Combination Therapy In Hypertension Research Articles

The prevalence of monotherapy and combination therapy in hypertension in China from 2019 to 2021: A nationwide population-based cross-sectional study.

There are no nationwide surveys on antihypertensive drugs in China. In order to assess the current status of antihypertensive drug therapy in patients with hypertension and analyzed factors that may affect combination therapy, using convenience sampling, we recruited 305,624 patients with hypertension from the Chinese Cardiovascular Association Database-Hypertension Center between January 2019 and December 2021. Chi-squared test was performed to analyze the administered antihypertensive drug types and their combinations in different hospital settings. Logistic regression was used to assess the factors influencing combination therapy. We found around 33.1% of the participants had stage 2 and above hypertension, of which 67.9% were treated with combination therapy. In community or general hospitals, the most common monotherapy was calcium channel blockers (CCB), angiotensin-converting enzyme inhibitor/angiotensin II receptor inhibitor (ACEI/ARB) and diuretic were the main single-pill combinations (SPCs), and ACEI/ARB and CCB were the main free combination. From 2019 to 2021, the rates of combination therapy increased (58.8%-64.1%) with SPCs from 25.9% to 31.0% and free combination from 31.9% to 32.6%. Patients aged<60 years, with stage 2 and above hypertension, with an education level of high school and above, visiting general hospitals, living in the eastern region of China, with hypertension risk factors and comorbidities, and without anxiety or depression were more likely to receive combination therapy (all P<.05). The combination therapy use rate increased yearly and the rate of SPCs rose obviously. Individual, hospital, and regional differences in patients with hypertension influenced combination therapy.

Trends in risk factor control and treatment among patients with non-alcoholic fatty liver disease and type 2 diabetes between 2000 and 2020: A territory-wide study.

We aimed to determine the trends in risk factor control and treatment among patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) in 2000-2020. We conducted a territory-wide cohort study of adult patients with NAFLD and T2D diagnosed between 1 January 2000 and 31 July 2021 in Hong Kong. T2D was defined by use of any anti-diabetic agents, laboratory tests and/or diagnosis codes. This study included 16,084 patients with NAFLD and T2D (mean age, 54.8± 12.0 years; 7124 male [44.3%]). The percentage of patients achieving individualised haemoglobin A1c (HbA1c ) targets increased from 44.5% (95% confidence interval [CI], 42.9-46.1) to 64.8% (95% CI, 64.1-65.5), and percentage of patients achieving individualised low-density lipoprotein-cholesterol (LDL-C) targets increased from 23.3% (95% CI, 21.9-24.7) to 54.3% (95% CI, 53.5-55.1) from 2000-2005 to 2016-2020, whereas percentage of patients achieving blood pressure control (<140/90 mm Hg) remained static at 53.1-57.2%. Combination therapy for diabetes increased, especially among those with poor glycaemic control, but there was no increase in combination therapy for hypertension. Fewer cirrhotic patients achieved blood pressure control and individualised LDL-C targets, but they were more likely to achieve individualised HbA1c targets than non-cirrhotics. Metformin and statins were underused in cirrhotic patients. Younger patients (18-44 years) were less likely to achieve individualised HbA1c targets than middle-aged (45-64 years) and older ones (≥65 years). From 2000 to 2020, glycaemic and lipid control improved significantly, whereas blood pressure control remained static among patients with NAFLD and T2D.

The Indian registry on current patient profiles & treatment trends in hypertension (RECORD): One year interim analysis.

