BP Reduction Research Articles

HOME BLOOD PRESSURE MONITORING WITH A DIGITAL BLOOD PRESSURE COACH. A PROSPECTIVE ANALYSIS OF INDIVIDUAL USER DATA

Objective: The influence of baseline BP category and measurement duration on home blood pressure monitoring (HBPM) are still poorly defined, particularly when used in conjunction with a digital application. Design and method: This is a prospective analysis of real-world user data from a digital BP-coach (Manoa app ) in the period from April 2020 (release of the Manoa app) to November 2021 in Germany. The app was freely available in Germany during this period in all major app stores (iOS, Android). We analysed temporal BP changes and performed BP classification tracking in users with self-reported hypertension performing HBPM with a digital and interactive blood pressure coach. Results: Of 3175 users who enrolled in HBPM, 74.1% completed the first measurement period. Overall, mean systolic BP dropped significantly after the first day, but stratification by BP category demonstrated that initial category influenced BP course. BP classification tracking revealed that time to reach final BP category was dependent on baseline category, with users in categories high-normal and grade 1 hypertension requiring more days to decrease BP class volatility and to reach their definitive BP class. This was driven by an intense switching between directly neighbouring categories until the middle phase of the HBPM period, while more distant class switching occurred less often and only early on. Overall, > 90% of users maintained their category by day 5. Omitting the first day from analysis lead to therapeutically relevant reclassification in 3.8% of users. Users who completed at least two HBPM periods (n = 864) showed a mean SBP/DBP decrease of 2.6/1.6 mmHg, which improved hypertension control from 55.6% to 68.1%. Conclusions: With a digital HBPM-protocol, five consecutive measurement days are required for a reliable diagnosis and BP categorization. However, especially at therapeutic thresholds, additional measurement days are often required. Excluding day 1 from the protocol resulted in blood pressure reclassifications in 8.4% of all cases, with therapeutic relevance in 3.8% of cases. The optimal length of HBPM period depends on BP category. HBPM with a digital coach is associated with a reduction in average BP and improvement in BP control.

A PROSPECTIVE MULTICENTER RANDOMIZED SHAM-CONTROLLED CLINICAL TRIAL TO EVALUATE THE SAFETY AND EFFECTIVENESS OF NETRODTM RADIOFREQUENCY RENAL DENERVATION SYSTEM FOR HYPERTENSION

Objective: To evaluate the safety and effectiveness of a novel basket-like six-electrode radiofrequency renal denervation (RDN) system (NetrodTM RDN System) in treating patients with uncontrolled hypertension. Design and method: This is a prospective, multicenter, randomized sham-controlled trial. Patients with uncontrolled hypertension (office BP > = 150/90 and <180/110mmHg, and average SBP > = 135mmHg by 24-hour ambulatory BP monitoring (ABPM), after taking > = 2 antihypertensive drugs with stable dose for > = 4 weeks) were screened after informed consent. All eligible patients first entered a lead-in period for > = 4 weeks of standardized medication (Nifedipine + hydrochlorothiazide), and those continued to meet definition of uncontrolled hypertension were randomized 2:1 to RDN group (using NetrodTM RDN System) and sham control group (renal artery angiography only). All continued with the 2-drug regimen and were evaluated at 7 days or discharge (whichever comes first), 1, 2, 3 and 6 months post procedure. Both patients and site investigators who evaluate the patients were blinded to treatment assignment. The primary endpoint is office SBP change from baseline at 6 months post procedure. Secondary endpoints include changes from baseline of office DBP. 24-hour ABPM at 6 months post procedure and safety events. Results: A total of 205 patients from 25 centers were enrolled and 139 randomized to RDN group and 66 to sham control group, with no statistical difference of baseline clinical characteristics between the 2 groups including baseline BP. Compared to baseline, at 6 months post procedure RDN group has a significantly greater office SBP reduction than sham group (25.53 ± 12.62mmHg vs 8.39 ± 11.89mmHg, p < 0.001). Office DBP change was -13.49 ± 8.09mmHg (RDN) vs -3.93 ± 9.04mmHg (sham), p < 0.001. For 24-hour ABPM, the average SBP and DBP reduction were also significantly greater in the RDN vs sham group (11.91 ± 12.23 vs 3.87 ± 12.45mmHg, p < 0.001; 6.03 ± 7.50 vs 1.68 ± 7.30mmHg, p < 0.001, respectively). Device or procedure related serious adverse events were rare throughout the trial. Conclusions: The novel NetrodTM RDN System is safe and effective in treating uncontrolled hypertension with significant reduction in both office and 24-hour ambulatory BP.

