Classes Of Antihypertensive Medications Research Articles

#1481 Renin-angiotensin-aldosterone system inhibitor (RAASi) optimisation after initiating outpatient SZC therapy: the GALVANIZE RAASi real-world study

Abstract Background and Aims Hyperkalaemia often occurs in patients with comorbidities that are treated with renin-angiotensin-aldosterone system inhibitors (RAASi), e.g., chronic kidney disease (CKD), heart failure or resistant hypertension. However, RAASi use can exacerbate hyperkalaemia. The GALVANIZE RAASi real-world study evaluated RAASi dose optimisation or maximisation following initiation of sodium zirconium cyclosilicate (SZC) therapy in the outpatient setting. Method A large US insurance claims database (from HealthVerity), spanning July 2018–December 2022, was used to identify adults initiating SZC therapy in the outpatient setting, who had an overlapping RAASi prescription fill (≥7 days; index date) and another RAASi prescription fill, within 90 days following the end of the index RAASi episode, during the 6-month follow-up period. Exclusion criteria included patients with a diagnosis of CKD Stage 5 or end-stage kidney disease, treatment with haemodialysis, or the absence of 6 months of continuous insurance coverage prior to, and after, the index date. During a 6-month follow-up period, the proportions of patients with an optimised (≥50% maximum dose; primary endpoint) or maximised (≥100% maximum dose; secondary endpoint) RAASi dose, per label indication, were assessed in the overall population and in sub-studies of patients with a diagnosis of CKD, heart failure, or hypertension (International Classification of Diseases, tenth revision). Diagnosis of hypertension with ≥3 classes of antihypertensive medications (including a diuretic) was defined as resistant hypertension. Multivariable logistic regression was used to identify factors associated with optimised or maximised doses of RAASi. Results Among 2973 eligible patients, mean age was 66.3 years and 41.6% of the population was female. Most patients had Stage 1 to 4 CKD (85.7%), including 46.2% with stage 3 CKD, and 33.0% with stage 4 CKD. Heart failure or resistant hypertension was present in 29.6% and 30.4% of patients, respectively. In the overall population, almost two-thirds of patients (63.7%) optimised their RAASi dose and over a quarter of patients maximised their RAASi dose (27.2%) during follow-up. Factors associated with optimised or maximised doses of RAASi are shown in Figs 1 and 2, respectively. In the sub-studies of patients with CKD (n = 2549), heart failure (n = 879) or resistant hypertension (n = 903), RAASi optimisation was achieved in 63.5%, 63.9% and 72.6% of patients, respectively, and RAASi maximisation was reached in 27.0%, 27.5% and 36.1% of patients, respectively. Conclusion In this real-world study of patients with hyperkalaemia who were receiving RAASi treatment, most individuals who initiated outpatient SZC therapy achieved RAASi dose optimisation overall and across the comorbidity-defined sub-studies evaluated, and more than a quarter of patients achieved dose maximisation within 6 months.

Social Determinants of Health and Incident Apparent Treatment-Resistant Hypertension Among White and Black US Adults: The REGARDS Study.

We examined the association of multilevel social determinants of health with incident apparent treatment-resistant hypertension (aTRH). We analyzed data from 2774 White and 2257 Black US adults from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study taking antihypertensive medication without aTRH at baseline to estimate the association of social determinants of health with incident aTRH. Selection of social determinants of health was guided by the Healthy People 2030 domains of education, economic stability, social context, neighborhood environment, and health care access. Blood pressure (BP) was measured during study visits, and antihypertensive medication classes were identified through a pill bottle review. Incident aTRH was defined as (1) systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, or systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg for those with diabetes or chronic kidney disease while taking ≥3 classes of antihypertensive medication or (2) taking ≥4 classes of antihypertensive medication regardless of BP level, at the follow-up visit. Over a median 9.5 years of follow-up, 15.9% of White and 24.0% of Black adults developed aTRH. A percent of the excess aTRH risk among Black versus White adults was mediated by low education (14.2%), low income (16.0%), not seeing a friend or relative in the past month (8.1%), not having someone to care for them if ill or disabled (7.6%), lack of health insurance (10.6%), living in a disadvantaged neighborhood (18.0%), and living in states with poor public health infrastructure (6.0%). Part of the association between race and incident aTRH risk was mediated by social determinants of health.

A novel dual inhibitor of the angiotensin and endothelin systems for the treatment of hypertension

