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Background: The prevalence of hypertension is on the rise, with approximately 200 million individuals affected by this condition in India. Epidemiological studies suggest that one in every three adults in India has hypertension. Fixed-dose combinations (FDCs) present a potential strategy to address the challenge of effective blood pressure control. They are now recommended for the initiation in most hypertensive patients by the guidelines. However, studies evaluating the safety and effectiveness of FDCs in large Indian populations with hypertension are few. Aim: The aim of this real-world study is to evaluate the safety and effectiveness of the fixed-dose combination of telmisartan and amlodipine in managing hypertension in Indian patients. Materials and methods: This prospective, multicenter, observational, real-world evidence study is designed to enroll 10,000 eligible participants from 1,000 study sites across India. Adult patients with newly diagnosed or uncontrolled hypertension on monotherapy would be eligible for enrollment in the study. The study participants would be administered the study treatment per the treating physician's routine clinical practice and followed up after 8 weeks. The primary endpoint is to measure the change in systolic blood pressure (SBP) from baseline to week 8, while secondary endpoints include determining the percentage of patients who reach their blood pressure targets., description of demographic characteristics of the Indian hypertensive population, and reporting of safety outcomes. Conclusion: The TACT India study will provide longitudinal, real-world data on the effectiveness and safety of telmisartan and amlodipine FDC among a large cohort of the Indian population with hypertension., (© Journal of the Association of Physicians of India 2024.)

Background: Single-pill combinations (SPCs) of three low-dose antihypertensive drugs can improve hypertension control but are not widely available. A key issue for any combination product is the contribution of each component to efficacy and tolerability. This trial compared a new triple SPC called GMRx2, containing telmisartan, amlodipine, and indapamide, with dual combinations of components for efficacy and safety., Methods: In this international, randomised, double-blind, active-controlled trial, we enrolled adults with hypertension receiving between zero and three antihypertensive drugs, with a screening systolic blood pressure (SBP) ranging from 140-179 mm Hg (on no drugs) to 110-150 mm Hg (on three drugs). Participants were recruited from Australia, the Czech Republic, New Zealand, Poland, Sri Lanka, the UK, and the USA. In a 4-week active run-in, existing medications were switched to GMRx2 half dose (telmisartan 20 mg, amlodipine 2·5 mg, and indapamide 1·25 mg). Participants were then randomly allocated (2:1:1:1) to continued GMRx2 half dose or to each possible dual combination of components at half doses (telmisartan 20 mg with amlodipine 2·5 mg, telmisartan 20 mg with indapamide 1·25 mg, or amlodipine 2·5 mg with indapamide 1·25 mg). At week 6, doses were doubled in all groups, unless there was a clinical contraindication. The primary efficacy outcome was mean change in home SBP from baseline to week 12, and the primary safety outcome was withdrawal of treatment due to an adverse event from baseline to week 12. Secondary efficacy outcomes included differences in clinic and home blood pressure levels and control rates. This study is registered with ClinicalTrials.gov, NCT04518293, and is completed., Findings: The trial was conducted between July 9, 2021 and Sept 1, 2023. We randomly allocated 1385 participants to four groups: 551 to GMRx2, 276 to telmisartan-indapamide, 282 to telmisartan-amlodipine, and 276 to amlodipine-indapamide groups. The mean age was 59 years (SD 11), 712 (51%) participants self-reported as female and 673 (48·6%) male, and the mean clinic blood pressure at the screening visit was 142/85 mm Hg when taking an average of 1·6 blood pressure medications. Following the run-in on GMRx2 half dose, the mean clinic blood pressure level at randomisation was 133/81 mm Hg and the mean home blood pressure level was 129/78 mm Hg. At week 12, the mean home SBP was 126 mm Hg in the GMRx2 group, which was lower than for each of the dual combinations: -2·5 (95% CI -3·7 to -1·3, p<0·0001) versus telmisartan-indapamide, -5·4 (-6·8 to -4·1, p<0·0001) versus telmisartan-amlodipine, and -4·4 (-5·8 to -3·1, p<0·0001) versus amlodipine-indapamide. For the same comparisons, differences in clinic blood pressure at week 12 were 4·3/3·5 mm Hg, 5·6/3·7 mm Hg, and 6·3/4·5 mm Hg (all p<0·001). Clinic blood pressure control rate below 140/90 mm Hg at week 12 was superior with GMRx2 (74%) to with each dual combination (range 53-61%). Withdrawal of treatment due to adverse events occurred in 11 (2%) participants in the GMRx2 group, four (1%) in telmisartan-indapamide, three (1%) in telmisartan-amlodipine, and four (1%) in amlodipine-indapamide, with none of the differences being statistically significant., Interpretation: A novel low-dose SPC product of telmisartan, amlodipine, and indapamide provided clinically meaningful improvements in blood pressure reduction compared with dual combinations and was well tolerated. This SPC provides a new therapeutic option for the management of hypertension and its use could result in a substantial improvement in blood pressure control in clinical practice., Funding: George Medicines., Competing Interests: Declaration of interests AR, AS, AES, CG, MS, XL, and NW are employed at The George Institute for Global Health (TGI), which holds an interest in George Medicines via its social enterprise arm, George Institute Ventures. None of the TGI staff has a personal financial interest in George Medicines. AR is seconded part-time to George Medicines. TGI holds patents for ultra-low-dose, fixed-dose combination products for the treatment of hypertension and diabetes, and AR is listed as one of the inventors (granted: US 10 369 156, US 10 799 487, US 10 322 117, US 11 033 544, US 11 478 462; pending: US 17/932 982, US 18/446 268, US 17/598 122, US 17/317 614, US 17/527 084, US 17/527 085, US 17/527 087). AR does not have a financial interest in these patents. None of the other authors has a financial interest in George Medicines or has received funding for their independent contribution to the GMRx2 programme. AR reports consulting fees as a data and safety monitoring board member for Idorsia; and a fellowship grant from the National Health and Medical Research Council of Australia (GNT 1160743). AES reports consulting fees or speaker honoraria from OMRON Healthcare, Aktiia, Medtronic, Servier, Abbott, Sanofi, Sun Pharmaceuticals, Novartis, and Skylabs; being co-chair of the National Hypertension Taskforce Australia; being a board member for Hypertension Australia and the Australian Cardiovascular Alliance; and an investigator grant from the National Health and Medical Research Council of Australia (GNT 2017504). DBO reports speaker honoraria from Novartis, AstraZeneca, Servier, Swipha, and Boehringer Ingelheim for speaking at educational meetings. KN reports speaker and consulting honoraria from Bausch Health, Berlin-Chemie/Menarini, Egis, Idorsia, Janssen, Gedeon Richter, Gilead, Krka, Novo Nordisk, Polpharma, Recordati, Sandoz, and Servier; and honoraria from or participation on advisory boards for Polpharma and Zentiva. MPS reports consulting fees or travel and research support from Medtronic, Abbott, Recor, Novartis, Servier, Pfizer, and Boehringer Ingelheim; and being current President of Hypertension Australia and Treasurer of the World Hypertension League. WCC reports institutional grants from Recor and George Medicines; and consulting fees from Alnylam Pharmaceuticals. NRP reports consultancy fees from Servier and Aktiia; support for research projects and staff from Servier and Pfizer; support for arranging and speaking at educational meetings from AstraZeneca, LRI-Therapharma, Napi, Servier, Sanofi, EVA Pharma, Pfizer, Emcure, Dr Reddy's Laboratories, and Zydus; and support by the National Institute for Health Research Senior Investigator Awards, Biomedical Research Centre funding, and the British Heart Foundation Research Centre Excellence Award. DEG reports funding to his department as part of the EU Horizon Hypermarker project. BW reports trial steering committee appointments for Novartis and AstraZeneca; lecture fees for Servier and Novartis; and an unremunerated role as President of the International Society of Hypertension. JTW reports institutional grants from the National Institutes of Health, the Ohio Department of Medicaid, and the Agency for Healthcare Research and Quality; travel support and participation on an advisory board for Medtronic; being chair of the data safety monitoring board for the IMPACTS MIND Trial at Tulane University; and being on the Northeast Ohio Neighbourhood Health Center Community Board of Directors. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Effective antihypertensive therapy is essential for achieving optimal blood pressure (BP) control and reducing cardiovascular events. This double-blind, multicenter, randomized trial aimed to compare the antihypertensive efficacy and safety of a combination of amlodipine (AML) and candesartan cilexetil (CC) versus AML monotherapy in patients with essential hypertension (HTN). After a 4-week run-in period with AML 5 mg, patients whose HTN remained uncontrolled (diastolic BP [DBP]) ≥ 90 mmHg and < 120 mmHg) were randomized to receive either AML + CC or AML alone for 8 weeks. Efficacy was assessed by measuring changes in DBP and systolic BP (SBP). The primary safety measure was the incidence of adverse events (AEs). A total of 174 participants were included in the efficacy analysis. After 8 weeks, DBP decreased by -9.92 ± 0.86 mmHg in the AML + CC arm and - 2.08 ± 0.86 mmHg in the AML arm (p < 0.0001). SBP decreased by -14.27 ± 1.39 mmHg in the AML + CC arm versus - 2.77 ± 1.39 mmHg in the AML arm (p < 0.0001). AEs occurred in 11.24% of the AML + CC group and 5.62% of the AML group (p = 0.1773). AML + CC combination therapy demonstrated superior efficacy with good tolerance, making it a promising option for patients with inadequately controlled hypertension on amlodipine alone., (© 2024. The Author(s).)