HYPERTENSIVE URGENCIES AND EMERGENCIES. A QUESTIONNAIRE AMONG EXCELLENCE CENTERS OF THE EUROPEAN SOCIETY OF HYPERTENSION

Objective: The diagnostic approach as well as drug treatment algorithms for hypertensive urgencies(HU), hypertensive emergencies(HE) and malignant hypertension(MH)may be different across Europe,which may also be true for the knowledge of recently updated scientific information. We aimed to explore these items in the Excellence Center(EC)network of the European Society of Hypertension. Design and method: We conducted an anonymized electronic survey among our ECs Results: Overall, 65 ECs from 17 European and 5 non-European countries participated, mostly residents, clinical specialty was mainly Internal Medicine, Cardiology and Nephrology. The definition of HU was correctly identified by 46.1%, the definition of MH was correctly identified in 27.7%. The use of COX-1 antagonists, COX-2 antagonists, steroids and illicit drugs (cocaine, meth) is regularly investigated in 63.1, 69.2, 87.7 and 89.2%, respectively. Small, standard, large and extra large cuffs are available in 73.8, 93.8, 95.4 and 63.1 %, respectively. BP is measured more than once in almost all centers. Common measures/investigations of organ damage performed are renal function(96.9%), electrocardiogram (95.4%), urinary protein(89.2%), echocardiography(80%), fundoscopy(69.2%), myocardial injury markers (64.6%), and chest radiography(53.8%). Dedicated protocols for management of HU/HE are available in 70.8% of centers. HUs are treated with oral antihypertensives in 70.8%, with i.v. antihypertensives in 20%, and combinations of both in the remainder. HEs are treated with i.v. antihypertensives in 84.6%, with oral antihypertensives in 4.6%, and combinations of both in the remainder. Commonly used antihypertensives in HE are i.v. nitrates(73.8%), i.v. furosemide (64.6%), i.v. labetalol(61.5%), i.v. nitroprusside(41.5%), i.v. urapidil (38.5%), i.v./i.m. clonidine (27.7%), i.v. nicardipine(24.6%), oral captopril(26.2%) and s.l. nifedipine (24.6%), while some of these drugs are not available in up to one quarter of ECs. BP reduction goals in HE have a tendency to depend on the clinical presentation in 44.6%, while achieving less than 25% of BP decrease in 36.9%. Reasons to admit patients to hospital include signs of acute organ damage(90.8%), and inability to decrease BP inspite of i.v. medications(47.7%), whereas a hypertension specialist is consulted in 10.8%. Conclusions: This survey higlights the need to further spread the updated scientific information on the management and treatment of HE and HU.

Evaluation of the Efficacy and Tolerability of a Fixed Dose Combination of Amlodipine And Indapamide in Patients Older Than 55 Years

Background: There is very limited real-life data on hypertension management in Bangladeshi population. Considering this fact, this study evaluated the effectiveness of treatment with an indapamide/amlodipine single-pill combination (SPC) in Bangladeshi patients over the age of 55 years, in an OPD setting with uncontrolledsystolic hypertension in real-life clinical practice. Methods: This was a 3-month, multicenter, observational, open-label study conducted in 3 divisional cities of Bangladesh among patients with grade I or II hypertensions who were either uncontrolled on previous antihypertensive treatment or treatment-naïve. The effectiveness of indapamide/amlodipine SPC was assessed by the change in office systolic blood pressure (SBP) and the rate of target SBP (< 140 mmHg)achievement at 2 weeks, 1 month and 3 months, in four age groups: 55–59 years, 60–69 years, 70–79 years, and80 years or older. Results: The COMBINE study recruited 213 patients, of whom 185 took indapamide/amlodipine 1.5/5 mg SPC forafull three-month course of therapy.Mean age was 62.4±7.4 years, 76 men [41.1%] and 109 women [58.9%]. The absolute decrease of SBP during 3 months of taking indapamide/amlodipine single-pill combination (SPC) was 27.7 mm Hg, DBP - 10.2 mm Hg.After 3 months of treatment significant SBPdecreases from baseline were observed in each age group:”29.9 mmHg (from 156.7 to 126.8),”25.1 mmHg (from 152.7 to 127.6),”26.1 mmHg (from 152.8 to 126.7),and “ 24.5 mmHg (from 151.8 to 127.3)in the 55–59, 60–69, 70–79, and 80 years and older age groups, respectively. Conclusion: This COMBINE study results showed that indapamide/amlodipine SPC was associated with significant and rapid reductions in BP even in a different age range of Bangladeshi patients in routine clinical practice. This study result is consistent with already achieved data of this SPC globally. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 200

A systematic review and meta-analysis of all sham and placebo controlled trials for resistant hypertension

