Antihypertensive Medication Use and Its Effects on Blood Pressure and Haemodynamics in a Tri-ethnic Population Cohort: Southall and Brent Revisited (SABRE)

Objectives:We characterised differences in BP control and use of antihypertensive medications in European (EA), South Asian (SA) and African-Caribbean (AC) people with hypertension and investigated the potential role of type 2 diabetes (T2DM), reduced arterial compliance (Ca), and antihypertensive medication use in any differences.Methods:Analysis was restricted to individuals with hypertension [age range 59–85 years; N = 852 (EA = 328, SA = 356, and AC =168)]. Questionnaires, anthropometry, BP measurements, echocardiography, and fasting blood assays were performed. BP control was classified according to UK guidelines operating at the time of the study. Data were analysed using generalised structural equation models, multivariable regression and treatment effect models.Results:SA and AC people were more likely to receive treatment for high BP and received a greater average number of antihypertensive agents, but despite this a smaller proportion of SA and AC achieved control of BP to target [age and sex adjusted odds ratio (95% confidence interval) = 0.52 (0.38, 0.72) and 0.64 (0.43, 0.96), respectively]. Differences in BP control were partially attenuated by controlling for the higher prevalence of T2DM and reduced Ca in SA and AC. There was little difference in choice of antihypertensive agent by ethnicity and no evidence that differences in efficacy of antihypertensive regimens contributed to ethnic differences in BP control.Conclusions:T2DM and more adverse arterial stiffness are important factors in the poorer BP control in SA and AC people. More effort is required to achieve better control of BP, particularly in UK ethnic minorities.

Difference in Antihypertensive Medication Pattern in the First Year Compared to More than a Year of Maintenance Hemodialysis: A Northern India Tertiary Care Experience

Introduction There is a high prevalence of hypertension in maintenance hemodialysis patients. Information regarding prevalent pattern of antihypertensive medications will help modify it to prevent future cardiovascular morbidity and mortality. Materials and Methods In this cross-sectional study, patients on maintenance hemodialysis, aged ≥18 years visiting Nephrology outpatient department (OPD) from April 2019 to May 2020 were included. The patients were divided into two groups based on their dialysis vintage, ≤12 months and >12 months. Their antihypertensive medication patterns and two-dimensional (2D) echocardiography (ECHO) findings were compared. Independent t-test was used to compare continuous variables. One-way analysis of variance was used to study the antihypertensive drug-dosing pattern in both the groups. Results Out of 250 patients, 131 had a dialysis vintage of ≤12 months, whereas 119 had a vintage of >12 months. There was no significant difference in the number of antihypertensive agents used in either of the vintage groups. Calcium channel blockers (87.02 and 89.07%, respectively, in ≤12 and >12 months' vintage groups) and β blockers (64.12 and 65.54%, respectively, in ≤12 and >12 months' vintage groups) were the commonly used antihypertensive agents. Metoprolol use was higher in ≤12 months' group, whereas carvedilol usage was higher in >12 months' group (p = 0.028). Mean pill burden was more than five in both the groups. Concentric left ventricular hypertrophy was significantly more common in >12 months' group. Renin–angiotensin system (RAS) blocking agent use was limited to 3% of patients. Conclusion This study shows a high antihypertensive pill burden in dialysis patients likely due to underlying chronic volume overload in addition to the perceived efficacy of certain class of drug in a frequent dosing pattern. Low use of RAS blocking agent was also underlined. This study highlights the need to bring about changes in the antihypertensive prescription pattern in line with the existing evidence.

Prescription audit of antihypertensive drugs used in stroke patients in a tertiary care teaching hospital

Background: Stroke is considered as one of the important reasons of death and disability worldwide. A rational use of medications is needed to prevent the recurrence and the disease related complications.Methods: The current study is a prospective observational study. All stroke cases, with patients above the age of 25 and treated with antihypertensive agents were included in the study. A total of 189 patients were found suitable for inclusion in the study. Using a suitably designed data collection form, all pertinent data such as patient demographics, prescribed medicines, drug interactions and adverse drug reactions were collected from the patient’s case file, nurses’ charts, and medication charts. Prescription pattern of antihypertensive drugs were obtained. The causality of the ADR was assessed using the Naranjo causality assessment scale and reported in the institution where the study was conducted.Results: Majority of patients included in the study were in the age group of 61-70 years. The incidence of stroke in this study was more in males than in the females. Ischemic stroke (72%) was more prevalent when compared to Hemorrhagic stroke. Among the antihypertensive agents, calcium channel blockers (32%) were the most commonly prescribed class of drugs. In our audit, drug related problems were observed in 27% of the cases which included cases with improper dose (3 cases), contraindications (4 cases), major drug interactions (20 cases), and adverse drug reactions (17 cases). Most of the prescriptions were legible. Drug related problems had a great impact on the overall stroketherapy.Conclusions: The drug related problems are a relevant aspect to be considered when treating patients with stroke and it can arise irrespective of adherence to guidelines.