Importance: With the high burden of hypertension in sub-Saharan Africa, there is a need for effective, safe and scalable treatment strategies., Objective: To compare, among Black African adults, the effectiveness and safety of a novel low-dose triple-pill protocol compared with a standard-care protocol for blood pressure lowering., Design and Setting: Randomized, parallel-group, open-label, multicenter trial conducted in public hospital-based family medicine clinics in Nigeria., Participants: Black African adults with uncontrolled hypertension (≥140/90 mm Hg) who were untreated or receiving a single blood pressure-lowering drug., Interventions: Participants were randomly allocated to low-dose triple-pill or standard-care protocols. The triple-pill protocol involved a novel combination of telmisartan, amlodipine, and indapamide in triple one-quarter, one-half, and standard doses (ie, 10/1.25/0.625 mg, 20/2.5/1.25 mg, and 40/5/2.5 mg), with accelerated up-titration. The standard-care protocol was the Nigeria hypertension treatment protocol starting with amlodipine (5 mg)., Main Outcomes and Measures: The primary effectiveness outcome was the reduction in home mean systolic blood pressure, and the primary safety outcome was discontinuation of trial treatment due to adverse events, both from randomization to month 6., Results: The first participant was randomized on July 19, 2022, and the last follow-up visit was on July 18, 2024. Among 300 randomized participants (54% female; mean age, 52 years; baseline mean home blood pressure, 151/97 mm Hg; and clinic blood pressure, 156/97 mm Hg), 273 (91%) completed the trial. At month 6, mean home systolic blood pressure was on average 31 mm Hg (95% CI, 28 to 33 mm Hg) lower in the triple-pill protocol group and 26 mm Hg (95% CI, 22 to 28 mm Hg) lower in the standard-care protocol group (adjusted difference, -5.8 mm Hg [95% CI, -8.0 to -3.6]; P < .001]). At month 6, clinic blood pressure control (<140/90 mm Hg) was 82% vs 72% (risk difference, 10% [95% CI, -2% to 20%]) and home blood pressure control (<130/80 mm Hg) was 62% vs 28% (risk difference, 33% [95% CI, 22% to 44%]) in the triple-pill compared with the standard-care protocol group; these were 2 of 21 prespecified secondary effectiveness end points. No participants discontinued trial treatment due to adverse events., Conclusions and Relevance: Among Black African adults with uncontrolled hypertension, a low-dose triple-pill protocol achieved better blood pressure lowering and control with good tolerability compared with the standard-care protocol., Trial Registration: Pan African Clinical Trials Registry Identifier: PACTR202107579572114.

Abstract: A 70-year-old woman under amlodipine treatment for hypertension presented with a hemorrhagic mass in the mandibular gingiva. Imaging studies revealed high signal intensity in T2-weighted MRI and moderate 18 F-FDG accumulation at the lesion's periphery. Although no malignancy was detected, the lesion continuously grew, prompting excision. Histopathological examination confirmed gingival hyperplasia attributed to amlodipine use. Drug-induced gingival hyperplasia typically presents as diffuse swelling; however, this lesion manifested as a polyp, posing diagnostic challenges. Reports on imaging findings for drug-induced gingival hyperplasia are limited. Understanding imaging patterns alongside clinical history aids in accurate diagnosis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin-converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin-converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclear., Methods and Results: We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial. We then determined the relation between declines in eGFR (treated as a binary variable, ≤15% versus >15% and separately, as a restricted spline variable) and the composite risk of fatal and nonfatal cardiovascular events using Cox proportional hazards models. We included 10 714 participants (median age 68 years [Q1 63, Q3 73]), of whom 1024 reached the trial end point over median follow-up of 2.8 years. Predictors of acute declines in eGFR>15% over 3 months included assignment to hydrochlorothiazide (versus amlodipine) and higher baseline albuminuria. Overall, declines in eGFR ≥15% (versus <15%) were associated with a 26% higher hazard of cardiovascular outcomes (95% CI, 1.07-1.48). In spline-based analysis, risk for cardiovascular outcomes was higher in the hydrochlorothiazide arm at every level of decline in eGFR compared with the same magnitude of eGFR decline in the amlodipine arm., Conclusion: Combined use of benazepril and amlodipine remains superior to benazepril and hydrochlorothiazide for cardiovascular outcomes, regardless of the magnitude of the decline in eGFR that occurred with initiation of therapy.

Objective: Several guidelines do not recommend beta-blocker as the first-line treatment for hypertension because of its inferior efficacy in stroke prevention. Combination therapy with beta-blocker is commonly used for blood pressure control. We compared the clinical outcomes in patients treated with amlodipine plus bisoprolol (A + B), a ß1-selective beta-blocker and amlodipine plus valsartan (A + V)., Methods: A population-based cohort study was performed using data from the Taiwan National Health Insurance Research Database. From 2012 to 2019, newly diagnosed adult hypertensive patients who received initial amlodipine monotherapy and then switched to A + V or A + B were included. The efficacy outcomes included all-cause death, atherosclerotic cardiovascular disease (ASCVD) event (cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization), hemorrhagic stroke, and heart failure. Multivariable Cox proportional hazards model was used to evaluate the relationship between outcomes and different treatments., Results: Overall, 4311 patients in A + B group and 10980 patients in A + V group were included. After a mean follow-up of 4.34 ± 1.79 years, the efficacy outcomes were similar between the A + V and A + B groups regarding all-cause death (adjusted hazard ratio [aHR] 0.99, 95% confidence interval [CI] 0.83-1.18), ASCVD event (aHR 0.97, 95% CI 0.84-1.12), and heart failure (aHR 1.06, 95% CI 0.87-1.30). The risk of hemorrhagic stroke was lower in A + B group (aHR 0.70, 95% CI 0.52-0.94). The result was similar when taking death into consideration in competing risk analysis. The safety outcomes were similar between the 2 groups., Conclusions: There was no difference of all-cause death, ASCVD event, and heart failure in A + B vs. A + V users. But A + B users had a lower risk of hemorrhagic stroke.

Background: In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals., Methods: This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90 mmHg) were randomized to perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4 mg/indapamide 1.25 mg plus amlodipine 5 mg (Per/Ind + Aml) for 6 months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2 months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90 mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM)., Results: A total of 532 patients were randomized: Per/Ind/Aml ( n  = 262) and Per/Ind + Aml ( n  = 269). Overall, the mean (±SD) age was 55.7 ± 8.8 years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2 mmHg. Systolic BP decreased in both groups at 2 months from baseline: -14.99 ± 14.46 mmHg Per/Ind/Aml versus -14.49 ± 12.87 mmHg Per/Ind +Aml. A predefined noninferiority margin of 4 mmHg was observed ( P  < 0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24 h. Both treatments were well tolerated., Conclusions: Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24 h in a single pill, with comparable safety., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy., Methods: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography., Findings: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study., Implications: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability., Clinical Trial Registration: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (-4.8 mm Hg [95% CI: -10.8, 1.3, p = 0.123] and a -4.9 mmHg (95% CI: -8.6, -1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312., (© 2024. The Author(s).)