IntroductionThere is a lack of consensus regarding the best add on therapy for treatment of resistant hypertension (RH). This is likely secondary to a paucity of data on the comparative effectiveness of proposed therapies for RH. MethodsPlacebo-controlled and sham-controlled randomized clinical trials testing therapies for the treatment of RH were included in this meta-analysis. Therapies with two or more studies were included as subgroups in this meta-analysis. The primary outcomes being tested were 24-hr systolic blood pressure (SBP) and office SBP. ResultsEight studies were identified that tested mineralocorticoid receptor antagonist (MRA) including 1,414 participants. The raw mean difference (RMD) between MRA and placebo control was statistically significant for 24-hour SBP (-10.56 mmHg; 95% confidence interval (CI) -12.82 to -8.30), 24-hour diastolic (DBP) (-5.48 mmHg; 95% CI -8.48 to -2.58), office SBP (-11.97 mmHg; 95% CI -16.41 to -7.54), and office DBP (-4.14 mmHg; 95% CI -5.62 to -2.65). Six studies were identified that tested renal denervation (RD) including 989 participants. The RMD between RD and sham control was not statistically significant for 24-hour SBP (-1.84 mmHg; 95% CI -3.92 to 0.24), 24-hour DBP (-0.66 mmHg; 95% CI -1.85 to 0.54), office SBP (-1.57 mmHg; 95% CI -6.04 to 2.89), and office DBP (-1.49 mmHg; 95% CI -3.52 to 0.55). Four studies were identified that tested endothelin receptor antagonists (ERA) including 1,193 participants. The raw mean difference (RMD) between ERA and placebo control was statistically significant for 24-hr systolic (SBP) (-7.02 mmHg; 95% CI -9.15 to -4.90, 24-hr diastolic (DBP) (-6.22 mmHg; 95% CI -7.61 to -4.82), office SBP (-5.84 mmHg; 95% CI -10.08 to -1.60), and office DBP (-3.73 mmHg; 95% CI -5.87 to -1.59). DiscussionMRA lowers BP in patients with RH more than RD, which seems to have little to no effect in RH. ERAs lead to a statistically significant reduction in BP but the confidence in efficacy is limited due to the low number of studies and differences in trial population. Individual factors and their impact on treatment response in RH should be investigated in future research.

Intravenous administration of apeling-13 induces a depressor response by releasing an unidentified substance

Apelin and APJ receptor play an important role in the regulating cardiovascular function; however, conflicting results have been reported regarding the effect of apelin on cardiovascular regulation. In this study, blood pressure and heart rate were measured by femoral arterial catheterization; and cardiac contractility was recorded by left ventricular catheterization through the right carotid artery in rats before and after intravenous administration of [pyr1]-apelin-13. The results show that intravenous administration of apelin-13 caused a dramatic reduction in BP but did not significantly alter heart rate and contractility. To study the mechanism of the apelin-induced depressor response, isometric tension was measured in isolated mesenteric arteries using a myograph approach. Surprisingly, treatment of the arteries with [pyr1]-apelin-13 did not cause relaxation of mesenteric arteries preconstricted with norepinephrine; however, treatment with plasma collected from rats that received intravenous administration of [pyr1]-apelin-13 caused pronounced relaxation of isolated arteries. Incubation with the guanylyl cyclase inhibitor, ODQ, blocked NO-induced relaxation, but did not significantly alter the relaxation response to the plasma from apelin-treated rats. Taken together, these findings demonstrate that intravenous injection of apelin causes a significant depressor response that is mediated by a NO-independent mechanism involving an unidentified substance released into the bloodstream leading to vasodilation.

Effectiveness of Amlodipine in the Control of 24-Hour Blood Pressure in Mild-to-Moderate Essential Hypertension: A Prospective, Multicenter, Observational Real-World Study from India.

Background Calcium-channel blockers (CCB) are a mainstay in the management of hypertension (HTN), and amlodipine is the preferred CCB due to its longer half-life and better safety. Patients and methods This practice-based, observational, real-world evidence study assessed the 24-hour ambulatory blood pressure (ABP) control in mild-to-moderate essential hypertensive patients (treatment naïve receiving amlodipine monotherapy, or as add-on therapy) in inadequately controlled blood pressure (BP goal not met after one month of existing therapy). One hundred four (62M/42F) patients between 18 and 65 years of age who received amlodipine 5/10 mg/day for >8 weeks were included after obtaining informed written consent. The primary outcome was a change from baseline in the mean 24-hSBP and DBP on ABP monitoring at eight (±1) weeks. Secondary outcomes were different from baseline in the mean morning, day-time, night-time, and last six-hour dosing interval period. Other outcomes assessed BP variability (dippers and non-dippers), and responder rates based on ABP monitoring and in-clinic trough cuff measurements. Safety outcomes included adverse effects reported, electrocardiogram, and laboratory abnormalities (hepatic and renal function). Changes in BP parameters in different sub-groups (age, gender, BMI, physical activity, occupation, duration of hypertension, the total daily dose of amlodipine, type of amlodipine therapy, and hypertension severity at baseline) were estimated. Results Of the 104 patients, 49 patients (completed eightweeks) were included in the per-protocol (PP) data for efficacy analysis. Safety analysis was done on the intent-to-treat (ITT) dataset. Significant reductions (p<0.0001) from baseline in all BP measurements on ABPM were observed at the end of eight weeks. Similar improvements were observed in office BP recordings. There was a marginal but non-significant (p>0.05) increase in the proportion of dippers and extreme dippers with amlodipine at the end of the eight-week treatment period. Conclusions Amlodipine 5/10 mg/day therapy used as monotherapy or adjuvant therapy provided significant reductions in both office BP and ambulatory BP over eight weeks.

