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Journal of the American Heart... Feb 2024The objective of the PERSONAL-CovidBP (Personalised Electronic Record Supported Optimisation When Alone for Patients With Hypertension: Pilot Study for Remote Medical... (Clinical Trial)
Clinical Trial
BACKGROUND
The objective of the PERSONAL-CovidBP (Personalised Electronic Record Supported Optimisation When Alone for Patients With Hypertension: Pilot Study for Remote Medical Management of Hypertension During the COVID-19 Pandemic) trial was to assess the efficacy and safety of smartphone-enabled remote precision dosing of amlodipine to control blood pressure (BP) in participants with primary hypertension during the COVID-19 pandemic.
METHODS AND RESULTS
This was an open-label, remote, dose titration trial using daily home self-monitoring of BP, drug dose, and side effects with linked smartphone app and telemonitoring. Participants aged ≥18 years with uncontrolled hypertension (5-7 day baseline mean ≥135 mm Hg systolic BP or ≥85 mm Hg diastolic BP) received personalized amlodipine dose titration using novel (1, 2, 3, 4, 6, 7, 8, 9 mg) and standard (5 and 10 mg) doses daily over 14 weeks. The primary outcome of the trial was mean change in systolic BP from baseline to end of treatment. A total of 205 participants were enrolled and mean BP fell from 142/87 (systolic BP/diastolic BP) to 131/81 mm Hg (a reduction of 11 (95% CI, 10-12)/7 (95% CI, 6-7) mm Hg, <0.001). The majority of participants achieved BP control on novel doses (84%); of those participants, 35% were controlled by 1 mg daily. The majority (88%) controlled on novel doses had no peripheral edema. Adherence to BP recording and reported adherence to medication was 84% and 94%, respectively. Patient retention was 96% (196/205). Treatment was well tolerated with no withdrawals from adverse events.
CONCLUSIONS
Personalized dose titration with amlodipine was safe, well tolerated, and efficacious in treating primary hypertension. The majority of participants achieved BP control on novel doses, and with personalization of dose there were no trial discontinuations due to drug intolerance. App-assisted remote clinician dose titration may better balance BP control and adverse effects and help optimize long-term care.
REGISTRATION
URL: clinicaltrials.gov. Identifier: NCT04559074.
Topics: Adolescent; Adult; Humans; Amlodipine; Antihypertensive Agents; Blood Pressure; COVID-19; Essential Hypertension; Hypertension; Pandemics; Pilot Projects; Smartphone; Treatment Outcome
PubMed: 38323513
DOI: 10.1161/JAHA.123.030749 -
Journal of Clinical Hypertension... Mar 2024Microalbuminuria and hyperuricemia management are crucial for the integrated management of hypertensive patients. This retrospective post hoc analysis aims to evaluate... (Randomized Controlled Trial)
Randomized Controlled Trial
Microalbuminuria and hyperuricemia management are crucial for the integrated management of hypertensive patients. This retrospective post hoc analysis aims to evaluate the optimal allisartan-isoproxil-based combination regimen for hypertensive patients with microalbuminuria or hyperuricemia. A total of 460 hypertensive patients with microalbuminuria and 486 hypertensive patients with hyperuricemia were included in this study. All patients were initially treated with allisartan-isoproxil for 4 weeks. Thereafter, patients with blood pressure (BP) < 140/90 mmHg continued the monotherapy for 8 weeks; patients with BP ≥140/90 mmHg were randomly assigned in a 1:1 ratio to receive allisartan-isoproxil + amlodipine (Group A + C) or allisartan-isoproxil + indapamide (Group A + D) for 8 weeks. The changes of BP, urinary albumin and serum uric acid (UA) were measured. In patients with microalbuminuria, the urinary albumin/creatinine ratio (UACR) significantly decreased by 10.4 mg/g in Group A + C (vs. baseline p = .0035) and 24.2 mg/g in Group A + D (vs baseline p < .0001), intergroup p = NS. In patients with hyperuricemia, serum UA level decreased by 44.5 µmol/L in Group A + C (vs. baseline p = .0003), but increased by 27.2 µmol/L in Group A + D (vs. baseline p = .0167), intergroup p < .0001. The results suggest that for hypertensive patients with microalbuminuria, angiotensin receptor blocker (ARB) + calcium channel blocker (CCB) or ARB+ diuretic both are good choices based on their improvement of microalbuminuria and BP. But for patients with hyperuricemia, ARB + diuretic may further increase the level of UA.
