Use Of Calcium Channel Blockers Research Articles

Potential drug-drug interactions in drug therapy for older adults with chronic coronary syndrome at hospital discharge: A real-world study.

Introduction: Polypharmacy are commonly observed among older adults with cardiovascular disease. However, multiple medications lead to increased risk of drug-drug interactions (DDIs). Therefore, identification and prevention actions related to harmful DDIs are expected in older adults. The study aimed to describe the prevalence of potential DDIs (pDDIs) in discharge prescriptions among older adults with chronic coronary syndrome (CCS). Methods: A single-center cross-sectional study was performed in a tertiary public hospital in Beijing, China. CCS patients aged 65 years and above who were admitted to cardiology wards over a 3-month period and alive at discharge were included. Electronic medical records and discharge prescriptions were reviewed. pDDIs were evaluated through the Lexi-Interact online. Results: pDDIs were identified in 72.9% of the 402 individuals (n = 293). A total of 864 pDDIs were obtained. 72.1% of patients were found with C DDIs (n = 290) and 20.3% were categorized in D and X DDIs (n = 82). The only X DDI was between cyclosporine and atorvastatin. Under category D, glycemia alterations within antidiabetics and increased chances of bleeding with antithrombotic were the most common. Concomitant use of clopidogrel and calcium channel blockers was a frequent situation within category C, followed by synergic blood pressure lowering agents and increased rosuvastatin concentration induced by clopidogrel. Conclusion: DDIs exposure was common in older CCS. DDIs screening tools should be introduced to alert potential adverse effects. Prescribers need to rigorously review or modulate therapies to prevent DDI-related adverse outcomes. Clinical pharmacists should be more involved in complex drug regimen management.

Delayed cerebral ischemia and therapeutic approaches after subarachnoid hemorrhage

Delayed cerebral ischemia after subarachnoid hemorrhage is one of the most important causes of mortality and poor functional outcome in patients. Initially, the etiology and treatment of delayed cerebral ischemia focused primarily on cerebral vasospasm. However, recent studies have detected that depolarization, microcirculation, and autoregulation disorder, which spreads together with cerebral vasospasm, also play a role in the etiology. The main treatment strategies in the prevention and treatment of delayed cerebral ischemia are the regulation of blood pressure and the use of calcium channel blockers, especially nimodipine. The main step in the early diagnosis and treatment of the disease is to monitor the neurological clinical status. In addition to transcranial Doppler ultrasonography, computed tomography, or magnetic resonance imaging angiography, continuous electroencephalography and invasive brain multimodal examination may be required in the follow-up period of the disease. In addition to blood pressure regulation, optimization of cardiac output, endovascular interventions, angioplasty, and/or intra-arterial vasodilator infusion are other treatment methods. This review aimed to evaluate delayed cerebral ischemia, one of the most important complications of subarachnoid hemorrhage, in the light of current literature.

Calcium channel antagonists interfere with the mechanism of action of elastin-derived peptide VGVAPG in mouse cortical astrocytes in vitro

Elastin-derived peptides (EDPs) contain replications of the Val-Gly-Val-Ala-Pro-Gly (VGVAPG) hexapeptide. It has been described that the VGVAPG peptide induces reactive oxygen species (ROS) production in murine monocytes and astrocytes, human fibroblasts, and the human neuroblastoma (SH-SY5Y) cell line. To date, there is growing evidence that calcium channel blockers (CCBs) reduce oxidative stress and development of inflammation in the nervous system. Therefore, the aim of the present study was to evaluate the impact of such CCBs as Nifedipine, Verapamil, and MK-801 on the expression of peroxisome proliferator-activated receptor (Pparγ), i.e. ROS-related and inflammation-related proteins, in mouse astrocytes exposed in vitro to the VGVAPG peptide. The experiments showed that Nifedipine or MK-801 used in co-treatment with the VGVAPG peptide potentiated the effect of this peptide on the Pparγ level after the 24-h and 48-h treatment. Moreover, all studied compounds decreased the VGVAPG-induced caspase-1 activity in both time intervals. The data also showed that the VGVAPG peptide decreased the interleukin 1 beta (IL-1β) level in both studied time intervals. Upon a short-time exposure, the use of CCBs intensified the decrease in IL-1β stimulated by the VGVAPG peptide, opposite to the longer treatment. Moreover, the VGVAPG peptide decreased the IL-1βR1 level in both studied time intervals. After 24 h, Nifedipine and Verapamil potentiated the effect of the VGVAPG peptide. The VGVAPG peptide decreased the catalase (Cat) protein expression only after 24 h, whereas CCBs did not affect the expression of Cat induced by the VGVAPG peptide. The VGVAPG peptide increased the expression of the superoxide dismutase 1 (Sod1) protein. After 24 h of exposure, Nifedipine and Verapamil potentiated the increase in the Sod1 protein expression. Finally, our data showed that VGVAPG did not change the level of estradiol (E2) in the astrocytes. Interestingly, Nifedipine and Verapamil in co-treatment with VGVAPG increased the E2 level. Summarizing, it can be assumed that increased amounts of the VGVAPG during lifetime can play a certain role in calcium channel functioning in neurodegenerative diseases.

