Combination Antihypertensive Therapy Research Articles

Risk of developing hyperkalemia in patients with hypertension treated with combination antihypertensive therapy - a retrospective register-based study.

The risk of hyperkalemia in relation to different combinations of antihypertensive therapy remains to be elucidated. In this Danish register-based study, we aimed to investigate the risk of developing hyperkalemia in relation to different combinations of antihypertensive therapy. Using incidence density matching, we matched a hyperkalemic patient to five normokalemic patients on eGFR groups, age, sex, and time between study entry and date of potassium measurement. Combination therapies were subdivided into eight groups: beta blockers (BB) + calcium channel blockers (CCB), BB + renin angiotensin system inhibitors (RASi), BB + RASi + mineralocorticoid receptor antagonists (MRA), CCB + RASi, CCB + RASi + thiazides, CCB + thiazides, RASi + thiazides, and other combinations. Multivariable conditional logistic regression was used to estimate the odds of hyperkalemia within 90 days for each of the eight antihypertensive combination therapies. A total of 793 patients with hyperkalemia were matched to 3598 normokalemic patients. In multivariable analysis, odds of developing hyperkalemia when being treated with BB + RASi + MRA was 1.95 (95% CI, 1.39-2.72) compared to RASi + thiazides (reference). CCB + thiazides (OR, 0.76 [95% CI, 0.45-1.28]) and CCB + RASi + Thiazid (OR 0.81 [95% CI, 0.51-1.28]) were among the others not significantly associated with hyperkalemia. Combinations of BB + RASi + MRA were significantly associated with an increased risk of developing hyperkalemia within 90 days of initiating treatment. Patients treated with BB + RASi + MRA within 90 days of treatment initiation, were associated with an increased hyperkalemia risk. When treating hypertensive patients with combination antihypertensive therapy, identifying and monitoring patients with a high risk of dyskalemias is a crucial goal to avoid serious adverse effects and detrimental outcomes related to dyskalemia.

Cardioprotective efficacy of combined therapy with azilsartan, indapamide, and nitrendipine in patients with essential hypertension

Abstract Objective To conduct a comparative assessment of the six-month cardioprotective efficacy of combined therapy using azilsartan with indapamide and nitrendipine in patients with essential hypertension (EH). Materials and Methods The study included 101 male and female patients with grade I–II arterial hypertension (AH) according to the classification (ESC/ESH, 2018), who were undergoing outpatient treatment at the Republican Specialized Scientific-Practical Medical Center of Cardiology. The mean age of the patients was 53.1±11.2 years, and the mean duration of AH was 8.5±7.2 years. Initially and after 6 months of therapy, echocardiography was performed to determine the left ventricular myocardial mass index (LVMMI) and left ventricular (LV) echo geometry types. Echocardiography (ECHO) was performed using the "En VisorC" ultrasound system (Philips, Netherlands). Statistical significance was considered for all analyses with p <0.05. Results All patients were divided into 2 groups: Group 1 - patients on combined antihypertensive therapy (AHT) with azilsartan and indapamide (n=50) and Group 2 - patients on therapy with azilsartan and nitrendipine (n=51). The mean daily dose of azilsartan was 49.3±6.0 mg, nitrendipine was 10.88±4.3 mg, and indapamide was 1.69±0.5 mg. In Group 1, the LVMMI initially was 127.4±32.9 g/m2, and after treatment, it was 110.3±29.0 g/m2 (p<0.001); in Group 2, it was 138.7±31.9 g/m2 and 116.6±30.3 g/m2, respectively (p<0.001). The degree of LVMMI reduction in Group 1 was -13.3±15.6% compared to Group 2, which was -14.4±17.9% (p>0.05). During therapy with azilsartan, indapamide, and nitrendipine, the reduction of LVMMI in EH patients was associated with a decrease in the concentric type of left ventricular hypertrophy (LVH) in both therapy groups: in both groups, a significant increase in the LV diastolic filling pattern index/LVMMI was observed, which was 0.51±0.07 ml/g before treatment and 0.57±0.14 ml/g after treatment in Group 1 (p<0.001), and 0.50±0.11 ml/g before treatment and 0.54±0.12 ml/g after treatment in Group 2 (p<0.02). Significant regression of LVH with 6-month combined therapy in both groups was accompanied by an improvement in LV echo geometry. Initially, there were 12 patients (11.9%) with unchanged LV echo geometry, concentric remodeling was detected in 9 patients (8.91%), eccentric LVH in 30 patients (29.7%), and concentric LVH in 50 patients (49.5%). In the dynamics, the number of patients with normal LV echo geometry increased to 41 patients (40.6%), with concentric LVH decreased to 34 patients (33.6%), with concentric remodeling decreased to 7 patients (7%), and with eccentric LVH decreased to 19 patients (18.8%) (χ2=21.635, p<0.001). Conclusion Achieving target blood pressure levels provided high cardioprotective efficacy of combined therapy with azilsartan, indapamide, and nitrendipine with improvement in LV echo geometry in both groups.

Comparative Analysis of The Effectiveness of Antihypertensive Therapy Including Spironolactone and Eplerenone in Patients With Essential Hypertension and Atrial Fibrillation.