Topics: Humans; Antihypertensive Agents; Hypertension; Angiotensin Receptor Antagonists; Retrospective Studies; Uric Acid; Hyperuricemia; Angiotensin-Converting Enzyme Inhibitors; Amlodipine; Calcium Channel Blockers; Blood Pressure; Diuretics; Albuminuria; Albumins; Drug Therapy, Combination; Biphenyl Compounds; Imidazoles
PubMed: 38319613
DOI: 10.1111/jch.14773 -
World Journal of Gastroenterology Jan 2024L-type calcium channels are the only protein channels sensitive to calcium channel blockers, and are expressed in various cancer types. The Cancer Genome Atlas database...
BACKGROUND
L-type calcium channels are the only protein channels sensitive to calcium channel blockers, and are expressed in various cancer types. The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue. Therefore, we hypothesized that amlodipine, a long-acting dihydropyridine L-type calcium channel blocker, may inhibit the occurrence and development of esophageal cancer (EC).
AIM
To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum (ER) stress.
METHODS
Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined. Subsequently, the inhibitory effects of amlodipine on proliferation and migration of EC cells were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays. experiments were performed using murine xenograft model. To elucidate the underlying mechanisms, cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine.
RESULTS
The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues. Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose- and time-dependent manner. animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice. Additionally, amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition (EMT). Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT. Moreover, amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein. The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis, EMT, and autophagy. Furthermore, blocking autophagy increases the ratio of apoptosis and migration.
CONCLUSION
Collectively, we demonstrate for the first time that amlodipine promotes apoptosis, induces autophagy, and inhibits migration through ER stress, thereby exerting anti-tumor effects in EC.
Topics: Humans; Mice; Animals; Amlodipine; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Apoptosis; Cell Proliferation; Endoplasmic Reticulum Stress; Cell Line, Tumor
PubMed: 38313237
DOI: 10.3748/wjg.v30.i4.367 -
Journal of Human Hypertension May 2024In this cohort study, we determined time to blood pressure (BP) control and its predictors among hypertensive PLHIV enrolled in integrated hypertension-HIV care based on...
Time to blood pressure control and predictors among patients receiving integrated treatment for hypertension and HIV based on an adapted WHO HEARTS implementation strategy at a large urban HIV clinic in Uganda.
In this cohort study, we determined time to blood pressure (BP) control and its predictors among hypertensive PLHIV enrolled in integrated hypertension-HIV care based on the World Health Organization (WHO) HEARTS strategy at Mulago Immunosuppression Clinic in Uganda. From August 2019 to March 2020, we enrolled hypertensive PLHIV aged 18 years and initiated Amlodipine 5 mg mono-therapy for BP (140-159)/(90-99) mmHg or Amlodipine 5 mg/Valsartan 80 mg duo-therapy for BP ≥ 160/90 mmHg. Patients were followed with a treatment escalation plan until BP control, defined as BP < 140/90 mmHg. We used Cox proportional hazards models to identify predictors of time to BP control. Of 877 PLHIV enrolled (mean age 50.4 years, 62.1% female), 30% received mono-therapy and 70% received duo-therapy. In the monotherapy group, 66%, 88% and 96% attained BP control in the first, second and third months, respectively. For patients on duo-therapy, 56%, 83%, 88% and 90% achieved BP control in the first, second, third, and fourth months, respectively. In adjusted Cox proportional hazard analysis, higher systolic BP (aHR 0.995, 95% CI 0.989-0.999) and baseline ART tenofovir/lamivudine/efavirenz (aHR 0.764, 95% CI 0.637-0.917) were associated with longer time to BP control, while being on ART for >10 years was associated with a shorter time to BP control (aHR 1.456, 95% CI 1.126-1.883). The WHO HEARTS strategy was effective at achieving timely BP control among PLHIV. Additionally, monotherapy anti-hypertensive treatment for stage I hypertension is a viable option to achieve BP control and limit pill burden in resource limited HIV care settings.