Iloprost Duration for Digital Ulcers in Systemic Sclerosis: French Retrospective Study at Two Centers and Literature Review.

ObjectiveIschemic digital ulcers (DUs) are frequent and severe complications of systemic sclerosis (SSc). Treatment options for SSc-related digital vasculopathy are based on aggressive vasodilation, with the objective to improve blood flow in ischemic areas. Intravenous prostanoids are recommended to treat active DUs. However, the level of evidence for the duration of 5 days is low. Therefore, the aim of this study was to determine whether prolonging the infusion beyond 5 days increases the rate of healing of active DUs in SSc.MethodsThis is an observational longitudinal retrospective bicenter study from 2000 to 2017. The objective was to compare the healing rate and time (defined by a healing of at least 50% of DUs) between two durations of iloprost administration: 5 days or less, or more than 5 days.ResultsForty-one patients, with a mean age of 47 ± 15 years at diagnosis and 32 (78%) females have been included. Systemic sclerosis was diffuse in 10 (24%) cases and 13 (32%) had an interstitial lung disease. A total of 243 iloprost infusions for DUs were performed: 140 infusions for 5 days or less, and 103 infusions for more than 5 days (prolonged duration). Patients with active DUs which received >5 days of iloprost had higher modified Rodnan skin scale at the time of iloprost infusion (median 33 vs. 15; p < 0.05), more interstitial lung disease (44 vs. 27%; p < 0.05), more anti-topoisomerase I antibody positivity (59 vs. 44%; p < 0.05), and received more previous cyclophosphamide therapy (48 vs. 19%; p < 0.05). While the number of active DUs before iloprost infusion was not significantly different among those who received ≤5 days and >5 days of iloprost, the time to healing after iloprost infusion significantly decreased in SSc patients who received >5 days iloprost infusion: 48 [7–392] vs. 91 [9–365] days (p < 0.05). The proportion of SSc patients with healed DUs tended to increase in patients with >5 days iloprost infusion (log rank = 0.06). The number of patients with complete DU healing at day 90 was significantly increased in SSc who received >5 days of iloprost: 53 (51%) vs. 52 (37%) (p < 0.05). In addition, the time to healing was not significantly associated with the use of calcium channel blockers, endothelin receptor antagonists or a combination of PDE-5 inhibitors.ConclusionProlonging duration of iloprost >5 days could improve the healing rate and the time to healing of SSc-related DUs. Prospective randomized studies are needed to confirm these data and define the optimal duration of iloprost therapy.

Calcium Channel Blockers Induced Gingival Overgrowth: A Comprehensive Review from a Dental Perspective.