Clinical outcomes of renin angiotensin system inhibitor-based dual antihypertensive regimens in chronic kidney disease: a network meta-analysis

This study comprehensively investigated clinical outcomes associated with renin angiotensin system inhibitor-based dual antihypertensive regimens in non-dialysis chronic kidney disease (CKD) patients. Keyword searches of databases were performed per PRISMA-NMA guidelines. Frequentist network meta-analysis were conducted with 16 head-to-head randomized controlled trials. The effect sizes of dichotomous and continuous variables were estimated with odds ratio (OR) and standard mean differences (SMD), respectively. The protocol is registered in PROSPERO (CRD42022365927). Dual antihypertensive regimens with combination of angiotensin receptor blockers (ARB) and calcium channel blockers (CCB) demonstrated substantially reduced odd of major cardiovascular disease (CVD) events over other regimens including angiotensin converting enzyme inhibitor (ACEI) monotherapy (OR 3.19) and ARB monotherapy (OR 2.64). Most significant reductions in systolic (SBP) and diastolic blood pressure (DBP) were observed with ARB-based CCB dual regimen over ACEI monotherapy (SMD 17.60 SBP and 9.40 for DBP), ACEI-based CCB regimen (SMD 12.90 for SBP and 9.90 for DBP), and ARB monotherapy (SMD 13.20 for SBP and 5.00 for DBP). However, insignificant differences were noticed for the odds of hyperkalemia, end stage renal disease progression, and all-cause mortality. ARB-based CCB regimen has the greatest benefits on BP reduction as well as major CVD risks in non-dialysis CKD patients.

Blood pressure dynamics during home blood pressure monitoring with a digital blood pressure coach-a prospective analysis of individual user data.

Self-monitoring of blood pressure at home is a better predictor of prognosis and recommended in hypertension guidelines. However, the influence of baseline blood pressure category and measurement schedule on BP values during a period of home blood pressure monitoring (HBPM) are still poorly defined, particularly when used in conjunction with a digital application. We analysed temporal BP changes and performed BP classification tracking in users with self-reported hypertension performing HBPM with a digital and interactive blood pressure coach. Of 3175 users who enrolled in HBPM, 74.1% completed the first measurement period. Overall, mean systolic BP dropped significantly after the first day, but stratification by BP category demonstrated that initial category influenced BP course. BP classification tracking revealed that time to reach final BP category was dependent on baseline category, with users in categories high normal and grade 1 hypertension requiring more days to decrease BP class volatility and to reach their definitive BP class. This was driven by an intense switching between directly neighbouring categories until the middle phase of the HBPM period, while more distant class switching occurred less often and only early on. Overall, >90% of users maintained their category by day 5. Omitting the first day from analysis lead to therapeutically relevant reclassification in 3.8% of users. Users who completed at least two HBPM periods (n = 864) showed a mean SBP/DBP decrease of 2.6/1.6 mmHg, which improved hypertension control from 55.6% to 68.1%. The optimal length of HBPM period depends on BP category. HBPM with a digital coach is associated with a reduction in average BP and improvement in BP control.

Evaluation of The Effects ofAmlodipine Therapy on Blood Pressure and KidneyFunction among Hypertensive Patients in Mosul City

The present snrdy was mnducted to evaluate fte effect of amlodipine on blmd p€ssurc and kidney function inpatients in Mosul clb,. Thirty patients participated in ftis S.rdy ( 14 female ard 16 nrale )Arnlodipine was administercd for a period of 8 weeks in doses of 5 to l0 mg once daily. Antlripentensive efficacy wasassesd by measurement of blood pressure by standand mercury sphygmomanometer before and afur rcdnent . Bloodsampleswercobtained fiomeachpatientbeforeardafurteatnentand tlreobtainedserawereanalpodforruralpaarnetasvririch they all measr"ned in serum by using mlorimetic and en4anaic mehod. Credinine cleararce was calculded bywingthe Cockoft and Gault ecluation.The resulb of the study showd that anlodipine drerqpy lead tl a sigrificant reduction in blood pressue tllrugfrout thestudy and about 5fflo ofthe patien8 exhibit BP reduction tc notmal values afur drerapy. CreAinine clearance was significarflyincreased afur the end of the sudy . All other renal parameten including urea , credinine, sodilnn and potassiumconcentdions showed a sigrificant reductions. It was concluded that therapy with arnlodipine car be useful ard effediveflrcmpyinhpefiensivepaientswith deterioratdkidneysfi.lictionin oncedailydosage.

Cost-effectiveness of a multicomponent quality improvement care model for diabetes in South Asia: The CARRS randomized clinical trial.

To assess the cost-effectiveness of a multicomponent strategy versus usual care in people with type 2 diabetes in South Asia. Economic evaluation from healthcare system and societal perspectives. Ten diverse urban clinics in India and Pakistan. 1146 people with type 2 diabetes (575 in the intervention group and 571 in the usual care group) with mean age of 54.2 years, median diabetes duration: 7 years and mean HbA1c: 9.9% (85 mmol/mol) at baseline. Multicomponent strategy comprising decision-supported electronic health records and non-physician care coordinator. Control group received usual care. Incremental cost-effectiveness ratios (ICERs) per unit achievement in multiple risk factor control (HbA1c <7% (53 mmol/mol) and SBP <130/80 mmHg or LDLc <2.58 mmol/L (100 mg/dL)), ICERs per unit reduction in HbA1c, 5-mmHg unit reductions in systolic BP, 10-unit reductions in LDLc (mg/dl) (considered as clinically relevant) and ICER per quality-adjusted life years (QALYs) gained. ICERs were reported in 2020 purchasing power parity-adjusted international dollars (INT$). The probability of ICERs being cost-effective was considered depending on the willingness to pay (WTP) values as a share of GDP per capita for India (Int$ 7041.4) and Pakistan (Int$ 4847.6). Compared to usual care, the annual incremental costs per person for intervention group were Int$ 1061.9 from a health system perspective and Int$ 1093.6 from a societal perspective. The ICER was Int$ 10,874.6 per increase in multiple risk factor control, $2588.1 per one percentage point reduction in the HbA1c, and $1744.6 per 5 unit reduction in SBP (mmHg), and $1271 per 10 unit reduction in LDLc (mg/dl). The ICER per QALY gained was $33,399.6 from a societal perspective. In a trial setting in South Asia, a multicomponent strategy for diabetes care resulted in better multiple risk factor control at higher costs and may be cost-effective depending on the willingness to pay threshold with substantial uncertainty around cost-effectiveness for QALYs gained in the short term (2.5 years). Future research needs to confirm the long-term cost-effectiveness of intensive multifactorial intervention for diabetes care in diverse healthcare settings in LMICs.

