Uncontrolled Essential Hypertension Research Articles

P042 EFFECTIVENESS OF STRUCTURED TELEMONITORING BLOOD PRESSURE IN PRIMARY CARE: UNCONTROLLED HYPERTENSE COHORTS

Introduction: E-health has emerged as a pivotal resource in healthcare delivery due to its widespread coverage, ease, and acceptance, particularly for chronic diseases. We aim to establish the effectiveness of structured telemonitoring in managing blood pressure among patients with uncontrolled essential arterial hypertension. Methods: An analytical observational retrospective cohort study of uncontrolled hypertensive patients aged ≥ 18 was conducted, with follow-ups at 150 and 240 days. Patients in the telemonitoring cohort were provided with validated digital blood pressure monitors, underwent remote monitoring, and received weekly feedback for 30 days from a multidisciplinary team. Conversely, the non-telemonitoring cohort received usual care consisting of attendance to in-person medical consultations as part of our institution's cardiovascular-risk-prevention program. Results: 350 patients were included, with median ages of 55 and 66 years in the telemonitoring and non-telemonitoring cohorts, respectively. Over the 240-day follow-up, the telemonitoring group achieved a significant reduction in systolic (-20.99 mmHg; 95% CI 14.99- 27.50; p 0.000) and diastolic blood pressure (- 14.99 mmHg; 95% CI 10.00- 18.99; p 0.000) compared to usual care, which demonstrated reductions of 19.99 mmHg (95% CI 16.49- 22.50; p 0.000) in systolic blood pressure and 6.50 mmHg, (95% CI 4.50- 9.00; p 0.000) in diastolic blood pressure. Conclusion: Telemonitoring is an effective strategy for patients with uncontrolled arterial hypertension, leading to earlier and significant blood pressure reductions.

P145 EFFICACY AND SAFETY OF PERINDOPRIL/INDAPAMIDE/AMLODIPINE/BISOPROLOL SINGLE PILL COMBINATION IN PATIENTS WITH ESSENTIAL HYPERTENSION UNCONTROLLED ON TRIPLE THERAPY: AN INTERNATIONAL, RANDOMIZED, DOUBLE-BLIND, PHASE III TRIAL

Background and objectives: In hypertensive patients uncontrolled on triple therapy, guidelines recommend the addition of a fourth drug such as mineral corticoid receptor antagonists, or alternatively, a betablocker. They also support the use of SPCs at any step of the treatment to increase treatment adherence and BP control. Currently, no SPC of 4 drugs is available. This 4-month phase III trial aimed to demonstrate the superiority in BP reduction, ofperindopril/indapamide/amlodipine/bisoprolol (Per/Ind/Aml/Biso) SPC versus a free combination of Per/Ind/Aml in hypertensive patients uncontrolled on triple therapy at optimal doses. Methods: After a 2-month run-in period on the combination of Per/Ind/Aml at optimal doses (10/2.5/5 or 10/2.5/10 mg), patients with sustained uncontrolled essential hypertension with office SBP≥140mmHg and SBP at 24h-ambulatory blood pressure monitoring (ABPM)≥130mmHg received the quadruple SPC of Per/Ind/Aml/Biso (10/2.5/5/5 or 10/2.5/10/5 mg) or continued the same triple therapy for two additional months. Efficacy was assessed on office-SBP (primary endpoint), DBP, BP control, 24h-ABPM and home-BPM (HBPM). Results: 183 patients were randomized: 53.0% were men, mean age was 57.4±10.6 years, mean BMI was 28.2±2.6 kg/m2, and mean office SBP/DBP was 150.35±8.49/90.09±8.23mmHg. After two months, significantly greater decrease in office-SBP (-8.0mmHg, 95%CI [-11.9; -4.0]; p<0.0001) was observed in the quadruple SPC group (n=80) versus the triple therapy group (n=83). Greater decrease in the 24h-systolic ABPM was achieved with the quadruple SPC therapy (-7.5mmHg, 95%CI [-10.9;-4.1]; p<0.0001). Higher percentage of patients achieved 24h-ABPM and HBPM control in the SPC group 51.2% vs 20.7% (p<0.0001) and 60.7% vs 25.4%, (p<0.0001) respectively. After intentional 1-day SPC omission in patient volunteers (n=28), mean 24h-ABPM remained below the 130/80mmHg target, supporting the sustained efficacy of the SPC. Both treatments were well tolerated. Conclusion: The first quadruple SPC of Per/Ind/Aml/Biso demonstrated its superiority to the free combination of Per/Ind/Aml, offering a new alternative to treat effectively and safely patients with hypertension uncontrolled with a combination of Per/Ind/Aml at optimal doses.

