showed that diltiazem use was associated with increased achievement of rate control target compared to metoprolol [14 studies, n = 1732, Odds Ratio (OR): 1.92; 95% Confidence Intervals (CI):1.26 to 2.90; I2 = 61%]. In the pooled analysis, no differences were seen in hypotension using diltiazem vs metoprolol [12 studies, n = 1477, OR: 0.96; 95% CI:0.61 to 1.52; I2 = 35%] or bradycardia [9 studies, n = 1203, OR: 2.44; 95% CI: 0.82 to 7.31; I2 = 48%]. CONCLUSIONS: Intravenous diltiazem is associated with increased achievement of rate control target in patients with AF-RVR compared to metoprolol, while both medications are associated with similar incidence of hypotension and bradycardia.

A rare cause of abdominal pain managed unconventionally: acute renal infarction caused by atrial fibrillation: a case report.

BACKGROUND: Atrial fibrillation is one of the most common arrhythmias. The main thrombotic complication of arterial fibrillation is ischemic stroke, but it can also cause acute renal infarction from embolization. The low incidence and nonspecific clinical manifestations of acute renal infarction make it difficult to diagnose, often leading to either delayed diagnosis or misdiagnosis. Due to its rarity, more efficient treatment guidelines are helpful for the management of acute renal infarction related to the thromboembolic complication of arterial fibrillation. CASE REPORTS: We report a case of acute renal infarction due to underlying arterial fibrillation, where a novel interventional therapeutic method was used. A 66-year-old Chinese man with arterial fibrillation, not on anticoagulation due to the patient's preference, and coronary artery disease post-percutaneous coronary intervention to left anterior descending artery about 1 year ago, was currently on dual antiplatelet therapy. He suddenly developed intermittent and sharp left-sided abdominal pain and was found to have an acute left renal infarction on computed tomography scan. Angiogram showed acute occlusion of the left renal artery due to thromboembolism. For this patient, a combination method of local thrombus aspiration, angioplasty, and infusion of nitroglycerin and diltiazem were used, restoring blood flow to the left kidney. After recovery, the patient was discharged on aspirin, clopidogrel, and warfarin. At 6 months follow-up, there was no residual kidney dysfunction. CONCLUSIONS: Acute renal infarction from thromboembolism is a rare but serious complication of arterial fibrillation. More efficient and different options for intervention methods will benefit the treatment of this disease. Here, we report a combination therapeutic method that has not been used in acute renal infarction associated with arterial fibrillation, and which restored renal perfusion and prevented long-term kidney injury.

Managing life-threatening 5-fluorouracil cardiotoxicity.

5-Fluorouracil (5-FU), a known cardiotoxin, is the backbone for the treatment of colorectal cancer. It is associated with arrhythmias, myocardial infarction and sudden cardiac death. Most commonly, it is associated with coronary vasospasm secondary to direct toxic effects on vascular endothelium.A woman with metastatic colon cancer, originally treated with a 5-FU infusion as part of the FOLFIRI (Folinic acid, 5-Fluorouracil, Irinotecan) regimen, was unable to tolerate the chemotherapy due to chest pain. She was transitioned from infusional 5-FU to inferior 1-hour bolus 5-FU, in an attempt to minimise cardiotoxicity, but had disease progression. A multidisciplinary decision was made to again trial 5-FU infusion and pretreat with diltiazem. She tolerated chemotherapy without adverse events. A multidisciplinary discussion is recommended for co-management of reversible 5-FU-associated cardiotoxicity. After coronary artery disease (CAD) risk stratification and treatment, empiric treatment with calcium channel blockers and/or nitrates may allow patients with suspected coronary vasospasm, from 5-FU, to continue this vital chemotherapy.

Diltiazem as a cyclosporine A-sparing agent in heart transplantation: Benefits beyond dose reduction.