To perform a comparative analysis of the efficacy of antihypertensive therapy (AHT) containing spironolactone or eplerenone in patients with essential arterial hypertension (AH) and atrial fibrillation (AF). The study included 99 male and female patients with essential AH complicated by permanent AF, who were receiving the outpatient treatment at the National Specialized Scientific and Practical Medical Center of Cardiology (Tashkent). The patients aged 61.3±9.5 years, the mean duration of AH was 12.9±8.3 years. All patients were divided into two groups: Group 1, patients who completed a 6-month combination AHT containing spironolactone (n=51); Group 2, patients who completed a 6-month combination AHT containing eplerenone (n=48). AF was diagnosed by electrocardiogram (ECG) and/or 24-hour ECG monitoring according to standard diagnostic criteria. The ECG study was performed in compliance with the American Society of Echocardiography Guidelines in M- and B-modes. The degree of structural vascular alterations was determined by the intima-media thickness of the common carotid artery by duplex scanning and microalbuminuria in morning urine. The concentrations of sex hormones were measured by the enzyme immunoassay. The serum concentrations of lipids, glucose, creatinine, and uric acid were measured by the enzymatic method. The glomerular filtration rate (GFR) was calculated with the EPI formula. Results of all studies were considered statistically significant at p<0.05. The proportion of patients who achieved the target diastolic blood pressure (BP) values was significantly greater in the eplerenone-containing treatment group than in the spironolactone-containing treatment group: 87.8% vs. 67.5% (p=0.043). The proportion of patients who simultaneously achieved the target systolic and diastolic BP values was slightly greater in the eplerenone-containing treatment group than in the spironolactone-containing group (100% vs. 92.1%, p=0.060). The best cardioprotective efficacy was observed in the group of combination AHT containing eplerenone. Specifically, in Group 2, the left ventricular ejection fraction (LVEF) was significantly improved compared to Group 1: from 55.4±10.6% at baseline to 52.6±9.1% in Group 1 (p>0.05) and from 54.8±8.8% at baseline to 58.2±6.4% in Group 2 (p<0.02). Only in Group 2, the left atrial volume index (LAVI) was significantly decreased compared to Group 1. Thus, in Group 1, the LAVI changed from 42.2±15.1 ml/m2 at baseline to 40.4±12.2 ml/m2 (p>0.05) and in Group 2, from 41.2±15.3 ml/m2 at baseline to 37.3±13.5 ml/m2 after the treatment (p<0.05); the ∆% LAVI in the eplerenone group was -5.9% vs. -0.36% in the spironolactone group. In men of Group 1, estradiol significantly increased from 13.9±12.6 pmol/l at baseline to 22.7±12.4 pmol/l (p<0.001). The good antihypertensive efficacy of the 6-month combination therapy containing eplerenone was significantly superior to spironolactone in achieving the target BP values. The eplerenone-containing treatment significantly improved LVEF and decreased LAVI compared to the spironolactone-containing treatment. A trend towards a beneficial effect of the AHT containing eplerenone on concentrations of sex hormones was noted in both women and men.

CLINICAL OUTCOMES OF MONO-THERAPY VERSUS DUAL ANTIHYPERTENSIVE THERAPY IN PATIENTS PRESENTING AT TEHSIL HOSPITAL IN PAKISTAN

Hypertension, a prevalent and potentially life-threatening condition, remains a significant public health concern in Pakistan. This article aims to investigate and compare the clinical outcomes of antihypertensive monotherapy versus combination therapy in patients treated at Tehsil Hospital, a critical healthcare facility in the Tehsil region of Pakistan. Objective: To assess and compare the clinical outcomes of hypertensive patients treated with monotherapy and those receiving a combination of antihypertensive medications at Tehsil Hospital, Pakistan. Methods: The study was carried out at Tehsil Hospital, Punjab-Pakistan. All adult participants (30 ≥ and ≤70 years) who were on antihypertensive medicine for at least 6 weeks and were diagnosed as hypertensive (average blood pressure of >140/90 mm Hg on at least two clinic visits) were included in the study from April 11 to June 20, 2022. The data was analyzed by SPSS 20. Statistical tests like chi-square were applied to obtain the required results. Results: A total of 136 study subjects were enrolled. Out of these, 113(81%) were male subjects, 23(17%) were female, 12(17.6%) smokers, and patients suffering from chronic liver disease were as 26(38.2%) treated with mono-therapy as compared with dual therapy with significant p-value 0.00 and 0.001. Other co-morbidities like the previous history of IHD, DM, and chronic kidney disease were treated with both therapies with insignificant p-values as > 0.05. Clinical outcomes were observed, and it was shown that more patients with stroke were treated with mono-therapy as p-value > 0.05 while comparing with major bleeding and control of hypertension showed a significant p-value of <0.05. Conclusion: Treatments in combination are effective and advised. The most important element in the management of hypertension, irrespective of whether medication is utilized, the goal is to get blood pressure down to the desired amount. Effective communication is essential for doctors, other healthcare professionals, and patients to treat patients.