Background and Objective: This study aimed to assess and compare the pharmacokinetics, safety, and tolerability of a fixed-dose combination product (FDCP) comprising four different drugs (two antihypertensive drugs, amlodipine and losartan, and two lipid-lowering agents, ezetimibe and rosuvastatin) with their separate tablets., Methods: A total of 60 participants were enrolled in this open-label, randomized, single-dose crossover study. Each participant received a single dose of FDCP and individual tablets during each period, with a 14-day washout period between the periods. The pharmacokinetic parameters of amlodipine, losartan, EXP3174 (an active metabolite of losartan), rosuvastatin, free ezetimibe, and total ezetimibe were evaluated and compared., Results: The pharmacokinetic profiles of amlodipine, losartan, rosuvastatin, and ezetimibe after administration of the individual products were similar to those of FDCP. The geometric mean ratios and 90% confidence intervals for maximum concentration (C max ) and area under the curve (AUC) of FDCP to individual tablets were within 0.8-1.25 for all six analytes. No clinically relevant changes were observed in the vital signs or physical, biochemical, hematological, electrocardiographic, or urinalysis findings during the study, and no serious adverse events were reported., Conclusion: This study demonstrated that a newly developed FDCP containing amlodipine, losartan, ezetimibe, and rosuvastatin exhibited pharmacokinetic equivalence with the individual products and met the regulatory criteria. Both formulations were well tolerated., Clinical Trial Registration: This trial (NCT04322266) was retrospectively registered on 9 September 2019., (© 2024. The Author(s).)

Background: Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed-dose combination (FDC) regimens is recommended by current guidelines. However, the clinical outcomes of different FDC dosages remain unknown. This study aimed to examine the clinical outcomes of FDC regimens and the free combination of amlodipine and atorvastatin at different dosages., Methods and Results: Patients with concurrent hypertension and hypercholesterolemia treated daily with an FDC of 5 mg amlodipine and 10 mg atorvastatin (5/10 fixed group), and FDC of 5 mg amlodipine and 20 mg atorvastatin (5/20 fixed group), or free combination of 5 mg amlodipine and 20 mg atorvastatin (5/20 free group) were identified from the National Health Insurance Research Database of Taiwan. The primary outcome was the composite cardiovascular outcomes, including cardiovascular death, acute myocardial infarction, stroke, and coronary intervention. A total of 9095 patients were eligible for inclusion. The incidence of primary outcome per 1000 person-years was 16.6 in the 5/10 fixed group, 12.6 in the 5/20 fixed group, and 16.5 in the 5/20 free group (5/20 fixed versus 5/20 free: hazard ratio [HR], 0.76 [95% CI, 0.64-0.91]; 5/20 fixed versus 5/10 fixed: HR, 0.76 [95% CI, 0.63-0.90])., Conclusions: Among patients with concomitant hypertension and hypercholesterolemia, treatment with an FDC of amlodipine and high-dose atorvastatin led to a lower risk of a composite of cardiovascular outcomes than treatment with the free combination or a similar FDC with a lower dose of atorvastatin.

This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman who consumed an overdose of multiple medications: nifedipine, azelnidipine, amlodipine besylate, olmesartan medoxomil, telmisartan, esaxerenone and vildagliptin. She presented with haemodynamic instability, necessitating intubation. Despite stabilising haemodynamic parameters within 24 hours, she manifested escalating extremity oedema. At 52 hours after ingestion, mottled skin was observed, along with necrotic alterations in the swollen hands and compartment pressures exceeding 30 mm Hg in all extremities. ACS was diagnosed, leading to fasciotomies. The aetiology is postulated to be drug-induced angio-oedema, possibly intensified by the concurrent overdose of olmesartan medoxomil, telmisartan and vildagliptin, each of which has a risk of angio-oedema even at standard dosages. This scenario is a very rare case caused by drug-induced angio-oedema, which underscores the importance of vigilant monitoring to detect ACS in patients with progressing limb oedema., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Little evidence exists about the comparative effects of first-line antihypertensive medications (i.e., renin-angiotensin-aldosterone converting enzyme inhibitors (RAASi), amlodipine, or thiazide diuretics) in older adults with limited life expectancy. We compared the rates of injurious falls and short-term cardiovascular events between different first-line antihypertensive medication classes in adults receiving care in nursing homes (NH)., Methods: This was a retrospective cohort of Medicare fee-for-service beneficiaries receiving care in NHs. Patients newly dispensed first-line antihypertensive medications were identified using Part D claims (2015-2018) and linked with clinical assessments (i.e., Minimum Data Set). Fall-related injuries (FRI), hip fractures, and major adverse cardiac events (MACE) outcomes were identified using hospitalization claims. Patients were followed from the date of antihypertensive dispensing until the occurrence of outcomes, death, disenrollment, or 6-month follow-up. Inverse-probability-of-treatment-weighted (IPTW) cause-specific hazards regression models were used to compare outcomes between patients who were new users of RAASi, amlodipine, or thiazides., Results: Our cohort included 16,504 antihypertensive users (RAASi, n = 9574; amlodipine, n = 5049; thiazide, n = 1881). Mean age was 83.5 years (± 8.2), 70.6% were female, and 17.2% were non-white race. During a mean follow-up of 5.3 months, 326 patients (2.0%) experienced an injurious fall, 1590 (9.6%) experienced MACE, and 2123 patients (12.9%) died. The intention-to-treat IPTW hazard ratio (HR) for injurious falls for amlodipine (vs RAASi) use was 0.85 (95% confidence interval (CI) 0.66-1.08) and for thiazides (vs RAASi) was 1.22 (95% CI 0.88-1.66). The rates of MACE were similar between those taking anti-hypertensive medications. Thiazides were discontinued more often than other classes; however, inferences were largely unchanged in as-treated analyses. Subgroup analyses were generally consistent., Conclusions: Older adults with limited life expectancy experience similar rates of injurious falls and short-term cardiovascular events after initiating any of the first-line antihypertensive medications., (© 2023 The American Geriatrics Society.)

Background: Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs. However, whether low-dose quadruple therapy is better than dual combination is unknown., Methods/design: A randomized double-blind crossover clinical trial will be conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension (140-179/90-109 mmHg). Ninety patients are required and will be recruited and randomly assigned in a 1:1 ratio to two crossover groups. Two groups will receive a different combination therapy for 4 weeks, then switch to the other combination therapy for 4 weeks, with a 2-week wash-out. Antihypertensive effects and related adverse effects of the two antihypertensive combination treatments will be compared. The primary outcome, i.e., mean 24-h systolic blood pressure in ambulatory blood pressure monitoring, will be assessed via linear mixed-effects model., Discussion: This statistical analysis plan will be confirmed prior to blind review and data lock before un-blinding and is sought to increase the validity of the QUADUAL trial., Trial Registration: ClinicalTrials.gov, NCT05377203. Registered May 11, 2022, https://clinicaltrials.gov/study/NCT05377203 ., (© 2024. The Author(s).)

Introduction: "Amlodipine/valsartan" or "amlodipine/candesartan" combinations represent two effective antihypertensive agents with complementary mechanisms of action. Nevertheless, a study has yet to be done to evaluate the effect of amlodipine/candesartan on central blood pressure and compare it with amlodipine/valsartan combination. To see how "amlodipine plus candesartan combination" reduces peripheral and central blood pressure compared to the most studied combination, "amlodipine plus valsartan"., Material and Methods: Eighty-six patients were randomized in an open-label, prospective study by 1:1 ratio to two groups. Group I (n=42) received the amlodipine and valsartan combination, and group II (n=44) received the amlodipine and candesartan combination. Peripheral and central blood pressure (CBP) was measured at baseline, at 6 and 12 weeks of follow-up., Discussion: Both treatment groups reduced peripheral systolic, diastolic, and mean blood pressure. There was no significant difference between and within both groups. The amlodipine/candesartan combination showed more reduction in peripheral systolic blood pressure (PSBP) after 12 weeks of treatment (p=<0.001). Both groups decreased CBP without significant differences between groups. The amlodipine/candesartan combination showed additional efficacy in decreasing CSBP after 12 weeks (p=<0.001). The two treatment groups did not exert significant efficacy in lowering heart rate (HR) and augmentation index% (AIx%)., Conclusion: To conclude, the amlodipine 10mg/candesartan 16mg combination was non-inferior to the amlodipine 10mg/valsartan 160mg combination in terms of reducing peripheral and CBP over time., (Copyright © 2024 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