Diltiazem (DZ) is widely prescribed in transplant recipients because of its drug-drug interactions with calcineurin inhibitors (CNI). However, these interactions have been primarily investigated in renal transplantation, and data regarding the long-term efficacy and safety of DZ in orthotopic heart transplantation (OHT) are still sparse. Our study aimed to elucidate the extent to which the co-prescription of DZ reduces the dose required to maintain adequate blood levels of cyclosporine A (CsA) and the resulting effect on morbidity and mortality in OHT recipients. We performed a retrospective single-center analysis of OHT recipients on a long-term immunosuppressive regimen based on CsA and mycophenolate mofetil (MMF). The study population consisted of 95 adult OHT recipients with a mean follow-up of 15.8 ±â€…6.7 years. DZ was co-prescribed in 39 subjects (41.1%) and was associated with a 28.6% reduction of the mean CsA daily dose (P < .001). Patients on DZ had less frequent rejection episodes (P = .002), better renal function (P = .009) and a lower rate of end-stage renal disease (P = .008). Additionally, they developed later cardiac allograft vasculopathy (CAV). We observed no prognostic relevance of DZ co-prescription in univariate and multivariate Cox-regression analyses. In addition to reducing the CsA dose required to maintain adequate blood through levels, DZ may have nephroprotective properties in OHT. The co-administration of DZ may decelerate the development of CAV and reduce the frequency of the rejection episodes. However, the beneficial influence on morbidity has no impact on mortality.

What is the Best Agent for Rate Control of Atrial Fibrillation With Rapid Ventricular Response?

BACKGROUND: Atrial fibrillation (AF) is a common dysrhythmia associated with significant morbidity and mortality. Although many patients have stable AF, some patients can present with a rapid ventricular response (RVR). In these patients, it is important to lower their heart rate. However, there are several options available for rate control in the emergency department setting. CLINICAL QUESTION: What is the most effective agent for rate control for the patient with AF in RVR? EVIDENCE REVIEW: Studies retrieved included two prospective, randomized, double-blind studies and six retrospective cohort studies. These studies provide estimates of the efficacy and safety of calcium channel blockers and ß-blockers for rate control in those with AF with RVR. CONCLUSION: Based upon the available literature, diltiazem likely achieves rate control faster than metoprolol, though both agents seem safe and effective. Clinicians must consider the individual patient, clinical situation, and comorbidities when selecting a medication for rate control.

Allopurinol, dipyridamole and calcium channel blockers in the treatment of bipolar disorder - A nationwide cohort study.

BACKGROUND: Improved treatments for bipolar disorder (BD) are needed. Drug repurposing aims to find novel targets for drugs that have been used for other indications. This study investigated the risk of psychiatric hospitalization associated with use of calcium-channel blockers (CCBs; dihydropyridines, diltiazem, verapamil) and adenosine modulators (allopurinol, dipyridamole) in BD in within-individual design. METHODS: Individuals diagnosed with BD (ICD-10: F30-F31) were identified from the inpatient, specialized outpatient, sickness absence, and disability pension registers during 1996-2018 in Finland (N = 60,045). The main outcome was hospitalization due to affective symptoms (ICD-10: F30-F39). Within-individual models in stratified Cox regression were used and adjusted hazard ratios (aHR) with 95 % confidence intervals (CIs) reported. RESULTS: Use of CCBs was associated with a decreased risk of hospitalization due to affective symptoms (aHR 0.83, 95 % CI 0.78-0.88) when all CCBs were analyzed together. Of specific CCBs, use of diltiazem (0.71, 0.55-0.91) and dihydropyridines (0.83, 0.78-0.89) were associated with a decreased risk but verapamil was not (0.93, 0.73-1.19). Use of adenosine modulators in general was associated with a decreased risk of hospitalizations due to affective symptoms (0.87, 0.79-0.96). Both allopurinol (0.85, 0.74-0.97) and dipyridamole (0.89, 0.78-1.00) were associated with a marginally decreased risk. Thiazide diuretic use as a negative control was not associated with the risk of hospitalization due to affective symptoms (0.97, 0.83-1.13). LIMITATIONS: Due to the observational nature of this study, causation cannot be confirmed. CONCLUSIONS: Dihydropyridines and diltiazem were associated with a decreased risk of psychiatric hospitalization in bipolar disorder. Results for allopurinol and dipyridamole were inconclusive.