ABSTRACTBackground:Gingival overgrowth (GO) as a manifestation of calcium channel blockers (CCBs) was first introduced in the literature by Ramon et al. in 1984. Since then, the use of CCBs as a treatment modality for hypertension has been recorded extensively in the literature for its association with GO. Aim:The aim of our study is to evaluate histopathology, treatment, and follow-up for the cases detailed in various studies and also to highlight the protocol mentioned to identify these presentations.Materials and Methods:A broad search was conducted from the period 1980 to 2021 using electronic databases PubMed Central, Scopus, Cochrane, and SciELO databases. About 293 articles were initially chosen. The articles further excluded did not fit the criteria for the study and eventually 50 articles which met the inclusion criteria were chosen as part of this literature review.Results:A comparative analysis was carried out regarding histopathology, treatment modalities, drug dosage, and duration to evaluate the differences in cases between 1980 and 2021. From the available studies, it was found that the histopathological and clinical findings were varied. Treatment strategies employed were different, though follow-ups in most cases were uniform.Conclusion:CCBs and their relationship with GO have been widely reported in the literature. Dentists should approach this condition by taking appropriate medical and dental history and follow evidence-based treatment guidelines to provide more relevant and judicious management of this condition. Inter-disciplinary treatment approaches would provide better outcomes.

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

BackgroundImproved 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. MethodsIndividuals 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. ResultsUse 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). LimitationsDue to the observational nature of this study, causation cannot be confirmed. ConclusionsDihydropyridines and diltiazem were associated with a decreased risk of psychiatric hospitalization in bipolar disorder. Results for allopurinol and dipyridamole were inconclusive.

ANTIHYPERTENSIVE TREATMENT INITIATION IN FRANCE: WHAT DID GENERAL PRACTITIONERS PRESCRIBE IN 2021?

Objective: Hypertension (HT) is the leading reason for visits to general practitioners (GPs). The diagnosis of HT and the decision to initiate drug treatment form an integral part of their natural field of practice. The recent national and international guidelines have made proposals that are specifically dedicated to this sequence of care. The objective of this study is to analyse the prescribing behaviours of GPs when initiating treatment for patients newly diagnosed with hypertension. Design and method: Data from the IQVIA Longitudinal Patient Database (LPD) France were used. LPD France is a permanent observatory to which a nationally representative panel of physicians – including GPs (n = 1200) – contribute anonymised electronic medical records (EMR). This analysis included all antihypertensive drug prescriptions made by the GPs from July 2020 to June 2021, which were then extrapolated to the entire population of mainland France. Initiation was defined by the establishment of an antihypertensive treatment for a patient already registered with the GP and who was receiving antihypertensive treatment for the first time in 24 months. Results: Over the 12-month period analysed, 869 283 patients had received an initial antihypertensive drug prescription following consultation with a GP. Monotherapy was prescribed in 71.5% of cases (versus 67.3% the previous year) and dual therapy in 21.5% of cases (versus 23.2% the previous year). Fixed-dose combinations accounted for 62% of the dual therapies. The therapeu tic classes of the prescribed monotherapies were distributed as follows: Conclusions: These findings reveal prescriptions that appeared to be consistent with the latest guidelines in which the first-line use of renin-angiotensin system blockers and calcium channel blockers is preferred. It is also interesting to note that treatment initiation with dual therapies was much less common, with a use rate of fixed-dose combinations slightly higher than that of the free-dose combinations. *IQVIA EMR LPD Médecins Généralistes / Cardiologues Libéraux’. EMR = Electronic Medical Records, LPD = Longitudinal Patient Data

Reno protective role of amlodipine in patients with hypertensive chronic kidney disease.

Chronic kidney disease (CKD) and hypertension (HTN) are closely associated with an overlapping and intermingled cause and effect relationship. Decline in renal functions are usually associated with a rise in blood pressure (BP), and prolonged elevations in BP hasten the progression of kidney function decline. Regulation of HTN by normalizing the BP in an individual, thereby slowing the progression of kidney disease and reducing the risk of cardiovascular disease, can be effectively achieved by the anti-hypertensive use of calcium channel blockers (CCBs). Use of dihydropyridine CCBs such as amlodipine (ALM) in patients with CKD is an attractive option not only for controlling BP but also for safely improving patient outcomes. Vast clinical experiences with its use as monotherapy and/or in combination with other anti-hypertensives in varied conditions have demonstrated its superior qualities in effectively managing HTN in patients with CKD with minimal adverse effects. In comparison to other counterparts, ALM displays robust reduction in risk of cardiovascular endpoints, particularly stroke, and in patients with renal impairment. ALM with its longer half-life displays effective BP control over 24-h, thereby reducing the progression of end-stage-renal disease. In conclusion, compared to other classes of CCBs, ALM is an attractive choice for effectively managing HTN in CKD patients and improving the overall quality of life.

