Changes in the Use of Hydrochlorothiazide and Other Antihypertensive Drugs in Switzerland in Association With the Swissmedic Safety Alert Regarding Non-melanoma Skin Cancer: An Interrupted Time-Series Analysis Using Swiss Claims Data.

PURPOSE: Long-term use of hydrochlorothiazide increases the risk of non-melanoma skin cancer. We aimed to evaluate potential changes in the use of hydrochlorothiazide in Switzerland after a direct healthcare professional communication (DHPC) in November 2018 by Swissmedic. METHODS: We performed interrupted time-series analyses using a large Swiss healthcare claims database (2015-2021). Within monthly intervals, we quantified the total number of claims and the total dispensed 'defined daily doses' (DDD) for preparations containing (1) hydrochlorothiazide, (2) angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II-receptor blockers (ARB), (3) calcium-channel blockers (CCB) and (4) thiazide-like diuretics per 10 000 persons. Using segmented linear regression, we quantified the pre-DHPC trend, the immediate change and the post-DHPC change in trend for total claims and DDD for the four drug classes weighted for the demographic distribution of the Swiss population. RESULTS: ACE inhibitors and ARB were the most frequently claimed antihypertensive drugs with 300-400 claims per 10 000 persons, which increased by 5.4% during the study period. The average number of hydrochlorothiazide claims (157/10 000 persons in 2015) declined by 35% between 2015 and 2021. The decrease started prior to the DHPC, but the DHPC was associated with an immediate 6.1% decline and an accelerated decline in claims over time after the DHPC (similar results for DDD). This coincided with a 23% increase in claims of CCB (dihydropyridine type) over 7 years, whereas use of other antihypertensives increased less. CONCLUSION: Our results suggest that the DHPC by Swissmedic in 2018 accelerated a pre-existing decline in the use of hydrochlorothiazide in Switzerland.

The first description of mucous membrane pemphigoid induced by enalapril maleate: a case report.

BACKGROUND: Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease (AIBD). Some reports suggest that it has a drug-related pathogenesis especially anti-hypertensive drug. CASE PRESENTATION: A 67-year-old man with a 7-year history of essential hypertension was prescribed enalapril maleate for 5 months. He presented at our department with pain, ulcers, and blisters on the oral mucosa. We performed clinical, histopathology, and direct immunofluorescence examinations, and findings were consistent with the diagnostic criteria for MMP. Consequently, we consulted with the cardiovascular physician and agreed to discontinue the enalapril maleate replacing it with irbesartan/hydrochlorothiazide tablets and topical corticosteroid therapies instead. The lesions healed without recurrence. CONCLUSIONS: ABID induced by antihypertensive drugs have been reported, and enalapril maleate has been implicated as an antihypertensive agent that may trigger AIBDs, such as MMP. This case highlights the potential relationship between antihypertensive drugs and MMP, of which clinicians should be aware to accurately diagnose and promptly relieve patients' pain.

[Beta-blockers and hypertension : an old actor returns to the stage]. / Bêtabloquants et hypertension artérielle : retour sur scène d'un vieil acteur.

For decades beta-blockers are a heterogenous group of drugs with diverse pharmacological properties, used in the treatment of high blood pressure. However, their benefit as therapy for hypertension without concomitant compelling indications is controversial. In this article we will discuss the concept of sympathetic overdrive and the theoretical rationale of the use of beta-blockers as antihypertensive drugs. The differences between beta-blockers' generations in terms of anti-hypertensive efficacy and side effects are discussed. Finally, we review the position of the last European guidelines published in 2023 about beta-blockers in the management of arterial hypertension.

Depuis des décennies, les bêtabloquants (BB) sont une gamme hétérogène de médicaments aux propriétés pharmacologiques diverses, utilisés dans le traitement de l'hypertension artérielle (HTA). Cependant, leur bénéfice, en tant que traitement de l'HTA en l'absence d'autre indication absolue à leur emploi, est controversé. Dans cet article, nous abordons le concept d'hyperactivité sympathique et la justification théorique de l'utilisation des BB comme médicaments antihypertenseurs. Les différences entre les générations de BB en termes d'efficacité antihypertensive et d'effets secondaires sont abordées. Enfin, nous revenons sur la position des dernières recommandations européennes publiées en 2023 sur les BB dans la prise en charge de l'hypertension artérielle.

Adverse social determinants of health elevate uncontrolled hypertension risk: a cardio-oncology prospective cohort study.