PD-1 Inhibitor-Induced Thyrotoxicosis Associated with Coronary Artery Spasm and Ventricular Tachycardia.

Programmed cell death protein 1 (PD-1) inhibitors open a new era of cancer immunotherapy, but they are associated with immune-related adverse events (irAEs) involving multiple endocrine organs of which thyroid dysfunction is the most common An uncommon condition of coronary artery spasm and ventricular tachycardia associated with thyrotoxicosis, induced by a PD-1 inhibitor, is discussed in this case. A 60-year-old male patient with a 1-week history of chest tightness and palpitation at rest was referred to us in July 2021. No obvious abnormalities were noted on physical examination and electrocardiography. He was being treated with a PD-1 inhibitor (camrelizumab, 200 mg) for lung metastasis of liver cancer; treatment stopped because he was found to have hyperthyroidism. Holter recorded intermittent STsegment arch back raised 0.5-14 mm upward lasting for 1-5 min, accompanied by ventricular tachycardia. He was treated with antivasospasm drugs (isosorbide mononitrate and diltiazem). Thyroid function was reexamined and revealed elevated FT3 and FT4 levels, decreased TSH levels, and negative thyroid-associated antibodies. After antivasospasm treatment and iodine taboo diet, his symptoms were relieved, and ST-segment elevation and ventricular tachycardia were disappeared. This case adds to our knowledge of the association between coronary artery spasms and thyrotoxicosis, which is an irAE induced by a PD-1 inhibitor. Patients treated with PD-1 inhibitors need regular follow-ups for cardiac complications, especially those with a history of heart disease.

In vitro and in vivo impacts of nifedipine and diltiazem on praziquantel chemotherapy in murine Schistosoma mansoni.

AIM: This study was planned to evaluate the in vitro and in vivo antischistosomal effects of the widely used antihypertensive drugs, nifedipine (NIF) and diltiazem (DTZ), and their combinations with praziquantel (PZQ) on early and late Schistosoma (S.) mansoni infections 21- and 45- days old stages. METHODS: In the In vitro study, Calcium channel blockers (CCBs), NIF and DTZ were added to schistosomula and adult worm cultures in different concentrations 10, 20 and 30 mg/ml. The mortality percentage was calculated 1, 12 and 24 h after incubation. In vivo, NIF and DTZ either alone or combined with PZQ were used to treat male albino mice. The parasitological and total immunoglobulin (Ig) G and IgM anti-soluble egg antigen (SEA) were assessed to demonstrate the disease severity. RESULTS: In the In vitro study, 10 mg/ml NIF induced 100% mortality percentage of both schistosomula and adult worms after 24 h incubation, while DTZ induced similar mortality percentage at 30 mg/ml concentration. In vivo results showed that early or late combination of 30 mg/kg of NIF, but not DTZ, significantly (P <0.05) enhanced the reductive efficacy of PZQ based on the parasitological data. The maximal reduction (P <0.05) of anti-SEA IgM and IgG levels was developed during NIF-PZQ administration 21- (1.12 ± 0.06 and 1.09 ± 0.04, respectively) or 45- (1.00 ± 0.03 and 0.8 ± 0.06, respectively) days post infection (PI), compared to either PZQ or NIF individual treatments. The decreased concentration of anti-SEA antibodies was correlated with the diminished granulomatous diameter and disease severity. CONCLUSION: Nifedipine improved PZQ chemotherapy targeting either early or late S. mansoni infection in mice compared to the PZQ mono-therapy. Administering NIF can be considered as a promising drug candidate for schistosomiasis chemotherapy.

Diltiazem inhibits SARS-CoV-2 cell attachment and internalization and decreases the viral infection in mouse lung.

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 Cav1.2 pore-forming subunit (Cav1.2 α1c) 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. Cav1.2 α1c 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 Cav1.2 α1c is a promising target for antiviral drug development for COVID-19.