Down syndrome patients with normal hearts: are they really normal?

Even though congenital heart disease is a common finding in down syndrome (DS) patients, some of them have anatomically normal hearts. However, the term "normal" might not be suitable, as these patients usually suffer from functional cardiac dysfunction. Several research highlighted that despite the absence of anatomical heart defects, subtle cardiac function derangements are present in DS patients. We aim to assess cardiac functions by Two-dimensional echocardiography and tissue Doppler imaging (TDI) in pediatric DS patients who have anatomically normal hearts. One hundred seventy-two patients with karyotyping confirmed DS with anatomically normal hearts and 165 healthy normal control children were enrolled in the current study. Their cardiac functions were assessed using both 2-dimensional echocardiography and TDI. Both patients and controls had structurally and anatomically normal hearts. In DS patients, the right side of the heart showed a significant reduction in both systolic and diastolic functions. Systolic dysfunction was evident by significantly decreased levels of Tricuspid annular plane systolic excursion and systolic wave by TDI. Diastolic dysfunction of the right ventricle was evident by prolonged deceleration time by conventional echocardiography and a significant decrease in annular tissue doppler velocity during early diastole/late diastole ratio by TDI. The E/De ratio was significantly increased. Even with anatomically normal hearts, DS patients should undergo cardiac function assessment by echocardiography & TDI. TDI is superior to conventional echocardiography in detecting subtle cardiac dysfunction especially left ventricular diastolic dysfunction in DS patients. TDI showed a significant decrease in the early/atrial ratio of mitral valve annulus and prolongation of left ventricle isometric relaxation time in DS children. Also, the left ventricle E/De ratio was prolonged denoting elevated filling pressures and diastolic dysfunction. This indicates that the TDI has higher sensitivity to detect diastolic dysfunction than conventional Echocardiography. Biventricular TDI-derived myocardial performance index was found to be significantly increased in DS children.

Efficacy and Safety of Fixed-Dose Combination of Efonidipine and Telmisartan in Stage II Hypertensive Patients: Results from Randomized Clinical Trial

Aim: The aim of this study was to evaluate the anti-hypertensive efficacy of a fixed-dose combination (FDC) of Efonidipine 40 mg and Telmisartan 40 mg in Stage II hypertensive patients.&#x0D; Study Design: Multicentric, randomized, double-blind, parallel, comparative Phase III clinical trial.&#x0D; Methodology: This clinical trial was conducted at six geographically distributed sites across India and enrolled 240 Stage II hypertensive patients. They were randomized into two groups in a ratio of 1:1 using computer-generated block randomization to receive E+T (FDC of Efonidipine 40 mg + Telmisartan 40mg) or C+T (FDC of Cilnidipine 10 mg + Telmisartan 40 mg) group intervention once daily for a period of 90 days. The study site staff, investigator and patients were blinded to the treatment allocation. The primary endpoint of the study evaluated the mean reduction in sitting systolic BP (SBP) and diastolic BP (DBP) from baseline to day 90 whereas the secondary endpoints assessed were mean reduction in BP from baseline to day 30 &amp; 60, patients achieving target BP (&lt;140/90 mmHg) and the safety and tolerability of the investigational products based on the incidences of adverse events (AEs) reported.&#x0D; Results: A total of 118 subjects were randomized to the E+T group wherein the mean (±SD) SBP and DBP at baseline was 167.25 ± 4.68/107.26 ± 5.19 mmHg. After 30 days of treatment with the E+T group, the mean reduction in SBP/DBP of 29.37/18.06 mmHg was observed whereas at Day 60 reduction of 38.55/22.69 mmHg was seen from the baseline. At Day 90, SBP/DBP decreased to 119.41±14.99/81.67±4.29 mmHg with a mean reduction of 47.94/25.89 mmHg in the E+T group. During the study period, the difference in systolic blood pressure between the treatments with E+T and C+T was -0.48 mmHg, with the two-sided 95% confidence interval (CI) ranging from -4.54 to 3.58 mmHg. The corresponding difference in diastolic blood pressure was -0.77 (95% CI: -2.60 to 1.06) mm Hg. The upper boundary of the 95% CI was below the margin of 10 mmHg, confirming the non-inferiority of E+T to C+T. A total of 92% of patients who had been assigned to E+T treatment achieved their target BP goal. Only one patient reported an adverse event with E+T treatment. No unexpected AEs were reported in the E+T group suggesting its good safety and tolerability. Overall, the E+T treatment was effective, safe and well-tolerated by the patients for 90 days.&#x0D; Conclusion: It was concluded that the FDC of Efonidipine 40 mg and Telmisartan 40 mg was efficacious in the management of Stage II hypertension.