S-amlodipine, a commonly prescribed antihypertensive agent, is widely used in clinical settings to treat hypertension. However, the potential adverse effects of long-term S-amlodipine treatment on the liver remain uncertain, given the cautionary recommendations from clinicians regarding its administration in individuals with impaired liver function. To address this, we conducted a study using an eight-week-old male rat model and administered a daily dose of 0.6 ~ 5 mg/kg of S-amlodipine for 7 weeks. Our findings demonstrated that 1.2 ~ 5 mg/kg of S-amlodipine treatment induced liver inflammation and associated dysfunction in rats, further in vitro experiments revealed that the observed liver inflammation and dysfunction were not attributable to direct effects of S-amlodipine on the liver. Metagenome sequencing analysis revealed that S-amlodipine treatment led to alterations in the gut microbiome of rats, with the bloom of E. coli (4.5 ~ 6.6-fold increase) and a decrease in A. muciniphila (1,613.4 ~ 2,000-fold decrease) and B. uniformis (20.6  ~  202.7-fold decrease), subsequently causing an increase in the gut bacterial lipopolysaccharide (LPS) content (1.4 ~ 1.5-fold increase in feces). S-amlodipine treatment also induced damage to the intestinal barrier and increased intestinal permeability, as confirmed by elevated levels of fecal albumin; furthermore, the flux of gut bacterial LPS into the bloodstream through the portal vein resulted in an increase in serum LPS content (3.3 ~ 4-fold increase). LPS induces liver inflammation and subsequent dysfunction in rats by activating the TLR4 pathway. This study is the first to show that S-amlodipine induces liver inflammation and dysfunction by perturbing the rat gut microbiome. These results indicate the adverse effects of S-amlodipine on the liver and provide a rich understanding of the safety of long-term S-amlodipine administration.

There lacks real-world study with a large sample size assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM-AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM-AML (20/5 mg) tablet were analyzed in the current prospective, single-arm, multi-center, real-world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was -10.8 ± 0.4/-6.6 ± 0.3 mmHg at W4 and -12.7 ± 0.5/-7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home-measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients' and physicians' satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug-related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM-AML tablet is one of the best antihypertensive agents in patients with essential hypertension., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

De novo - or as a continuum of antenatal hypertension -postpartum hypertension complicates ~2% of pregnancies. Many maternal complications, such as eclampsia and cerebrovascular accidents, occur in the postpartum period. Despite widespread use of antihypertensives during pregnancy and childbirth, there is a paucity of data on preferred medications in the postpartum period. This randomized controlled study enrolled 130 women who were started on antihypertensives. They were randomized to receive oral Labetalol(LAB, maximum 900 mg per day in three doses) or oral Amlodipine(AML, maximum 10 mg per day given in two doses). In the immediate postpartum, all women were closely monitored for neurological symptoms, blood pressure, heart rate, respiratory rate, urine output, and deep tendon reflex. The primary outcome was the time to achieve sustained blood pressure control for 12 h from the initiation of medication; secondary outcomes included side effects of both medications. Mean time to achieve sustained blood pressure control was lower in women who received AML than in those who received LAB-(mean difference 7.2 h; 38 95% CI 1.4, 12.9, p = 0.011). There were fewer severe hypertensive episodes among those with AML than in those who received LAB. However, the proportion of women who continued to require antihypertensives at discharge was higher in the AML group than in the LAB group (55.4% versus 32.3%, p = 0.008). None of the participants developed drug-related side effects. Among women with postpartum persistence or new-onset hypertension, oral AML achieved sustained blood pressure control in a shorter duration, with fewer hypertensive emergencies than oral LAB. (CTRI/2020/02/023236).Trial Registration details: The study protocol was registered with Clinical Trial Registry of India with CTRI Number CTRI/2020/02/023236 dated 11.02.2020. Protocol can be accessed at https://www.ctri.nic.in/Clinicaltrials/pdf&#95;generate.php?trialid=40435&EncHid=&modid=&compid=%27,%2740435det%27 ., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead to iron overload. Cardiovascular dysfunction caused by iron overload is the leading cause of morbidity and mortality in people with transfusion-dependent beta-thalassaemia. Iron chelation therapy has reduced the severity of systemic iron overload, but removal of iron from the myocardium requires a very proactive preventive strategy. There is evidence that calcium channel blockers may reduce myocardial iron deposition. This is an update of a Cochrane Review first published in 2018., Objectives: To assess the effects of calcium channel blockers plus standard iron chelation therapy, compared with standard iron chelation therapy (alone or with a placebo), on cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia., Search Methods: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books, to 13 January 2022. We also searched ongoing trials databases and the reference lists of relevant articles and reviews., Selection Criteria: We included randomised controlled trials (RCTs) of calcium channel blockers combined with standard chelation therapy versus standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia., Data Collection and Analysis: We used standard Cochrane methods. We used GRADE to assess certainty of evidence., Main Results: We included six RCTs (five parallel-group trials and one cross-over trial) with 253 participants; there were 126 participants in the amlodipine arms and 127 in the control arms. The certainty of the evidence was low for most outcomes at 12 months; the evidence for liver iron concentration was of moderate certainty, and the evidence for adverse events was of very low certainty. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may have little or no effect on cardiac T2* values at 12 months (mean difference (MD) 1.30 ms, 95% confidence interval (CI) -0.53 to 3.14; 4 trials, 191 participants; low-certainty evidence) and left ventricular ejection fraction (LVEF) at 12 months (MD 0.81%, 95% CI -0.92% to 2.54%; 3 trials, 136 participants; low-certainty evidence). Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may reduce myocardial iron concentration (MIC) after 12 months (MD -0.27 mg/g, 95% CI -0.46 to -0.08; 3 trials, 138 participants; low-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on heart T2*, MIC, or LVEF after six months, but the evidence is very uncertain. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may increase liver T2* values after 12 months (MD 1.48 ms, 95% CI 0.27 to 2.69; 3 trials, 127 participants; low-certainty evidence), but may have little or no effect on serum ferritin at 12 months (MD 0.07 μg/mL, 95% CI -0.20 to 0.35; 4 trials, 187 participants; low-certainty evidence), and probably has little or no effect on liver iron concentration (LIC) after 12 months (MD -0.86 mg/g, 95% CI -4.39 to 2.66; 2 trials, 123 participants; moderate-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on serum ferritin, liver T2* values, or LIC after six months, but the evidence is very uncertain. The included trials did not report any serious adverse events at six or 12 months of intervention. The studies did report mild adverse effects such as oedema, dizziness, mild cutaneous allergy, joint swelling, and mild gastrointestinal symptoms. Amlodipine may be associated with a higher risk of oedema (risk ratio (RR) 5.54, 95% CI 1.24 to 24.76; 4 trials, 167 participants; very low-certainty evidence). We found no difference between the groups in the occurrence of other adverse events, but the evidence was very uncertain. No trials reported mortality, cardiac function assessments other than echocardiographic estimation of LVEF, electrocardiographic abnormalities, quality of life, compliance with treatment, or cost of interventions., Authors' Conclusions: The available evidence suggests that calcium channel blockers may reduce MIC and may increase liver T2* values in people with transfusion-dependent beta thalassaemia. Longer-term multicentre RCTs are needed to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should also investigate the role of baseline MIC in the response to calcium channel blockers, and include a cost-effectiveness analysis., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction: Patients with hypertension and additional cardiovascular risk factors pose a challenge by requiring more intensive blood pressure (BP) control. Single-pill combination (SPC) therapy can benefit these patients by improving medication adherence., Methods: This prospective, multicenter observational study assessed the real-world safety and effectiveness of an SPC containing olmesartan, amlodipine, and hydrochlorothiazide (O/A/H) in South Korean patients with hypertension and cardiovascular risk factors. BP control rates, defined as the percentage of patients achieving systolic BP (SBP) < 130 mmHg and diastolic BP (DBP) < 80 mmHg for intensive BP control, and < 140 mmHg and < 90 mmHg, respectively, for standard BP control, were investigated across various cardiovascular risk groups, along with changes in SBP and DBP from baseline to week 24., Results: The most prevalent cardiovascular risk factor was age (≥ 45 years in men, ≥ 55 years in women, 86.1%), followed by cardiovascular diseases (64.4%), dyslipidemia (53.7%), body mass index ≥ 25 kg/m 2 (53.5%), and diabetes mellitus (DM) (46.3%). Switching to O/A/H showed significant BP reduction, with a mean change of - 17.8 mmHg/- 9.3 mmHg in SBP/DBP within 4 weeks. The intensive BP control rate was 41.4% (95% confidence interval [CI] 39.5, 43.4), and the standard BP control rate was 73.3% (95% CI 71.5, 75.1), with better control rates in the risk age group (43.1% and 74.1%, respectively) and cardiovascular disease group (42.0% and 73.8%, respectively). The DM group had relatively lower control rates (37.5% for intensive control and 69.4% for standard control). Common adverse drug reactions included dizziness (2.91%), hypotension (1.51%), and headaches (0.70%)., Conclusion: The SPC therapy of O/A/H caused a rapid and sustained reduction in SBP/DBP in patients' hypertension and additional cardiovascular risk factors. The therapy was safe and well tolerated., Study Registration Number: KCT0003401 ( https://cris.nih.go.kr/cris/search/detailSearch.do/20795 )., (© 2023. The Author(s).)