Topics: Humans; Female; Male; HIV Infections; Hypertension; Middle Aged; Uganda; Antihypertensive Agents; Adult; Blood Pressure; Treatment Outcome; Time Factors; Amlodipine
PubMed: 38302611
DOI: 10.1038/s41371-024-00897-3 -
International Journal of Critical... 2023Complications involving the heart are rare in leptospirosis, and cardiac tamponade is still rarer. We report the case of a 42-year-old hypertensive woman who presented...
Complications involving the heart are rare in leptospirosis, and cardiac tamponade is still rarer. We report the case of a 42-year-old hypertensive woman who presented with complaints of cough for 2 months and breathlessness for 1 month. One month later, she developed shortness of breath and loss of consciousness. The patient had a history of hemiparesis. Serum anti- immunoglobulin M ELISA was positive. Ultrasound showed pericardial tamponade and hemorrhagic collection. Two-dimensional echocardiography showed minimal effusion posterior to the left ventricle and no effusion present to the right ventricle. High-resolution computerized tomography revealed patchy areas of ground glass opacities in bilateral upper and bilateral lower lobes, prominent bronchovascular markings bilaterally, and minimal pericardial thickening. Magnetic resonance imaging of the brain showed small chronic infarcts in bilateral corona radiata and basal ganglia. A magnetic resonance angiogram of the brain showed a basilar top aneurysm, which was an incidental finding. No signs of rupture of the aneurysm were seen. Digital subtraction angiography showed 50%-70% stenosis at the junction of the V3-V4 segments of the vertebral artery. The right lower limb immobilization, along with ecosprin, ivabradine, amlodipine, and fluconazole, was started, to which the patient responded well.
PubMed: 38292400
DOI: 10.4103/ijciis.ijciis_26_23 -
European Heart Journal Apr 2024Visit-to-visit systolic blood pressure variability (BPV) is an important predictor of cardiovascular (CV) outcomes. The long-term effect of a period of blood pressure...
BACKGROUND AND AIMS
Visit-to-visit systolic blood pressure variability (BPV) is an important predictor of cardiovascular (CV) outcomes. The long-term effect of a period of blood pressure (BP) control, but with differential BPV, is uncertain. Morbidity and mortality follow-up of UK participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure-Lowering Arm has been extended for up to 21 years to determine the CV impact of mean systolic blood pressure (SBP) control and BPV during the trial, and amongst those allocated to amlodipine- and atenolol-based treatment.
METHODS
Eight thousand five hundred and eighty hypertensive participants (4305 assigned to amlodipine ± perindopril-based and 4275 to atenolol ± diuretic-based treatment during the in-trial period (median 5.5 years) were followed for up to 21 years (median 17.4 years), using linked hospital and mortality records. A subgroup of participants (n = 2156) was followed up 6 years after the trial closure with a self-administered questionnaire and a clinic visit. In-trial mean SBP and standard deviation of visit-to-visit SBP as a measure of BPV, were measured using >100 000 BP measurements. Cox proportional hazard models were used to estimate the risk [hazard ratios (HRs)], associated with (i) mean with SBP and BPV during the in-trial period, for the CV endpoints occurring after the end of the trial and (ii) randomly assigned treatment to events following randomization, for the first occurrence of pre-specified CV outcomes.