In India, hypertension constitutes a significant health burden. This observational, non-interventional, prospective study was conducted in five centres across India to evaluate the current clinical practices for the management of hypertension. Participants were enrolled if they were newly diagnosed with essential hypertension or had pre-existing hypertension and were on the same therapeutic plan for the previous three months. At baseline, three months, six months, and one year, information on the patient and their treatment regimen was documented, and their quality of life (QoL) was evaluated. A total of 2000 individuals were enrolled in this study, with a mean age of 54.45 yr. Of these, 55.7 per cent (n=1114) were males, and 957 (47.85%) were newly diagnosed with hypertension, while 1043 (52.15%) had pre-existing hypertension. Stage 2 hypertension (systolic blood pressure (BP) >140 or diastolic BP ≥90 mmHg) accounted for more than 70 per cent of the participants (70.76% of pre-existing and 76.29% of newly diagnosed); the average duration of pre-existing hypertension was 68.72 months. Diabetes (31.6%) and dyslipidaemia (15.8%) were the most common comorbidities. In 43.3 per cent of the participants, monotherapy was used, and in 56.7 per cent (70.55% fixed-dose combination), combination therapy was used. Telmisartan (31.6%), amlodipine (35.2%), and a combination of the two (27.1%) were the most commonly prescribed treatment regimens. At three months, six months, and one year, treatment modifications were observed in 1.4, 1.05, and 0.23 per cent of the participants receiving monotherapy and 2.74, 4.78 and 0.35 per cent receiving combination therapy, respectively. In both groups, the proportion of individuals with controlled hypertension (≤140/90 mmHg) increased by more than 30 per cent after a year. At one year, physical and emotional role functioning, social functioning, and health improved considerably. Combination therapy for hypertension is increasingly preferred at the time of initial diagnosis. The efficacy, safety, and tolerance of the recommended medications were reflected by improvements in the QoL and the minimal changes in the therapeutic strategy required.

Abstract 14094: Characterizing Dual Combination Therapy Use In Treatment Escalation Of Hypertension: Real-world Evidence From Multinational Cohorts

Introduction: Over one billion adults have hypertension globally, of whom 70% cannot achieve hypertension control with monotherapy. Data are lacking on patterns of dual combination therapies prescribed to patients who escalate from monotherapy. Methods: We described dual combination therapy utilization using eleven electronic health record databases covering 118 million patients across eight countries. We identified patients who newly initiated dual combination of four most commonly used antihypertensive drug classes (angiotensin-converting enzyme inhibitor [ACEi] or angiotensin receptor blocker [ARB]; calcium channel blocker [CCB]; beta-blocker; and thiazide or thiazide-like diuretic) after being on monotherapy. Results: We identified 980,648 patients with hypertension initiating dual combination therapy with antihypertensive agents after being on monotherapy: 12,541 from Australia, 6,980 from South Korea, 2,096 from Singapore, 7,008 from China, 16,663 from Taiwan, 103,994 from France, 76,082 from Italy, and 754,137 from the United States (US). Significant variations in treatment utilization existed across countries and patient subgroups. In Australia and Singapore, starting an ACEi/ARB monotherapy followed by a CCB was most common while in South Korea, China and Taiwan, starting a CCB monotherapy followed by an ACEi/ARB was most common. In Italy, France, and the US, sequential use of an ACEi/ARB monotherapy followed by a diuretic was most common. Younger patients were more likely to be prescribed ACEi/ARB followed by either a CCB or a diuretic compared with older patients. Women were more likely to be prescribed diuretics then an ACEi/ARB or a CCB compared with men. Conclusion: A large variation in the transition between monotherapy and dual combination therapy for hypertension was observed across countries. These results highlight the need for future research to identify which dual combination therapy is most effective for which patients.

Starting Antihypertensive Drug Treatment With Combination Therapy

Starting Antihypertensive Drug Treatment With Combination Therapy

Adherence to Single-Pill Versus Free-Equivalent Combination Therapy in Hypertension: A Systematic Review and Meta-Analysis.