HYPERTENSION IN THE ELDERLY: CHALLENGES IN MANAGEMENT AND TREATMENT

Hypertension is a prevalent and significant health issue among the elderly, contributing to increased risks of cardiovascular diseases, stroke, and kidney failure. Managing hypertension in older adults poses unique challenges due to age-related physiological changes, comorbidities, and polypharmacy. This review explores the complex pathophysiology of hypertension in the elderly, including age-related changes in vascular function and the impact of comorbid conditions. It examines the difficulties in diagnosing hypertension, such as variability in blood pressure readings, white coat syndrome, and masked hypertension, highlighting the need for accurate monitoring through home and ambulatory techniques. The review discusses current management strategies, emphasizing the importance of setting appropriate treatment goals, implementing lifestyle modifications, and utilizing pharmacological treatments, including new antihypertensive drugs and combination therapies. It also addresses challenges such as adverse drug reactions, medication adherence, and the management of polypharmacy. Recent advances, including innovations in drug delivery systems and digital health technologies, offer promising solutions for improving hypertension management. Future research directions include exploring precision medicine, understanding the role of the gut microbiome, and addressing health disparities. Clinicians are advised to adopt personalized treatment approaches, integrate technological tools, and address socioeconomic barriers to optimize hypertension management in the elderly. This review underscores the need for ongoing research and tailored strategies to improve outcomes and quality of life for older patients with hypertension.

P203 IMPACT OF IMPLEMENTING A COMMUNITY CARE STRATEGY TO REDUCE THE RISK OF CARDIOVASCULAR DISEASE IN SANTANDER, COLOMBIA: PRELIMINARY RESULTS OF THE RE-HOPE STUDY

Background: Hypertension is the main risk factor of cardiovascular disease (CVD), affecting 1.28 billion adults and resulting in 1.16 million deaths. In Colombia, hypertension affected 7.8 million adults in 2019. Different sociocultural and health system-related barriers may interfere with hypertension management. Our aim was to determine the preliminary impact of this community-based strategy on the changes in hypertension control in Colombia. Methods The Re-Hope study is a community-based strategy to reduce CVD risk in 13 municipalities of Santander, Colombia. Nursing assistants referred patients to the cardiovascular risk program (CVRP), facilitated medical appointments, and provided health counseling. A longitudinal analysis was conducted on data from the first three follow-up visits. Included were adults >18 years with hypertension not enrolled in the CVRP. Standardized questionnaires gathered sociodemographic, medication, and lifestyle data. Anthropometric and blood pressure measurements were taken. Hypertension was defined as systolic BP >140 mmHg, diastolic BP >90 mmHg, self-reported hypertension, or antihypertensive medication use. Pharmacological adherence was assessed with the Morisky 4-item scale. Tobacco and alcohol use were categorized as never or current consumers. Blood pressure changes were evaluated with a paired t-test, and categorical variable changes with McNemar and Stuart-Maxwell tests. Analysis was done using Stata software. Results A total of 2,585 participants were included. The mean age was 65.1 years (SD 11.9) and 64.3% were women. After 6 months of follow-up, the mean systolic and diastolic blood pressure reduced 17.03 mmHg (SD 17.95) and 7.04 mmHg (SD 11.22), respectively. Hypertension control increased on 11.7%. Antihypertensive combination therapy increased by 4.4% for dual therapy and 4.6% for triple therapy. The low pharmacological adherence was reduced by 3.35%. Conclusions The implementation of a community-based care strategy in Santander at the first three visits achieved a relevant reduction of hypertension values and greater use of combined antihypertensive therapy. Continuation of the study is required to identify the total results.

Характеристика факторів серцево-судинного ризику в пацієнтів з артеріальною гіпертензією, які приймають подвійну комбінацію антигіпертензивних препаратів: результати дослідження ФАКТОР-дуо

The aim – to study the characteristics of cardiovascular risk factors, the structure and effectiveness of treatment in hypertensive patients (pts) on the background of a dual combination of antihypertensive drugs, to evaluate the efficacy and tolerability of calcium channel blockers (CCB) (amlodipine and lercanidipine) when added to the combination of renin-angiotensin-aldosterone system (RAAS) inhibitor with a diuretic.Materials and methods. A multicenter study with 1616 hypertensive pts who received dual combination antihypertensive therapy. Cardiovascular risk factors were studied (smoking status, alcohol consumption, physical activity, family history of cardiovascular disease), concomitant cardiovascular diseases, carbohydrate metabolism disorders, and body mass index were determined, and current antihypertensive therapy and its effectiveness were evaluated based on office blood pressure (BP) measurements. Amlodipine 5-10 mg/day or lercanidipine 10–20 mg/day was added to the combination of RAAS blocker with a diuretic in the case of office BP ≥ 140/90 mm Hg. 1198 hypertensive pts received triple combined therapy. The effectiveness and tolerability of the treatment were evaluated after 4 weeks according to data from office BP measurements and home BP monitoring (HBPM). Lercanidipine was taken by 76 % of pts and amlodipine was taken by 24 % of pts.Results and discussion. Hypertensive pts were characterized by a significant prevalence of obesity (38.6 %), smoking (27.9 %), and insufficient physical activity (31.2 %). A significantly higher percentage of smoking and alcohol consumption was registered among men, while a lower level of physical activity was registered among women. Concomitant type 2 diabetes was present in almost a quarter of pts, stroke/TIA in 8.7 %, and myocardial infarction/revascularization in 8.3 %. At the same time, 53.2 % of the pts received statin therapy, and 64.7 % received antiplatelet drugs.Conclusions. The addition of CCB contributed to office BP target achievement in 69.1 % of pts, and optimal BP according to HBPM data in 54.3 % of pts. Lercanidipine and amlodipine have demonstrated comparable antihypertensive efficacy. Lercanidipine demonstrated a better tolerability profile compared to amlodipine: the incidence of side effects was significantly lower, respectively, 3.6 vs. 12.3 %; edema of the lower legs occurred in 6.5 times more often under amlodipine treatment than lercanidipine.