Sex-Based Difference in the Effect of Metoprolol on Heart Rate and Bradycardia in a Population-Based Setting.

Background: Metoprolol, a beta-blocker, is used to reduce the heart rate. Although it has been demonstrated that the metoprolol plasma concentration is higher in women than in men, the same dose is recommended. In this study, we investigated whether the metoprolol concentration was associated with a stronger heart-rate reduction and bradycardia in women than in men. Methods: This study is part of the Rotterdam Study (RS), a population-based prospective cohort study. Blood samples from a random subset of 2000 participants were used to assess metoprolol plasma levels. An analysis of heart rate (beats per minute, bpm) and bradycardia (<60 bpm) was performed in metoprolol users with an ECG at the day of blood collection to study sex-specific differences in heart rate and the risk of bradycardia. Results: In total, 40 women and 39 men were included. There was a statistically significant association between metoprolol concentration and heart rate in women (p-value: 0.014) but not in men (p-value: 0.639). Furthermore, women in the highest concentration group had a more than 15-times-higher risk of bradycardia than women in the lowest concentration group (OR = 15.6; 95% CI = 1.1, 217.3); however, this was not seen in men (OR = 1.3; 95% CI = 0.1, 12.4). After adjustment for age, BMI, time between blood sample and ECG, hypertension, myocardial infarction, heart failure, atrial fibrillation, digoxin use, and calcium channel blocker use, the association between concentration and bradycardia in women remained statistically significant. Conclusions: Women, but not men, had a statistically significantly lower heart rate at higher metoprolol plasma concentration and a statistically significantly increased risk of bradycardia.

Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension.

AimsSeveral observational studies have examined the potential protective effect of angiotensin‐converting enzyme inhibitor (ACE‐I) use on the risk of age‐related macular degeneration (AMD) and have reported contradictory results owing to confounding and time‐related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE‐I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK.MethodsIn this study, 53 832 and 43 106 new users of ACE‐I and CCB were included between 1995 and 2019, respectively. In an on‐treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow‐up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE‐I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD.ResultsDuring a median follow‐up of 2 years (interquartile range 1–5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2–2.6) and 2.2 (2.0–2.4) per 1000 person‐years among the weighted new users of ACE‐I and CCB, respectively. There was no association of ACE‐I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on‐treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90–1.27] and 0.87 [0.71–1.07], respectively).ConclusionWe found no evidence that the use of ACE‐I is associated with risk of AMD in patients with hypertension.

Calcium Channel Blocker Use and the Risk for Breast Cancer: A Population-Based Nested Case-Control Study.

Simple SummaryCalcium channel blockers (CCBs) are widely used among hypertension and heart disease patients. These drugs are effective and well-tolerated. Some studies have found that patients who used CCBs have a higher incidence of breast cancer (BCa). However, other studies did not find such an association. We investigate whether exposure to CCBs in patients with hypertension is associated with an increased risk of BCa. From a cohort of patients prescribed their first antihypertensive medication between 2000 and 2016, we detected 4875 BCa cases. For each case, we matched ten patients without BCa (controls). We found no association between CCB users and an increased risk of BCa compared to the use of other antihypertensive medications. There was no increase in risk even with longer exposure to CCBs (above eight years) and high doses. Considering that CCBs are a widely used antihypertensive drug class, our results provide important safety information on a population level, especially for patients with increased BCa risk.We investigated whether long-term exposure to calcium channel blockers (CCBs) is associated with an increased risk of breast cancer (BCa). We designed a nested case–control study based on data from the Clalit electronic database, the largest Israeli Health Services organization. All newly diagnosed breast cancer (BCa) cases were selected from a cohort of patients with hypertension. Ten controls were matched for each BCa case. The odds ratios (ORs) of BCa among CCBs users were calculated using multivariate conditional logistic regression analyses. A total of 4875 patients with newly diagnosed BCa were identified from the cohort with a median follow-up of 5.15 years. The exposure to CCBs was not associated with an increased risk of BCa (OR = 0.98; 95% CI, 0.92–1.04). Additionally, there was no association between long-term exposure to CCBs (above eight years) and increased BCa risk (OR = 0.91; 95% CI, 0.67–1.21). Higher cumulative doses of CCBs were not associated with an elevated risk of BCa (OR = 0.997; 95% CI, 0.962–1.034, calculated per 1000 DDD). Based on this large population-based study, long-term exposure to CCBs was not associated with an increased risk of BCa. Considering that CCBs are widely used medications, our results provide important safety information on a population level, especially for patients with an increased risk of BCa.