Home blood pressure-lowering effect of a non-steroidal mineralocorticoid receptor blocker, esaxerenone, versus trichlormethiazide for uncontrolled hypertension: the EXCITE-HT randomized controlled study.

The EXCITE-HT study aimed to evaluate the efficacy and safety of esaxerenone versus thiazide diuretics (trichlormethiazide) as second-line treatment for Japanese patients with uncontrolled essential hypertension. This was a 12-week, multicenter, randomized, open-label, parallel-group study. The non-inferiority of esaxerenone to trichlormethiazide was confirmed if the upper limit of the two-sided 95% confidence interval (CI) for the difference in systolic blood pressure (SBP)/diastolic blood pressure (DBP) change between groups was below 3.9/2.1 mmHg. A total of 295 and 290 patients were included in the esaxerenone and trichlormethiazide groups, respectively. The non-inferiority of esaxerenone to trichlormethiazide was demonstrated: least squares mean change differences in morning home SBP/DBP at end of treatment (EOT) were -2.2 (95% CI, -3.6, -0.8) mmHg for SBP/-0.6 (-1.4, 0.2) mmHg for DBP. Morning home, bedtime home, and office BP significantly decreased (all p < 0.001) from baseline to EOT in both groups. The urinary albumin-to-creatinine ratio and N-terminal pro-brain natriuretic peptide level decreased from baseline to Week 12 in both groups, with no notable intergroup difference. Serum potassium elevations occurred more frequently with esaxerenone, while serum potassium reductions occurred more with trichlormethiazide. Uric acid elevations were observed in both groups, but more frequently with trichlormethiazide than esaxerenone. No cases of gout occurred in this study. Reductions in estimated glomerular filtration rate were similarly observed in both groups. EXCITE-HT is the first randomized controlled study to demonstrate evidence that esaxerenone is non-inferior to trichlormethiazide as second-line treatment for Japanese patients with uncontrolled essential hypertension, with no new safety concerns. The EXCITE-HT study demonstrated the non-inferiority of esaxerenone to trichlormethiazide in its morning home blood pressure lowering effect and safety profile in Japanese patients with uncontrolled essential hypertension who were previously treated with an angiotensin II receptor blocker or calcium channel blocker.

Effects of olmesartan and amlodipine on blood pressure, endothelial function, and vascular inflammation

BackgroundAnti-hypertensive drugs can improve vascular endothelial function. However, the mechanism remains to be elucidated. ObjectivesThis study sought to investigate mechanisms of anti-hypertensive drugs on improvement of vascular endothelial function in patients with essential hypertension. MethodsForty-five patients (mean age 58.5 ± 11.2 years) with uncontrolled essential hypertension were randomly assigned to receive olmesartan, an angiotensin II type 1 receptor blocker (ARB) (N = 23), or amlodipine, a calcium channel blocker (CCB) (N = 22), for 6 months. Endothelial function was evaluated by flow-mediated dilatation (FMD) of the brachial artery. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR) within the carotid arteries using 18F-fluorodeoxyglucose-positron emission tomography combined with computed tomography. ResultsThere were no significant differences of baseline clinical data between the ARB and CCB groups. Both anti-hypertensive drugs comparably lowered blood pressure and increased %FMD. TBR values were reduced by olmesartan (P < .001), while blood pressure variability was decreased by amlodipine (P = .004). Changes in %FMD from baseline (Δ%FMD) were inversely associated with ΔTBR in the olmesartan group (r = − .606, P = .003) and with Δsystolic blood pressure variability in the amlodipine group (r = − .434, P = .039). ConclusionOur study indicated that olmesartan and amlodipine could improve endothelial function in patients with essential hypertension in different manners, suppression of vascular inflammation, and decrease in blood pressure variability, respectively.

Efficacy of single-pill combination in uncontrolled essential hypertension: A systematic review and network meta-analysis.