Background: Allisartan isoproxil is a selective nonpeptide angiotensin II (AT1) receptor blocker developed by China, this study aimed to assess its clinical efficacy for essential hypertension (EH)., Methods: Patients with mild-to-moderate EH, selected at 44 sites in China from September 9, 2016, to December 7, 2018, were administered 240 mg allisartan isoproxil daily for 4 weeks. Patients with controlled blood pressure (BP) continued monotherapy for 8 weeks, others were randomly assigned (1:1) to A + D group (allisartan isoproxil 240 mg + indapamide 1.5 mg) or A + C group (allisartan isoproxil + amlodipine besylate 5 mg) for 8 weeks. BP were measured at week 4, 8 and 12., Results: 2,126 patients were included in the analysis. After 12 weeks of treatment, systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased by 19.24 ± 12.02 and 10.63 ± 8.89 mm Hg, respectively, and the overall BP control rate was 78.56%. The sitting blood pressures (SBP/DBP) decreased by 19.12 ± 11.71/10.84 ± 8.73 mm Hg in patients with 12 weeks allisartan isoproxil monotherapy (both P < 0.0001). The BP reductions and control rates were comparable between A + D and A + C groups. 48 patients with monotherapy-controlled BP underwent ambulatory BP monitoring, with a mean decrease in ambulatory BP of 10.04 ± 10.87/5.50 ± 8.07 mm Hg after 12 weeks of treatment, and consistent reductions between day and night. SBP and DBP had trough-to-peak ratios of 64.64% and 62.63% and smoothness indices of 3.82 and 2.92, respectively., Conclusions: An allisartan isoproxil-based antihypertensive regimen can effectively control BP in patients with mild-to-moderate EH., Project Registration No: CTR20160138 (Registration and Information Disclosure Platform for China Drug Clinical Studies, http://www.chinadrugtrials.org.cn/index.html)., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Azelnidipine is one of the newer Calcium Channel Blockers (CCB) approved in China, Japan, and India. Some studies have found that the blood pressure-lowering effect of azelnidipine is more than amlodipine, and others found the effect similar., Aim: This meta-analysis was conducted to evaluate the efficacy of azelnidipine in managing hypertensive patients by lowering Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) as compared to amlodipine., Methods: PubMed/MEDLINE, Google Scholar, PROQUEST, and International Clinical Trial Registry Platform (ICTRP) were searched for published articles to evaluate the clinical efficacy of azelnidipine in the management of hypertension patients. Data were extracted from the selected 11 randomized clinical trials (RCTs). The risk of bias 2 (RoB2) tool was used for the quality assessment of the included studies, and the random-effects model was used to estimate the effect size., Results: There were no statistically significant differences in the reduction of SBP (Mean Difference, MD: - 1.07; 95% CI: - 4.10, 1.95, p-value: 0.49) and DBP (MD: 0.27; 95% CI: - 2.66, 3.20, p-value: 0.86) between both the drugs. In terms of HR reduction, there was a statistically significant difference (MD: - 3.63; 95% CI: - 5.27, - 2.00, p-value: < 0.0001) between both drugs. Egger's test excluded any publication bias for the included studies (p = 0.21). Meta-regression excluded the effect of the duration of treatment on outcome parameters., Conclusion: Though no significant difference between azelnidipine and amlodipine was found, in terms of reduction in SBP and DBP, azelnidipine reduced heart rate significantly compared to amlodipine., Prospero Registration: CRD42023390361., (© 2023. Italian Society of Hypertension.)

Incorrect dispensing of medications by community pharmacies can lead to accidental poisonings. This may not be considered by emergency medicine physicians in patients describing vague symptoms. We present a case of a paediatric ingestion of amlodipine, resulting from a community pharmacy dispensing error, that was recognized by the child's mother, and consider the liability implications.

Hypertension is the leading cause of death worldwide, affecting 1.4 billion people. Treatment options include the widely used calcium channel blockers, among which amlodipine, a dihydropyridine, has unique characteristics that distinguish it from other drugs within this class. This review aims to provide an updated overview of the evidence supporting the use of amlodipine over the past 30 years and highlights its cardiovascular benefits in current hypertension management. Amlodipine has low renal clearance (7 mL/min/mg) and long half-life (35-50 h) and duration of action, which allows it to sustain its anti-hypertensive effect for more than 24 h following a single dose. Additionally, blood pressure (BP) control is maintained even when a dose has been missed, providing continuous protection in case of incidental noncompliance. It has proven to reduce BP variability and successfully lower BP. Amlodipine also controls BP in patients with a systolic/diastolic BP of 130/80 mm Hg or higher, diabetes, or chronic kidney disease without worsening glycemic or kidney function. Additionally, amlodipine is a wise choice for older adults due to its ability to control BP and protect against stroke and myocardial infarction. Side effects of amlodipine include edema, palpitations, dizziness, and flushing, which are more common with the higher dose of 10 mg. Amlodipine is cost effective and predicted to be cost saving when compared with usual care., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg in hypertensive patients. This is a multicenter, double-blind, active-controlled, phase 3, randomized trial. Patients are randomized to triple combination (telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg, TEL/AML/CHTD group) or dual combination (telmisartan 40 mg/amlodipine 5 mg, TEL/AML group) treatment and then dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. The primary endpoint is the change of mean sitting systolic blood pressure (MSSBP) at week 8. A Target BP achievement rate, a response rate, and the safety endpoints are also evaluated. Total 374 patients (mean age = 60.9 ± 10.7 years, male = 78.3%) were randomized to the study. The baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. After 8 weeks treatment, the change of MSSBPs at week 8 are -19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and -11.4 ± 14.7 mm Hg (TEL/AML) (p < .0001). The achievement rates of target BP (53.8% vs. 37.8%, p = .0017) and responder rate (54.8% vs. 35.6%, p = .0001) at week 8 were significantly higher in TEL/AML/CHTD. There are no serious adverse event and no one discontinued medication due to adverse event. Among the TEL 80/AML5/CHTD25mg treatment group, patients of female or age ≥ 65 years old showed higher rate of target BP achievement than relatively young male. (61.4 vs. 46.8%, p = .042) Our study showed standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg is efficacious and safe in treatment of primary hypertension. Target BP achievement with triple therapy would be facilitated in female or old age., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included 259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL-C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set [FAS]: -7.08%, 95% CI: -11.79 to -2.38, p = .0034, per-protocol analysis set [PPS]: -6.97%, 95% CI: -11.76 to -2.19, p = .0046). Also, there was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: -10.13%, 95% CI: -15.41 to -4.84, p = .0002, PPS: -10.96%, 95% CI: -15.98 to -5.93, p < .0001). There was no significant difference in the adverse events rates between RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, and ATV 20 mg/AML 5 mg. In conclusion, while maintaining safety, RSV 10 mg/AML 5 mg and the RSV 20 mg/AML 5 mg more effectively reduced LDL-C compared with the ATV 20 mg /AML 5 mg (Clinical trial: NCT03951207)., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Hyperhomocysteinemia with hypertension can synergistically increase the risk of stroke. The China stroke primary prevention trial showed that combining 0.8 mg folic acid (FA) with angiotensin-converting enzyme inhibitor (ACEI) can effectively lower plasma total homocysteine (tHcy) and blood pressure (BP); and reduce first stroke risk by additional 21% compared to ACEI alone. However, intolerance to ACEI is common in Asians and amlodipine can be alternative. This is a multicenter, randomized, double-blind, parallel-controlled clinical trial (RCT) which evaluated whether amlodipine combined with FA is more efficacious than amlodipine alone in lowering tHcy and BP among Chinese hypertensive with hyperhomocysteinemia and intolerance to ACEI. 351 Eligible patients were randomly assigned by 1:1:1 ratio to receive amlodipine-FA tablet daily (amlodipine 5 mg/FA 0.4 mg, A group); amlodipine 5 mg/FA 0.8 mg tablet daily (B group); amlodipine 5 mg daily (C group, control group). Follow-up was conducted at 2, 4, 6, and 8 weeks. The primary outcome was efficacy of lowering both tHcy and BP at the end of 8-week treatment. Compared with C group, A group had a significantly higher rate of lowering both tHcy and BP (23.3% vs. 6.0%; Odds Ratio [OR], 8.68; 95% CI, 3.04-24.78, P < .001); B group also had a higher rate of lowering both tHcy and BP (20.3% vs. 6.0%; OR: 5.90; 95% CI, 2.11-16.47, P < .001). This RCT showed amlodipine combined with FA compared with amlodipine alone, each had significantly higher efficacy of lowering both tHcy and BP. No difference was found in BP-lowering and occurrence of adverse events between the three groups., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Objective: To evaluate the antihypertensive effect and safety of bisoprolol 5 mg (BISO5mg) and amlodipine 5 mg (AMLO5mg) combination in comparison to AMLO5mg in hypertensive subjects uncontrolled with AMLO5mg., Methods: Phase III, prospective, randomized, double-blind, placebo-controlled, 8-week trial with parallel design (EudraCT Number: 2019-000751-13)., Results: 367 patients aged 57.58 ± 14.62 years were randomized to BISO5mg once daily on top of AMLO5mg ( n  = 181) or placebo on top of AMLO5mg ( n  = 186). Systolic/diastolic blood pressure (SBP/DBP) in the bisoprolol-treated group was reduced by 7.2 ± 12.74/3.95 ± 8.85 mmHg at 4 weeks (both p  < .0001) and by 5.5 ± 12.44/3.84 ± 9.46 mmHg at 8 weeks ( p  < .0001/ p  < .0002) compared to placebo control. Bisoprolol-treated group had lower heart rate than placebo control (difference -7.23 ± 9.84/-6.25 ± 9.26 beats per minute at 4 and 8 weeks, respectively, both p  < .0001). Both target SBP and DBP was achieved at 4 weeks by 62 vs. 41% ( p  = .0002) and at 8 weeks by 65 vs. 46% ( p  = .0004) of bisoprolol-treated patients and placebo group patients, respectively. SBP <140 mmHg was achieved at 4 and 8 weeks in 68 and 69% of bisoprolol-treated patients and 45 and 50% of placebo group patients, respectively. No deaths and serious adverse events were reported. Adverse events occurred in 34 bisoprolol-treated patients vs. 22 patients in the placebo group ( p  = .064). Bisoprolol was withdrawn due to adverse events in 7 patients, mostly ( n  = 4) due to asymptomatic bradycardia., Conclusions: Addition of bisoprolol to patients uncontrolled with amlodipine monotherapy significantly improves blood pressure control. We can expect additional 7.2/3.95 mmHg SBP/DBP lowering effect by adding bisoprolol 5 mg to amlodipine 5 mg.

