Administration Of Calcium Channel Blockers Research Articles

Vasospasm in Pediatric Subarachnoid Hemorrhage.

Cerebral vasospasm (CV) is a common severe complication of subarachnoid hemorrhage (SAH), a severe type of intracranial bleeding that is uncommon in children. The purpose of this article is to review the current literature regarding this potentially devastating complication. CV may be asymptomatic and is less common in children compared to adults. Several molecular phenomena, including inflammatory ones, contribute to its pathophysiology. Better collateral circulation and higher cerebral blood flow are protective factors in children. When clinically apparent, CV may manifest as a change in the child's neurologic status or vital signs. CV can be diagnosed using brain vessel imaging, such as computed tomography angiography, magnetic resonance angiography, digital subtraction angiography, transcranial Doppler ultrasonography, and computed tomography perfusion. A reduction of < 50% in the artery's caliber confirms the diagnosis. Besides general supportive measures and causative treatment of SAH, CV management options include the administration of calcium channel blockers and neurointerventional approaches, such as intra-arterial vasodilators and balloon angioplasty. Long-term outcomes in children are usually favorable.

Iron Overload Cardiomyopathy

Iron overload cardiomyopathy is a condition of excessive iron accumulation in cardiomyocytes due to abnormal iron absorption or repeated blood transfusion. In the early stages, the patient may be asymptomatic with good ventricular systolic function. Iron deposit in ventricular cause dyspnea on effort due to left ventricular systolic dysfunction then in atrial cause atrioventricular block and supraventricular arrhythmic. For severe symptom due to dilated cardiomyopathy is characterized by left ventricular dilatation and risk of sudden cardiac death. Diagnosis of iron overload cardiomyopathy can be made if there is evidence of heart disease, the presence of iron overload (serum ferritin &gt; 300 ng/mL and transferrin saturation &gt; 55%) and cardiac siderosis with cardiac MRI T2 * &lt; 20 ms as gold standard. Patient management involves lowering systemic iron levels and preventing iron entry into cardiomyocytes. Therapy with phlebotomy or iron chelation as indicated. Administration of calcium channel blockers and resveratrol antioxidant therapy may be considered to reduce morbidity and mortality due to cardiac siderosis.

Psoriasiform drug eruption: A case series with a review of the literature.

The present case series examined five instances of psoriasiform drug eruption diagnosed between 2014 and 2022 at the study site and 23 cases of drug eruption manifesting psoriasiform lesions which had been reported between 1986 and 2022. The causative drug, distribution of the skin eruptions, clinical latency to eruption, treatment course, and histopathological findings were investigated. The most common causative agents were calcium channel blockers (CCB) (64.5%). Of the 28 cases of psoriasiform drug eruption for which details of the eruption sites were reported, 46.4% occurred on the face, which was slightly higher than the usual distribution of psoriasis. CCB were responsible for 80.0% of the cases of facial skin rash. The mean time from the administration of the suspected drug to eruption onset was 25.0 months (range: 0.5-120 months; median: 13.0 months). In all the cases, the skin rash improved after the causative drug was discontinued. CCB were the most common causative agent, and the eruptions more commonly occurred on the face than in normal psoriasis, suggesting that it is especially important to confirm whether there is a history of CCB administration in psoriasis patients with extensive, facial skin eruptions.

First use of intraventricular nicardipine in a pediatric patient with vasospasm secondary to meningitis: illustrative case.

Cerebral vasospasm is commonly associated with adult aneurysmal subarachnoid hemorrhage but can develop in children. The standard vasospasm treatment includes induced hypertension, avoidance of hypovolemia, systemic use of the calcium channel blocker (CCB) nimodipine, and cerebral angiography for intraarterial therapy. Emerging treatments in adults, such as intraventricular CCB administration, have not been investigated in children. This study demonstrates the successful use of an intraventricular CCB in a pediatric patient with refractory vasospasm secondary to meningitis. A 12-year-old female presented with Streptococcus pneumoniae meningitis and ventriculitis with refractory symptomatic cerebral vasospasm. She received a 5-day course of intrathecal nicardipine through an existing external ventricular drain. Her clinical status, transcranial Doppler studies, and radiography improved. Treatment was well tolerated. Pediatric vasospasm is uncommon and potentially devastating. The management of vasospasm in adults occurs frequently. Principles of this management are adapted to pediatric care given the rarity of vasospasm in children. The use of intraventricular nicardipine has been reported in the care of adults with level 3 evidence. It has not been adequately reported in children with refractory vasospasm. Here, the first use of intraventricular nicardipine in treating pediatric cerebral vasospasm in the setting of meningitis is described and highlighted.