Poor adherence to antihypertensive therapy is a major cause of poor blood pressure (BP) control in patients with hypertension. Regimen simplification may improve adherence and BP control. This systematic review assessed whether single-pill combination (SPC) therapy led to improved adherence, persistence, and better BP control compared with free-equivalent combination (FEC) therapy in patients with hypertension. PubMed, Medline, Embase, and the Cochrane Library were searched until July 2020, in addition to manual searching of relevant congress abstracts from 2014 to 2020 for studies including adults with hypertension aged ≥18 years receiving SPC or FEC antihypertensive therapy measuring any of the following: adherence, persistence, and reductions in systolic BP and/or diastolic BP. Adherence and persistence were summarized in a narrative analysis; direct pair-wise meta-analysis was conducted to compare BP reductions with SPC therapy versus FEC therapy using fixed-effect and random-effects models. Following screening, 44 studies were included. The majority (18 of 23) of studies measuring adherence showed adherence was significantly improved in patients receiving SPCs versus FECs. Overall, 16 studies measured persistence, of which 14 showed that patients receiving SPCs had significantly improved persistence or were significantly less likely to discontinue therapy than patients receiving FECs. Systolic BP (mean difference, -3.99 [95% CI, -7.92 to -0.07]; P=0.05) and diastolic BP (-1.54 [95% CI, -2.67 to -0.41]; P=0.0076) were both significantly reduced with SPC therapy compared with FEC therapy at week 12. SPC therapy leads to improved adherence and persistence compared with FEC therapy and may lead to better BP control in patients with hypertension.

Effects of an Antihypertensive Combination in Japanese Hypertensive Outpatients Based on the Long-acting Calcium Channel Blocker Benidipine on Vascular and Renal Events: A Sub-analysis of the COPE Trial

In the trial known as COPE (Combination Therapy of Hypertension to Prevent Cardiovascular Events), three benidipine (a Calcium Channel Blocker; CCB) regimens were compared. Hypertensive Japanese outpatients aged 40-85 years (n=3,293) who did not achieve the target blood pressure of <140/90 mmHg with benidipine 4 mg/day were treated with the diuretic thiazide (n=1,094) or a β-blocker (n=1,089) or an additional Angiotensin Receptor Blocker (ARB; n=1,110). A significantly higher incidence of hard cardiovascular composite endpoints and of fatal or non-fatal strokes was observed in the benidipine-β-blocker group compared to the benidipine-thiazide group. We further evaluated the treatment effects of the three benidipine-based regimens on vascular and renal events in a sub-analysis of the COPE patients. A total of 10 vascular events (0.8 per 1,000 person-years) including one aortic dissection (0.1 per 1,000 person-years) and nine cases of peripheral artery disease (0.8 per 1,000 person-years) were documented, as was a total of seven renal events (0.6 per 1,000 person-years). No significant differences in vascular and renal events were revealed among the three treatment groups: vascular events, p=0.92; renal events, p=0.16, log-rank test. Blood pressure-lowering therapy with benidipine combined with an ARB, β-blocker, or thiazide was similarly effective in the prevention of vascular and renal events in hypertensive outpatients, although there are not enough events to compare the difference in the three treatment groups.

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

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

Hypertension and menopause

The climacteric period (menopause) is one of the most important periods in a woman’s life, reflecting the natural extinction of the reproductive function. Current hormonal changes and developing menopausal disorders initiate the formation of pathological conditions that have a negative impact on both the health and expectancy of life and its quality. Cardiovascular diseases are one of the most common pathological conditions. Arterial hypertension (AH) is a key risk factor for the development of cardiovascular diseases, in different periods of menopause has various clinical and pathogenetic features that must be considered during treatment. Indapamide have pronounced antihypertensive effect, organ-protective properties and metabolic neutrality. It is drug of choice for mono- or combination therapy for women with hypertension during different periods of menopause. Effective antihypertensive and organ-protective action, metabolic neutrality and safety of nitrendipine use allow us to recommend this drug for combination therapy of hypertension in women in distant menopause. The combination of indapamide and nitrendipine may be one of the most effective tools for hypertension treating in women in distant climacteric period.