The role of social determinants of health (SDOH) in controlling hypertension (HTN) in cancer patients is unknown. We hypothesize that high SDOH scores correlate with uncontrolled HTN in hypertensive cancer patients. In our prospective study, patients completed the Protocol for Responding to & Assessing Patients' Assets, Risks & Experiences questionnaire. After integrating home and clinic blood pressure readings, uncontrolled HTN was defined as systolic blood pressure greater than or equal to 140 mm Hg and/or diastolic blood pressure greater than or equal to 90 mm Hg. Using Cox regression, we analyzed the impact of SDOH on HTN control, adjusting for relevant factors. The study involved 318 participants (median age 66.4, median follow-up 166 days, SDOH score 6.5 ± 3.2), with stress, educational insecurity, and social isolation as prevalent adverse SDOH. High SDOH scores led to 77% increased risk of uncontrolled HTN (adjusted hazards ratio = 1.77; 95% confidence interval = 1.10 to 2.83, P = .018). Urban residents with high SDOH scores were at an even greater risk. Identifying SDOH and mitigating underlying factors may help control HTN, the most typical disease process treated in all cardio-oncology clinics.

Prostaglandin analogues signal detection by data mining in the FDA Adverse Event Reporting System database.

OBJECTIVE: This study aims to identify safety signals of ophthalmic prostaglandin analogues through data mining the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: A data mining search by proportional reporting ratio, reporting OR, Bayesian confidence propagation neural network, information component 0.25 and χ2 for safety signals detection was conducted to the FAERS database for the following ophthalmic medications: latanoprost, travoprost, tafluprost and bimatoprost. RESULTS: 12 preferred terms were statistically associated: diabetes mellitus, n=2; hypoacusis, n=2; malignant mediastinal neoplasm, n=1; blood immunoglobulin E increased, n=1; cataract, n=1; blepharospasm, n=1; full blood count abnormal, n=1; skin exfoliation, n=1; chest discomfort, n=1; and dry mouth, n=1. LIMITATION OF THE STUDY: The FAERS database's limitations, such as the undetermined causality of cases, under-reporting and the lack of restriction to only health professionals reporting this type of event, could modify the statistical outcomes. These limitations are particularly relevant in the context of ophthalmic drug analysis, as they can affect the accuracy and reliability of the data, potentially leading to biased or incomplete results. CONCLUSIONS: Our findings have revealed a potential relationship due to the biological plausibility among malignant mediastinal neoplasm, full blood count abnormal, blood immunoglobulin E increased, diabetes mellitus, blepharospasm, cataracts, chest discomfort and dry mouth; therefore, it is relevant to continue investigating the possible drug-event association, whether to refute the safety signal or identify a new risk.

The evolution of clinical trials for pediatric pulmonary hypertension: are the needs of patients and their caregivers being met?

INTRODUCTION: Pediatric pulmonary hypertension is a rare condition. Survival remains poor in the current management era. There is a lack of data regarding the medical management of pediatric pulmonary hypertension and most pulmonary vasodilators are used off-label in children. AREAS COVERED: Pediatric pulmonary hypertension clinical trials' design and realization face many hurdles, including poor recruitment, limited available pharmacologic and physiologic data in children of various ages, ethical issues, and the lack of validated trial endpoint. Innovative clinical trial designs have emerged and may allow us to overcome some of these issues. Extrapolation of adult data to children, with additional pharmacokinetic and safety data, remains extremely important and valid in etiologies where the pediatric and the adult pathophysiologies are believed to be similar. EXPERT OPINION: Close collaboration between sponsors, regulators, patients, caregivers, physicians and researchers is necessary to develop efficacious and safe drugs for pediatric pulmonary hypertension. The increasing involvement of patients' and caregivers' participation in the development of clinical trials should help shape future research that is feasible and meaningful to the patients.

One-year experience with latanoprostene bunod ophthalmic solution 0.024% in clinical practice: A retrospective observational study.