Outcomes following therapeutic intervention of post-traumatic vasospasm: A systematic review and meta-analysis

BackgroundVasospasm occurrence following traumatic brain injury may impact neurologic and functional recovery of patients, yet treatment of post-traumatic vasospasm (PTV) has not been well documented. This systematic review and meta-analysis aims to assess the current evidence regarding favorable outcome as measured by Glasgow Outcome Scale (GOS) scores following treatment of PTV. MethodsA systematic review of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included manuscripts were methodically scrutinized for quality; occurrence of PTV; rate of favorable outcome following each treatment modality; and follow-up duration. Treatments evaluated were calcium channel blockers (CCBs), endovascular intervention, and dopamine-induced hypertension. Outcomes were compared via the random-effects analysis. ResultsFourteen studies with 1885 PTV patients were quantitatively analyzed: 982 patients who received tailored therapeutic intervention and 903 patients who did not receive tailored therapy. For patients undergoing treatment, the rate of favorable outcome was 57.3 % (500/872 patients; 95 % CI 54.1 – 60.6 %) following administration of CCBs, 94.1 % (16/17 patients; 95 % CI 82.9 – 100.0 %) following endovascular intervention, and 54.8 % (51/93 patients; 95 % CI 44.7 – 65.0 %) following dopamine-induced hypertension. Of note, the endovascular group had the highest rate of favorable outcome but was also the smallest sample size (n = 17). Patients who received tailored therapeutic intervention for PTV had a higher rate of favorable outcome than patients who did not receive tailored therapy: 57.7 % (567/982 patients; 95 % CI 54.1 – 60.8 %) versus 52.0 % (470/903 patients; 95 % CI 48.8 – 55.3 %), respectively. ConclusionsThe available data suggests that tailored therapeutic intervention of PTV results in a favorable outcome. While endovascular intervention of PTV had the highest rate of favorable outcome, both CCB administration and dopamine-induced hypertension had similar lower rates of favorable outcome.

Self-administered intranasal etripamil using a symptom-prompted, repeat-dose regimen for atrioventricular-nodal-dependent supraventricular tachycardia (RAPID): a multicentre, randomised trial

Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 min. RAPID was a multicentre, randomised, placebo-controlled, event-driven trial, conducted at 160 sites in North America and Europe as part 2 of the NODE-301 study. Eligible patients were aged at least 18 years and had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes (≥20 min) as documented by electrocardiogram. Patients were administered two test doses of intranasal etripamil (each 70 mg, 10 min apart) during sinus rhythm; those who tolerated the test doses were randomly assigned (1:1) using an interactive response technology system to receive either etripamil or placebo. Prompted by symptoms of paroxysmal supraventricular tachycardia, patients self-administered a first dose of intranasal 70 mg etripamil or placebo and, if symptoms persisted beyond 10 min, a repeat dose. Continuously recorded electrocardiographic data were adjudicated, by individuals masked to patient assignment, for the primary endpoint of time to conversion of paroxysmal supraventricular tachycardia to sinus rhythm for at least 30 s within 30 min after the first dose, which was measured in all patients who administered blinded study drug for a confirmed atrioventricular-nodal-dependent event. Safety outcomes were assessed in all patients who self-administered blinded study drug for an episode of perceived paroxysmal supraventricular tachycardia. This trial is registered at ClinicalTrials.gov, NCT03464019, and is complete. Between Oct 13, 2020, and July 20, 2022, among 692 patients randomly assigned, 184 (99 from the etripamil group and 85 from the placebo group) self-administered study drug for atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia, with diagnosis and timing confirmed. Kaplan-Meier estimates of conversion rates by 30 min were 64% (63/99) with etripamil and 31% (26/85) with placebo (hazard ratio 2·62; 95% CI 1·66-4·15; p<0·0001). Median time to conversion was 17·2 min (95% CI 13·4-26·5) with the etripamil regimen versus 53·5 min (38·7-87·3) with placebo. Prespecified sensitivity analyses of the primary assessment were conducted to test robustness, yielding supporting results. Treatment-emergent adverse events occurred in 68 (50%) of 99 patients treated with etripamil and 12 (11%) of 85 patients in the placebo group, most of which were located at the administration site and were mild or moderate, and all of which were transient and resolved without intervention. Adverse events occurring in at least 5% of patients treated with etripamil were nasal discomfort (23%), nasal congestion (13%), and rhinorrhea (9%). No serious etripamil-related adverse events or deaths were reported. Using a symptom-prompted, self-administered, initial and optional-repeat-dosing regimen, intranasal etripamil was well tolerated, safe, and superior to placebo for the rapid conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm. This approach could empower patients to treat paroxysmal supraventricular tachycardia themselves outside of a health-care setting, and has the potential to reduce the need for additional medical interventions, such as intravenous medications given in an acute-care setting. Milestone Pharmaceuticals.