Co-Amorphous Simvastatin-Nifedipine with Enhanced Solubility for Possible Use in Combination Therapy of Hypertension and Hypercholesterolemia.

The high index of simultaneous incidence of hypertension and hypercholesterolemia in the population of many countries demands the preparation of more efficient drugs. Therefore, there is a significant area of opportunity to provide as many alternatives as possible to treat these illnesses. Taking advantage of the solubility enhancement that can be achieved when an active pharmaceutical ingredient (API) is obtained and stabilized in its amorphous state, in the present work, new drug-drug co-amorphous formulations (Simvastatin SIM- Nifedipine NIF) with enhanced solubility and stability were prepared and characterized. Results show that the co-amorphous system (molar ratio 1:1) is more soluble than the pure commercial APIs studied separately. Aqueous dissolution profiles showed increments of solubility of 3.7 and 1.7 times for SIM and NIF, correspondingly, in the co-amorphous system. The new co-amorphous formulations, monitored in time, (molar fractions 0.3, 0.5 and 0.7 of SIM) remained stable in the amorphous state for more than one year when stored at room temperature and did not show any signs of crystallization when re-heating. Inspection on the remainder of a sample after six hours of dissolution showed no recrystallization, confirming the stability of co-amorphous system. The enhanced solubility of the co-amorphous formulations makes them promising for simultaneously targeting of hypertension and hypercholesterolemia through combination therapy.

Effects of Long- and Intermediate-Acting Dihydropyridine Calcium Channel Blockers in Hypertension: A Systematic Review and Meta-Analysis of 18 Prospective, Randomized, Actively Controlled Trials.

Dihydropyridine calcium channel blockers are a heterogeneous group of antihypertensive drugs. Long-acting dihydropyridine agent amlodipine is widely used for monotherapy and combination therapy for hypertension in clinical practice, while intermediate-acting dihydropyridine agents have shown inconsistent results in randomized clinical trials (RCTs). A meta-analysis of 18 RCTs enrolling a total of 80,483 patients with hypertension followed for a mean of 51.4 months was performed. Amlodipine therapy was associated with 25% higher risk of heart failure (relative risk [RR]: 1.25, 95% confidence interval [CI], 1.05-1.49, P = .019) but 17% lower risk of stroke (RR: 0.83, [95% CI, 0.72-0.97], P = .009) without statistically significant effect on acute myocardial infarction (AMI) compared to major alternative antihypertensive therapy (MAAT), including β-blocker, diuretic, angiotensin-converting enzyme inhibitor, or angiotensin-receptor blocker. Intermediate-acting dihydropyridine calcium channel blocker therapy was associated with 25% higher risk of heart failure (RR: 1.25, [95% CI, 1.06-1.47], 0.005, P = .005) and 26% higher risk of AMI (RR: 1.26, [95% CI, 1.05-1.51], 0.019, P = .019) compared to MAAT. Results of the subgroup analysis suggested that the intermediate-acting dihydropyridine calcium channel blocker was associated with higher risk of heart failure (RR: 1.30, [95% CI, 1.08-1.56], P = .005) and AMI (RR: 1.50, [95% CI, 1.01-2.22], P = .043) compared to renin-angiotensin system blockers and a trend toward higher risk of AMI (RR: 1.17, [95% CI, 0.99-1.38], P = .064) compared to conventional therapy, including β-blockers and diuretics. Meta-regression analyses suggested that long-acting dihydropyridine calcium channel blocker is associated with lower risk of AMI ( B: -0.327, [95% CI, -0.530 to -0.123], P = .002) with a trend toward lower risk of stroke ( B: -0.203, [95% CI, -0.410 to 0.003] P = .054). This study suggests that Amlodipine offers greater protection against major complications of hypertension compared to intermediate-acting dihydropyridine calcium channel blockers.

Effectiveness of fixed-dose combination therapy in hypertension: systematic review and meta-analysis.