PURPOSE: We evaluated the IOP-lowering efficacy and safety of latanoprostene bunod (LBN) ophthalmic solution 0.024% (Vyzulta®), the first topical nitric oxide-donating prostaglandin analog (PGA), in clinical practice. MATERIALS AND METHODS: A retrospective medical chart review from July 2021 to July 2023 of patients with open-angle glaucoma receiving LBN with at least 1 year follow-up was conducted. All included patients received LBN 0.024% as a replacement for a PGA, with examinations at 1-, 3-, 6-and 12-months follow-up. Main outcome measures were IOP, retinal nerve fiber layer thickness, visual fields before/after LBN use and adverse effects. Subgroup analysis with glaucoma types and PGA use were performed for additional IOP reduction after LBN use. RESULTS: Among 78 included patients, 47 patients (81 eyes), 60% with open-angle glaucoma (OAG) remained on LBN throughout 12-month follow-up. Baseline IOP was 18.2±4.2 mm Hg, and Prostaglandin analog (PGA)-IOP was 14.4 ± 3.0 mm Hg (21% mean IOP reduction). After switched to LBN, mean additional IOP reduction was 1.0 mm Hg at month 1, and the greatest reduction was 1.6 mm Hg (8.8% additional mean IOP reduction) at month 12 (P<0.0001). Subgroup analysis (NTG, 73%) showed that mean additional IOP reduction at month 12 was 1.3±2.0 mm Hg in NTG group and 2.1±3.2 mm Hg in POAG group (7.7% vs. 8.7% additional IOP reduction rates, P = 0.23). Subgroup analysis of PGA use at month 12 was 1.8±2.3 mm Hg in tafluoprost group and 0.5±1.7 mm Hg in travoprost group (9.5% vs.2.6% additional IOP reduction rates, P = 0.02). Tolerable ocular adverse effects included irritation (n = 16, 19.8%), mild conjunctival hyperemia (n = 11, 13.6%), dark circles (n = 4, 4.9%) and blurred vision (n = 2, 2.5%). There were no significant visual field and retinal nerve fiber layer thickness changes after 12 months of treatment with LBN 0.024%. CONCLUSIONS: Although high intolerable adverse effects including conjunctival hyperemia and eye irritation happened in the first month, remaining sixty percent of patients exhibited statistically significant additional IOP reductions in the replacement of other PGAs during 12 months of clinical use of LBN 0.024%.

The causal relationship between antihypertensive drugs and depression: a Mendelian randomization study of drug targets.

Background: Depression ranks as a leading contributor to the global disease burden. The potential causal relationship between the use of antihypertensive medications and depression has garnered significant interest. Despite extensive investigation, the nature of this relationship remains a subject of ongoing debate. Therefore, this study aims to evaluate the influence of antihypertensive medications on depression by conducting a Mendelian randomization study focused on drug targets. Method: We focused on the targets of five antihypertensive drug categories: ACE Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), Calcium Channel Blockers (CCBs), Beta-Blockers (BBs), and Thiazide Diuretics (TDs). We collected single-nucleotide polymorphisms (SNPs) associated with these drug targets from genome-wide association study (GWAS) statistics, using them as proxies for the drugs. Subsequently, we conducted a Mendelian randomization (MR) analysis targeting these drugs to explore their potential impact on depression. Results: Our findings revealed that genetic proxies for Beta-Blockers (BBs) were associated with an elevated risk of depression (OR [95%CI] = 1.027 [1.013, 1.040], p < 0.001). Similarly, genetic proxies for Calcium Channel Blockers (CCBs) were linked to an increased risk of depression (OR [95%CI] = 1.030 [1.009, 1.051], p = 0.006). No significant associations were identified between the genetic markers of other antihypertensive medications and depression risk. Conclusion: The study suggests that genetic proxies associated with Beta-Blockers (BBs) and Calcium Channel Blockers (CCBs) could potentially elevate the risk of depression among patients. These findings underscore the importance of considering genetic predispositions when prescribing these medications, offering a strategic approach to preventing depression in susceptible individuals.

Proposal of a Modified Classification of Hypertensive Crises: Urgency, Impending Emergency, and Emergency.

Systemic arterial hypertension (HTN) is the main cause of morbidity and mortality, and HTN crises contribute significantly to an unfavourable clinical course. For decades, HTN crises have been dichotomized into hypertensive emergency (HTN-E) and hypertensive urgency (HTN-U). The main difference between the two is the presence of acute hypertension-mediated organ damage (HMOD) - if HMOD is present, HTN crisis is HTN-E; if not, it is HTN-U. Patients with HTN-E are in a life-threatening situation. They are hospitalized and receive antihypertensive drugs intravenously (IV). On the other hand, patients with HTN-U are usually not hospitalized and receive their antihypertensives orally. We suggest a modification of the current risk stratification scheme for patients with HTN crises. The new category would be the intermediate risk group, more precisely the 'impending HTN-E' group, with a higher risk in comparison to HTN-U and a lower risk than HTN-E. 'Impending HMOD' means that HMOD has not occurred (yet), and the prognosis is, therefore, better than in patients with ongoing HMOD. There are three main reasons to classify patients as having impending HTN-E: excessively elevated BP, high-risk comorbidities, and ongoing bleeding/high bleeding risk. Their combinations are probable. This approach may enable us to prevent some HTNEs by avoiding acute HMOD using a timely blood pressure treatment. This treatment should be prompt but controlled.