A 12-year-old boy was referred with a painless swelling of the labial gingiva. The swelling was caused by the antihypertensive amlodipine, which he used because of arterial hypertension due to a chronic kidney disease. The treatment consisted of discontinuation of the causative drug after which the swelling of the gingiva slowly subsided.

Background: Few data are available regarding the efficacy and safety of a single-pill combination (SPC) consisting of four medications in patients with concomitant hypertension and dyslipidemia., Objective: We aimed to determine the efficacy and tolerability of a fixed-dose SPC consisting of 5 mg amlodipine, 100 mg losartan, 20 mg rosuvastatin, and 10 mg ezetimibe (A/L/R/E) in patients with concomitant hypertension and dyslipidemia., Methods: This was a 14-week, randomized, multicenter, double-blind, placebo-controlled, phase III clinical trial. In total, 145 patients were randomized to receive A/L/R/E, A/L, or L/R/E. The primary endpoints were the average change in the low-density lipoprotein cholesterol (LDL-C) level in the A/L/R/E and A/L groups and the sitting systolic blood pressure (sitSBP) in the A/L/R/E and L/R/E groups. The numbers of patients with adverse drug reactions (ADRs) were compared as safety variables., Results: The average percentage change in the LDL-C level as the least squares mean (LSM) from the baseline LDL-C level at the end of the 8-week treatment was - 59.0% in the A/L/R/E group and 0.2% in the A/L group (LSM difference - 59.2, 95% confidence interval [CI] - 68.1 to - 50.4; p < 0.0001). The average change in the sitSBP as the LSM was - 15.8 mmHg in the A/L/R/E group and -4.7 mmHg in the L/R/E group (LSM difference - 11.1, 95% CI - 16.8 to - 5.4; p = 0.0002). No ADRs occurred in the A/L/R/E group., Conclusions: A/L/R/E as an SPC could be an effective treatment for patients with hypertension and dyslipidemia without significant safety issues., Clinical Trials Registration: NCT04074551 (registered 30 August 2019)., (© 2023. The Author(s).)

The brain is among the target organs of hypertension. Patients with hypertension have a higher risk of developing stroke as well as experiencing a decline in cognitive functions and dementia. Changes in the white matter and atrophy of the grey matter of the brain induced by high blood pressure develop insidiously since the onset of hypertension, even in young individuals. The effect of high blood pressure on the vessel wall cumulates in time; therefore, hypertension in younger people implies an increased risk of dementia in older age. Hypertension in young age cannot be considered a benign condition. Hypertension in middle age increases the risk of dementia by 61 %. Consistent and early hypertension control can reverse the adverse development towards dementia and lack of self-sufficiency in the patient. Data comparing individual antihypertensive drugs in terms of preventing dementia are scarce. However, renin angiotensin system blockers have been found to protect against Alzheimer's disease more than other classes of antihypertensive drugs. To achieve rapid and effective hypertension control, a combination of antihypertensive drugs is usually required. Using a fixed-dose triple combination of perindopril, indapamide, and amlodipine, blood pressure targets of &lt; 130/80 mm Hg can be achieved within three months in 93 % of patients.

Purpose: Oral administration of 5-aminolevulinic acid hydrochloride (5-ALA-HCl) has been reported to enhance the hypotensive effects associated with anesthetics, especially in elderly hypertensive patients treated with antihypertensive agents. The present study aimed to clarify the effects of antihypertensive-agent- and anesthesia-induced hypotension by 5-ALA-HCl in spontaneously hypertensive rats (SHRs)., Methods: We measured blood pressure (BP) of SHRs and normotensive Wistar Kyoto (WKY) rats treated with amlodipine or candesartan before and after administration of 5-ALA-HCl. We also investigated the change in BP following intravenous infusion of propofol and intrathecal injection of bupivacaine in relation to 5-ALA-HCl administration., Findings: Oral administration of 5-ALA-HCl significantly reduced BP in SHRs and WKY rats with amlodipine and candesartan. Infusion of propofol significantly reduced BP in SHRs treated with 5-ALA-HCl. Intrathecal injection of bupivacaine significantly declined SBP and DBP in both SHRs and WKY rats treated with 5-ALA-HCl. The bupivacaine-induced decline in SBP was significantly larger in SHRs compared with WKY rats., Conclusion: These findings suggest that 5-ALA-HCl does not affect the antihypertensive agents-induced hypotensive effect, but enhances the bupivacaine-induced hypotensive effect, especially in SHRs, indicating that 5-ALA may contribute to anesthesia-induced hypotension via suppression of sympathetic nerve activity in patients with hypertension., Competing Interests: Declaration of competing interest M.A., N.F., and M.K. signed a joint research agreement with SBI Pharmaceuticals Co., Ltd. relevant to this article. H.I., T.H., N.O., and M.I. are employees of SBI Pharmaceuticals Co. Ltd., (Copyright © 2023 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

To observe the effect of amlodipine besylate combined with metoprolol in treating hypertension and heart failure. Total number of patients with hypertension combined with HF admitted to our hospital was One hundred and fifty from May 2017 to May 2022 selected for the study and they were distributed into single drug group and combination group by the method of random number table, with the total number of 75 cases in every group. Metoprolol treatment was given to the single drug group and metoprolol combined with amlodipine besylate treatment was given to the combination group. Both groups' scientific outcomes were compared, including their ventricular function, inflammatory factors, hemodynamics and liver and kidney function. Adverse treatment-related side events for patients were also tallied. Compared to the single drug group, the combination group's overall treatment effectiveness was higher (P<0.05). The combined group had better ventricular function, improved hemodynamics and lower levels of inflammatory factors (P<0.05). The liver, kidney function and adverse effects outcomes were the same in both groups (P>0.05). Amlodipine besylate combined with metoprolol has a better clinical effect in treating hypertension combined with heart failure, which can more effectively improve patients' cardiac function, inflammation and hemodynamics.