PS-BPC06-4: RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM INHIBITORS VERSUS CALCIUM CHANNEL BLOCKERS IN ASSOCIATION WITH MORTALITY RATE IN COVID-19 HYPERTENSIVE PATIENTS: THE EFFECT OF AGE

Objective: To study the association of calcium channel blockers (CCBs), the renin-angiotensin-aldosterone system (RAAS) inhibitors or their combination as antihypertensive medications and the clinical outcome of COVID-19 infection. Design and method: This is a retrospective cohort study using de-identified data retrieved from clinical records of COVID-19 patients in two isolation centers. Medical history, demographic data, symptoms, complications and laboratory investigations were extracted from clinical records of 406 confirmed COVID-19 hospitalized patients between Feb 2020 and July 2021. Hypertension and antihypertensive treatments were confirmed by medical history and clinical records. Continuous variables were presented as means ± standard deviation (SD) while categorical variables were presented as percent proportions. Logistic regression was used to assess the impact of antihypertensive drugs (RAAS inhibitors, CCBs, combination of RAAS inhibitors and CCBs and those not receiving medication) on the prognosis of COVID-19 patients and to explore the risk factors associated with mortality. Result: Out of 406 hospitalized COVID-19 patients, 242 (59.6%) had a history of hypertension. Hypertensive patients under the age of 65 years and receiving RAAS inhibitors or the combination of both RAAS inhibitors and CCBs were at higher risk of mortality than those on CCBs only (odds ratio [OR]: 4.45, 95% confidence interval [CI]: 1.56–12.56, P = 0.005 and OR:3.57, CI: 1.03–12.36, P = 0.045 respectively). Antihypertensive medications did not seem to influence mortality rates among hypertensive patients above 65 years. Routine laboratory investigations were not significantly different between the subgroups receiving different antihypertensive medications regardless of age. Cough was the only symptom associated with mortality among patients under 65 years (OR:2.34, CI:1.24–4.41, P = 0.009). Type II respiratory failure was significantly associated with death among hypertensives under 65 years (OR:5.43, CI:1.08–28.07, P = 0.044) whereas acute kidney injury and septic shocks are the common complications related to death among hypertensives above 65 years (OR:3.59, CI:1.54–8.36, P = 0.003 and OR:7.87, CI: 1.68–36.78, P = 0.009 respectively). Conclusion: Administration of CCBs may improve the outcome of COVID-19 hypertensive patients under 65 years of age. Antihypertensive treatment does not seem to influence the prognosis of COVID-19 patients above 65 years. Such results may affect management strategy of COVID-19 hypertensive patients. Type-II respiratory failure among patients under 65 years of age, acute kidney injury and septic shock among those above 65 years are the most serious complications that can lead to death regardless of blood pressure.