This study aimed to evaluate the efficacy of single-pill combination (SPC) antihypertensive drugs in patients with uncontrolled essential hypertension. Through Searching Pubmed, EMBASE, the Cochrane Library, and Web of Science collected only randomized controlled trials on the efficacy of single-pill combination antihypertensive drugs in people with uncontrolled essential hypertension. The search period is from the establishment of the database to July 2022. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias Assessment, and statistical analyses were performed using Review Manage 5.3 and Stata 15.1 software. This review ultimately included 32 references involving 16 273 patients with uncontrolled essential hypertension. The results of the network meta-analysis showed that a total of 11 single-pill combination antihypertensive drugs were included, namely: Amlodipine/valsartan, Telmisartan/amlodipine, Losartan/HCTZ, Candesartan/HCTZ, Amlodipine/benazepril, Telmisartan/HCTZ, Valsartan/HCTZ, Irbesartan/amlodipine, Amlodipine/losartan, Irbesartan/HCTZ, and Perindopril/amlodipine. According to SUCRA, Irbesartan/amlodipine may rank first in reducing systolic blood pressure (SUCRA: 92.2%); Amlodipine/losartan may rank first in reducing diastolic blood pressure (SUCRA: 95.1%); Telmisartan/amlodipine may rank first in blood pressure control rates (SUCRA: 83.5%); Amlodipine/losartan probably ranks first in diastolic response rate (SUCRA: 84.5%). Based on Ranking Plot of the Network, we can conclude that single-pill combination antihypertensive drugs are superior to monotherapy, and ARB/CCB combination has better advantages than other SPC in terms of systolic blood pressure, diastolic blood pressure, blood pressure control rate, and diastolic response rate. However, due to the small number of some drug studies, the lack of relevant studies has led to not being included in this study, which may impact the results, and readers should interpret the results with caution.

Novel Therapies on the Horizon of Hypertension Management.

The rates of uncontrolled hypertension, along with downstream cardiovascular outcomes, has been worsening in this country. Despite the plethora of antihypertensive medications on the market, the prevalence of resistant hypertension (RH) is estimated to be 13.7%. Therefore in addition to increased clinical education and focus on lifestyle management of hypertension and medication compliance, new therapies are needed to address this rise in hypertension. A systematic review of the available medical literature was performed to identify emerging treatment options for RH. Six different pharmacologic classes and 2 procedural interventions were identified as being appropriate for review in this paper. The pharmacologic classes to be explored are non-steroidal mineralocorticoid receptor antagonists, aminopeptidase A inhibitors, dual endothelin antagonists, aldosterone synthetase inhibitors, atrial natriuretic peptide inhibitors, and attenuators of hepatic angiotensinogen. Discussion of procedural interventions to lower blood pressure will focus on renal denervation and devices that increase carotid baroreceptor activity. Promising medication and procedural interventions are being developed and studied to expand our treatment arsenal for patients with uncontrolled essential hypertension and RH.

Ambulatory blood pressure response to S-amlodipine in Korean adult patients with uncontrolled essential hypertension: A prospective, observational study.

Although amlodipine is recommended as the first‐line therapy for the treatment of hypertension, its use is limited by its potential side effects. S‐amlodipine is expected to be able to minimize side effects of amlodipine with a similar antihypertensive effect by removing the malicious R‐chiral form. However, sustainable blood pressure control with S‐amlodipine has not been well established yet. The purpose of the current study was to evaluate ambulatory blood pressure (ABP) profiles before and after a 12‐week treatment of S‐amlodipine. Patients received once‐daily S‐amlodipine 2.5 or 5 mg. ABP during 24 hr and office blood pressure were measured at baseline and after the 12‐week treatment. Primary endpoints were changes of systolic and diastolic 24 hr ABP. After 12‐week S‐amlodipine treatment, mean systolic ABP (‐15.1 ± 16.2 mmHg, p < .001) and diastolic ABP (‐8.9 ± 9.8 mmHg, p < .001) were decreased significantly. Both daytime and night‐time mean systolic BP and diastolic BP were also significantly decreased after the 12‐week treatment. Global trough‐to‐peak ratio and smoothness index after 12‐week S‐amlodipine treatment were .75 and .79 for SBP and .65 and .61 for DBP, respectively. Age ≥65 years (hazard ratio [HR]: 3.13; 95% confidence interval [CI]: 1.67–14.3) and nonalcohol drinking (HR: 3.09; 95% CI: 1.34–7.17) were independent clinical factors for target ABP achievement. Adverse drug reactions (ADR) were developed in 16 (6.4%) patients, including two (.8%) cases of peripheral edema. In conclusion, this study demonstrated the efficacy and safety of S‐amlodipine in patients with uncontrolled essential hypertension.