Pedal oedema is a well-known adverse effect of amlodipine, but significantly less frequent if only half of the maximum recommended dosage is used. Diuretics are ineffective. To cause as few side effects as possible, options for managing are prioritised in this review: Reduce dosage, switch to lercanidipine/lacidipine, switch to another group, add/increase dosage of an ACE-inhibitor/angiotensin II-receptor blocker, administer at night, or switch to verapamil/diltiazem. Non-pharmacologic actions or observation may be considered when the oedemas are mild and not bothersome.

Background and Objectives : Blood pressure measurement is essential evidence to establish that the chosen medicine and dosage are appropriate, and also indirectly indicates whether the medicine is being used at all. Therefore, current research compares adherence to the target blood pressure at home and in the hospital between different age groups, using similar combinations of the drugs prescribed by the doctor within ongoing antihypertensive therapy. Moreover, it is very important to develop a method for the determination of amlodipine and its metabolite, which would suitable for clinical applications, when the result is needed as quick as possible. Materials and Methods : This prospective study included patients aged ≥18 years who were diagnosed with hypertension. Subjects were divided into two age groups according to European Society of Cardiology (ESC) hypertension guidelines; older patients (≥65 years) and adult patients (<65 years). Assessment of adherence rate to antihypertensive medications was performed using a measurement of systolic blood pressure and comparing this to ESC hypertension guideline data. A simple liquid chromatography-tandem mass spectrometer (LC-MS/MS) method for determination of amlodipine and dehydroamlodipine was developed and validated according to the European Medicines Agency guideline on bioanalytical method validation at the Latvian Institute of Organic Synthesis. Results : A total of 81 patients with arterial hypertension were enrolled in this study. A significant number of patients were overweight (N = 33, 40.7%) and obese (N = 36, 44.4%). To control arterial hypertension, 70 (86.4%) patients used fixed-dose combinations, where one of the components was amlodipine. Practically, 36 (44.4%) hypertensive subjects were not able to comply with target blood pressure. Nonetheless, 38 (46.9%) patients who received fixed-dose combinations were able to comply with target blood pressure. Conclusions : Adherence to ESC hypertension guideline proposed target blood pressure was relatively low among hypertensive subjects even though a significant number of patients were taking fixed-dose combinations. Therefore, optimizing prevention, recognition, and care of hypertensive young adults require intensive educational interventions. Moreover, survey data suggest that therapeutic drug monitoring using the validated simple, sensitive LC-MS/MS method is pivotal for further understanding factors influencing adherence.

Objective: A significant global health issue that affects 25.5% of Saudi people is hypertension (HTN). According to international recommendations, most HTN patients require more than one therapy to reach their blood pressure targets (BP). Therefore, it would be preferable to utilize two medications from distinct classes separately or in a predetermined combination. According to recent studies, a single-pill combination (SPC) may be more efficient. This study evaluated the safety and tolerability of Amlodipine/Valsartan (Aml/Val) SPC in Saudi hypertensive patients, as well as the effectiveness of the medication., Patients and Methods: Observational research was done prospectively at the King Fahad Armed Forces Hospital in Jeddah, Saudi Arabia. The effectiveness of the treatment and the percentage of 159 hypertensive patients who achieved the target blood pressure values (140/90; 130/80 mmHg) among those with diabetes mellitus (DM), chronic kidney disease (CKD), other cardiovascular disorders, and responders were assessed from the beginning to the endpoint (week 23)., Results: According to the results, taking Aml/Val SPC significantly lowered all patients' baseline systolic and diastolic blood pressure readings by -17.97 and 8.58 mmHg, respectively. 43.4% of patients successfully met their BP therapeutic objectives by bringing their blood pressure levels back to normal, including 51.4% of patients under 65, 39.3% of patients with chronic kidney disease, and 26.2% of diabetic patients. Aml/Val 10/160 mg significantly lowers SBP, more than Aml/Val 5/160 mg (-13.32% vs. -9.00%, p<0.050). Vertigo (6.30%), respiratory tract infections (4.0%), and ankle edema (2.50%) were the most frequent adverse events., Conclusions: Aml/Val SPC therapy effectively lowered BP and had few side effects while being well-tolerated in people with hypertension.

Background: There is a lack of sufficient evidence regarding efficacy and safety of amlodipine on treating hypertension during pregnancy., Objective: To compare antihypertensive efficacy, pregnancy outcome and safety of amlodipine with nifedipine on hypertension during pregnancy., Methods: A systematic search of PubMed, Embase, Cochrane Library, clinicaltrials.gov, Chinese National Knowledge Infrastructure, Wanfang Database and China Biology Medicine disc of randomized controlled trials (RCTs) up to April l5, 2021 was conducted on RCTs comparing amlodipine to nifedipine for the treatment of hypertension during pregnancy. Screening, data extraction, and quality assessment were done by two independent reviewers. To estimate relative effects from all available evidence, a meta-analysis was conducted., Results: Seventeen RCTs were included. Amlodipine was found the efficacy is slightly superior to nifedipine on treating hypertension during pregnancy (RR 1.06, 95% CI 1.01 to 1.10) with a decreased risk for maternal side effects (RR 0.42, 95% CI 0.29 to 0.61). Subgroup analysis found amlodipine can get a better control on SBP (RR - 11.68, 95% CI - 17.98 to - 5.37) and DBP (RR - 7.44, 95% CI - 13.81 to - 1.06) compared with intermediate-/long-acting nifedipine. In addition, there was no difference between amlodipine and nifedipine on pregnancy outcomes including caesarean section, premature labour, placental abruption, FGR, fetal distress, neonatal asphyxia., Conclusions: Given the results of this systematic review and meta-analysis, amlodipine can be effectively and safely used for hypertension during pregnancy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cilnidipine, an upcoming anti-hypertensive drug, is a combined L- and N-type calcium channel blocker. It is proposed to be more efficacious and safer due to its two-pronged approach in treating hypertension., Methods: The study was a randomized open-label parallel-group study, conducted in the Department of General Medicine, Sri Ramachandra Medical College Hospital, Chennai, during the period September 2014 to May 2015. 50 patients were randomized to the amlodipine group and 50 to the cilnidipine group. The blood pressure, pulse rate and adverse effects were monitored in each patient over 12 weeks. The difference in the Systolic Blood Pressure(SBP), Diastolic Blood Pressure(DBP) and Heart Rate(HR) before and after treatment within each group, and between the two groups were analyzed using paired and unpaired t tests respectively. The adverse effects reported in each group were analyzed using Chi-square test., Results: There was no statistically significant difference in the reduction of SBP and DBP between the two groups (p&gt;0.05). The HR however, showed an increase of 1.07/min in the amlodipine group and decreased by 1.16/min in the cilnidipine group. The patients in the cilnidipine group experienced significantly less adverse effects such as pedal edema and palpitations when compared to those in the amlodipine group (p&lt;0.05)., Conclusions: Cilnidipine therapy is an effective and safe alternative in the treatment of essential hypertension. It can be used as a first line antihypertensive drug since its efficacy is comparable to that of amlodipine with a better safety profile than amlodipine., (© Journal of the Association of Physicians of India 2011.)