IntroductionClinical studies have revealed that fixed-dose combinations (FDCs) of drugs can have a better effect on blood pressure than free-equivalent combinations (FECs). Our objectives were to perform an up-to-date assessment of the effectiveness of FDCs and FECs in antihypertensive therapy, to provide more accurate results by using a stratified meta-analysis.Material and methodsA systematic review was performed in PubMed, Web of Science, and Cochrane databases according to PRISMA guidelines. The outcomes were adherence (compliance), persistence to medication, reduction of blood pressure and the safety profile. We used the Newcastle Ottawa scale or the Delphi list for the assessment of the quality of cohort studies or clinical trials, respectively. Heterogeneity was assessed using the Cochrane Q test and I 2 statistic.ResultsOf 301 abstracts screened, 26 primary studies and 2 other meta-analyses were identified, of which 12 studies were included in the meta-analyses and 3 studies were included in the narrative review. The FDC treatment is associated with a significant improvement in adherence and persistence in comparison with FEC treatment, e.g., the average medicine possession ratio increased with FDC by 13.1% (p < 0.001). For endpoints correlated with higher adherence (e.g., a reduction in blood pressure), a nonsignificant benefit was observed for FDCs. Moreover, it was demonstrated that higher adherence can lead to a lower risk of cardiovascular events.ConclusionsIn comparison with FECs, the FDC treatment is associated with a significant improvement in the cooperation between a doctor and a patient and with increased patients’ adherence to the treatment schedule.

Olmesartan-based monotherapy vs combination therapy in hypertension: A meta-analysis based on age and chronic kidney disease status.

Antihypertensive monotherapy is often insufficient to control blood pressure (BP). Several recent guidelines advocate for initial combination drug therapy in many patients. This meta‐analysis of seven randomized, double‐blind studies (N = 5888) evaluated 8 weeks of olmesartan medoxomil (OM)–based single‐pill dual‐combination therapy (OM+amlodipine/azelnidipine or hydrochlorothiazide) vs OM monotherapy in adults with hypertension. BP‐lowering efficacy, goal achievement, and adverse events were assessed in the full cohort and subgroups (elderly/nonelderly and patients with and without chronic kidney disease). In the full cohort at week 8, for dual therapy vs monotherapy, seated BP was lower (137.5/86.1 mm Hg vs 144.4/89.9 mm Hg), and the mean change from baseline in BP and BP goal achievement (<140/90 mm Hg) were greater (−22.7/−15.0 mm Hg vs −16.0/−11.3 mm Hg and 51.2% vs 34.7%, respectively). Adverse events were similar between groups. BP‐lowering efficacy among subgroups mirrored the findings in the full cohort whereby changes were significantly greater following OM dual‐combination therapy vs OM monotherapy.

One year adherence of ramipril versus ramipril/amlodipine fixed dose combination therapy in hypertension

In the treatment of hypertension avoiding adverse cardiovascular complications to achieve target blood pressure is essential. The appropriate drug selection, and if necessary to change to combination therapy, patients adherence is important which may help fixed dose combination. The aim of the authors was to investigate the one year adherence of the ramipril and ramipril/amlodipine fixed dose combination in hypertensive patients. Prescriptions database of the National Health Insurance Fund in Hungary on pharmacy-claims was analysed between October 1, 2012 and September 30, 2013. The authors identified patients who filled prescriptions for ramipril monotherapy and fixed dose combinations of ramipril/amlodipine prescribed for the first time in hypertensive patients who have not received similar drugs in the previous year. To model the adherence, the apparatus of survival analysis was used, where "survival" was the time to abandon the medication. As it was available to month precision, discrete time survival analysis was applied: a generalized linear model was estimated with complementary log-log link function with the kind of drug being the only explanatory variable. 92,546 patients met the inclusion criteria. During the trial period, ramipril therapy or ramipril/amlodipine fixed dose combination was started in 82,251 and 10,295 patients, respectively. One year persistence rate in patients with ramipril was 30% and 54% in patients with ramipril/amlodipine fixed dose combination therapy. Considering only the 360-day study period, the mean duration of persistence was 189.9 days in patients on ramipril and 270.6 days on ramipril/amlodipine fixed dose combination therapy. The hazard of discontinuation was more than twofold higher during treatment with ramipril compared with the use of the ramipril/amlodipine fixed dose combination therapy (HR = 2.11 [95% CI: 2.05-2.17], p<0,001). There is a significant difference between the one year persistence of ramipril and ramipril/amlodipine fixed dose combination therapy in hypertension. The result demonstrated that ramipril/amlodipine fixed dose combination therapy has a better one year persistence rate. When the next step is necessary to achieve target blood pressure, ramipril/amlodipine fixed dose combination therapy is preferable. Orv Hetil. 2017; 158(42): 1668-1673.