Short-term efficacy of non-pharmacological interventions for global population with elevated blood pressure: A network meta-analysis.

This study aims to compare the potential short-term effects of non-pharmacological interventions (NPIs) on prehypertensive people, and provide evidence for intervention models with potential in future community-based management. In this Bayesian network meta-analysis, Pubmed, Embase, and Web of science were screened up to 16 October 2021. Prehypertensive patients (systolic blood pressure, SBP 120-139 mmHg/diastolic blood pressure, DBP 80-89 mmHg) with a follow-up period longer than 4 weeks were targeted. Sixteen NPIs were identified during the scope review and categorized into five groups. Reduction in SBP and DBP was selected as outcome variables and the effect sizes were compared using consistency models among interventions and intervention groups. Grade approach was used to assess the certainty of evidence. Thirty-nine studies with 8,279 participants were included. For SBP, strengthen exercises were the most advantageous intervention group when compared with usual care (mean difference = -6.02 mmHg, 95% CI -8.16 to -3.87), and combination exercise, isometric exercise, and aerobic exercise were the three most effective specific interventions. For DBP, relaxation was the most advantageous intervention group when compared with usual care (mean difference = -4.99 mmHg, 95% CI -7.03 to -2.96), and acupuncture, meditation, and combination exercise were the three most effective specific interventions. No inconsistency was found between indirect and direct evidence. However, heterogeneity was detected in some studies. NPIs can bring short-term BP reduction benefits for prehypertensive patients, especially exercise and relaxation. NPIs could potentially be included in community-based disease management for prehypertensive population once long-term real-world effectiveness and cost-effectiveness are proven. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=151518, identifier: CRD42020151518.

PS-BPP04-9: THE RXPATH RANDOMIZED TRIAL OF THE HYPERTENSION CANADA PROFESSIONAL CERTIFICATION PROGRAM: A NOVEL IMPLEMENTATION STRATEGY FOR HYPERTENSION GUIDELINES

The uptake of clinical practice guidelines into practice is poor for many chronic conditions, including hypertension. We designed a guidelines-based educational program for primary care clinicians, the Hypertension Canada Professional Certification Program (HC-PCP, www.hypertension.ca/professional-certification-program). It consists of four online modules, an online prospective patient registry, and expert evaluations of the blood pressure measurement technique and case management by the learner. We then evaluated its impact on patient level outcomes. Objective: The objective of RxPATH was to determine the effect of the HC-PCP for pharmacists on systolic blood pressure reduction in patients with poorly controlled hypertension. Design and Methods: Design: Stepped wedge cluster randomized trial (unit of randomization was the pharmacy). Setting: Community pharmacies in Alberta, Canada Population: Pharmacists with prescriptive authority volunteered to participate. We enrolled patients with poorly controlled hypertension (BP &gt; 140/90mmHg or &gt; 130/80mmHg in those with diabetes), identified by their pharmacist. Intervention: Pharmacists were enrolled in the HC-PCP. They then provided this care to their patients with poorly controlled hypertension. Control: Pharmacists were given a copy of the Hypertension Canada Guidelines and provided usual care to their patients prior to undertaking the HC-PCP. Outcomes: The primary outcome was difference in change in systolic blood pressure between intervention and control groups at 3 months. We also evaluated patient satisfaction using the Consultant Satisfaction Questionnaire (CSQ). Results: We enrolled 890 patients from 61 pharmacies (104 pharmacists). Mean age was 61.6 (SD 14.1) years, 46% were female, 35.5% had diabetes, and mean baseline BP was 152.4 (SD 13.8)/87.0 (SD 10.6)mmHg. Change in systolic BP was 9.9 (SD 16.5) for the intervention group, compared to 9.9 (SD 16.2) mmHg in the control group, p = 0.29. Patient satisfaction using the CSQ was high at 76 (of 90 maximum). Conclusions: Most educational programs do not get evaluated at the patient level. RxPATH demonstrated that the HC-PCP intervention did not result in a greater reduction in systolic BP compared to control. While both groups did have clinically meaningful reductions in BP, possible reasons for lack of a difference with the intervention include: COVID-19 staffing/workload issues in pharmacies, selection bias for pharmacists interested in hypertension/contamination of usual care group, and short follow-up duration. Feedback on the HC-PCP from pharmacists was positive, patient satisfaction was high, and we plan to make this program widely available to primary care providers.