Removing the FDA's Boxed Hepatotoxicity Warning and Liver Function Testing Requirement for Ambrisentan.

Importance: Endothelin receptor antagonists are first-line therapy for pulmonary arterial hypertension (PAH). The first 2 agents approved in the class, bosentan and ambrisentan, initially carried boxed warnings for hepatotoxicity and required monthly liver function tests (LFTs) as part of a risk evaluation and mitigation strategy (REMS); however, in 2011, as further safety data emerged on ambrisentan, the boxed hepatotoxicity warning and LFT requirements were removed. Objective: To analyze changes in the use of and LFT monitoring for ambrisentan and bosentan after changes to the ambrisentan labeling and REMS. Design, Setting, and Participants: This serial cross-sectional study used data from 3 longitudinal health care insurance claims databases-Medicaid, Optum's deidentified Clinformatics Data Mart, and Merative Marketscan-to perform an interrupted time series analysis of prescription fills and LFTs for patients taking ambrisentan and bosentan. Participants were patients filling prescriptions for ambrisentan and bosentan from July 1, 2007, to December 31, 2018. Data analysis was performed from April 2021 to August 2023. Exposure: Removal of the boxed warning for hepatotoxicity and the REMS LFT monitoring requirements on ambrisentan in March 2011. Main Outcomes and Measures: The primary outcomes were use of ambrisentan (ie, individuals with at least 1 dispensing per 1 000 000 individuals enrolled in the 3 datasets) vs bosentan and LFT monitoring (ie, proportion of initiators with at least 1 ordered test) before initiation and before the first refill. Results: A total of 10 261 patients received a prescription for ambrisentan during the study period (7442 women [72.5%]; mean [SD] age, 52.6 [17.6] years), and 11 159 patients received a prescription for bosentan (7931 women [71.1%]; mean [SD] age, 47.7 [23.7] years). Removal of the ambrisentan boxed hepatotoxicity warning and LFT monitoring requirement was associated with an immediate increase in the use of ambrisentan (1.50 patients per million enrollees; 95% CI, 1.08 to 1.92 patients per million enrollees) but no significant change in the use of bosentan. There were reductions in recorded LFTs before drug initiation (13.1% absolute decrease; 95% CI, -18.2% to -8.0%) and before the first refill (26.4% absolute decrease; 95% CI, -34.4% to -18.5%) of ambrisentan but not bosentan. Conclusions and Relevance: In this serial cross-sectional study of ambrisentan, labeling changes and removal of the REMS-related LFT requirement were associated with shifts in prescribing and testing behavior for ambrisentan but not bosentan. Further clinician education may be needed to maximize the benefits of REMS programs and labeling warnings designed to ensure the safe administration of high-risk medications.

Orthostatic Hypotension and Antihypertensive Treatment in Lung Transplant Recipients: A Cross-Sectional Study.

OBJECTIVES: Lung transplant is the ultimate treatment of many end-stage lung diseases. Calcineurin inhibitors, crucial in immunosuppression for lung transplant recipients, are linked to secondary hypertension, necessitating antihypertensive treatment. In addition, lung transplant recipients frequently experience orthostatic hypotension, occasionally stemming from autonomic dysfunction, but also commonly attributed as a negative side effect of antihypertensive treatment. Our study aimed to evaluate the frequency of orthostatic blood pressure irregularities and investigate the involvement of antihypertensive treatment as a potential risk factor in the occurrence among lung transplant recipients. MATERIALS AND METHODS: Fifty-six consecutive lung transplant recipients, both inpatient and outpatient, at the University Hospital Zurich (Switzerland) were monitored from 1999 to 2013. Transplant recipients underwent a Schellong test (an active standing test). Our evaluation encompassed their initial traits, such as the existence of supine hypertension. We computed the odds ratio for the comparison of the likelihood of experiencing orthostatic hypotension while using a minimum of 1 type of antihypertensive medication versus absence of antihypertensive drugs. RESULTS: Of the lung transplant recipients, 25% showed a positive Schellong test. Within this group, 64% had supine hypertension, and 29% displayed symptoms of orthostatic hypotension. Among the patients, 71% were using at least 1 type of antihypertensive medication. The odds ratio for showing orthostatic hypotension while taking at least 1 type of antihypertensive drug versus the absence of antihypertensive medications was 1.64 (95% exact CI, 0.39-6.90) with P = .50. This finding remained consistent regardless of age, sex, inpatient or outpatient status, and the duration since transplant. CONCLUSIONS: Orthostatic blood pressure dysregulation is prevalent among lung transplant recipients, frequently without noticeable symptoms. In our cohort, the use of antihypertensive medications did not elevate the risk of orthostatic hypotension.