Abstract P480: Effects Of Long And Intermediate Acting Dihydropyridine Calcium Channel Blockers In Hypertension: A Systematic Review And Aeta-analysis Of 18 Prospective, Actively Controlled, Randomized Clinical Trials

Background: Dihydropyridine calcium channel blockers are a heterogeneous group of antihypertensive drugs. Long acting dihydropyridine agent Amlodipine is widely used for mono and combination therapy for hypertension in clinical practice, while intermediate acting dihydropyridine agents such as Felodipine, Nifedipine-GITS etc. have shown inconsistent results in randomized clinical trials (RCTs). Methods and Results: A meta-analysis of 18 prospective, actively controlled RCTs enrolling a total of 80,069 hypertensive patients followed for a mean of 51.7 months was performed. Amlodipine therapy was associated with 24% higher risk of heart failure (RR: 1.24, [95%CI: 1.04 to 1.48], p= 0.019) but 16% lower risk of stroke (RR: 0.84, [95%CI: 0.73 to 0.95], p=0.009) without statistically significant effect on acute myocardial infarction (AMI) (RR: 0.90, [95%CI: 0.78 to 1.03], p=0.128) or cardiovascular event (CVE) (RR: 0.99, [95%CI: 0.93 to 1.06], p=0.814). Intermediate acting dihydropyridine calcium channel blocker therapy was associated with 24% higher risk of heart failure (RR: 1.24, [95%CI: 1.07 to 1.44], p=0.005), 27% higher risk of AMI (RR: 1.27, [95%CI: 1.04 to 1.55], p=0.019), 14% higher risk of CVE (RR: 1.14, [95%CI: 1.01 to 1.29], p=0.034) without statistically significant effect against stroke (RR: 1.03, [95%CI: 0.87 to 1.21], p=0.580). Amlodipine showed higher risk of heart failure (RR: 1.20, [95%CI: 1.00 to 1.43], p=0.045) and lower risk of stroke (RR; 0.85, [95%CI: 0.75 to 0.96], p= 0.007) compared to Renin-angiotensin-system (RAS) blockers. Intermediate acting dihydropyridine calcium channel blocker showed higher risk of heart failure (RR: 1.31, [95%CI: 1.09 to 1.57], p=0.004) and AMI (RR: 1.46, [95%CI: 1.00 to 2.14], p=0.050) compared to RAS blockers. Multivariate meta-regression suggested that the effect size may differ between intermediate and long acting agents for stroke (B: -0.27, [95%CI: -0.50 to -0.05], p=0.012) and AMI (B: -0.42, [95%CI: -0.69 to -0.16], p=0.002) after adjustment for baseline presence of diabetes. Conclusions: This study suggests that Amlodipine offers greater protection against major complications of hypertension compared to intermediate acting dihydropyridine calcium channel blockers.

P1654Which is the best choice? One year persistence of ramipril, ramipril/amlodipin free and fixed dose combination therapy in hypertension

P1654Which is the best choice? One year persistence of ramipril, ramipril/amlodipin free and fixed dose combination therapy in hypertension

Czy terapia nadciśnienia tętniczego może zmniejszyć ryzyko zaburzeń funkcji poznawczych i otępienia?