Renin-angiotensin-aldosterone system genotypes and cardiac remodeling response to essential hypertension

Abstract Background/Introduction Cardiac remodeling represent a response to uncontrolled essential hypertension (EHT). The morphological response is expressed by left ventricular (LV) mass index values and/or relative wall thickness (RWT) &amp;gt;0.42. Functionally response is expressed by isolated alteration of LV diastolic function (E/A&amp;lt;1). Purpose We aimed to establish the association between anatomical and functional adaptation to EHT, with two genetic variants of the renin-angiotensin-aldosterone system (RAAS): M235T-AGT and A3123C-R2 AngII. Methods In 139 hypertensive subjects cohort, we determined the M235T-AGT and A3123C-R2 AngII genotypes, using polymerase chain reaction-restriction fragment length polymorphism methods. The relationship between the studied RAAS gene polymorphisms and morphological and functional cardiac remodeling was assessed by multiple logistic regressions. Results We found that the C/C, A/C genotypes of the A3123C-R2 AngII polymorphism were statistically significantly associated with RWT&amp;lt;0.42 (p=0.033), so hypertensive patients carrying this genotype had a 2.7-fold increased risk to have a non-concentric type of cardiac response. The association was maintained even after adjustment for confounders - age, body mass index (BMI), systolic blood pressure (BP), and diastolic BP (p=0.008). We found statistically significant associations between LV diastolic dysfunction in hypertensive patients cohort carrying the T/T, M/T genotypes (M235T-AGT polymorphism) (p=0.037). Moreover, the association remained statistically significant even after adjustment for age, BMI, systolic BP, and diastolic BP (p=0.039). We could not identify any statistically significant associations between M235T-AGT, A3123C-R2 AngII polymorphisms, and LV mass index. Conclusion(s) Non-concentric type of cardiac response to essential hypertension was associated with A3123C-R2 AngII polymorphism. M235T-AGT polymorphism was found to be statistically significantly associated with alteration of LV diastolic function. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, as part of Doctoral Research Projects (DRP) 2016

Renal Denervation in Asia: Consensus Statement of the Asia Renal Denervation Consortium.

The Asia Renal Denervation Consortium consensus conference of Asian physicians actively performing renal denervation (RDN) was recently convened to share up-to-date information and regional perspectives, with the goal of consensus on RDN in Asia. First- and second-generation trials of RDN have demonstrated the efficacy and safety of this treatment modality for lowering blood pressure in patients with resistant hypertension. Considering the ethnic differences of the hypertension profile and demographics of cardiovascular disease demonstrated in the SYMPLICITY HTN (Renal Denervation in Patients With Uncontrolled Hypertension)-Japan study and Global SYMPLICITY registry data from Korea and Taiwan, RDN might be an effective hypertension management strategy in Asia. Patient preference for device-based therapy should be considered as part of a shared patient-physician decision process. A practical population for RDN treatment could consist of Asian patients with uncontrolled essential hypertension, including resistant hypertension. Opportunities to refine the procedure, expand the therapy to other sympathetically mediated diseases, and explore the specific effects on nocturnal and morning hypertension offer a promising future for RDN. Based on available evidence, RDN should not be considered a therapy of last resort but as an initial therapy option that may be applied alone or as a complementary therapy to antihypertensive medication.

ASSOCIATION OF ANGIOTENSINOGEN M235T AND ANGIOTENSIN CONVERTING ENZYME I/D POLYMORPHISMS WITH HYPERTENSION-MEDIATED CARDIAC, CAROTID DAMAGE AND DYSLIPIDEMIA