Effect of Antihypertensives by Class on Cerebral Small Vessel Disease: A Post Hoc Analysis of SPRINT-MIND.

Treatment of uncontrolled arterial hypertension reduces the risk of cerebral small vessel disease (CSVD) progression, although it is unclear whether this reduction occurs due to blood pressure control or class-specific pleiotropic effects, such as improved beat-to-beat arterial pressure variability with calcium channel blockers. The goal of this study was to investigate the influence of antihypertensive medication class, particularly with calcium channel blocker, on accumulation of white matter hyperintensities (WMH), a radiographic marker of CSVD, within a cohort with well-controlled hypertension. We completed an observational cohort analysis of the SPRINT-MIND trial (Systolic Blood Pressure Trial Memory and Cognition in Decreased Hypertension), a large randomized controlled trial of participants who completed a baseline and 4-year follow-up brain magnetic resonance image with volumetric WMH data. Antihypertensive medication data were recorded at follow-up visits between the magnetic resonance images. A percentage of follow-up time participants were prescribed each of the 11 classes of antihypertensive was then derived. Progression of CSVD was calculated as the difference in WMH volume between 2 scans and, to address skew, dichotomized into a top tertile of the distribution compared with the remaining. Among 448 individuals, vascular risk profiles were similar across WMH progression subgroups except age (70.1±7.9 versus 65.7±7.3 years; P<0.001) and systolic blood pressure (128.3±11.0 versus 126.2±9.4 mm Hg; P=0.039). Seventy-two (48.3%) of the top tertile cohort and 177 (59.2%) of the remaining cohort were in the intensive blood pressure arm. Those within the top tertile of progression had a mean WMH progression of 4.7±4.3 mL compared with 0.13±1.0 mL (P<0.001). Use of angiotensin-converting enzyme inhibitors (odds ratio, 0.36 [95% CI, 0.16-0.79]; P=0.011) and dihydropyridine calcium channel blockers (odds ratio, 0.39 [95% CI, 0.19-0.80]; P=0.011) was associated with less WMH progression, although dihydropyridine calcium channel blockers lost significance when WMH was treated as a continuous variable. Among participants of SPRINT-MIND trial, angiotensin-converting enzyme inhibitor was most consistently associated with less WMH progression independent of blood pressure control and age.

National Trends in Antihypertensive Treatment Among Older Adults by Race and Presence of Comorbidity, 2008 to 2017.