RESULTS
Using BP data from the in-trial period, in the post-trial period, although mean SBP was a predictor of CV outcomes {HR per 10 mmHg, 1.14 [95% confidence interval (CI) 1.10-1.17], P < .001}, systolic BPV independent of mean SBP was a strong predictor of CV events [HR per 5 mmHg 1.22 (95% CI 1.18-1.26), P < .001] and predicted events even in participants with well-controlled BP. During 21-year follow-up, those on amlodipine-based compared with atenolol-based in-trial treatment had significantly reduced risk of stroke [HR 0.82 (95% CI 0.72-0.93), P = .003], total CV events [HR 0.93 (95% CI 0.88-0.98), P = .008], total coronary events [HR 0.92 (95% CI 0.86-0.99), P = .024], and atrial fibrillation [HR 0.91 (95% CI 0.83-0.99), P = .030], with weaker evidence of a difference in CV mortality [HR 0.91 (95% CI 0.82-1.01), P = .073]. There was no significant difference in the incidence of non-fatal myocardial infarction and fatal coronary heart disease, heart failure, and all-cause mortality.
CONCLUSIONS
Systolic BPV is a strong predictor of CV outcome, even in those with controlled SBP. The long-term benefits of amlodipine-based treatment compared with atenolol-based treatment in reducing CV events appear to be primarily mediated by an effect on systolic BPV during the trial period.
Topics: Humans; Blood Pressure; Atenolol; Antihypertensive Agents; Hypertension; Amlodipine; Risk Factors
PubMed: 38291599
DOI: 10.1093/eurheartj/ehad814 -
Medicine Jan 2024This case report presents a challenging medical scenario involving a young adult male who exhibited an unusual combination of symptoms, including abrupt weight loss,...
RATIONALE
This case report presents a challenging medical scenario involving a young adult male who exhibited an unusual combination of symptoms, including abrupt weight loss, declining renal function, proteinuria, and concurrent onset of diabetes mellitus. Remarkably, the patient had no previous medical history or family history of similar conditions, necessitating a comprehensive investigation.
PATIENT CONCERNS
On March 10, 2021, a 25-year-old male sought medical attention due to the aforementioned symptoms. Initial assessments revealed stage 5 chronic kidney disease, with elevated blood urea nitrogen (BUN) and serum creatinine (Cr) levels, as well as significant proteinuria. The only notable physical finding was obesity, and renal ultrasound showed normal-sized kidneys without cysts.
DIAGNOSIS
A treatment plan was initiated to stabilize creatinine levels, including medications such as Glimepiride, Glyxambi, Bisoprolol, Amlodipine, and Valsartan. However, despite diligent medication management, proteinuria persisted, prompting further evaluation. A renal biopsy was performed on April 12th, 2023, leading to the diagnosis of glomerulocystic kidney disease with early-stage changes indicative of diabetic nephropathy.
INTERVENTIONS
The patient continues to receive ongoing care and follow-up at our outpatient clinic to optimize therapeutic interventions and elucidate the underlying etiology of this complex clinical scenario.
OUTCOMES
Ongoing investigations and therapeutic interventions are crucial to understand the underlying cause and optimize patient care in this intricate clinical scenario.
LESSONS
This case underscores the complexity of diagnosing and managing a young adult presenting with concurrent renal dysfunction, proteinuria, and diabetes mellitus in the absence of prior underlying conditions. It highlights the importance of comprehensive evaluation and ongoing care in such challenging cases.
Topics: Adult; Humans; Male; Diabetes Mellitus; Diabetic Nephropathies; Kidney; Kidney Failure, Chronic; Obesity; Proteinuria
PubMed: 38277556
DOI: 10.1097/MD.0000000000036952 -
BMC Medicine Jan 2024Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients.
METHODS
In a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis.
RESULTS
In the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was - 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and - 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of - 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were - 1.47 (p = 0.18) in 24-h diastolic BP, - 2.86 (p = 0.13) and - 2.74 (p = 0.03) in daytime systolic and diastolic BP, and - 0.45 (p = 0.82) and - 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04).
CONCLUSIONS
The amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03682692. Registered on 18 September 2018.
Topics: Humans; Antihypertensive Agents; Amlodipine; Hydrochlorothiazide; Hypertension; Hypotension; China; Cough
PubMed: 38263021
DOI: 10.1186/s12916-023-03244-4 -
Experimental and Therapeutic Medicine Feb 2024Essential hypertension is a notable threat for the older (age, ≥65 years) population. However, to the best of our knowledge, a real-world study assessing olmesartan...