Introduction: Primary care provides an opportunity to prevent community acquired, medicine or drug-induced acute kidney injury. One of the barriers to proactive prevention of medicine-induced kidney injury in primary care is the lack of a list of nephrotoxic medicines that are most problematic in primary care, particularly one that provides a comparison of risks across medicines., Objective: The aim of this study was to consolidate evidence on the risks associated with medicines and acute kidney injury, with a focus on medicines used in primary care., Method: We searched the MEDLINE and EMBASE databases to identify published studies of all medicines associated with acute kidney injury identified from spontaneous report data. For each medicine positively associated with acute kidney injury, as identified from spontaneous reports, we implemented a sequence symmetry analysis (SSA) and a case-control design to determine the association between the medicine and hospital admission with a primary diagnosis of acute kidney injury (representing community-acquired acute kidney injury). Administrative claims data held by the Australian Government Department of Veterans' Affairs for the study period 2005-2019 were used., Results: We identified 89 medicines suspected of causing acute kidney injury based on spontaneous report data and a reporting odds ratio above 2, from Japan, France and the US. Spironolactone had risk estimates of 3 or more based on spontaneous reports, SSA and case-control methods, while furosemide and trimethoprim with sulfamethoxazole had risk estimates of 1.5 or more. Positive association with SSA and spontaneous reports, but not case control, showed zoledronic acid had risk estimates above 2, while candesartan telmisartan, simvastatin, naproxen and ibuprofen all had risk estimates in SSA between 1.5 and 2. Positive associations with case-control and spontaneous reports, but not SSA, were found for amphotericin B, omeprazole, metformin, amlodipine, ramipril, olmesartan, ciprofloxacin, valaciclovir, mycophenolate and diclofenac. All with the exception of metformin and omeprazole had risk estimates above 2., Conclusion: This research highlights a number of medicines that may contribute to acute injury; however, we had an insufficient sample to confirm associations of some medicines. Spironolactone, furosemide, and trimethoprim with sulfamethoxazole are medicines that, in particular, need to be used carefully and monitored closely in patients in the community at risk of acute kidney injury., (© 2022. The Author(s).)

Introduction: Hypertension represent the commonest cause of death in 2017. Hypertension is classified into two types which are primary or essential hypertension and secondary hypertension. The perindopril-amlodipine combination showed a significant effect in reduction of the elevated BP and the cardiovascular complications., Aim: To evaluate the efficacy and safety of a fixed-dose single-pill combination of perindopril-amlodipine in hypertensive patients., Methods: We searched PubMed, Medline, SCOPUS, and Web of Science for relevant clinical trials. Quality appraisal was evaluated according to GRADE and we assessed the risk of bias using Cochrane's risk of bias tool. We included the following outcomes: systolic blood pressure, diastolic blood pressure, pulse pressure, mean blood pressure, heart rate, cough, dizziness, headache, and peripheral edema. We performed the analysis of homogeneous data under the fixed-effects model, while analysis of heterogeneous data was analyzed under the random-effects model. We conducted a meta-regression according to the dose., Results: We included ten clinical trials. The pooled analysis showed that there was a significant reduction of the systolic blood pressure, diastolic blood pressure, pulse plessure, mean blood pressure, and heart rate after the the perindopril-amlodipine combination (MD = 18.96 [14.32, 23.60], P < 0.0001), (MD = 11.90 [8.45, 15.35], P < 0.0001), (MD = 8.44 [6.91, 9.97], P = 0.0001), (MD = 13.07 [5.86, 20.29], P = 0.0004), and (MD = 2.93 [0.89, 4.96], P = 0.005), respectively. The results of the meta-regression revealed that the efficacy is increased by increasing the dose (P < 0.001) CONCLUSION: The use of the perindopril-amlodipine combination had a significant effect on the reduction of SBP, DBP, mean blood pressure, pulse pressure, and HR., (© 2022. Italian Society of Hypertension.)

Introduction: Amlodipine belongs to a class of calcium channel blockers that relax blood vessels to allow easier flow of blood. Higher blood pressure (BP) is associated with cerebrovascular disease and is an important contributor to cognitive decline and dementia., Aim: This study aimed to evaluate the effect of 24 weeks of S-amlodipine besylate therapy on cognitive function in patients with hypertension and cerebrovascular disease., Methods: The data were obtained from a study of post-market surveillance of S-amlodipine besylate., Results: A total of 545 subjects (mean age 67 ± 9.68 years) with hypertension and ischemic cerebrovascular disease were enrolled. Patients with a baseline Mini-Mental State Examination (MMSE) score above 26 were assigned to the cognitive normal (CN) (n = 294) group, and those with MMSE score less than 26 were in the cognitive decline (CD) (n = 251) group. After 24 weeks of treatment with S-amlodipine besylate 5 mg, MMSE and Global Deterioration Scale (GDS) were evaluated again. Changes in MMSE were compared in the target BP reached (TBPR) and non-reached (NTBPR) groups and for CN and CD groups. Treatment with 5 mg of S-amlodipine besylate for 24 weeks improved MMSE and GDS scores (p < 0.001). The CD group showed improvement in MMSE score regardless of whether target BP was obtained (TBPR: p < 0.001, NTBPR: p < 0.01). However, the CN classification was not significant for either TBPR or NTBPR groups., Conclusions: S-amlodipine besylate improved cognition of the CD group with hypertension and cerebrovascular disease regardless of obtaining target BP., (© 2022. Italian Society of Hypertension.)

Background: Children and adolescents undergoing kidney transplantation may present oral conditions after the procedure, but a few studies have recently described them., Aim: To describe the oral conditions of post-renal transplant children and adolescents., Design: Two calibrated dentists examined all the participants by assessing caries experience, enamel defects, periodontal condition and soft tissue lesions., Results: A total of 120 participants were included in the study, in which 63 (52.5%) were male and 57 (47.5%) were female, with a mean age of 12.78 ± 3.9 years. Among the participants, 104 (86.7%) showed at least one oral change directly related to kidney disease. The most frequent oral findings were enamel defect (49/120; 40.8%) and drug-induced gingival overgrowth (DIGO) (20/120; 16.7%). Gingival bleeding was observed on probing in 115 (95.8%) participants, whereas 69 (57.5%) presented dental calculus and 51 (42.5%) had caries experience., Conclusion: Gingival bleeding, enamel defects and DIGO were the most frequent oral findings in kidney transplant children and adolescents. The use of amlodipine and anticonvulsants was associated with DIGO, and there was a positive correlation between oral ulcers and use of everolimus., (© 2022 BSPD, IAPD and John Wiley & Sons Ltd.)

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder involving progressive pancreatic dysfunction. A substantial proportion of patients with T2DM cannot achieve euglycemia despite pharmacologic therapy. Preceding clinical studies have shown that hypertension contributes to glucose dysregulation, and investigators in this study hypothesized that antihypertensive treatment may improve glycemic control in patients with T2DM., Methods: This prospective cohort study investigates the effect of adding the antihypertensive drug Amlodipine to standard diabetes therapy on serum glycosylated hemoglobin A1c (HbA1c) and lipid profile in patients with newly diagnosed T2DM. The study enrolled a total of 168 participants with newly diagnosed T2DM., Results: Recipients of additional antihypertensive drug Amlodipine demonstrated significantly lower serum HbA1c (6.62% vs. 7.01%, P = 0.01), systolic blood pressure (132 mm Hg vs. 143 mm Hg, P < 0.001), and diastolic blood pressure (78.9 mm Hg vs. 86.0 mm Hg, P <0.001) compared to recipients of standard diabetes therapy after 24 weeks., Conclusion: Antihypertensive treatment with Amlodipine in addition to standard diabetes therapy improves glycemic control in patients with T2DM and may be an appropriate option in people with diabetes and concomitant hypertension to help maintain euglycemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Cheng, Huang, Jian, Wu and Lin.)

Objectives: Drug-induced gingival overgrowth (DIGO) is a frequent adverse medication reaction that is generally caused by cyclosporine, phenytoin, and nifedipine, which belong to the category of immunosuppressants, anticonvulsants, and calcium channel blockers, respectively. This bibliometric analysis aims to depict the main citation characteristics and analyze the research trends in DIGO investigations., Methods: An exhaustive search was performed in the Scopus database to create the bibliometric list of DIGO in the syntax. Furthermore, the information related to the number of citations, drugs related to DIGO, study topic and design, authorship, publication year, journal, contributing institution, country of origin, and the department was extracted., Results: In total, 399 papers on DIGO were retrieved in this study. The total number of citations and that after the removal of self-citations were 7,814 and 7,314, respectively. The mean number of citations was 19.6 in a range of 0-608. The main paper types were articles (76.94%) and reviews (19.55%). A remarkable increasing trend in the number of citations has been observed since 1994. Cyclosporine (44.89%) is the most commonly used drug that shares a close relationship with DIGO, followed by phenytoin (18.22%), nifedipine (17.93%), and amlodipine (6.81%). The review (27.82%) type constituted the most widely used design in the DIGO studies. According to the top 20 keywords, the risk factors and pathogenesis of DIGO have been prominent topics of research works for several years., Conclusions: This bibliometric analysis will facilitate the understanding of researchers and clinicians, especially those at the beginning of their careers in periodontology on DIGO, by identifying landmark research and providing an overview of this field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Wu, Zhu, Wang and Song.)