In 2014, hypertension guidelines for older adults endorsed increased use of fixed-dose combinations, prioritized thiazide diuretics and calcium channel blockers (CCBs) for Black patients, and no longer recommend beta-blockers as first-line therapy. To evaluate older adults' antihypertensive use following guideline changes. Time series analysis. Twenty percent national sample of Medicare Part D beneficiaries aged 66 years and older with hypertension. Eighth Joint National Committee (JNC8) guidelines MAIN MEASURES: Quarterly trends in prevalent and initial antihypertensive use were examined before (2008 to 2013) and after (2014 to 2017) JNC8. Analyses were conducted among all beneficiaries with hypertension, beneficiaries without chronic conditions that might influence antihypertensive selection (hypertension-only cohort), and among Black patients, given race-based guideline recommendations. The number of beneficiaries with hypertension increased from 1,978,494 in 2008 to 2,809,680 in 2017, the proportions using antihypertensives increased from 80.3 to 81.2%, and the proportion using multiple classes and fixed-dose combinations declined (60.8 to 58.1% and 20.7 to 15.1%, respectively, all P<.01). Prior to JNC8, the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and CCBs was increasing. Use of CCBs as initial therapy increased more rapidly following JNC8 (relative change in quarterly trend 0.15% [95% CI, 0.13-0.18%), especially among Black beneficiaries (relative change 0.44% [95% CI, 0.21-0.68%]). Contrary to guidelines, the use of thiazides and combinations as initial therapy consistently decreased in the hypertension-only cohort (13.8 to 8.3% and 25.1 to 15.7% respectively). By 2017, 65.9% of Black patients in the hypertension-only cohort were initiated on recommended first-line or combination therapy compared to 80.3% of non-Black patients. Many older adults, particularly Black patients, continue to be initiated on antihypertensive classes not recommended as first-line, indicating opportunities to improve the effectiveness and equity of hypertension care and potentially reduce antihypertensive regimen complexity.

Blood Pressure Control Among Non-Hispanic Black Adults Is Lower Than Non-Hispanic White Adults Despite Similar Treatment With Antihypertensive Medication: NHANES 2013-2018.

BACKGROUNDControlled blood pressure can prevent or reduce adverse health outcomes. Social and structural determinants may contribute to the disparity that despite equivalent proportions on antihypertensive medication, non-Hispanic Black (Black) adults have lower blood pressure control and more cardiovascular events than non-Hispanic White (White) adults.METHODSData from 2013 to 2018 National Health and Nutrition Examination Survey were pooled to assess control among Black and White adults by antihypertensive medication use and selected characteristics using the 2017 American College of Cardiology/American Heart Association (ACC/AHA) Blood Pressure Guideline definition (systolic blood pressure <130 mm Hg and diastolic blood pressure <80 mm Hg) among 4,739 adults.RESULTSAmong those treated with antihypertensive medication, an estimated 34.9% of Black and 45.0% of White adults had controlled blood pressure. Control was lower for Black and White adults among most subgroups of age, sex, education, insurance status, usual source of care, and poverty–income ratio. Black adults had higher use of diuretics (28.5%—Black adults vs. 23.5%—White adults) and calcium channel blockers (24.2%—Black adults vs. 14.7%—White adults) compared with White adults. Control among Black adults was lower than White adults across all medication classes including diuretics (36.1%—Black adults vs. 47.3%—White adults), calcium channel blockers (30.2%—Black adults vs. 40.1%—White adults), and number of medication classes used.CONCLUSIONSSuboptimal blood pressure control rates and disparities warrant increased efforts to improve control, which could include addressing social and structural determinants along with emphasizing implementation of the 2017 ACC/AHA Blood Pressure Guideline into clinical practice.

Combined Use of Calcium-channel Blockers With Ombitasvir/Paritaprevir/Ritonavir Exacerbates Peripheral Edema in Elderly Japanese Patients

The antiviral agent ritonavir is a substrate for cytochrome P450 3A4 (CYP3A4); therefore, concomitant use of CYP3A4-metabolising drugs might cause adverse reactions to this drug. We investigated the plasma level of calcium channel blockers (CCBs) as CYP3A4 substrates and peripheral edema as a potential adverse drug reaction possibly caused by the anti-hepatitis C virus (HCV) regimen of ombitasvir/paritaprevir/ritonavir (OPR) and CCBs. We enrolled Japanese patients prescribed OPR for HCV infection. Peripheral edema was graded according to the Common Terminology Criteria for Adverse Events ver. 4. Plasma samples were collected on days 0, 7, 14, 28, and 42 after antiviral treatment, at the trough level. Out of 52 patients, 64% experienced grade 1 or grade 2 peripheral edema, but not grade 3. Concomitant use of CCBs significantly increased the emergence of grade 2 edema (62%), compared with patients treated solely with OPR (48%). The use of OPR significantly increased the plasma concentration of amlodipine. Peripheral edema in patients treated with OPR and CCBs, although tolerable, should be closely monitored.