Hypertension, affecting nearly half of the US adult population, is a primary cause of morbidity and mortality worldwide. Despite the availability of several classes of antihypertensive medications, only 25% of patients have their blood pressure under control, highlighting the need for novel antihypertensive therapeutics with better effcacy. Among hypertensive cases, salt-sensitive and drug-resistant hypertension are particularly concerning, as they are unresponsive to a combined regimen of three or more classes of medications, including angiotensin II (Ang II) receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEis), and diuretics. Salt-sensitive, observed in 50% of the general and 73% of black hypertensive patients, disproportionately affects the latter, leading to significantly higher mortality. Salt-sensitive hypertension in humans, as well as in various experimental models of hypertension (e.g., Ang II-induced, Dahl-salt sensitive [DSS] rats, deoxycorticosterone acetate [DOCA]-salt hypertensive rats), is characterized by significantly elevated levels of plasma endothelin-1 (ET-1), oxidative stress, and kidney dysfunction. ET-1 is often considered a final common pathway in orchestrating cardiovascular dysfunction through a range of proinflammatory mediators such as Ang II, cytokines, hypoxia, thrombin, reactive oxygen species (ROS), oxidized LDL, and vasopressin, all of which stimulate ET-1 production. In this capacity, we report the discovery of a gut microbiota-derived metabolite, indole-3-acetic acid (IAA), that simultaneously blocks ET-1 receptors (ETAR and ETBR) and the ET-biosynthetic enzyme ECE-1. Our data demonstrate that IAA inhibits ET-1-induced constriction of resistance mesenteric arteries, ROS production in human aortic smooth muscle cells, activation of cultured endothelial cells, adhesion molecule expression, and leukocyte adhesion. IAA inhibited purified human ECE-1 and suppressed Ang-II-induced and hypoxia-elicited ET-1 production from endothelial cells in vitro. Administration of a once-daily, extended-release formulation of IAA inhibits blood pressure elevation and kidney dysfunction in both DSS and Ang II-induced hypertension. IAA treatment preserved endothelial nitric oxide (NO) production and maintained smooth muscle sensitivity to a NO donor, sodium nitroprusside. Furthermore, IAA inhibited the expression of ROS-associated proteins such as Nox2 and Nox4, reduced oxidative damages, and decreased the production of ET-1 in vivo. Overall, IAA is the first compound that, through novel dual targeting of both the angiotensin and endothelin systems, demonstrates profound antihypertensive action in both salt-sensitive and angiotensin II-induced hypertension. Thus, IAA has the potential to effectively treat hypertension that does not respond to conventional therapies. American Heart Association. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Association of intensive blood pressure management with cardiovascular outcomes in patients using multiple classes of antihypertensive medications: a post-hoc analysis of the STEP Trial

High medication burden is associated with poor treatment effect and high risk of cardiovascular outcomes. This study aimed to investigate the association between the antihypertensive medication burden and cardiovascular outcomes in the STEP trial. This post-hoc analysis of the STEP trial enrolled 8511 participants, including 8041 with low burden and 470 with high burden. High antihypertensive medication burden was defined as being treated with ≥3 different classes of prescribed antihypertensive medications. The primary outcome was a composite of cardiovascular outcomes. Fine-Gray model was used in this study. Among all participants, high antihypertensive medication burden was associated with a higher risk of the primary outcome compared with low medication burden (HR, 1.52; 95% CI, 1.03–2.24), which was consistent in the standard group (HR, 1.95; 95% CI, 1.20–3.18) and the intensive group (HR, 1.10; 95% CI, 0.57–2.13; Pinteraction = 0.18). The beneficial effects of intensive systolic blood pressure (SBP) control on the primary outcome remained significant in the high burden group (HR, 0.42; 95% CI, 0.19–0.95) and the low burden group (HR, 0.79; 95% CI, 0.63–0.98; Pinteraction = 0.18). At 24 months, the percentage of participants achieving the target SBP was lower in the high medication burden group (risk ratio, 0.93; 95% CI, 0.89–0.98). In both standard and intensive treatment groups, participants with a high medication burden were harder to achieve the target SBP (Pinteraction = 0.65). High antihypertensive medication burden was associated with worse SBP control and a greater risk of cardiovascular events. Intensive SBP control showed cardiovascular benefits in both medication burden groups. Trial registration: STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

Association of antihypertensives and Parkinson's disease in a primary care population matched for underlying diagnosis.

To examine the association of several antihypertensive medication classes with incidence of Parkinson's disease (PD), taking into account possible underlying conditions. In a case-control study based on a large primary care database and including 21,981 PD cases and 21,981 non-PD controls matched for age, sex, and possible treatment indications associations with different antihypertensive medication groups, including diuretics, betablockers, calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin-II receptor-blockers and PD were examined. Antihypertensive medications overall were associated with a lower risk of subsequent diagnosis of PD (OR: 0.94, 95% CI 0.90-0.97), with the negative association most significant for medications acting on the renin-angiotensin-aldosterone system. A positive association with diagnosis of PD was only seen for betablockers and restricted to those with relatively young age and not in those with longer treatment duration. When taking into account underlying diagnoses, antihypertensive medications overall were associated with a reduced incidence of PD.