Effect of different single and combined antihypertensive drug regimens on the mortality of critical care patients.

To investigate the effect of different single and combined pre-admission antihypertensive drug regimens on the prognosis of critically ill patients. We performed a retrospective cohort study using data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. All initial ICU admission records of patients with hypertension and previous antihypertensive exposure before ICU admission were included. Our primary outcome was 90-day mortality. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to balance the distribution of baseline characteristics. Logistic regression analysis and subgroup analysis were performed to determine the independent effect of different single and combined antihypertensive drug regimens on 90-day mortality. A total of 13,142 patients were included in the final analysis. The 90-day mortality rate in the combined groups is lower than that in the single therapy group (10.94% vs 11.12%), but no statistical significance was found in the original cohort (p = 0.742). After adjustment for potential confounders, the significantly decreased 90-day mortality rate was found in the combined groups (10.78% vs 12.65%, p = 0.004 in PSM; 10.34% vs 11.90%, p = 0.007). Patients who were exposed to either ACEIs or ARBs had a better prognosis than those not exposed (7.19% vs 17.08%, p < 0.001 in single antihypertensive groups; 8.14% vs18.91%, p < 0.001 in combined antihypertensive groups). The results keep robustness in the PSM and IPTW cohorts. In the logistic regression model analysis, combined therapy was associated with a 12%-20% reduced risk of 90-day death after adjusting potential confounders (OR 0.80-0.88, all p < 0.05), while exposure to ACEIs or ARBs was associated with the decreased risk of 90-day death by 52%-62% (OR 0.38-0.48, all p < 0.001) and 40%-62% (OR 0.38-0.60, all p < 0.001) in the single and combined therapy groups, respectively. The results were still robust to subgroup analysis. Pre-admission combined antihypertensive therapy is associated with a significantly lower risk of death than exposure to single antihypertensives in critically ill patients. Meanwhile, either ACEIs or ARBs seem to be the optimal candidates for both single and combined therapy. Further high-quality trials are needed to confirm our findings.

Comparative Effectiveness of Single Versus Combination Antihypertensive Therapy in PROLANIS Hypertension Patients: A Retrospective Study in Purbalingga Regency

The PROLANIS program in Indonesia aims to manage chronic diseases like hypertension. While combination antihypertensive therapy is recommended for many patients, evidence on its effectiveness in the PROLANIS setting remains limited. This study investigated the comparative effectiveness of single versus combination antihypertensive therapy in achieving blood pressure control among PROLANIS hypertension patients in Purbalingga Regency. A retrospective cohort study was conducted using data from PROLANIS hypertension patients in Purbalingga Regency from January-December 2023. Patients were categorized into two groups: those receiving single antihypertensive therapy and those receiving combination therapy. The primary outcome was the proportion of patients achieving blood pressure control (&lt;140/90 mmHg). Secondary outcomes included changes in blood pressure, medication adherence, and adverse events. Multivariable logistic regression was used to adjust for potential confounders. A total of 1,250 patients were included, with 680 receiving single therapy and 570 receiving combination therapy. The proportion of patients achieving blood pressure control was significantly higher in the combination therapy group (65%) compared to the single therapy group (52%) (adjusted odds ratio [OR] 1.72, 95% confidence interval [CI] 1.35-2.20). Combination therapy was also associated with greater reductions in systolic and diastolic blood pressure. No significant differences were observed in medication adherence or adverse events between the two groups. Combination antihypertensive therapy is more effective than single therapy in achieving blood pressure control among PROLANIS hypertension patients in Purbalingga Regency. These findings support the use of combination therapy as the preferred approach for managing hypertension in this population.

Management of Hypertension in Patients with Type 2 Diabetes Mellitus: Indian Guideline 2024 by Association of Physicians of India and Indian College of Physicians.