S-38-2: PREVENTION OF EXPERIMENTAL GENETIC HYPERTENSION - GENOMIC CLUES FROM THE KIDNEY

Brief treatment with renin-angiotensin system (RAS) inhibitors permanently reduces the genetic hypertension of the spontaneously hypertensive rat (SHR). The kidney is involved in this reprogramming, but relevant molecular genetic changes are unknown. We studied SHR kidney RNA differential expression (controlling for non-specific effects of lower BP) and DNA methylation 6 weeks after treatment with the angiotensin receptor blocker losartan from 10 to 14 weeks of age. RNA sequencing revealed a significant 6-fold (P &lt; 0.0001) increase in renin gene (Ren) expression during treatment. Six weeks later direct mean arterial pressure remained lower than untreated SHR (123 vs 140 mmHg, P = 0.001) and kidney Ren expression was reduced by 23% (P = 0.03) and DNA methylation within the Ren promoter region was significantly increased (P = 0.04). Experiments with the ACE inhibitor perindopril and renin immunohistochemical analyses confirmed significant long-term reduction in kidney Ren expression following RAS inhibition. Genomic RNA sequencing analysis identified 13 candidate genes (Grhl1, Ammecr1l, Hs6st1, Nfil3, Fam221a, Lmo4, Adamts1, Cish, Hif3a, Bcl6, Rad54l2, Adap1, Dok4) and the miRNA miR-145-3p that were significantly differentially expressed and correlated closely with decreased Ren expression. Ten of the candidates were central to gene networks that exhibited significant enrichment for genes relevant to BP and the RAS. We propose that reduced renin gene expression is a legacy of early RAS inhibition and responsible for the persistent reduction in BP in SHR.

Antihypertensive effect of telmisartan versus perindopril in hypertensive patients.

We performed this meta-analysis determining the antihypertensive effect of telmisartan versus perindopril in patients with essentialhypertension. The comparison of antihypertensive effects between telmisartan and perindopril were controversial. Pubmed, Web of Science, and Cochrane Central were searched for all published studies. The antihypertensive effects were assessed in 753 patients included in 7 trials with a mean follow-up of 20 ± 16 weeks. There was no significant difference between telmisartan and perindopril in reduction of systolic blood pressure (SBP, weighted mean differences (WMD) 0.02 (95% confidence interval (CI), ‒2.78, 2.81) mm Hg, p > 0.05). The reduction of diastolic BP (DBP) treated with telmisartan was greater than perindopril in these patients (WMD ‒2.05 (95% CI, ‒2.60, ‒1.49) mm Hg, p < 0.001). Considering the effects of different doses on BP reduction, a sub-analysis was performed. The reduction of DBP treated with 40 mg/day telmisartan was greater than 4‒5 mg/day perindopril (WMD ‒2.18 (95% CI, ‒2.83, ‒1.53) mm Hg, p 0.05). The reduction of DBP is greater treated with telmisartan than perindopril in patients with essentialhypertension (Tab. 2, Fig. 4, Ref. 34). Text in PDF www.elis.sk Keywords: essential hypertension, blood pressure, telmisartan, perindopril, meta-analysis.

S-21-3: EFFECTIVENESS AND ACCEPTABILITY OF MOBILE PHONE TEXT MESSAGING INTERVENTION TO IMPROVE BLOOD PRESSURE CONTROL (TEXT4BP) AMONG HYPERTENSIVE PATIENTS IN NEPAL

Objectives: In LMICs, the rapid uptake and availability of mobile phones provide excellent opportunities for host of an intervention. However, research on the effectiveness and acceptability of mHealth in these settings remains limited. The main objective of this feasibility study was to assess the effectiveness and acceptability of a mobile phone text messaging intervention (TEXT4BP) to improve blood pressure control and treatment adherence among hypertensive patients in Nepal. Design and Methods: The TEXT4BP study was a two-arm, parallel-group, unblinded, randomized controlled pilot trial that recruited 200 clinically diagnosed hypertensive patients aged 18–69 years visiting at a tertiary referral hospital in Kathmandu, Nepal. We co-designed the contextual text messages informed by the formative qualitative studies that used COM-B (capability, opportunity, motivation, and behavior) model and Technology Acceptance Model (TAM) model. Patients in the intervention arm (n = 100) received text messages containing information on hypertension, diet, medication, and physical activity three times per week for three months. The control arm (n = 100) received standard care. Primary outcomes were changes in blood pressure and medication adherence at three months. Secondary outcomes included blood pressure control, medication adherence self-efficacy, and hypertension knowledge. Feasibility measures, such as attrition rate, was calculated. A nested qualitative study assessed the acceptability of the intervention. Results: Over the 12 weeks of follow-up, the retention rate was 77%. The intervention group had a greater reduction in systolic and diastolic BP vs usual care [-7.09/-5.86 (p = 0.003) vs -0.77/-1.35 (p = 0.28) mmHg] [adjusted difference: systolic B = -6.50 (95% CI, -12.6; -0.33) and diastolic BP B = -4.60 (95% CI, -8.16; -1.04)] (fig 1), coupled with a greater proportion achieving target BP (70% vs 48%, p = 0.006) at three months. The intervention arm showed an improvement in compliance to antihypertensive therapy (p &lt; 0.001), medication adherence (p &lt; 0.001), medication adherence self-efficacy (p = 0.023), and knowledge on hypertension and its treatment (p = 0.013). In addition, intervention participants expressed a high rate of acceptability and desire to continue the TEXT4BP intervention in the future too. Conclusion: The TEXT4BP study has generated promising evidence that text messaging intervention is feasible, acceptable, and effective in improving blood pressure control in low-resource settings like Nepal. The findings will inform further large-scale mHealth research and contribute to clinical practice with evidence-based hypertension guidelines in Nepal. Trial reg: ACTRN12619001213134