Surgical treatment of intracranial aneurysms in acute period of hemorrhage in Hunt-Hess grade IV-V patients at Burdenko Neurosurgical Center between 2006 and 2020

Management of patients in acute period of aneurysmal subarachnoid hemorrhage Hunt-Hess grade IV-V is still a complex and unsolved problem, especially regarding surgical treatment and various complications. To analyze postoperative outcomes in patients undergoing surgery in acute period of aneurysmal subarachnoid hemorrhage Hunt-Hess grade IV-V between 2006 and 2020, as well as to assess various factors influencing treatment outcomes. We analyzed 163 patients who underwent surgery within 21 days after aneurysmal subarachnoid hemorrhage Hunt-Hess grade IV-V. All patients were divided into 2 groups depending on the period: 2006-2011 (group 1) and 2012-2020 (group 2). Mortality reduced from 28.6% in group 1 to 8.3% in group 2. At the same time, incidence of vegetative state (GOS grade 2) increased from 4.8% to 17.4%. Incidence of outcomes GOS grade 3 - 5 was similar. Large or giant aneurysm, repeated preoperative subarachnoid hemorrhage, intraoperative aneurysm rupture and prolonged temporary clipping can impair postoperative outcomes in patients with hemorrhage Hunt-Hess grade IV-V. External ventricular drainage, intraarterial injection of verapamil, intracisternal administration of calcium channel blockers and active surgical tactics improve postoperative outcomes and reduce mortality.

Prevention and non-surgical periodontal therapy of calcium channel blockers induced severe gingival overgrowth.

Gingival overgrowth is an adverse drug reaction in patients on long-term calcium channel blocker therapy. The aim of this study was to assess the efficacy of non-surgical pocket therapy in patients suffering from Grade III drug-related gingival overgrowth. 10 (7 female and 3 male) patients (age between 50-69 years) diagnosed with severe, Grade III gingival overgrowth were treated in our department. Non-surgical periodontal therapy consists of improving of individual oral hygiene, scaling, polishing and subgingival mechanical debridement instrumentation. The main periodontal parameters (probing pocket depth, bleeding index, plaque index and mobility) were scored in this study. Bone loss was evaluated by orthopantomograms and periapical radiographs. Calcium channel blockers have not been replaced by any other medications during the whole course of periodontal treatment. Compared with baseline parameters, all scores improved after therapy. All patients showed decrease in the average probing pocket depth, deepest probing pocket depth, bleeding scores, plaque scores and tooth mobility. None of the patients needed further surgical treatment. In our followed-up patients, recurrence of gingival overgrowth has not been observed during the two-year meticulous supportive periodontal care in the patient group. Non-surgical periodontal treatment can be a potential definitive therapy in Grade III gingival overgrowth associated with gingivitis or moderate periodontitis. Periodontal screening and treatment before or simultaneously with the administration of calcium channel blockers can prevent the gingival enlargement in the majority of patient. These results outline the importance of the successful cause related periodontal therapy, started before or simultaneously with the administration of anithypertensive medications and in this way a series of further expensive therapies could be anticipated. Orv Hetil. 2022; 163(13): 506-512.

Calcium Channel Blockers with and without Nitrates for the Prognosis of Patients with Coronary Vasospastic Angina: A Meta-Analysis

Background: A systematic review and meta-analysis was conducted to assess the most effective treatment (long-term administration of calcium channel blockers [CCBs] with and without any form of long-acting nitrates [nitrates]) for reducing the incidence of major adverse cardiac events (MACEs) in patients with vasospastic angina (VSA).

Impact of Calcium Channel Blockers on Aspirin Reactivity in Patients with Coronary Artery Disease.

Calcium channel blockers (CCBs) do not reduce the risk of initial or recurrent myocardial infarction (MI) in patients diagnosed with stable coronary artery disease (CAD). The aim of this current study was to evaluate the association between CCBs and aspirin resistance in patients with CAD. Patients with stable CAD who were regularly taking aspirin (75-100 mg qd) for at least 1 month prior to enrollment in the study were included. The VerifyNow system was used for platelet function testing with high on-aspirin platelet reactivity (HAPR) defined as aspirin reaction units (ARU) >550. We compared patients treated with CCBs versus control group. Five hundred three patients with CAD were included in this study, and 88 were treated with CCBs. Mean age (67.9±9.7 in the CCB group vs. 66.5±11.4 in the control group), gender (77.3 male vs. 82.9%), rates of diabetes mellitus (34.7 vs. 36.9%), rates of CKD (23.5 vs. 23.5%), dyslipidemia (85.1 vs. 85.3%), and statin therapy (89.5 vs. 90.7%) were similar. The mean ARU was 465.4±70.0 for patients treated with CCBs versus 445.2±60.0 in controls (p=0.006). Similarly, 15.9% of CCB patients demonstrated HAPR compared to 7.0% (p=0.006). The administration of CCBs was independently associated with HAPR in a multivariate analysis (OR 1.72, 95% CI: 1.04-8.91, p=0.047) as well as in propensity score matched analysis (OR 1.56; CI: 1.22-1.93; p<0.001). Usage of CCBs is positively correlated with aspirin resistance. These findings may suggest an adverse pharmacologic effect of CCBs among patients with stable CAD treated with aspirin.