In India and the Southeast Asian population, hypertension and type 2 diabetes mellitus (T2DM) are the leading lifestyle-related diseases, responsible for a majority burden of morbidity and mortality. Multiple population-spanning studies have revealed the staggering prevalence of both diseases in India, and the prevalence of both will only increase further due to factors such as an aging population, rapid urbanization, increased obesity, and sedentary lifestyles. More than 50 percent of hypertensive patients in India are also diagnosed with T2DM, and a detailed management protocol for the same is required, especially when a major portion of the disease is managed at the primary care level. The Association of Physicians of India (API) guidelines for the management of hypertension in patients with T2DM have been formulated based on consultation with leading physicians, cardiologists, diabetologists, and endocrinologists of India and Southeast Asia, keeping in mind the challenges faced by the patients in these countries and the appropriate management protocols that will be beneficial. While standard office-based blood pressure (BP) measurement forms the cornerstone of hypertension diagnosis and demands a uniform methodology to be followed, home blood pressure monitoring (HBPM) is recommended for long-term follow-up with validated devices. Ambulatory blood pressure monitoring (ABPM) offers comprehensive insights crucial for cardiovascular (CV) risk stratification. The complications of diabetic hypertension can span from increased CV risk, heart failure (HF), and renal dysfunction, and nonpharmacological and pharmacological management should be aimed toward not only control of the BP values but also protecting the end organs. While nonpharmacological measures include a focus on nutrition and diet, they also focus on approaches to weight loss, including a novel section covering the benefits of yoga. The guideline also focuses on a novel section of factors influencing CV risk, especially in the Indian population. For the pharmacological management, the guidelines address each of the categories of antihypertensive drugs, emphasizing the significance of combination therapies in the management of diabetic hypertension. In line with leading global guidelines for the management of hypertension in T2DM, for diabetic patients who often struggle with BP management and carry a high CV risk, the recommended dual combination antihypertensive therapy is particularly crucial and should be considered as first-line management therapy. While angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) play a highly beneficial role in the management of diabetic hypertension, a combination of ACEi or ARB with dihydropyridine calcium channel blockers (DHP-CCBs) is recommended to reduce the risk of complications and enhance patient adherence. To achieve the target of effective BP control and end-organ protection, it is beneficial and recommended to include newer CCBs (e.g., cilnidipine) in the management protocol in combination with ACEi/ARBs. Combination therapy including ARBs and DHP-CCBs should be preferred over β-blockers and thiazides. Among the CCBs, cilnidipine, a novel molecule, is a more effective and safer option for diabetic hypertensive patients in India. β-blockers should be used if there is a history of myocardial infarction (MI), HF, coronary artery disease (CAD), or stable angina along with the initial hypertensive regimen. The guideline also focuses on the novel reno- and cardioprotective molecules such as finerenone and sodium-glucose cotransporter 2 inhibitors (SGLT2i) and their benefits in the management of diabetic hypertension.

Estimated impact of guidelines-based initiation of dual antihypertensive therapy on long-term cardiovascular outcomes in 1.1 million individuals.

Guidelines recommend initiation of dual combination antihypertensive therapy, preferably single-pill combination (SPC), in most patients with hypertension. Evidence on narrowing gaps in clinical practice relative to guidelines is limited. Monte Carlo simulation was applied to 1.1 million patients qualifying for dual combination therapy from a previously conducted retrospective analysis of clinical practice, hospital statistics, and national statistics in the UK. We provide 10-year Kaplan-Meier event rates for the primary endpoint representing a composite of nonfatal myocardial infarction, nonfatal stroke (ischemic or hemorrhagic), nonfatal heart failure hospitalization or cardiovascular death. Cox model results from a previously conducted study were utilized to estimate baseline risk, together with evidence on risk reduction from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) meta-analysis and published evidence on BP-lowering efficacy of antihypertensive therapies. In the overall population, estimated 10-year event rates for the primary endpoint in patients with 100% persistence in monotherapy were 17.0% for irbesartan (I) and 17.6% for ramipril (R). These rates were only modestly better than that observed in clinical practice (17.8%). In patients with 100% persistence in dual therapy, estimated event rates were 13.6% for combinations of Irbesartan+Amlodipine (ARR=8.7% compared to untreated) and 14.3% for Ramipril+Amlodipine (ARR=8.0% compared to untreated). The absolute risk of the primary endpoint was reduced by 15.9% in patients with ASCVD and 6.6% in those without ASCVD. Similarly, the absolute risk was reduced by 11.7% in diabetics and 7.8% in those without diabetes. This study represents the first to investigate guidelines-based treatment in hypertensive patients and demonstrates the opportunity for considerable risk reduction by ensuring recommended dual therapy in clinical practice, particularly in the form of SPC with high persistence, relative to no treatment or monotherapy.

Cost-effectiveness of single-pill and separate-pill administration of antihypertensive triple combination therapy: a population-based microsimulation study

BackgroundSingle-pill combination (SPC) of three antihypertensive drugs has been shown to improve adherence to therapy compared with free combinations, but little is known about its long-term costs and health consequences. This study aimed to evaluate the lifetime cost-effectiveness profile of a three-drug SPC of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic vs the corresponding two-pill administration (a two-drug SPC plus a third drug separately) from the Italian payer perspective.MethodsA cost-effectiveness analysis was conducted using multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged ≥ 40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug dispensation until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies, assigning each of them to each cohort member. Costs and life-years gained were discounted by 3%. Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty.ResultsCompared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61–1.14), with a mean cost differential of -€12 (95% CI -9,719–8,131), making it the dominant strategy (ICER = -14, 95% CI -€15,871–€7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17–7,813) and €2,027 (95% CI 19–8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574–10,640 vs. €3,710, 95% CI 263–11,955). The cost-effectiveness profile did not significantly change according to age, sex, and clinical status.ConclusionsThe SPC was projected to be cost-effective compared with the two-pill combination at almost all reasonable willingness-to-pay thresholds. As it is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system.

Prevalence, awareness, treatment, and control of hypertension in community-dwelling older adults with chronic kidney disease: the Irish longitudinal study on ageing.