Pharmacogenomics of hypertension in chronic kidney disease: the CKD-PGX study

Background: Patients with chronic kidney disease (CKD) often have uncontrolled hypertension despite polypharmacy. Pharmacogenomic drug-gene interactions (DGIs) may impact the metabolism or efficacy of antihypertensive agents. We report changes in hypertension control after providing a panel of 11 pharmacogenomic predictors of antihypertensive response. Methods: A prospective cohort with CKD and hypertension was followed to assess feasibility of pharmacogenomic testing implementation, self-reported provider utilization, and blood pressure control. The analysis population included 382 hypertensive subjects genotyped for cross-sectional assessment of DGIs and 335 subjects followed for 1 year to assess systolic (SBP) and diastolic blood pressure (DBP). Results: Most participants (58.2%) with uncontrolled hypertension had a DGI reducing the efficacy of > 1 antihypertensive agent. Subjects with a DGI had 1.85-fold (95% CI 1.2-2.8) higher odds of uncontrolled hypertension as compared to those without a DGI, adjusted for race, health system (safety net hospital versus other locations) and advanced CKD (eGFR < 30 ml/min). CYP2C9 reduced metabolism genotypes were associated with losartan response and uncontrolled hypertension (Odds Ratio 5.2, CI 1.9 -14.7). CYP2D6 intermediate or poor metabolizers had less frequent uncontrolled hypertension compared to normal metabolizers taking metoprolol or carvedilol (OR 0.55, CI 0.3-0.95). In 335 subjects completing 1 year follow-up, SBP (-4.0 mmHg, CI 1.6- 6.5) and DBP (-3.3 mmHg, CI 2.0-4.6) were improved. No significant difference in SBP or DBP change were found between individuals with and without a DGI. Conclusions: There is a potential role for the addition of pharmacogenomic testing to optimize antihypertensive regimens in patients with CKD.

STRUCTURAL FEATURE STUDY OF QUINOLINES DERIVATIVES WITH THERMODYNAMIC AND OTHER DESCRIPTORS: A QSAR APPROACH

Quantitative structure activity relationship analysis was performed on a series of thirty-three quinoline derivatives to establish the structural features required for angiotensin II receptor activity. QSAR models were derived by stepwise multiple regression analysis employing the method of least squares, using quantum chemical, thermodynamic, electronic and steric descriptors. Model showed best predictability of activity with cross validated value (q2 ) =0.7485, coeffi cient of determination (r2 ) =0.8734 and standard error of estimate (s) = 0.2690. These guidelines may be used to develop new antihypertensive agents based on the quinoline analogues scaffold.

Identifying drug-related attributes to personalise antihypertensive agents: the outcome report of patients receiving metoprolol therapy

Background Currently, numerous antihypertensive drugs from different pharmacological classes are available; however, blood pressure control is achieved in only less than a third of patients treated for hypertension. Moreover, providing optimal and personalised treatment for hypertension is challenging. Therefore, in this study, we propose a ‘drug-related attributes’ sensitive spectrum. This novel concept can assist clinicians in selecting an optimal antihypertensive drug and improve blood pressure control after examining the attributes of a patient. Methods We collected clinical data on attributes related to hypertension and its therapy of inpatients from West China Hospital who received metoprolol therapy and constructed the sensitive spectrum using data-visualisation tools. Results Our analysis revealed that haematocrit, haemoglobin, serum creatinine, serum cystatin C, serum urea, age, sex, systolic pressure, diastolic pressure, pulse pressure, and heart rate are metoprolol-related attributes. Conclusion Our study showed that all metoprolol-related attributes identified are reasonable and helpful in improving the personalisation of metoprolol therapy. The proposed drug-related attributes spectrum can help personalise antihypertensive medication. Moreover, data-visualisation tools can be effectively used to mine the drug-related attributes sensitive spectrum.

Dosing Time Matters? Nighttime vs. Daytime Administration of Nifedipine Gastrointestinal Therapeutic System (GITS) or Amlodipine on Non-dipper Hypertension: A Randomized Controlled Trial of NARRAS