Objective: Uncontrolled essential hypertension (EHT) may cause left ventricular hypertrophy (LVH), carotid atherosclerosis (ATS) and increased intima media thickness (cIMT). The renin-angiotensin aldosterone system polymorphism could be associated with uncontrolled EHT. We analyze the relationship of M235T (angiotensinogen-AGT gene) and I/D (angiotensin converting enzyme-ACE gene) polymorphisms with carotid ATS, LVH and dyslipidemia as possible risk factors for ischemic cardiac events in EHT. Design and method: We included 153 patients with EHT. We collected data concerning BMI, triglyceride (TG), LDL cholesterol (LDL-C) levels. We performed cardiac and carotid ultrasound for LVH, carotid ATS presence, cIMT value. Genotype was determined using PCR and restriction fragment length polymorphism. Statistical analysis was performed using the EpiInfo7 software. Results: 69.93% of hypertensive patients were carriers of the M235T-AGT polymorphism, of which 67.3% were heterozygous. The prevalence of I/D-ACE in hypertensive patients was 62.6%, of which 59.4% was represented by carriers of the homozygous DD genotype. 7.84% of patients with EHT were homozygous for both genetic variations. 75.7% of carriers of the M235T-AGT polymorphism had LDL-hypercholesterolemia (HC), 44.8% had hypertriglyceridemia (HTG). Patients with HTG, carriers of the M235T-AGT, had a 2.58-fold increased risk (p < 0.007) to develop EHT. The presence of LVH, carotid ATS and c-IMT>1 mm was in 65.4%, 46.7% and 44% of hypertensive patients positive for the M235T-AGT polymorphism. Hypertensive patients with carotid ATS, carriers of the M235T-AGT polymorphism, had a 1.8-fold (p < 0.05) increased risk to develop ESH. The presence of c-IMT>1 mm showed a correlation trend without statistical significance (OR-1.7, p < 0.06). 69.2% of hypertensive patients, carriers of the I/D-ACE polymorphism, had LDL-HC, 37.3% had HTG. We evidenced the presence of LVH, carotid ATS and c-IMT>1 mm in 67%, 39.5% and 39.5% of hypertensive patients positive for the M235T-AGT polymorphism. Hypertensive patients with LDL-HC, carriers of the M235T-AGT polymorphism, had a 0.3-fold increased risk (p < 0.005) to develop EHT. LVH showed a correlation trend without statistical significance (OR-1.67, p < 0.06). Conclusions: Patients with EHT, carriers of the M235T-AGT polymorphism, presented HTG and carotid ATS as potential risk factors for ischemic cardiac events. Association between I/D-ACE polymorphism and LDL-HC is a protective factor for EHT.

Spontaneously hypertensive rats have greater impairments in regulating abdominal temperature than brain cortex temperature following physical exercise.

This study aimed to evaluate the changes in brain (Tbrain) and abdominal (Tabd) temperatures in spontaneously hypertensive rats (SHRs) following fatiguing exercise. Male normotensive Wistar rats (NWRs) and SHRs were used at 16 weeks of age. Their arterial pressure was measured by tail plethysmography prior to the experiments to confirm the hypertensive status of the SHRs. Then, the rats underwent implantation of an abdominal temperature sensor to measure Tabd and a guide cannula in the frontal cortex to enable the insertion of a thermistor to measure Tbrain. After a familiarization period, each animal was subjected to incremental speed exercises until fatigue in either a temperate (25 °C) or warm (32 °C) environment, followed by a 60-min post-exercise period at the same temperature at which they exercised. Tbrain, Tabd and tail-skin temperature (Tskin) were measured every min throughout the experiments. SHRs exhibited higher Tabd values than NWRs, and these higher values were transiently and persistently observed at 25 °C and 32 °C, respectively. For example, at 32 °C, Tabd was 0.84 °C higher in SHRs at the 25th min (large effect size). In contrast, regardless of the ambient temperature, SHRs exhibited similar Tbrain values as NWRs, indicating preserved Tbrain regulation following exercise in hypertensive rats. SHRs presented higher Tskin during the last half of the post-exercise period at 25 °C, whereas no inter-group differences were observed at 32 °C. In conclusion, the present results highlight that SHRs, an animal model that mimics uncontrolled essential hypertension in humans, exhibited greater impairments in regulating Tabd than Tbrain during the post-exercise period.

Correction to: Randomized trial of an increased dose of calcium channel blocker or angiotensin II type 1 receptor blocker as an add-on intensive depressor therapy in type 2 diabetes mellitus patients with uncontrolled essential hypertension: the ACADEMIE Study.

In the Original publication of the article, the legend appearing inside the flow chart has been incorrectly published.