Hypertension is highly prevalent in chronic kidney disease (CKD), posing a significant but modifiable risk for adverse clinical outcomes. This study explored the prevalence, awareness, treatment, and control of hypertension in older Irish adults with CKD. Data were analysed from participants in Wave 1 of The Irish Longitudinal Study on Ageing (TILDA) who were aged 50 years and older. CKD was defined as eGFR <60ml/min/1.72 m2, hypertension defined as systolic blood pressure (SBP) ≥140mmHg and/or diastolic blood pressure (DBP) ≥90mmHg and/or self-reported use of antihypertensive medication. Participant awareness and treatment of hypertension was based on self-report and SBP/DBP <140/90mmHg. Multivariable logistic regression examined relationships with awareness, treatment, and control of hypertension expressed as adjusted odds ratios. Prevalence of hypertension was significantly higher in participants with CKD than without (81.9%vs 59.7%, P<.001). Among hypertensive individuals, 70.1% (95% CI: 65.8-74.1) were aware, 83.5% (95% CI 80.0-86.6) were on treatment, yet blood pressure control <140/90mmHg and SBP <120mmHg were achieved in only 49.3% (CI 44.0-54.7%) and 17.9% (CI 14.4-22.1), respectively. In multivariable analysis, advancing age 1.05 (CI 1.01-1.10), obesity 6.23 (CI 2.51-15.5), diabetes 5.78 (CI 1.55-21.5), and cardiovascular disease 9.89 (CI 3.27-29.9) were associated with higher odds of treatment, while cardiovascular disease 2.35 (CI 1.39-3.99) and combination antihypertensive therapy 1.76 (CI 1.03-3.01) were associated with blood pressure control. The prevalence of hypertension is substantial in older Irish adults with CKD; however, control is poor. Approximately, one-third of participants were unaware of their hypertensive status and approximately one-fifth were untreated.

Efficacy of combined antihypertensive therapy in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease with various polymorphisms of the CYP2C9 gene

Background. The difficulty of achieving target blood pressure (BP) levels in patients with arterial hypertension (AH) is often due to their type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). In turn, taking into account the individual genetic characteristics of the body helps to personalize treatment and make it more effective. Aim. To compare the antihypertensive efficacy of a fixed combination of amlodipine and olmesartan medoxomil (Aml/Ol-M) in patients with hypertension and T2DM, with and without NAFLD, depending on the polymorphism of the CYP2C9 gene. Materials and methods. The study included 139 patients with uncontrolled hypertension and concomitant T2DM; after diagnosis of NAFLD, they were randomized into 2 groups: without NAFLD (group 1, n=70), with NAFLD (group 2, n = 69). After discontinuation of previous ineffective antihypertensive therapy, they were prescribed a combination of Aml/Ol-M in doses of 5-10/20-40 mg/day. At baseline, 4, 8, 12 and 24 weeks, their office BP levels were determined; Also, at the initial visit and after 24 weeks of treatment, the main indicators of 24-hour blood pressure monitoring (ABPM) were measured. Patients who did not reach the blood pressure target within 12 weeks of therapy were excluded from the study. Those who continued to participate in the amplifierThe Rotor Gene-Q allele discrimination method revealed the following distribution of polymorphic variants of the CYP2C9 gene: *1/*1 was found in 52 and 47, *1/*2 – in 6 and 5, *1/*3 – in 5 and 6 subjects, for groups 1 and 2, respectively. Results. The initial levels of office BP values were significantly higher in patients of group 2 and amounted to 153,5 mm Hg for systolic and 93 mm Hg for diastolic blood pressure, compared with 145 mm Hg and 88 mm Hg those included in group 1. After 12 weeks of therapy, the achievement of target blood pressure was registered in 63 (90 %) patients of group 1 and in 58 (84,1 %) of group 2. After 24 weeks of observation, in both groups a beneficial effect of the studied combination of drugs on all indicators of ABPM was noted, but a more pronounced improvement was noted in patients with NAFLD. Along with this, significant improvements in daily blood pressure profiles were registered in both groups 1 and 2: an increase in the number of patients with the “dipper” profile and a decrease in the number of patients with the pathological “non-dipper” profile. The antihypertensive effectiveness of Aml/Ol-M has been demonstrated for all isolated allelic variants of the CYP2C9 gene. Conclusions. A 24-week study with the use of Aml/Ol-M demonstrated a high incidence of achieving office BP target values in patients with hypertension and T2DM, with and without NAFLD. However, a more pronounced decrease in ABPM levels was found in patients with NAFLD. Carriage of any of the identified polymorphic gene variantsCYP2C9 had no effect on the clinical effects of the studied combination.

Clinical Effectiveness of the Fixed‐Dose vs Free‐Dose Triple Combinations in Patients with Uncontrolled Arterial Hypertension