PS-C34-4: EVALUATION OF EFFECTS ON BP AND CHOLESTEROL CHANGES AFTER MULTIPLE IMPUTATION FOR MISSING VALUES IN OBSERVATIONAL STUDY DATA OF POLYPILL

Purpose: The purpose of this study is to prove the effect of polypill on BP and cholesterol reduction effects by analyzing observational study data including missing. Method: Medical records were collected for a minimum of 8 weeks and a maximum of 24 weeks after the first prescription of the polypill for each subject for patients who changed their administration to the polypill, which was collected in a retrospective observational study at 71 centers in Korea. In the collected data, there were 1412 subjects, but at 8 weeks, 16 weeks, and 24 weeks, BP and cholesterol information were 30–50% or more missing. Therefore, the available data were analyzed with GLM and LMM, and complete case data with missing removed and the imputed data by MICE estimated with pmm algorithm at all time points were analyzed by LMM. Results: As a result of analyzing the available data with GLM in the improvement effect of SBP, it decreased relatively linearly until the 24th week, and as a result of analyzing the complete case data with LMM, overestimation appeared. However, as a result of analyzing the available data by MICE and LMM, the effect appears until the 8th week, which can be judged as relatively normal data, and is maintained thereafter. Available data can also be analyzed by LMM, and in this case, when the missingness is less than 50%, the results are similar to the case with MICE and LMM analysis. The improvement effects of DBP and LDL-C were similar to SBP. According to the data of this observational study, the administration of the polypill reduced SBP by 3.7 mmHg, DBP by 2.8 mmHg, and LDL-C by 14.8 mg/dL within 8 weeks of comsuming the polypill compared to the previous treatment. The effect was well maintained by 24 weeks. Conclusion: Interpretation of such RWD requires a lot of attention. Basically, errors in analyzing repeatedly measured data with GLM and errors in randomly deleting subjects with missing data should be taken care of. In addition, if there are less than 50% missing, it is convenient to LMM the available data, but if there are more than 50% missing, an unreasonable result has shown. In conclusion, it is expected that the change of administration to polypill can show additional improvement effects in the control of blood pressure and lipids in patients who are taking two or more of the existing antihypertensive and antidyslipidemic drugs at the same time.

PS-C31-5: COMPARISON OF THE BLOOD PRESSURE MANAGEMENT BETWEEN SODIUM GLUCOSE CO-TRANSPORTER 2 INHIBITORS AND GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONISTS

Background: Several large clinical studies using not only sodium-glucose co-transporter 2 inhibitors (SGLT-2is) but also glucagon-like peptide 1 receptor agonists (GLP-1Ras) showed the superiority on the renal outcome on patients with type 2 diabetes (T2DM). There is no direct comparison of renoprotective effects between these two drugs, further, the mechanism for the renoprotective effects is not fully understood. Our previous survey revealed the superiority of SGLT2i treatment for the renoprotective effects compared to GLP1Ra. We also reported the importance of the reduction of BP during treatment, however, there is no direct comparison between their BP lowering efficacies. Aim: This study aimed to compare the rates of achieving a target BP and the renal effects, with SGLT-2i and GLP-1Ra treatments, administered in Japanese patients with T2DM and poorly controlled BP. Methods: Kanagawa Physicians Association separately carried out retrospective surveys that included patients with T2DM receiving therapy with SGLT-2i or GLP-1Ra for more than one year. After excluding the patients who used both SGLT2i and GLP1Ra, 384 SGLT-2i- and 160 GLP-1Ra-treated patients, with a BP more than 130/80 mmHg, before treatment were included in this study. Propensity score (PS) for the SGLT2i treatment were calculated using logistic regression and the inverse probability weighting method with average effect for treatment (ATE) weight and the trimming of patients with 0.05 ≦ PS≦ 0.95. The BP control rates were compared using a generalized linear model. Results: In this study, the rage of the standardized difference between two treatments was form 0.02 to0.20. SGLT-2i treatment resulted in significantly higher BP control rates than GLP1Ra treatment (odds ratio [95%confidence interval] = 2.09 [1.08, 4.03], p = 0.03). Compared with GLP-1Ra-treated patients, SGLT-2i-treated patients had significantly larger decreases in diastolic BP, mean arterial pressure, and body weight (-3.8[-6.6, -1.1] mmHg, P = 0.006; -4.1[-7.2, -1.0] mmHg, P = 0.01; and -1.5 [-2.7, -0.4], P = 0.008, respectively) and increased annual estimated glomerular filtration rate (eGFR; 1.5 [0.05, 2.9] mL/min/1.73 m2/year, P = 0.04). Conclusion: In T2DM patients with poorly controlled BP, compared with GLP-1Ra, SGLT-2i treatment significantly improved BP management and increased eGFR. When the renoprotective effect is expected in the clinical practice, it is necessary to consider the degree of contribution to the achievement of BP control in addition to the characteristics of the drugs.