Background: Non-dipper hypertension is often characterized by a blunted decrease of nocturnal blood pressure (BP) and is associated with increased risk of target organ damage and cardiovascular (CV) events, while the optimal treatment strategy is yet to be established. This trial was designed to evaluate whether nocturnal BP reduction and arterial stiffness improvement differ from antihypertensive agents and time of administration.Methods: Young and middle-aged adults (18–65 years) with non-dipper hypertension were randomly assigned to nifedipine GITS (gastrointestinal therapeutic system) 30 mg or amlodipine besylate 5 mg once daily for 8 weeks, either taken in the morning or at night. Dose was doubled at 4-week if BP is not at goal. Twenty-four hour ambulatory BP monitoring (ABPM) and arterial stiffness were evaluated before and after 8 weeks of pharmacotherapy. The primary efficacy measure was the average nighttime systolic BP reduction.Results: A total of 98 non-dipper hypertensive patients (mean age 46.3 years) were randomized during Dec, 2016 and Dec, 2020, of whom 72 (73%) patients completed all ABPM and follow-up evaluations. Nighttime systolic BP significantly reduced at 8 weeks vs. baseline with nifedipine GITS or amlodipine, irrespective of dosing at nighttime (−9.9 vs −9.9 mmHg, P &gt; 0.05) or daytime (−11.5 vs. −10.9 mmHg, P &gt; 0.05). No difference was seen between these two agents, when combining the data of nighttime and daytime dosing together (−10.8 vs. −10.5 mmHg, respectively, P = 0.898). Daytime, 24-h systolic BP, diastolic BP at different time and pulse wave velocity reduced significantly and comparably, and recovery of dipping rhythm were similar among groups.Conclusion: Nighttime dosing of long-acting antihypertensive preparations, nifedipine GITS or amlodipine demonstrated similar effects on nocturnal BP reduction, dipping rhythm restoration and arterial elasticity improvement in younger subjects with non-dipper hypertension. These effects were comparable with morning dosing.

Antihypertensive Treatment and Central Arterial Hemodynamics: A Meta-Analysis of Randomized Controlled Trials

Background: Antihypertensive treatment may have different effects on central arterial hemodynamics. The extent of the difference in effects between various antihypertensive drugs remains undefined.Methods: We conducted a systematic review and meta-analysis of randomized controlled trials that explored the effects of antihypertensive agents on both central and peripheral systolic blood pressure (SBP) and pulse pressure (PP) or central augmentation index, with a special focus on the comparison between newer [renin-angiotensin-aldosterone system (RAS) inhibitors and calcium-channel blockers (CCBs)] and older antihypertensive agents (diuretics and β- and α-blockers).Results: In total, 20 studies (n = 2,498) were included. Compared with diuretics (10 studies), β-blockers (16 studies), or an α-blocker (1 study), RAS inhibitors (21 studies), and CCBs (6 studies) more efficaciously (P &lt; 0.001) reduced both central and peripheral SBP by a weighted mean difference of −5.63 (−6.50 to −4.76 mmHg) and −1.97 mmHg (−2.99 to −0.95 mmHg), respectively. Compared with older agents, the newer agents also more efficaciously (P &lt; 0.001) reduced central PP (−3.27 mmHg; −4.95 to −1.59 mmHg), augmentation index (−6.11%; −7.94 to −4.29) and augmentation (−3.35 mmHg; −5.28 to –1.42 mmHg) but not peripheral PP (p ≥ 0.09). Accordingly, the newer agents reduced central-to-peripheral PP amplification significantly less than the older agents (0.11 mmHg; 0.05 to 0.17 mmHg; P &lt; 0.001).Conclusion: Newer agents, such as RAS inhibitors and CCBs, were significantly more efficacious than older agents in their effects on central hemodynamics.

Antihypertensive effects of rosuvastatin in patients with hypertension and dyslipidemia: A systemic review and meta-analysis of randomized studies

Some studies have suggested the antihypertensive effects of statins, a class of lipid-lowering agents, particularly in patients with hypertension. However, the evidence for the role of statins in blood pressure (BP) lowering is controversial, and no meta-analysis of rosuvastatin therapy has been conducted to assess its BP-lowering effects. Therefore, the aim of this meta-analysis of randomized controlled trials (RCTs) was to investigate the effects of rosuvastatin on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with hypertension. We systematically searched the electronic databases MEDLINE, EMBASE, and Cochrane Library to identify RCTs in which patients were assigned to groups of rosuvastatin plus antihypertensive agents vs. antihypertensive agents. The three authors independently selected the studies, extracted data, and assessed methodological quality. We included five RCTs in this meta-analysis with 288 patients treated with rosuvastatin and 219 patients without rosuvastatin. The mean DBP in the rosuvastatin group was significantly lower than that in the non-rosuvastatin group by −2.12 mmHg (95% confidence interval (CI) −3.72 to −0.52; Pfixed-effects model = 0.009; I2 = 0%, Pheterogeneity = 0.97). Rosuvastatin treatment also lowered the mean SBP compared with the non-rosuvastatin treatment by −2.27 mmHg, but not significantly (95% CI − 4.75 to 0.25; Pfixed-effects model = 0.08; I2 = 0%, Pheterogeneity = 0.82). In this study, we reviewed the antihypertensive effects of rosuvastatin in patients with hypertension and dyslipidemia. We demonstrated a modest significant reduction of DBP and a trend toward a lowered SBP in patients with hypertension with rosuvastatin therapy. Rosuvastatin could be beneficial to control hypertension and, consequently, contribute toward reducing the risk of cardiovascular events in patients with hypertension and dyslipidemia.