Gastrointestinal symptom severity and progression in systemic sclerosis.

To evaluate the severity and evolution of patient-reported gastrointestinal tract (GIT) symptoms in systemic sclerosis (SSc) patients, assess predictive factors for progression and determine the impact of standard of care treatment. SSc patients from the Leiden and Oslo cohorts were included. We assessed clinical data and patient-reported GIT symptoms measured by the validated University of California, Los-Angeles Gastrointestinal-tract (UCLA-GIT) score at baseline and annually. GIT severity and progression was determined. Logistic regression was applied to identify risk factors associated with baseline GIT symptom severity. Linear mixed-effect models were applied to assess progression in GIT symptom burden and to identify predictive factors. We repeated all analysis in patients with early disease (inception cohort) to exclude the effect of longstanding disease and increase insights in development of GIT symptom burden early in the disease course. We included 834 SSc patients with baseline UCLA GIT scores, 454 from Leiden and 380 from Oslo. In the total cohort, 28% reported moderate-severe GIT symptoms at baseline, with increased risk for severity conferred by ACA, smoking and corticosteroid use, while use of calcium channel blockers appeared protective. In the inception cohort, 23% reported moderate-severe GIT symptoms at baseline, with increased risk for females and with smoking. Over time, symptom burden increased mainly for reflux/bloating. Female sex and ACA predicted GIT symptom progression. High GIT symptom burden is present early in SSc disease course. Both for prevalence and for progression of GIT symptom burden, female sex and smoking were identified as risk factors.

Association between dihydropyridine calcium channel blockers and ischemic strokes in patients with nonvalvular atrial fibrillation.

Outside of clinical trials, the prophylactic effect of dihydropyridine calcium channel blockers (CCBs) on ischemic events in patients with nonvalvular atrial fibrillation (NVAF) has not been confirmed. We compared the effect of dihydropyridine CCBs on ischemic events in anticoagulated NVAF patients. We conducted a multicenter historical cohort study at 71 centers in Japan. The inclusion criterion was taking vitamin K antagonists for NVAF. The exclusion criteria were mechanical heart valves and a history of pulmonary thrombosis or deep vein thrombosis. Consecutive patients (N = 7826) were registered in February 2013 and were followed until February 2017. The primary outcomes were ischemic events and ischemic strokes; the secondary outcomes were all-cause mortality, major bleeding, and hemorrhagic strokes. The mean patient age was 73 years old, and 67% of the patients were male. Seventy-eight percent of the patients had hypertension, and dihydropyridine CCBs were used by 2693 (34%) patients (CCB group). The cumulative incidences of ischemic events and ischemic strokes at 4 years in the CCB and No-CCB groups were 5.9% vs. 5.2% and 5.6% vs. 4.8%, respectively. The adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of the CCB group for ischemic events and ischemic strokes were 1.22 (0.95-1.57) and 1.32 (1.02-1.71), respectively; the adjusted HRs (95% CIs) of the CCB group for all-cause mortality, major bleeding, and hemorrhagic strokes were 0.85 (0.69-1.04), 1.12 (0.92-1.35), and 1.08 (0.62-1.88), respectively. Dihydropyridine CCB use by anticoagulated NVAF patients significantly increased ischemic strokes in a real-world setting.

Assessing the role of blood pressure in amyotrophic lateral sclerosis: a Mendelian randomization study