Hypertension is an important risk factor for cardiovascular diseases and dementia. The efficacy of antihypertensive therapy, however, is still insufficient. Combination therapy of hypertension at least two drugs achieves the target blood pressure. The combination of perindopril and amlodipine is extensively studied well the combination of drugs, for which demonstrated a reduction in total mortality and cardiovascular events and stroke. The review explores molecular and clinical studies that might help explain the relation between the renin-angiotensin system, hypertension, and dementia and whether treatment with ACE inhibitor (perindopril) and CCB (amlodipine) have a part to play in the management of the disease.

Kombinační léčba hypertenze se zaměřením na fixní kombinace

Kombinační léčba hypertenze se zaměřením na fixní kombinace

DUAL NEPRILYSIN AND AT1-ANGIOTENSIN RECEPTOR BLOCKADE: A NOVEL APPROACH FOR ANTIHYPERTENSIVE AND NEPHROPROTECTIVE THERAPY

The review presents data on the role of natriuretic peptides in the pharmacodynamics of LCZ696 (sacubitril/valsartan) and the results of clinical studies evaluating its clinical efficacy in patients with arterial hypertension (HTN), including those with impaired renal function. LCZ696 when administered as monotherapy at doses 200–400 mg/day for 8 weeks causes a clinically significant antihypertensive effect in patients with essential HTN 1–2 degree, as well as when used in combination therapy in HTN 3 degree. Short-term use of the drug is not accompanied by angioedema occurrence or other side effects. These results apply mainly to patients with primary HTN with relatively preserved kidney function and without diabetes mellitus, as subjects with serum creatinine > 133 micromole/L and patients with type 1 and 2 diabetes mellitus were excluded. Available data show that LCZ696 at doses 200–400 mg/day for 8 weeks also provides obvious antihypertensive effect and a moderate decrease in albuminuria in patients with HTN 1–2 degree and chronic kidney disease 3–4 stage. The long-term, large-scale clinical trials are needed for a more complete assessment of the clinical efficacy and safety of LCZ696 in hypertensive patients, including patients with impaired renal function.

Evaluation of a Pharmacokinetic Interaction between Telmisartan and Chlorthalidone in Healthy Male Adult Subjects.

Combination therapy is recommended for the effective management of hypertension according to most treatment guidelines, including those of the US Joint National Committee. Therefore, pharmacokinetic drug interactions are an important issue in combination therapy for hypertension. In this study, the pharmacokinetic properties of telmisartan and chlorthalidone were evaluated to investigate their pharmacokinetic interactions in healthy subjects. Two separate, randomized, multiple-dose, two-period, one-sequence studies were conducted. In study A, 43 participants received 80mg of telmisartan orally for 7days, and were then administered oral chlorthalidone 25mg for 14days (days 8-21), coadministered with 80mg of telmisartan from day 15. In study B, 14 participants received oral chlorthalidone (25mg) for 13days, followed by coadministration with 80mg of telmisartan orally for 7days. The geometric mean ratios (GMRs) (90% confidence intervals [CIs]) of the maximum plasma concentration (C max,ss) and area under the concentration-time curve for the dosing interval at steady state (AUCτ,ss) of telmisartan (with and without chlorthalidone) were 1.018 (0.861-1.203) and 1.099 (1.015-1.190), respectively. For chlorthalidone (with/without telmisartan), the GMRs (90% CIs) for C max,ss and AUCτ,ss were 0.996 (0.922-1.075) and 0.992 (0.925-1.064), respectively. The GMRs and 90% CIs for telmisartan and chlorthalidone were all within the 0.80-1.25 range. Thus, in this study, there was no significant pharmacokinetic interaction between telmisartan and chlorthalidone. CLINICALTRIAL. NCT01806363.