Abstract 11430: Etripamil Nasal Spray Reduces Heart Rate in Patients with Paroxysmal Supraventricular Tachycardia Prior to Conversion to Sinus Rhythm

Introduction: Etripamil (E) is a rapidly and short acting, nasally administered calcium channel blocker being developed to terminate AV nodal-dependent PSVT. The NODE-301 first in class, multicenter study, evaluated self-administration of E nasal spray 70 mg outside a healthcare environment for acute termination of PSVT. This post-hoc analysis addresses the effect of E on heart rate (HR) during PSVT prior to conversion to sinus rhythm (SR). Methods: In NODE-301, 156 subjects experienced a vagal-maneuver refractory, symptomatic episode of confirmed PSVT, 107 subjects self-administered E and 49 placebo (P) (2:1 randomization) during PSVT. Each PSVT was documented by an ambulatory cardiac monitoring system that was placed on the chest after symptoms began. Baseline (average of four values before drug administration), and every minute of HR data were captured from baseline until one minute before the PSVT was converted to SR. Adequate HR data were available for 150 subjects, 102 on E and 48 on P. Six subjects were not included in this analysis, 4 converted before one minute (3 E and 1 P) and 2 E subjects experienced an early defect of recording. Results: Baseline mean (±SE) HR were 179 (±2.8) and 174 (±4.0) bpm for E and P respectively. Mean change in HR from baseline was greater in the E group than P group ( p &lt;0.0001). This decrease appeared within the first minute (-5 bpm ±0.9), 3 min (-10 bpm ±1.2), 10 min (-16 bpm ±2.1), 30 min (-14 bpm ±3.4) and 40 min (-13 bpm ±2.9) after E administration. The notable decrease in the E group was sustained through the 60minute observation period. A statistically significant difference in HR was reached between E and P notably at 3 ( p &lt;0.03), 10 ( p &lt;0.0001), 30 ( p &lt;0.0002), and 40 min ( p &lt;0.004). Conclusion: Etripamil significantly decreases the HR in PSVT prior to conversion to SR and is sustained over the 60 min observation. This finding may provide clinical benefits to patients for self-management of PSVT.

RELATIONSHIPS BETWEEN ANTI-HYPERTENSIVE DRUGS AND NOCTURIA: A SYSTEMATIC REVIEW

Objective: Nocturia frequently occurs with age in both men and women, and it is the worst symptom among the lower urinary tract symptoms which deteriorate the quality of life. The cause is an increase in urine volume at night or day and night, and a decrease in bladder capacity. Hypertension is one of the diseases to cause nocturia. However, no systematic review has been performed to collate the evidence on the relationships between antihypertensive drugs and nocturia. The objective of this systematic review is to synthesize the research evidence on relationships between antihypertensive drugs and nocturia. Design and method: A comprehensive search was conducted of the following electronic databases in English and Japanese: PubMed, MEDLINE, The Cochrane Central Register Controlled Trials (CENTRAL), NPO Japan Medical Abstracts Society's Ichushi - Web database, in March 2019. The title and abstracts of the studies were reviewed by two independent reviewers against the inclusion/exclusion criteria. The keywords were as follows: [hypertensive medications], [calcium channel blockers], [angiotensin converting enzyme inhibitors], [angiotensin receptor blockers], [diuretics], [beta blockers] AND [nocturia]. Results: 132 studies were screened (46 articles were about calcium channel blockers. 6 articles were about angiotensin converting enzyme inhibitors and angiotensin II receptor blockers. 70 articles were about diuretics. 10 articles were about beta blockers), 24 (14 retrospective studies, 8 case control studies, and 2 reviews) were included in the systematic review. Hypertensive drugs had showed close relationships with nocturia. Calcium channel blockers worsened symptoms of nocturia. Lower urinary tract symptoms(LUTS) should be evaluated before and after calcium channel blockers administration. While thiazide diuretics worsened urination symptoms, loop diuretics worsened nocturia. People without gender, the use of diuretics was significantly correlated with the number of urinations at least 3 times / night and the rate of increased urinations was especially high in women. Conclusions: Hypertension is a risk factor of nocturia. When we treat hypertensive patients with nocturia, we need to consider antihypertensive drugs may worsen the symptoms of LUTS and select drugs which can improve those symptoms.

Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension

The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to >200 countries posing a global public health concern. Patients with comorbidity, such as hypertension suffer more severe infection with elevated mortality. The development of effective antiviral drugs is in urgent need to treat COVID-19 patients. Here, we report that calcium channel blockers (CCBs), a type of antihypertensive drug that is widely used in clinics, inhibited the post-entry replication events of SARS-CoV-2 in vitro, while no in vitro anti-SARS-CoV-2 effect was observed for the two other major types of antihypertensive drugs, namely, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. CCB combined with chloroquine showed a significantly enhanced anti-SARS-CoV-2 efficacy. A retrospective clinical investigation on hospitalized COVID-19 patients with hypertension as the only comorbidity revealed that the CCB amlodipine besylate therapy was associated with a decreased case fatality rate. The results from this study suggest that CCB administration to COVID-19 patients with hypertension as the comorbidity might improve the disease outcome.

Predictors of Clopidogrel Hyper-Responsiveness in Neuro-Interventional Procedures

BackgroundHyper-responsiveness to clopidogrel abnormally inhibits platelet aggregation and increases hemorrhagic complications. The present study investigated clinical factors related to clopidogrel hyper-responsiveness in neuro-interventional procedures. MethodsTwo hundred twenty-four patients receiving clopidogrel for coil embolization to treat unruptured cerebral aneurysm or carotid artery stenting to treat carotid artery stenosis at the internal carotid artery origin were retrospectively reviewed for their P2Y12 reactivity unit (PRU) values and clinical characteristics. Hyper-responsiveness to clopidogrel was defined as a PRU of <95. ResultsThe mean PRU was 218.2 ± 77.8. Hyper-responsiveness to clopidogrel was observed in 12 patients (5.4%). Hyper-responsiveness was observed in younger patients, patients with a lower concentration of hemoglobin A1c, and patients with a higher low-density lipoprotein cholesterol (LDL-C) concentration compared with non-hyper-responsive patients (P = 0.01, P < 0.01, P < 0.01, respectively). On analysis of concomitant drugs, the patients in the hyper-responsive group were less frequently administered calcium channel blockers (CCBs) compared with the non-hyper-responsive group (P = 0.01). No significant differences in the usage of proton pump inhibitors or statins were observed. A LDL-C concentration of >120 mg/dL and no usage of CCBs were significant independent predictors of hyper-responsiveness to clopidogrel with a multivariate analysis (OR; 6.16, 95% CI, 1.57–26.64, P = 0.01, OR; 0.09, 95% CI, 0.01–0.82, P = 0.03, respectively). ConclusionThe present study shows that a higher LDL-C concentration and no usage of CCBs are independent predictors of clopidogrel hyper-responsiveness. These results are useful to predict perioperative hemorrhagic complications. Considering dose reduction of clopidogrel or alternative drugs in high risk cases is necessary to prevent perioperative hemorrhagic complications.

1421Dyskalemias in hypertensive patients treated with combination of antihypertensive drugs: a nested case-control study using Danish national registries