Prevalence and real-world assessment of central aortic blood pressure in adult patients with essential hypertension uncontrolled on single anti-hypertensive agents

ObjectiveTo assess the prevalence of high central aortic pressure (CAP) in Indian patients with uncontrolled essential hypertension while on anti-hypertensive monotherapy. Also, to determine correlation between brachial blood pressure (BBP) and CAP, and ascertain if it is impacted by anti-hypertensive drug class and patients’ age. MethodsIn this real-world, observational, prospective study, patients (30–70 years) with uncontrolled BBP (systolic BP [SBP] ≥140 mmHg or diastolic BP [DBP] ≥90 mmHg) were enrolled. Treatment was adjusted at Visit 1 (baseline), based on BBP and at treating physicians’ discretion. Primary endpoint was proportion of patients with uncontrolled central aortic SBP (>125 mmHg) at baseline. Secondary endpoints were comparison of BBP and CAP across drugs classes and age groups at baseline and Visit 2 (End-of-study, ∼8 weeks post-baseline), and proportion of patients with uncontrolled central SBP at end-of-study. ResultsOf 2030 patients screened, 1949 patients reported at baseline and 1740 patients completed end-of-study visit. Central SBP was >125 mmHg for 84.3% patients at baseline, and 48% patients at end-of-study. Interestingly, at end-of-study, 6.6% patients still had uncontrolled brachial SBP and controlled central SBP, while 13.6% patients had uncontrolled central SBP and controlled brachial SBP. At both visits, brachial SBP and central SBP showed positive correlation across most drug classes and age groups. At baseline, ACE inhibitors showed better efficacy than other drug classes. At end-of-study, BP control was better with fixed-dose combinations, though free–drug combinations were more frequently prescribed. ConclusionMeasurement of CAP along with BBP can be vital in management of hypertension. Ctri registration numberCTRI/2015/10/006302.

Randomized trial of an increased dose of calcium channel blocker or angiotensin II type 1 receptor blocker as an add-on intensive depressor therapy in type 2 diabetes mellitus patients with uncontrolled essential hypertension: the ACADEMIE Study.

There is a lack of data on how to treat hypertensive patients with diabetes when treatment with medium doses of calcium channel blocker and angiotensin II type 1 receptor blocker (ARB) is insufficient to achieve the target blood pressure (BP). A total of 121 participants with type 2 diabetes and uncontrolled essential hypertension, who were receiving medium doses of amlodipine (5mg/day) and ARB, were enrolled. Participants were randomized to receive either a high dose of amlodipine (10mg/day) plus a medium dose of ARB (high-AML) or a medium dose of amlodipine (5mg/day) plus a high dose of ARB (high-ARB). The depressor effects of these two regimens were monitored using a telemonitoring home BP-measuring system. Fifty-four patients were excluded after an observation period, and the remaining 67 eligible participants were randomized into the two groups; 42 which had a record of their home BP for analysis. The change in morning home systolic and diastolic BP was greater in the high-AML than in the high-ARB (systolic BP; - 7.9mmHg vs. + 2.7mmHg; p = 0.0002, diastolic BP; - 3.9mmHg vs. + 0.6mmHg; p = 0.0007). In addition, the home systolic and diastolic BP before going to bed and office systolic BP were significantly reduced from week 0 only in the high-AML. An increased dose of amlodipine, but not ARB, reduced home morning BP in hypertensive patients with type 2 diabetes who were already receiving combination therapy with medium doses of amlodipine and ARB.

Serum concentration of renin-angiotensin system components in association with ACE I/D polymorphism among hypertensive subjects in response to ACE inhibitor therapy

ABSTRACTBackground: Renin-angiotensin system (RAS) is a complex network of enzymes and peptides with the essential role in blood pressure control. The relationships between RAS components, RAS-related genetic polymorphisms and therapy response in essential hypertension (EH) were widely explored but the results were inconclusive.Aim: The aim of this study was to explore the functional role of ACE insertion/deletion (I/D) polymorphism on the systemic quantity of angiotensin-converting enzyme (ACE), its homolog - ACE2, chymase and angiotensin II in EH patients with respect to achieved therapeutic blood pressure control.Results: Genotyping of ACE I/D polymorphism was performed among 140 patients with EH from Bulgaria. The serological analyses reveal the significant elevation of the serum quantity of all investigated enzymes in EH than normotensive controls. In addition, serum ACE2 (183.57 pg/ml; vs. 151.78 pg/ml; p = 0.02) and chymase (68.5 pg/ml; vs. 23.66 pg/ml; p = 0.034) were significantly higher in patients with uncontrolled EH than controlled EH in response to ACE-inhibitory therapy. Also, ACE I/D polymorphism showed a significant impact on the serum ACE and chymase levels. ACE quantity was the highest among carriers of DD-genotype, followed by ID and II-genotype. Contrary, chymase was in the highest quantity in II-genotype compared to ID-genotype (p = 0.025) and DD-genotype (p = 0.044).Conclusions: Our results suggest that insufficient blood pressure control by ACE-inhibitory therapy could be associated with elevation of serum ACE2 and chymase levels. Also, it appears that ACE I/D polymorphism may influence the circulating quantity of chymase in addition to ACE.