Abstract P318: Provider Barriers and Facilitators to Treatment Intensification for Patients With Uncontrolled Blood Pressure

Background: Hypertension is the leading cause of cardiovascular disease and premature death worldwide, however, therapeutic inertia, failure to intensify pharmacotherapy when blood pressure (BP) is not at goal, is a key obstacle to hypertension control. We aimed to identify barriers and facilitators to increasing the dose or adding a different antihypertensive medication class for patients with uncontrolled BP. Methods: We conducted a qualitative study of healthcare providers from Kaiser Permanente Southern California (KPSC). Using a stratified purposeful sampling approach, we identified 300 providers across 15 medical centers and specialties and with a mix of treatment intensification rates. In 2 separate waves, we emailed a letter of invitation to 150 eligible providers followed by 2 reminder emails each two weeks apart. We sought to conduct 30 semi-structured interviews about management of patients newly diagnosed with hypertension including use of single-pill combination therapy (SPC) (the recommended first-line therapy within KPSC), barriers to therapeutic intensification and use of home BP monitoring for treatment intensification decision making. We used rapid analysis methods to code responses and develop themes. Results: A total of 11 interviews were completed with providers from family medicine (n=7), internal medicine (n=3) and cardiology (n=1) who had an average of 6 years of practice within KPSC. The majority of providers reported using monotherapy as first-line treatment while SPC therapy was reserved for younger patients and those with baseline systolic BP >160 mm Hg. Monotherapy was often preferred to help providers determine if the first-line medication is causing side effects. Nearly all providers reported maximizing the dose of one medication before adding another medication class. Providers ranked the barriers to intensifying patients’ treatment in order of importance as 1) side effects such as frequent urination, hyperkalemia, and hypotension, 2) nonadherence to the current antihypertensive medication regimen and patient preference/hesitancy, 3) comorbidities (e.g., kidney function), and 4) age-related factors such as memory loss and ability to complete follow-up labs. All providers reported using patients’ home BP readings for treatment decision-making with most recognizing that patients’ out-of-clinic BP may be lower than clinic BP. Conclusion: Providers embraced stepped-care treatment for newly diagnosed patients with hypertension with most preferring monotherapy as first-line treatment. Concerns with side effects, nonadherence to the medication regimen and shared decision-making are key factors in providers’ decisions to intensify therapy for patients with uncontrolled BP. Targeted interventions to address provider barriers to treatment intensification may be needed.

Real-World Impact of Blood Pressure Control in Patients With Apparent Treatment-Resistant or Difficult-to-Control Hypertension and Stages 3 and 4 Chronic Kidney Disease.

Chronic kidney disease (CKD) is a common comorbidity in patients with apparent treatment-resistant hypertension (aTRH). We assessed clinical outcomes, healthcare resource utilization events, and costs in patients with aTRH or difficult-to-control hypertension and stage 3-4 CKD with uncontrolled vs. controlled BP. This retrospective cohort study used linked IQVIA Ambulatory EMR-US and IQVIA PharMetrics Plus claims databases. Adult patients had claims for ≥3 antihypertensive medication classes within 30 days between 01/01/2015 and 06/30/2021, 2 office BP measures recorded 1-90 days apart, ≥1 claim with ICD-9/10-CM diagnosis codes for CKD 3/4, and ≥1 year of continuous enrollment. Baseline BP was defined as uncontrolled (≥130/80 mm Hg) or controlled (<130/80 mm Hg) BP. Outcomes included risk of major adverse cardiovascular events plus (MACE+; stroke, myocardial infarction, heart failure hospitalization), end-stage renal disease (ESRD), healthcare resource utilization events, and costs during follow-up. Of 3,966 patients with stage 3-4 CKD using ≥3 antihypertensive medications, 2,479 had uncontrolled BP and 1,487 had controlled BP. After adjusting for baseline differences, patients with uncontrolled vs. controlled BP had a higher risk of MACE+ (HR [95% CI]: 1.18 [1.03-1.36]), ESRD (1.85 [1.44-2.39]), inpatient hospitalization (rate ratio [95% CI]: 1.35 [1.28-1.43]), and outpatient visits (1.12 [1.11-1.12]) and incurred higher total medical and pharmacy costs (mean difference [95% CI]: $10,055 [$6,741-$13,646] per patient per year). Patients with aTRH and stage 3-4 CKD and uncontrolled BP despite treatment with ≥3 antihypertensive classes had an increased risk of MACE+ and ESRD and incurred greater healthcare resource utilization and medical expenditures compared with patients taking ≥3 antihypertensive classes with controlled BP.

Korea Hypertension Fact Sheet 2023: analysis of nationwide population-based data with a particular focus on hypertension in special populations