Abstract Aims Little is known about the occurrence of potassium disturbances in relation to combination therapy in hypertension. Using data from Danish electronic registries, we investigated the association between different combinations of antihypertensive therapy and potassium imbalances, in 22,060 individuals, between 1995–2012. Methods Using incidence density matching, two comparison patients without hypokalemia were matched to each corresponding patient with hypokalemia on age, gender, renal function, time from HTN date to date of potassium measurement. The same approach was applied to identify matches for patients with hyperkalemia. The ten most common antihypertensive drug combinations in our population were: (1) Beta-blockers + Angiotensin converting enzyme inhibitors, (2) Angiotensin converting enzyme inhibitors + Thiazides, (3) Angiotensin converting enzyme inhibitors + Thiazides + Potassium supplement, (4) Angiotensin receptor blockers + Other diuretics, (5) Beta-blockers + Angiotensin converting enzyme inhibitors + Potassium supplement (ATC: A12B), (6) Beta-blockers + Calcium channel blockers, (7) Beta-blockers + Thiazides + Potassium supplement, (8) Calcium channel blockers + Angiotensin converting enzyme inhibitors, (9) Calcium channel blockers + Thiazides + Potassium supplement, (10) Other antihypertensive drug combinations. We used conditional logistic regression analysis to examine the risk of developing hypo- and hyperkalemia in relation to different combinations of antihypertensive drugs within one year. The multivariable model was adjusted for serum sodium, malignancy, inflammatory bowel disease, diabetes, alcoholism and beta2-agonists. Results The multivariable analysis showed 10.5 times increased odds for developing hypokalemia if administered Calcium channel blockers + Thiazides + Potassium supplement (95% CI 4.97–22.06) compared to Angiotensin converting enzyme inhibitors + Beta blockers. Other drug combinations significantly associated with increased hypokalemia risk were: Angiotensin converting enzyme inhibitors + Thiazides (OR 5.01, 95% CI 2.32–10.79), Angiotensin converting enzyme inhibitors + Loop + Potassium supplement (A12B) (OR 4.03, 95% CI 1.69–9.62), Angiotensin converting enzyme inhibitors + Thiazides + Potassium supplement (OR 4.16, 95% CI 2.01–8.64) and Calcium channel blockers + Angiotensin converting enzyme inhibitors (OR 4.04, 95% CI 1.72–9.50). None of the ten groups were associated with increased odds for developing hyperkalemia in the multivariable analysis. Cumulative incidence curves for hypokale Conclusion Thiazide diuretics in combination with angiotensin converting enzyme inhibitors or calcium channel blockers were strongly associated with hypokalemia risk within one year from treatment initiation. Acknowledgement/Funding None

Azelnidipine Ameliorates Dementia in Streptozotocin Treated Rats: Interplay between Oxidative Stress and Calcium

Deregulation of brain Ca2+ homeostasis is linked with oxidative stress, mitochondrial dysfunction, neurodegeneration, loss of synaptic plasticity, and cholinergic deficits. Earlier chronic administration of calcium channel blockers (L-type CCBs) has afforded relief in Alzheimer’s disease (AD) symptoms. Azelnidipine (AZL) is a long duration L-type Ca2+ channel blocker recently included in anti-hypertensive therapy. The present study reveals the role of AZL in the management of ICV-STZ induced AD in rats. Wistar rats of either sex (aged 12–15 weeks and weight range 260–280 g) were divided into 6 groups in single blind fashion and stereotaxic surgery was performed. Streptozotocin (3 mg/kg) was injected (ICV) in five groups and one group was administered with ACSF. AZL was administered (1.5, 3 and 6 mg/kg; p.o.) to separate groups of ICV-STZ pre-treated rats for 14 successive days. Memory of rats was measured using elevated plus maze and novel object recognition task. After behavioral evaluation, the animals were sacrificed and whole brains were isolated for estimation of AChE activity, TBARS and GSH levels. ICV-STZ treatment increased the brain AChE activity, TBARS level, decreased GSH level, and thereby impaired the memory of rats. The Ca2+ antagonistic property of AZL attenuated the STZ induced derangement of biochemical parameters and resurrected the memory functions in rats. This study exhibited that long-term blockade of the L-type Ca2+ channels using azelnidipine mitigates AD type dementia owing to its neuroprotective and antioxidant properties.

Coronary Artery Vasospasm Induced by 5-fluorouracil: Proposed Mechanisms, Existing Management Options and Future Directions.