Rifampicin reverses nicardipine effect inducing uncontrolled essential hypertension

Dihydropyridine calcium-channel blockers are a known substrate for the cytochrome P450 isoform 3A4. Rifampicin, an antitubercular agent, is one of the most potent inducers of hepatic and intestinal CYP3A4 thus increasing dihydropyridine metabolism. We report a case of a 67-year-old hypertensive female treated with a four-drug antihypertensive regimen including a dihydropyridine (nicardipine 50mg bid), who was admitted for septic arthritis of the knee requiring antibiotic treatment with teicoplanin 400mg od and rifampicin 600mg bid. Six days after rifampicin initiation, she presented with Posterior Reversible Encephalopathy Syndrome due to uncontrolled hypertension. We hypothesized that disequilibrium of previously controlled hypertension was partially due to nicardipine ineffectiveness. Plasma nicardipine concentration was assessed through high-performance liquid chromatography 5 hours after coadministration of the two drugs and proved undetectable.

Blood pressure-lowering efficacy and safety of perindopril/indapamide/amlodipine single-pill combination in patients with uncontrolled essential hypertension

This 4-month, double-blind, randomized, controlled trial was designed to demonstrate the superiority of perindopril/indapamide/amlodipine single pill over perindopril/indapamide after 1 month and to determine further up-titration efficacy and safety in patients with mild-to-moderate hypertension. After a 1-month run-in period on perindopril/indapamide 5/1.25 mg, patients with SBP/DBP at least 150/95 mmHg and no diabetes or renal insufficiency received perindopril/indapamide/amlodipine 5/1.25/5 mg single pill or continued on the same treatment. At 1, 2, and 3 months, patients with uncontrolled blood pressure (SBP/DBP ≥ 140/90 mmHg) were gradually up-titrated with a higher dose of the triple therapy up to perindopril/indapamide/amlodipine 10/2.5/10 mg in both groups. Efficacy was assessed on office supine SBP (main criterion) and DBP, blood pressure control, and response rates. Treatment effect on ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM) parameters was also assessed in two subpopulations of 276 and 263 patients, respectively. A total of 454 hypertensive patients (diabetes and renal insufficiency excluded) were randomized, 227 to each group (56% were men, mean age was 55 years, blood pressure 162.3/101.1 mmHg). After 1 month, superior SBP (-3.1 mmHg, P = 0.02) and DBP (-2.8 mmHg, P < 0.001) reductions were observed with perindopril/indapamide/amlodipine, which were even more pronounced after excluding white-coat effect in the sustained hypertension population (-5.3/-3.7 mmHg). Similar results were observed in terms of blood pressure response (72 vs. 53%, P < 0.0001) and control rates (32 vs. 25%, P = 0.005). Up-titration was effective at each visit in both treatment arms (P < 0.001). Both ABPM and HBPM results confirmed the superiority of the triple therapy at 1 month on ASBP/ADBP and HSBP/HDBP: -4.5/-2.0 mmHg for ABPM (P < 0.001/P = 0.04), and -4.9/-3.1 mmHg for HBPM (both, P < 0.001). Up-titration steps resulted in further significant decreases in both ABPM and HBPM. Both treatment regimens were well tolerated regarding adverse events or laboratory testing. In particular, peripheral edema known to be amlodipine dose dependent, appeared in only a few cases, none with the highest dose. Hypotension, orthostatic hypotension, and cough whatever the dose were infrequent. There were no treatment-related serious adverse events. Perindopril/indapamide/amlodipine in a single pill produces superior reductions in blood pressure compared with dual therapy. Triple therapy up-titration was well tolerated and effective leading to BP control rates of over 80%. Analysis of 24-h ABPM and HBPM results corroborated these findings.

Single-Pill Combination of Perindopril/Indapamide/Amlodipine in Patients with Uncontrolled Hypertension: A Randomized Controlled Trial.