BackgroundThe Korea Hypertension Fact Sheet 2023, presented by the Korean Society of Hypertension, offers an overview of the prevalence and management of hypertension, along with recent trends.MethodsData for the Fact Sheet were derived from the Korea National Health and Nutrition Examination Survey spanning 1998 to 2021, and the National Health Insurance Big Data from 2002 to 2021.ResultsAs of 2021, hypertension affected 28.0% of Korean adults aged 20 and older, totaling approximately 12.3 million individuals, with 5.3 million (43.5%) aged 65 or older. Among those with hypertension, awareness stood at 74.1%, treatment rates at 70.3%, and control rates at 56.0%. Over the years, the number of hypertension diagnoses increased from 3.0 million in 2002 to 11.1 million in 2021. During the same period, the utilization of antihypertensive medications rose from 2.5 million to 10.5 million, with treatment adherence also improving from 0.6 million to 7.8 million individuals. In 2021, the predominant antihypertensive drug class was angiotensin receptor blockers (75.1%), followed by calcium channel blockers (61.7%), diuretics (23.4%), and beta blockers (15.3%). Notably, 60.2% of all antihypertensive prescriptions involved combination therapy with at least two classes of antihypertensive medication. There was a positive trend towards stricter blood pressure control targets (systolic/diastolic blood pressure < 130/80 mmHg) among elderly hypertensive patients, as well as those with diabetes, obesity, and high-risk hypertension. However, this trend declined in individuals aged 80 years or older and those with chronic kidney disease in recent years.ConclusionIn Korea, hypertension management is making strides, yet the total number of hypertensive individuals is rising. Effectively addressing the growing population of elderly hypertensive patients and the persistently low treatment rates among younger individuals with hypertension is a critical challenge. Additionally, developing more efficient and customized policies for blood pressure control and cardiovascular disease prevention is imperative.

Supplemental Nutrition Assistance Program and Adherence to Antihypertensive Medications

Nonadherence to antihypertensive medications is associated with uncontrolled blood pressure, higher mortality rates, and increased health care costs, and food insecurity is one of the modifiable medication nonadherence risk factors. The Supplemental Nutrition Assistance Program (SNAP), a social intervention program for addressing food insecurity, may help improve adherence to antihypertensive medications. To evaluate whether receipt of SNAP benefits can modify the consequences of food insecurity on nonadherence to antihypertensive medications. A retrospective cohort study design was used to assemble a cohort of antihypertensive medication users from the linked Medical Expenditure Panel Survey (MEPS)-National Health Interview Survey (NHIS) dataset for 2016 to 2017. The MEPS is a national longitudinal survey on verified self-reported prescribed medication use and health care access measures, and the NHIS is an annual cross-sectional survey of US households that collects comprehensive health information, health behavior, and sociodemographic data, including receipt of SNAP benefits. Receipt of SNAP benefits in the past 12 months and food insecurity status in the past 30 days were assessed through standard questionnaires during the study period. Data analysis was performed from March to December 2021. Status of SNAP benefit receipt. The main outcome, nonadherence to antihypertensive medication refill adherence (MRA), was defined using the MEPS data as the total days' supply divided by 365 days for each antihypertensive medication class. Patients were considered nonadherent if their overall MRA was less than 80%. Food insecurity status in the 30 days prior to the survey was modeled as the effect modifier. Inverse probability of treatment (IPT) weighting was used to control for measured confounding effects of baseline covariates. A probit model was used, weighted by the product of the computed IPT weights and MEPS weights, to estimate the population average treatment effects (PATEs) of SNAP benefit receipt on nonadherence. A stratified analysis approach was used to assess for potential effect modification by food insecurity status. This analysis involved 6692 antihypertensive medication users, of whom 1203 (12.8%) reported receiving SNAP benefits and 1338 (14.8%) were considered as food insecure. The mean (SD) age was 63.0 (13.3) years; 3632 (51.3%) of the participants were women and 3060 (45.7%) were men. Although SNAP was not associated with nonadherence to antihypertensive medications in the overall population, it was associated with a 13.6-percentage point reduction in nonadherence (PATE, -13.6 [95% CI, -25.0 to -2.3]) among the food-insecure subgroup but not among their food-secure counterparts. This analysis of a national observational dataset suggests that patients with hypertension who receive SNAP benefits may be less likely to become nonadherent to antihypertensive medication, especially if they are experiencing food insecurity. Further examination of the role of SNAP as a potential intervention for preventing nonadherence to antihypertensive medications through prospectively designed interventional studies or natural experiment study designs is needed.

Implications of Untreated Hypertension on Chronic Kidney Disease: A Literature Review

The untreated progression of hypertension holds significant implications for the development and progression of chronic kidney disease (CKD). Therefore, necessitating the implementation of strategic hypertension management measures to mitigate its impact on CKD. This review highlights the necessity of precise diagnostic methodologies that employ oscillometric equipment and advocates for pharmacological interventions, the incorporation of combination therapies such as the "Polypill" to effectively control hypertension, and lifestyle adjustments. The pivotal role of the renin-angiotensin-aldosterone system (RAAS) in hypertension is acknowledged, noting the importance of stringent blood pressure regulation and the utilization of RAAS-blocking agents to attenuate its association with CKD. A comprehensive analysis is provided on the effects of various classes of antihypertensive medications on renal function, encompassing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and nonsteroidal mineralocorticoid receptor antagonists. Additionally, both non-invasive and invasive therapeutic modalities for managing resistant hypertension in CKD patients are examined, alongside discussions on prognostic indicators and outcomes across different stages of CKD. Lifestyle modifications such as sodium restriction, weight management, and moderation of alcohol intake are assessed for their influence on CKD prognosis. The review also extensively delves into the impact of ethnicity on the prevalence and outcomes of hypertension-induced CKD, highlighting disparities and distinctive trends among diverse ethnic cohorts including Indian, African American, Middle Eastern, Chinese, Pacific Islander, Native American, and Hispanic populations. Additionally, this study addresses the intricate relationship between cardiovascular abnormalities and CKD, the significance of gastrointestinal disorders, and the importance of multidisciplinary approaches in CKD management. Furthermore, insights are provided into the significance of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for identifying renal injury and CKD progression, alongside factors influencing adverse prognosis and life expectancy in CKD patients. This study accentuates the importance of tailored treatment assessments and interventions to address varied patterns and obstacles within ethnic groups, with the aim of optimizing CKD management strategies and reducing health disparitie