Cardiovascular disease and cancer are leading contributors to the global disease burden. As a result of cancer therapy-related cardiotoxicities, cardiovascular disease results in significant morbidity and mortality in cancer survivors and patients with active cancer. There is an unmet need for management of cardio-oncology conditions, which is predicted to reach epidemic proportions, and better understanding of their pathophysiology and treatment is urgently required. The proposed mechanisms underlying cardiotoxicity induced by 5-fluorouracil (5-FU) are vascular endothelial damage followed by thrombus formation, ischaemia secondary to coronary artery vasospasm, direct toxicity on myocardium and thrombogenicity. In patients with angina and electrocardiographic evidence of myocardial ischaemia due to chemotherapy-related coronary artery vasospasm, termination of chemotherapy and administration of calcium channel blockers or nitrates can improve ischaemic symptoms. However, coronary artery vasospasm can reoccur with 5-FU re-administration with limited effectiveness of vasodilator prophylaxis observed. While pre-existing coronary artery disease may increase the ischaemic potential of 5-FU, cardiovascular risk factors do not appear to completely predict the development of cardiac complications. Pharmacogenomic studies and genetic profiling may help predict the occurrence and streamline the treatment of 5-FU-induced coronary artery vasospasm. Echocardiographic measures such as the Tei index may help detect subclinical 5-FU cardiotoxicity. Further research is required to explore the cardioprotective effect of agents such as coenzyme complex, GLP-1 analogues and degradation inhibitors on 5-FU-induced coronary artery vasospasm.

Calcium Channel Blocker-Related Chylous Ascites: A Systematic Review and Meta-Analysis.

Background: Chylous ascites is an uncommon condition characterized by a white, milky-appearing peritoneal fluid, and is related to disruption of the lymphatic system from any cause. There have been very few previous reports of calcium channel blockers (CCBs) as potential causes of chylous ascites, and most of the patients were undergoing peritoneal dialysis. Aims: To review the pathogenesis, clinical manifestations, laboratory examinations, treatment options, and prognosis of patients with CCB-related chylous ascites. Method: A retrospective analysis was conducted for patients with CCB-related chylous ascites from publications in PubMed, EMBASE, and LILACS between January 1993 and December 2018. Results: A total of 48 cases were included. The average age at disease onset was 50.2 ± 10.9 years, with a male:female ratio of 1.5:1.0. The symptoms of abdominal distension/pain and chylous ascites were observed within 48–72 h of drug initiation and disappeared within 24 h of drug withdrawal. Rechallenge was performed in 10 patients, and all (100%) of them showed chylous effluents that disappeared within 24 h after stopping drug treatment. Conclusions: To summarize, CCB-related chylous ascites is formed of white, milky ascites/effluents that appear after administration of CCBs. Physicians must be aware of the possibility of chylous ascites when administering CCBs, particularly in patients with renal function impairment or patients with end-stage renal disease who are undergoing peritoneal dialysis.

Relationship between periodontal inflammation and calcium channel blockers induced gingival overgrowth-a cross-sectional study in a Japanese population.

Periodontal inflammation is regarded as a risk factor for drug-induced gingival overgrowth (DIGO). In order to elucidate the involvement of periodontal inflammation in DIGO, the periodontal status of subjects who do not develop DIGO despite receiving causative drugs (non-responders) needs to be examined. Therefore, the aim of the present study which was a pilot study was to assess periodontal inflammatory variables in responders (calcium channel blocker induced-GO patients), non-responders, and patients who did not receive causative drugs (non-consumers). The following parameters were measured: (1) existence of gingival overgrowth, (2) number of teeth, (3) mean periodontal pocket depth (PPD), and (4) percentage of positive sites for bleeding on probing (BOP). The periodontal inflamed surface area (PISA) and periodontal epithelial surface area (PESA) and the PISA/PESA ratio which indicated the degree of periodontal inflammation in each patient were also used to evaluate periodontal inflammation. Thirteen responders, 32 non-responders, and 83 non-consumers were included in the analyses. The mean PPD, percentage of BOP, PESA, and PISA, and the PISA/PESA ratio were significantly higher in responders than in non-responders and non-consumers (p < 0.01). The BOP, PISA, and PISA/PESA ratio were significantly lower in non-responders than in non-consumers (p < 0.05). A positive correlation was found between PPD and age in non-consumers. On the other hand, a negative correlation was noted between PPD and age in non-responders. Periodontal inflammation may be associated with the initiation of DIGO. It could be speculated that periodontal therapy before the administration of calcium channel blockers may prevent the development of gingival overgrowth.