IntroductionPatients with hypertension often require a combination of three antihypertensive agents to achieve blood pressure control, but very few single-pill triple combinations are available. The aim of this study was to determine whether a single-pill triple combination of perindopril, indapamide, and amlodipine was as effective as a dual-pill combination of perindopril/indapamide plus separate amlodipine at reducing blood pressure in patients with uncontrolled, essential hypertension.MethodsThis international, multicenter, open-label, randomized controlled trial was conducted in men or women aged ≥18 years old with confirmed essential hypertension (SBP ≥140 and <160 mmHg and DBP ≥90 and <100 mmHg), uncontrolled on maximal dose antihypertensive monotherapy or with a single dose of dual therapy. Patients were randomly assigned to: single-pill triple combination of perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) or dual-pill combination perindopril 5 mg/indapamide 1.25 mg + amlodipine 5 mg (Per/Ind + Aml) once daily for 12 weeks. The primary endpoint was change in office supine SBP and DBP from baseline to week 12. The proportion of responders defined as those with normalized BP (SBP <140 mmHg and DBP <90 mmHg), and/or decrease of SBP ≥20 mmHg, and/or decrease of DBP ≥10 mmHg at week 12 (W12) compared with baseline was also assessed. Secondary efficacy endpoints included change in office supine SBP and DBP, response, and BP control at weeks 4 and 8. The tolerability of the treatments was also assessed.ResultsA total of 148 patients were randomized: 75 to Per/Ind/Aml and 73 to Per/Ind + Aml. Mean supine SBP and DBP were 149.1 ± 4.7 and 94.1 ± 3.1 mmHg, respectively, with no relevant between-group difference. At week 12, both triple-therapy regimens were associated with clinically significant reductions in SBP compared with baseline (−21.5 ± 11.7 and −20.0 ± 12.9 mmHg, respectively). Reductions in office supine DBP were also clinically significant (−15.3 ± 7.8 and −14.8 ± 9.0 mmHg, respectively). The proportion of treatment responders was high in both groups: 89.2 and 87.1%, respectively. The reduction in office supine SBP/DBP was already evident at week 4 and maintained for the duration of the study in both groups. The majority of patients were treatment responders at week 4 (89.2 and 82.9%, respectively) and had achieved BP control (87.8 vs. 78.6%, respectively), which was maintained until week 12 in both treatment groups. Both treatments were well tolerated with no between-group differences.ConclusionsIn adult patients with uncontrolled essential hypertension on treatment, single-pill triple-combination therapy with Per/Ind/Aml is as effective as the same dose dual-pill combination of Per/Ind + Aml. Both treatments were associated with clinically significant BP reductions compared with baseline and were well tolerated. Clinical trials number: http://www.controlled-trials.com ISRCTN: 16442558. Funding: Les Laboratoires Servier.Electronic supplementary materialThe online version of this article (doi:10.1007/s40119-017-0085-7) contains supplementary material, which is available to authorized users.

Home and Online Management and Evaluation of Blood Pressure (HOME BP) digital intervention for self-management of uncontrolled, essential hypertension: a protocol for the randomised controlled HOME BP trial

IntroductionSelf-management of hypertension, including self-monitoring and antihypertensive medication titration, lowers blood pressure (BP) at 1 year compared to usual care. The aim of the current trial is to assess the...

PS 14-41 SINGLE-PILL TRIPLE COMBINATION OF PERINDOPRIL/INDAPAMIDE/AMLODIPINE IN PATIENTS WITH ESSENTIAL HYPERTENSION

Objective: Hypertension is the major risk factor in Serbia for the morbidity and mortality of cardiovascular and cerebrovascular diseases. The majority of patients in Serbia need two or more antihypertensive drugs for adequate control of blood pressure. Design and Method: Study group consisted of 12 patients with uncontrolled essential hypertension without comorbidities randomized in two groups and followed for 12 weeks. The first group was treated with single-pill combination perindopril 5 mg/indapamide 1.25 mg and an additional tablet of amlodipine 5 mg. The second group received single-pill triple combination of perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg. Results: Our research showed a significant decrease in systolic (132.5 vs. 140.5 mmHg, P = 0.05) and diastolic (84.50 vs. 83.83 mmHg, P < 0.05) blood pressure from baseline (153/84.50 mmHg vs. 149.17/94 mmHg) in both groups after 12 weeks of treatment. There was a higher proportion of patients achieving target blood pressure (<140/90 mmHg) in the single-pill triple combination group (69.7%) in comparison with the other group (50%). Conclusions: Our results showed significant reductions in blood pressure and a high BP control rate with the single-pill triple combination perindropil/amlodipine/indapamide in patients with uncontrolled essential hypertension without comorbidities.