Medication Regimens against Hypertension Utilized in the Systolic Blood Pressure Intervention Stud

Context: Standard and intensive Systolic Blood Pressure (SBP) interventions would be contextualized by describing the antihypertensive medication regimens used in the SPRINT (Systolic Blood Pressure Intervention Trial). This information may also help future implementation efforts to meet population-wide intensive SBP goals. Methods: At the rerandomization and 12-month visits, we provided SPRINT participants with comprehensive medication data. The class of antihypertensive medications was used to categorize regimens. The analyses were divided into groups based on the kind of treatment (intensive target SBP &lt;120 mm Hg versus standard goal SBP &lt;140 mm Hg) Findings: The median number of classes used at the rerandomization visit was 2.0 for 7860 individuals (83.7% of 9361 randomized), and 2.0 for the standard and intensive groups (P=0.559). After a year, the intensive and conventional groups used a median of 3.0 and 2.0 classes, respectively (P&lt;0.001). In the intensive and standard groups, the most common regimens were rerandomization, Angiotensin-Converting Enzyme inhibitor (ACE), or Angiotensin-II Receptor Blocker (ARB) monotherapy (12.6% versus 12.2%). After a year, 5.3% of participants in the intense group and 14.7% of participants in the normal group still used ACE/ARB monotherapy. The following multidrug regimens were utilized at 12 months by both the intensive and regular participants: a calcium channel blocker and thiazide (12.2% and 7.9%) combined in an ACE/ARB thiazide, and calcium channel blocker (11.4% and 4.3%); an ACE/ARB, thiazide, calcium channel blocker, and beta-blocker (6.5% and 1.2%); and 6.2% and 6.8% of each category. Conclusions: Compared to ACE/ARB monotherapy, SPRINT investigators preferred combining ACEs or ARBs, thiazide diuretics, and calcium channel blockers to aim SBP &lt;120 mm Hg.

GENETIC VARIANTS ASSOCIATED WITH BLOOD PRESSURE PHENOTYPES IN OLDER ADULTS

Abstract African Americans (AAs) suffer from higher rates of uncontrolled HTN even when receiving commonly prescribed classes of antihypertensive medications. Variation in blood pressure (BP) in older adults is known to be associated with a variety of cardiovascular endpoints, yet our understanding of underlying mechanisms is limited. This study aimed to determine if HTN genetic variants influence blood pressure variation within a population of AA older adults taking antihypertensives. Community-dwelling older adults from the Translational Approaches to Personalized Health (TAPH) cohort were recruited to enroll in a 24-hour ambulatory BP monitoring (ABPM) phenotyping study. The Quant Studio 12-K Flex system was used for genotyping participants for three previously established CACNA1C and CACNB2 genetic risk alleles (rs758173, rs2228645, and rs2357790). 69 participants had ABPM data that passed the minimum 80% successful readings threshold: age=68□6, Female=50.3%, Black=73%, White=21%, and Other=6%. ABPM revealed 50.7% controlled HTN, 27.5% Sustained uncontrolled HTN, 14.5 % White coat uncontrolled HTN and 7.2% Masked uncontrolled HTN. ANOVA and Linear regression models found that the CACNB2 genetic risk allele rs2228645 broadly impacts ABPM Phenotypes (C/C SBP= 120.8+/-12.9 mmHg, C/T SBP= 125.73+/-13.5, and T/T SBP= 140+/-34.8 mmHg, p=0.011), mean awake 24-hour SBP (C/C SBP= 124+/-12.7 mmHg, C/T SBP= 133.5+/-14.8, and T/T SBP= 143.7+/-25.6 mmHg, p=0.012), and mean sleep SBP (C/C SBP= 114+/-16 mmHg, C/T SBP= 125.4+/-15, and T/T SBP= 136+/-50 mmHg, p=0.024). CACNA1C and CACNB2 genetic variants influence blood pressure phenotypes in older AAs. Determining genetic variants that affect antihypertensive effectiveness could lead to improved antihypertensive therapy for individuals with HTN/CVD.

Fall risk and cardiovascular outcomes of first-line antihypertensive medications in nursing home residents.