Background: The purpose of our study was a comparative assessment of the antihypertensive effectiveness of 2 triple combination antihypertensive therapy (AHT) regimens in a free-dose and fixed-dose combination of perindopril, indapamide, and amlodipine in hypertensive patients with high cardiovascular risk and a poor response to the 2-drug combinations in the clinic practice. Methods and Results: Our study included 143 patients (79 men and 88 women) with arterial hypertension (AH) Grades 1-3 (ESC/ESH, 2018) and high cardiovascular risk who did not achieve the target blood pressure (TBP) on dual combination AHT. The mean age of patients was 55.76±9.35 years; the average duration of AH was 10.69±6.61 years. All patients underwent the examinations according to the 2018 ESC/ESH Guidelines for the management of arterial hypertension. Patients included in the study were divided into 2 groups using the envelope method: Group 1 (n=84) received a fixed-dose, triple combination of perindopril, indapamide, and amlodipine; Group 2 (n=83) received a free-dose combination of these drugs. In both groups, treatment began after discontinuation of previous therapy, with a low dose of a triple combination of antihypertensive drugs (perindopril [5 mg/day], indapamide [1.25 mg/day], amlodipine [5 mg/day]) in the form of a fixed or free combination. The initial doses of perindopril/indapamide/amlodipine in both groups were not statistically different: 6.9±2.4/1.74±0.6/7.1±2.4mg/day in Group 1 and 6.9±2.7/1.95±0.6/7.1±2.5 mg/day in Group 2. After 4 weeks of therapy, if necessary, the doses of drugs were increased, starting with perindopril; the next adjustment of drug doses was carried out after 12 weeks of therapy. The final treatment results were determined after 24 weeks of AHT. Target blood pressure (TBP) of &lt;140/90 mmHg was reached by 94.4% of patients in Group 1 and 83.3% in Group 2 (χ²=7.471, Р=0,006); TBP of &lt;130/80 mmHg was reached by 70% of patients in Group 1 and 42% in Group 2 (χ²=11.61, Р=0,0001). A significant improvement in the diurnal BP profile was also revealed during treatment. According to ABPM data, both groups achieved TBP in terms of the average 24-h and average daytime systolic blood pressure (SBP) and diastolic blood pressure (DBP). Regarding average nighttime SBP and DBP and normalization of average nighttime diastolic blood pressure variability, target values were achieved only in Group 1(P=0.028). In both groups, 24-week triple-combination therapy led to a significant decrease in central SBP, central DBP, and pulse wave velocity (PWV). At the same time, the positive dynamics of central SBP were more pronounced in Group 1 than in Group 2 (Table 4), and PWV in Group 1 reached standard values. Conclusion: The results of our study showed that in the treatment of uncontrolled hypertension on previous therapy in AH patients with high cardiovascular risk, a single-pill triple combination of the ACEI perindopril, the CCB amlodipine, and the thiazide-like diuretic indapamide contributed to the effective daily blood pressure control, the improvement of diurnal blood pressure profile, and a positive effect on central blood pressure and PWV, thereby having a positive impact on the prognosis and quality of life of AH patients with high cardiovascular risk.

Review of international clinical guidelines for the management of hypertension in patients with diabetes mellitus?

Arterial hypertension (AH) is one of the leading problems of cardiological communities around the world. In patients with diabetes mellitus (DM), hypertension occurs 2 times more often than in the general population, being mutually aggravating diseases and leading risk factors for coronary heart disease, stroke, congestive heart failure and chronic kidney disease, which lead to disability and increased cardiovascular mortality. Various cardiological and endocrinological communities pay special attention to the management of hypertension in patients with DM, taking into account comorbidity. The present review examines modern approaches to the management of hypertension in DM patients based on current international clinical recommendations. Most of the current practical guidelines and clinical recommendations emphasize the need for early combined antihypertensive therapy for diabetes, which is due to the complex multifactorial pathogenesis and a more severe course of hypertension in disorders of carbohydrate metabolism. The main groups of antihypertensive drugs recommended for diabetes include: angiotensin converting enzyme inhibitors/angiotensin receptor blockers, thiazide/thiazide-like diuretics, calcium antagonists.

SINGLE-PILL COMBINATION ANTIHYPERTENSIVE THERAPY IN HYPERTENSIVE, OBESE PATIENTS: A PROSPECTIVE, EPIDEMIOLOGICAL STUDY IN ROMANIA

Objective: To assess the blood pressure (BP) management in obese, hypertensive patients under treatment with single-pill combination (SPC) antihypertensive therapy. Design and method: Prospective, observational, multicenter study, involving 192 investigators (85 cardiologists and 107 general practitioners) randomly selected from Romanian healthcare system, which included 1299 obese, hypertensive patients (Body Mass Index (BMI) of 30 kg/m2 or higher); 56.22±11years; 53.89% females) (1-month recruitment). The total study duration was 5 months (May-Aug 2023), while the patient observational period was 12 weeks (including 3 visits: baseline, at one month and at three months after inclusion). At enrolment visit each patient received a SPC antihypertensive therapy as per investigator’s decision, based on his/her own best medical judgement and in line with the current practice guidelines. Demographic data, comorbidities and data regarding hypertension and evolution of BP values in relation to the antihypertensive treatments were collected. Results: The study population had the following characteristics: BMI 34.35±4.21 kg/m2; 20.94% smokers, 56.81% with CV family history, and 52.12% had comorbidities. Among the patients with comorbidities the most frequently identified were diabetes mellitus type 2 (37.37%), valvular heart disease (20.97%), angina (19.35%) and heart failure (16.24%). At study inclusion the investigators’ perception regarding the cardiovascular (CV) risk was that only 27.02% of patients are in “very high” risk category, while according to SCORE2 and SCORE2-OP the actual calculated CV “very high” risk, was identified in 68.82% of patients. The most frequent recommended double SPC at study inclusion were perindopril/indapamide (81.68%) and olmesartan/amlodipine (5%). Hypertension was treated in all patients and systolic and diastolic BP values (SBP and DBP) and heart rate (HR) decreased significantly throughout the study (p&lt;0.001) (Fig. 1). Analyzing the patients treated with different double SPC a significant decrease in BP and HR values was observed (p&lt;0.001) for the perindopril/indapamide SPC, and olmesartan/amlodipine, respectively (Fig. 2). Conclusions: This study showed that single pill antihypertensive combinations are effective in decreasing BP and HR values in hypertensive obese patients, while correct CV risk estimation by clinicians remains challenging in their daily practice, with the tendency of underestimation.