BackgroundObservational studies have suggested a close but controversial relationship between blood pressure (BP) and amyotrophic lateral sclerosis (ALS). It remains unclear whether this association is causal. The authors employed a bidirectional two-sample Mendelian randomization (MR) approach to evaluate the causal relationship between BP and ALS. Genetic proxies for systolic blood pressure (SBP), diastolic blood pressure (DBP), antihypertensive drugs (AHDs), ALS, and their corresponding genome-wide association study (GWAS) summary datasets were obtained from the most recent studies with the largest sample sizes. The inverse variance weighted (IVW) method was adopted as the main approach to examine the effect of BP on ALS and four other MR methods were used for sensitivity analyses. To exclude the interference between SBP and DBP, a multivariable MR approach was used.ResultsWe found that genetically determined increased DBP was a protective factor for ALS (OR = 0.978, 95% CI 0.960–0.996, P = 0.017) and that increased SBP was an independent risk factor for ALS (OR = 1.014, 95% CI 1.003–1.025, P = 0.015), which is supported by sensitivity analyses. The use of calcium channel blocker (CCB) showed a causal relationship with ALS (OR = 0.985, 95% CI 0.971–1.000, P = 0.049). No evidence was revealed that ALS caused changes in BP.ConclusionsThis study provides genetic support for a causal effect of BP and ALS that increased DBP has a protective effect on ALS, and increased SBP is a risk factor for ALS, which may be related to sympathetic excitability. Blood pressure management is essential in ALS, and CCB may be a promising candidate.

Evaluating the efficacy and safety of calcium channel blockers as adjunctive analgesics to opioid therapy: a literature review

AbstractCalcium channel blockers have been postulated as opioid adjuncts, due to their complementary mechanism of action, which may reduce pain signal transduction. The purpose of this study was to conduct a literature review regarding the safety and efficacy of calcium channel blockers alongside opioids in pain management. From August 2020 to January 2021, PubMed, Scopus, and ProQuest were searched using the following terminology: calcium channel blocker OR verapamil OR diltiazem OR amlodipine OR nicardipine OR nimodipine OR nifedipine AND analgesia. Studies included were those with adult human subjects that had reported efficacy and safety outcomes for calcium channel blocker use as opioid adjuncts. Exclusion criteria for the analysis were articles including pregnant patients, those not readily translatable to English and those detailing the use of calcium channel blockers for an alternative diagnosis or indication. Ten studies were included in this review. Five were randomised controlled trials, one involving verapamil, one addressing diltiazem, one including nifedipine and three examining nimodipine. A sixth clinical trial involving verapamil, diltiazem and nimodipine was reviewed. The seventh and final clinical trial included nimodipine or nifedipine use during aorto‐coronary bypass surgery. One conclusive study addressed nimodipine’s use in cancer patients treated with morphine and the other nifedipine’s morphine adjunct potential postoperatively. Currently, there is insufficient data to support the use of calcium channel blockers as adjuncts to opioid therapy in pain management. When compared, the studies came to varying conclusions and demonstrated conflicting data indicating the need for more research regarding this topic.

Evaluation of a Beta-Blocker-Edema-Loop Diuretic Prescribing Cascade: A Prescription Sequence Symmetry Analysis.

Drug-related adverse events associated with antihypertensive therapy may result in subsequent prescribing of other potentially harmful medications, known as prescribing cascades. The aim of this study was to assess the magnitude and characteristics of a beta-blocker-edema-loop diuretic prescribing cascade. A prescription sequence symmetry analysis was used to assess loop diuretic initiation before and after initiation of beta-blockers among patients 20 years or older without heart failure, atrial fibrillation, other arrythmias, or use of calcium channel blocker within a U.S. private insurance claims database (2005-2018). The temporality of loop diuretic initiation relative to a beta-blocker or negative control (renin-angiotensin system blocker) initiation was tabulated. Secular trend-adjusted sequence ratios (aSRs) with 95% confidence intervals (CIs) compared the initiation of loop diuretic 90 days before and after initiation of beta-blockers. Among 988,675 beta-blocker initiators, 9,489 patients initiated a new loop diuretic prescription 90 days after and 5,245 patients before beta-blocker initiation, resulting in an aSR of 1.78 (95% CI, 1.72-1.84). An estimated 1.72 beta-blocker initiators per 100 patient-years experienced the prescribing cascade in the first 90 days. The aSR was disproportionately higher among older adults (aSR 1.97), men (aSR 2.25), and patients who initiated metoprolol tartrate (aSR 2.48), labetalol (aSR 2.18), or metoprolol succinate (aSR 2.11). Negative control results (aSR 1.09, 95% CI, 1.05-1.13) generally corroborated our findings, but suggested modest within-person time-varying confounding. We observed excess use of loop diuretics following beta-blocker initiation that was only partially explained by secular trends or hypertension progression.