Little evidence exists about the comparative effects of first-line antihypertensive medications (i.e., renin-angiotensin-aldosterone converting enzyme inhibitors (RAASi), amlodipine, or thiazide diuretics) in older adults with limited life expectancy. We compared the rates of injurious falls and short-term cardiovascular events between different first-line antihypertensive medication classes in adults receiving care in nursing homes (NH). This was a retrospective cohort of Medicare fee-for-service beneficiaries receiving care in NHs. Patients newly dispensed first-line antihypertensive medications were identified using Part D claims (2015-2018) and linked with clinical assessments (i.e., Minimum Data Set). Fall-related injuries (FRI), hip fractures, and major adverse cardiac events (MACE) outcomes were identified using hospitalization claims. Patients were followed from the date of antihypertensive dispensing until the occurrence of outcomes, death, disenrollment, or 6-month follow-up. Inverse-probability-of-treatment-weighted (IPTW) cause-specific hazards regression models were used to compare outcomes between patients who were new users of RAASi, amlodipine, or thiazides. Our cohort included 16,504 antihypertensive users (RAASi, n = 9574; amlodipine, n = 5049; thiazide, n = 1881). Mean age was 83.5 years (± 8.2), 70.6% were female, and 17.2% were non-white race. During a mean follow-up of 5.3 months, 326 patients (2.0%) experienced an injurious fall, 1590 (9.6%) experienced MACE, and 2123 patients (12.9%) died. The intention-to-treat IPTW hazard ratio (HR) for injurious falls for amlodipine (vs RAASi) use was 0.85 (95% confidence interval (CI) 0.66-1.08) and for thiazides (vs RAASi) was 1.22 (95% CI 0.88-1.66). The rates of MACE were similar between those taking anti-hypertensive medications. Thiazides were discontinued more often than other classes; however, inferences were largely unchanged in as-treated analyses. Subgroup analyses were generally consistent. Older adults with limited life expectancy experience similar rates of injurious falls and short-term cardiovascular events after initiating any of the first-line antihypertensive medications.

Associations of antihypertensive medication (AHM) consumption and drug‐drug interaction with Statin and Metformin with reduced Alzheimer’s disease and related dementias (ADRD) risk among hypertensive patients with mild cognitive impairment (MCI) using high volume claims data

AbstractBackgroundWhile hypertension is a modifiable risk factor of Alzheimer’s disease and related dementias (ADRD), limited studies have been conducted on drug effectiveness of antihypertensive medications (AHMs) on ADRD progression from mild cognitive impairment (MCI) or on drug‐drug interactions of AHMs with drugs for other risk factors such as type 2 diabetes and hypercholesterolemia.Method128,683 unique hypertensive patients with MCI on US‐based Optum claims data were identified. Diuretics, beta blockers (BBs), calcium channel blockers (CCBs), angiotensin‐converting enzyme inhibitors (ACE inhibitors), and angiotensin II receptor antagonists (ARBs) were identified as five major AHM classes. Baseline characteristics were compared. Cox proportional hazards (PH) models were used to study the association between specific AHM exposure and the progression from MCI to ADRD while controlling for demographic variables, comorbidities, and use of Statin and Metformin. To examine the association of AHM‐Statin or AHM‐Metformin interaction with ADRD progression, we also investigated models controlling for aforementioned confounders, as well as drug‐drug interaction terms.ResultThe study included 100,678 patients who were taking at least one class of AHM and 28,005 who were not taking any AHMs. AHM users had higher ratios for the comorbidities (all P≤0.039) and consumption of Metformin and Statin (both P&lt;0.001) compared to non‐users. Users of each major AHM class showed significantly lower risk of developing ADRD compared to non‐users of that specific drug class (adjusted hazard ratio (aHR): 0.96‐0.98; all P≤0.048). Within patients on monotherapy (using only one AHM drug), no specific AHM class had significantly lower risk of ADRD diagnosis compared to other AHM drug classes (aHR: 0.97‐1.11; all P≥0.053). Use of Diuretics or CCBs in combination with Metformin consumption (aHR: 0.89, 0.91, respectively) showed lower risk of MCI to ADRD progression than that under Metformin non‐consumption (aHR: 0.97, 0.98), whereas use of any of the five major AHMs under Statin consumption (aHR: 0.91‐0.94) all showed lower risk than that under Statin non‐consumption (aHR: 0.98‐1.04).ConclusionAll five major AHM classes show a protective effect against ADRD progression among hypertensive patients with MCI. Also, AHMs combined with consumption of Metformin or Statin showed a stronger protective effect compared to non‐consumption.

Polypill Therapy for Cardiovascular Disease Prevention and Combination Medication Therapy for Hypertension Management

Although various guidelines for cardiovascular disease prevention have been established, the optimal drug therapy is often not implemented due to poor medication adherence and the clinical inertia of healthcare practitioners. Polypill strategies are one solution to this problem. Previous studies have established the usefulness of polypills, i.e., combination tablets including three or more medications, for the prevention of cardiovascular disease. For this purpose, the polypills generally contain an antiplatelet medication, an antihypertensive medication, and a statin. For the specific management of hypertension, combination therapy including more than two classes of antihypertensive medications is recommended by most international guidelines. Combination tablets including two classes of antihypertensive medications, such as renin-angiotensin system (RAS) inhibitors (angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) and Ca-channel blockers or thiazide diuretics, have been reported to be useful for cardiovascular disease prevention and lowering blood pressure (BP) levels. The use of RAS inhibitors is recommended for a wide range of complications, including diabetes, chronic heart failure, and chronic kidney disease. The combination of an RAS inhibitor and diuretic or Ca-channel blocker is thus recommended for the management of hypertension. Finally, we expect that novel medications such as angiotensin receptor neprilysin inhibitors (ARNIs) and sodium glucose cotransporter 2 inhibitors (SGLT2i), which have a more diverse range of effects in hypertension, heart failure, or diabetes, may be a solution to the problem of polypharmacy. Evidence is accumulating on the benefits of polypill strategies in cardiovascular disease prevention. Combination tablets are also effective for the treatment of hypertension.