Efficacy and safety of olmesartan medoxomil‑amlodipine besylate tablets (Sevikar) in older patients with essential hypertension: Subgroup analysis from the Sevikar study.
Essential hypertension is a notable threat for the older (age, ≥65 years) population. However, to the best of our knowledge, a real-world study assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablets in older Chinese patients with essential hypertension has not been performed. Therefore, the present study aimed to evaluate the efficacy and safety of OM-AML tablets in these patients. A total of 463 older Chinese patients with essential hypertension treated with OM-AML (20/5 mg) tablets (Sevikar) were analyzed in a prospective, single-arm, multi-center, real-world study. Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, and at week (W)4 and W8 after OM-AML tablet administration were measured. The mean ± standard error change of SeSBP/SeDBP was -10.3±0.8/-4.6±0.5 and -12.5±0.8/-5.6±0.5 mmHg at W4 and W8, respectively. At W4, 74.1 and 26.8% of patients achieved BP target according to the China and American Heart Association (AHA) criteria, while at W8, 78.0 and 38.7% of patients reached these BP targets accordingly. Finally, 76.5 and 80.5% of patients achieved BP response at W4 and W8, respectively. Furthermore, home-measured SeSBP and SeDBP were significantly decreased from W1 to W8 (both P<0.001). Additionally, the satisfaction of both patients and physicians was elevated at W8 compared with at W0 (both P<0.001). The medication possession rate from baseline to W4 and W8 was 95.5 and 92.5%. The most common drug-associated adverse events by system organ classes were nervous system disorder (4.5%), vascular disorder (2.8%), and general disorder and administration site conditions (2.6%), which were generally mild. In conclusion, OM-AML tablets may be considered effective and safe in lowering BP, enabling the achievement of guideline-recommended BP targets in older Chinese patients with essential hypertension.
PubMed: 38234624
DOI: 10.3892/etm.2023.12338 -
Drug Design, Development and Therapy 2024The objective of this study was to evaluate the effect of a high-fat meal on the pharmacokinetics and safety of 80/5 mg valsartan/amlodipine tablets in healthy subjects. (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
BACKGROUND
The objective of this study was to evaluate the effect of a high-fat meal on the pharmacokinetics and safety of 80/5 mg valsartan/amlodipine tablets in healthy subjects.
SUBJECTS AND METHODS
These results were derived from a bioequivalence trial where subjects were randomly assigned to take valsartan/amlodipine 80/5mg under fed conditions or after a high-fat meal contained 978.6 kilocalories (54.6% from fat). The blood samples were collected and plasma concentrations of valsartan/amlodipine were measured using high-performance liquid chromatography-mass spectrometry. The non-compartmental module of Phoenix WinNonlin Version 8.2 was used to calculate pharmacokinetic parameters. The BE module of WinNonLin was used to analyze the statistics of the maximum plasma concentration (C), the area under the concentration-time curve from zero to the last quantifiable time point (AUC), and the area under the concentration-time curve from zero to infinity(AUC) in plasma. 88 healthy subjects were enrolled and divided into in a fasted group and a fed group.
RESULTS
The Cmax, AUC, and AUC of valsartan in plasma under fed conditions were 51%, 56%, and 57% lower, respectively, than those under fasted conditions, and the 90% confidence interval (90% CI) were outside the 80.00-125.00% range. All the pharmacokinetic parameters for amlodipine under fed conditions were similar to those observed under fasted conditions, and the 90% CIs were within the 80.00-125.00% range. The incidence of treatment emergent adverse events (TEAE) was similar between the fasted group and the fed group, while adverse drug reaction (ADR) was more frequent in the fasted group which may be related to the higher blood concentrations of valsartan, but all were mild.
CONCLUSION
The result indicated that the high-fat meal had a significant effect on the pharmacokinetics of valsartan, but no effect on amlodipine. All treatments were safe and well tolerated in healthy subjects under fed and fasted conditions.
Topics: Humans; Amlodipine; Valsartan; Healthy Volunteers; Therapeutic Equivalency; Fasting; Area Under Curve; Tablets; Cross-Over Studies
PubMed: 38225972
DOI: 10.2147/DDDT.S423374