Efficacy and safety of a single-pill versus free combination of perindopril/indapamide/amlodipine: a multicenter, randomized, double-blind study in Chinese patients with hypertension.

In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals. This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90 mmHg) were randomized to perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4 mg/indapamide 1.25 mg plus amlodipine 5 mg (Per/Ind + Aml) for 6 months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2 months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90 mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM). A total of 532 patients were randomized: Per/Ind/Aml ( n = 262) and Per/Ind + Aml ( n = 269). Overall, the mean (±SD) age was 55.7 ± 8.8 years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2 mmHg. Systolic BP decreased in both groups at 2 months from baseline: -14.99 ± 14.46 mmHg Per/Ind/Aml versus -14.49 ± 12.87 mmHg Per/Ind +Aml. A predefined noninferiority margin of 4 mmHg was observed ( P < 0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24 h. Both treatments were well tolerated. Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24 h in a single pill, with comparable safety.

Predictors of cardiovascular and renal complications in patients with resistant arterial hypertension during long-term follow-up

The aim – to evaluate the incidence of cardiovascular and renal complications and its predictors in resistant hypertensive (RH) patients during the long-term follow-up.Materials and methods. The frequency of cardiovascular and renal events was studied in 240 true resistant hypertensive patients. The duration of observation was 5.1±0.1 years. The comparison group consisted of 228 patients with controlled arterial hypertension (CAH) on a triple combination antihypertensive therapy. Cardiovascular endpoints included stroke/transient ischemic attack, myocardial infarction, cardiovascular death, myocardial revascularization, development of atrial fibrillation, hospitalization due to heart failure, and lower limb arterial disease. Kidney outcomes included dialysis or GFR decline by 40 % or greater. All the endpoints formed a composite primary endpoint. New cases of type 2 diabetes mellitus were also estimated.Results and discussion. The patients with resistant hypertension on multi-component antihypertensive therapy and significant reduction in arterial blood pressure (BP) levels (achievement of controlled office BP in 49.6 % of patients, office and ambulatory BP in 34.2 % of patients), maintained a higher risk of cardiovascular and renal events compared to patients with controlled arterial hypertension. It was found that the frequency of occurrence of the composite primary endpoint in resistant hypertensive patients was four times higher than in the group of patients with controlled hypertension – 30.0 % (72/240) versus 7.0 % (16/228) (p=0.001). The frequency of new cases of type 2 diabetes mellitus in patients with RH exceeded compared to CAH patients by 3.7 times (p=0.03).Conclusions. Independent predictors of the risk of cardiovascular and renal complications in patients with RH were the initial indicators of circulating endothelial progenitor cells if their concentration in the blood was ≤ 1818 cells/ml (HR 0.41; 95 % CI (0.21–0.79); p=0.007), the content of citrulline in the blood is more than 68 μmol/l (HR 1.13; 95 % CI (1.07–1.20); p&lt;0.001); value of initial average daily systolic BP &gt; 163 mm Hg (HR 1.10; 95 % CI (1.03–1.18); p=0.008).

Final conclusions of the own investigations of combined antihypertensive treatment on clinical state in patients with arterial hypertension without and with diabetes mellitus: use of own materials in education in nation. and Engl. languages at pre- and po

General practice – family medicine department. Object of investigation – patients with confirmed diagnosis of arterial hypertension without and with diabetes mellitus of second type, which were under observation at the primary medical care centers. &#x0D; The aim of the investigation was the study of efficiency of the combined (calcium channel blocker – amlodipin besilat and angiotensin II receptor antagonist – valsartan) antihypertensive treatment in patients with arterial hypertension combined with diabetes mellitus from the start of the treatment in the practice of primary care physician.&#x0D; Methods of the investigation included physical examination, general clinical, instrumental and laboratory methods, monitoring of side effects.&#x0D; As a result it was found, that combined antihypertensive treatment (amlodipin and valsartan) is effective and safe in patients with arterial hypertension and diabetes mellitus of 2 type, which helps to reach the target level of arterial pressure in 72 % of patients and can be recommended from the beginning of the treatment in the practice of family physician. Maximal effect of the treatment in patients with arterial hypertension of II-III degree and diabetes mellitus of 2 type was observed only at 12th week of treatment. At combined antihypertensive treatment (amlodipin and valsartan) they observed tendency to the reduction of left ventricle hypertrophy. Despite the rate and percentage of the reaching of target arterial pressure were lower in the group of patients, which have diabetes mellitus of 2 type, it is necessary to recommend more active modification of the way of life in the named group of patients. It was found reduction of heart and vascular risks in the group of patients with arterial hypertension II–III degree with diabetes mellitus 2 type. This makes the basis for more active modification of life style and using from the start of the treatment combined antihypertensive therapy immediately. Consider all found results using from the start of the treatment combined antihypertensive therapy immediately by the primary care physician is proved for patients with arterial hypertension combined with diabetes mellitus.&#x0D; Accumulated materials (including theoretical reviews, demonstrative poster reports etc.) are used at training of interns in speciality «general practice – family medicine», during practical classes for higher courses education in national and English languages