Abstract 17562: Real-World Evidence for Comparative Effectiveness of Antihypertensive Therapeutic Intensification Strategies: Increasing Dose versus Adding a New Medication

Background: Clinical efficacy research indicates a placebo-adjusted 7-11 mmHg reduction in SBP can be expected from adding an antihypertensive (AH) medication class compared to a 2-3 mmHg reduction from doubling the dose of a currently prescribed AH medication. Given the relative dearth of real-world data required for external validity and generalizability, we examined the comparative BP effects of AH class addition vs. dose escalation in electronic health records from adult ambulatory primary care clinics. Methods: Analysis was performed with observational data from five distinct health care organizations in 2020-2022. The BP-lowering effect in patients with existing AH medication (n=10,119) was compared for AH intensification (adding a class), versus a dose increase. One-to-one propensity-score (PS) matching was used to decrease the presence of bias and confounding in effect estimation. Results: After PS matching on 20 different clinical and demographic variables, 6,826 patients were included in the final model. Simple linear regression found a 1.31 mmHg greater SBP reduction (14.02 vs. 12.71 mmHg, p=0.0052) after adding a new medication compared to increasing dose. To control for regression to the mean, each group was compared to another group with no medication changes, and a 2.96 vs 1.50 mmHg difference was detected. Removing instances of class additions that resulted in known less than additive combinations of AH medications led to a more pronounced difference, with class additions having a 1.93 mmHg greater SBP reduction than dose increases (p=0.00003). Conclusion: This study provides quasi-experimental real-world evidence for a greater magnitude of SBP reduction after a new AH class is added than after increasing the dose of existing AH medication, although the magnitude of effect is much less than in efficacy studies. Further research to better understand the nuanced dynamics of dose escalation vs. class addition could improve the AH response to treatment intensification.

Antihypertensive medications and risk of colorectal cancer in British Columbia.

Introduction: There is conflicting evidence for the association between antihypertensive medications and colorectal cancer risk, possibly reflecting methodological limitations of previously conducted studies. Here, we aimed to clarify associations between commonly prescribed antihypertensive medication classes and colorectal cancer risk in a large, retrospective, cohort study. Methods: Using linked administrative data between 1996 and 2017 from British Columbia, we identified a cohort of 1,693,297 men and women who were 50years of age or older, initially cancer-free and nonusers of antihypertensive medications. Medication use was parameterized as ever use, cumulative duration, and cumulative dose. Cox proportional hazard models were used to estimate hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) for associations of time-varying medication use [angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and diuretics] with colorectal cancer risk. Results: There were 28,460 incident cases of colorectal cancer identified over the follow-up period (mean = 12.9years). When medication use was assessed as ever/never, diuretics were associated with increased risk of colorectal cancer (HR 1.08, 95% CI 1.04-1.12). However, no similar association was observed with cumulative duration or cumulative dose of diuretics. No significant associations between the other four classes of medications and colorectal cancer risk were observed. Conclusion: No compelling evidence of associations between antihypertensive medications and colorectal cancer were observed.

FRI190 Catching A Chimera: A Case Of Suspected Glucocorticoid Remediable Aldosteronism

Abstract Disclosure: A. Khan: None. B. Ramchandani: None. H.B. Aftab: None. Introduction: Familial hyperaldosteronism type 1 (FH-I), also known as glucocorticoid remediable aldosteronism (GRA) is responsible for 1% of cases of primary aldosteronism (PA). It is caused by a chimeric fusion of the CYP11B2 and CYP11B1 genes resulting in ACTH-sensitive aldosterone production. We describe a case of suspected GRA and outline the diagnosis of this rare condition. Case. A 52-year-old female with history of type 2 diabetes mellitus, obesity, sleep apnea, SVT with ablation presented with long-standing history of resistant hypertension (HTN). HTN was diagnosed in her late twenties. She was previously trialed on eight different classes of antihypertensive medications excluding mineralocorticoid antagonists or potassium-sparing diuretics but HTN remained uncontrolled. Current regimen included hydralazine, nebivolol, and furosemide. Her sister had HTN diagnosed in her forties, a nephew with HTN diagnosed in his early twenties and mother with HTN with unclear age of diagnosis. Her systolic and diastolic BP averaged 150 mmHg and 90 mmHg, respectively, on both home and clinic monitoring. Physical examination was significant for mild cushingoid appearance. Screening tests for pheochromocytoma and hypercortisolism were normal. Plasma aldosterone concentration (PAC) was noted to be at 14.4 ng/dl (&amp;lt;39.2) with a plasma renin activity (PRA) of &amp;lt;0.6 ng/mL/h (2.9 - 10.8), with aldosterone to renin ratio (ARR) of 24. Repeat testing showed PAC of 15.1 ng/dl, PRA&amp;lt;0.6 ng/ml/hr (ARR: 25.1) with potassium of 3.3 mmol/L (3.5 -5.1). PAC levels remained unsuppressed above 10 ng/dL following four-hour, seated, 2 L IV saline suppression test with serum potassium of 3.5 mmol/L. CT abdomen showed normal appearance of the adrenal glands. Given early age of onset of HTN and strong family history, 3-day dexamethasone test was performed using 1 mg oral dexamethasone every 12 hours following which PAC suppressed to &amp;lt;1 ng/dl. Patient was started on spironolactone 25 mg twice daily and at the time of writing is awaiting genetic testing to confirm the diagnosis of GRA. Discussion: GRA is a rare subtype of PA which has an increased risk of cardiovascular and cerebrovascular complications. Our case highlights the importance of screening for GRA in patients who have a personal and/or family history of early onset HTN who have screened positive for PA. Genetic testing for chimeric CYP11B1/B2 gene is the confirmatory step of diagnosis, however, a 3-day dexamethasone suppression test can be used to screen for GRA with a high sensitivity. Elevated levels of urine 18-hydroxycortisol and 18-oxocortisol are also noted but these are not widely available tests. Treatment of GRA is with medical management only; since surgical intervention is not required; proper diagnosis can also save the patient from unnecessary and invasive tests such as adrenal vein sampling. Presentation: Friday, June 16, 2023

Screening for orthostatic hypotension in the geriatric population in a real-world primary care setting reduces prescribed antihypertensive medications.

To determine if outpatient screening for orthostatic hypotension (OH) in the geriatric population results in fewer prescribed antihypertensive medications and if a relationship exists between OH and specific pharmacologic classes of antihypertensive medications. Patients ≥ 65 years were screened for OH, defined as a decrease in systolic blood pressure (SBP) ≥ 20 mm Hg or a decrease in diastolic blood pressure (DBP) ≥ 10 mm Hg after standing for 3 minutes. Sitting blood pressure (BP) was measured after patients had been seated quietly in an exam room. Patients then stood for approximately 3 minutes at which time standing BP was recorded. OH prevalence was 18%. Standing DBP was significantly different between the two groups (70 mmHg ± 18, 80 mmHg ± 13, P = 0.007). Compared to patients without OH, patients with OH were more likely to have been previously prescribed beta-blockers (56% vs. 32%, P = 0.056) and potassium-sparing diuretics (11% vs. 1%, P = 0.026). Physicians discontinued an antihypertensive medication more often in patients who screened positive for OH than in to those who did not (17% vs. 4%, P = 0.037). Calcium channel blockers were the most frequently discontinued class of medication. Asymptomatic OH is prevalent in geriatric patients. Screening for OH may lead to de-escalation of antihypertensive regimen and a reduction in polypharmacy. Positive screening for OH was associated with de-prescribing of antihypertensive medications. Prior use of beta-blockers and potassium-sparing diuretics was most largely associated with OH.

Korea hypertension fact sheet 2022: analysis of nationwide population-based data with a special focus on hypertension in the elderly

BackgroundThe Korean Society of Hypertension has published the Korea Hypertension Fact Sheet 2022 to provide an overview of the magnitude and management status of hypertension and their recent trends.MethodsThe Fact Sheets were based on the analyses of Korean adults aged 20 years or older of the 1998–2020 Korea National Health and Nutrition Examination Survey and the 2002–2020 National Health Insurance Big Data.ResultsAs of 2020, 29.4% of the adult population aged 20 or older in Korea, about 12.6 million people, have high blood pressure, of which 5.0 million (40%) are 65 years of age or older and 1.2 million (10%) are 80 years of age or older. Among those with hypertension, the awareness rate is 69%, the treatment rate is 65%, and the control rate is 47%. The number of people diagnosed with hypertension increased from 3.0 million in 2002 to 10.5 million in 2020. During the same period, the number of people using antihypertensive medication increased from 2.5 million to 9.9 million, and the number of people adherent to treatment increased from 0.6 million to 7.4 million. Among those treated for hypertension in 2020, 74% used angiotensin blockers, 61% used calcium channel blockers, 24% used diuretics, and 15% used beta blockers. Combination therapy with at least two classes of antihypertensive medication consisted of 60% of all antihypertensive prescriptions. The number of people with hypertension aged 65 or older is increasing very rapidly compared to those aged 20–64. Awareness and treatment rates of hypertension improved rapidly, especially in those aged 65 or older, but the rate of improvement slowed since 2012.ConclusionsIn Korea, the level of hypertension management is improving, but the absolute number of people with hypertension, especially elderly hypertension, is increasing due to the rapid aging of the population. It is necessary to develop more efficient and target-specific policies to control blood pressure and prevent cardiovascular disease.