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Trials Jan 2024Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial... (Randomized Controlled Trial)
Randomized Controlled Trial
Initial treatment with a single capsule containing half-dose quadruple therapy versus standard-dose dual therapy in hypertensive patients (QUADUAL): statistical analysis plan for a randomized, blinded, crossover trial.
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 .
Topics: Humans; Amlodipine; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cross-Over Studies; Double-Blind Method; Drug Combinations; Hypertension; Irbesartan; Treatment Outcome
PubMed: 38218924
DOI: 10.1186/s13063-023-07803-1 -
Medicine Dec 202317α-Hydroxylase/17, 20-lyase deficiency (17OHD) is a recessively inherited autosomal disease caused by CYP17A1 gene mutations. It is characterized by failure to...
RATIONALE
17α-Hydroxylase/17, 20-lyase deficiency (17OHD) is a recessively inherited autosomal disease caused by CYP17A1 gene mutations. It is characterized by failure to synthesize cortisol, adrenal androgens and gonadal steroids. However, it is rare in clinic combining with type 2 diabetes mellitus (T2DM).
PATIENT CONCERNS
A 21-year-old woman was transferred to an endocrinology clinic because of paroxysmal paralysis. In addition, she presented with hypertension, primary amenorrhea and lack of pubertal development. Blood evaluation revealed hypokalemia, and a low cortisol level with an increased adrenocorticotropic hormone concentration. The renin activity and testosterone and estrogen levels were suppressed, and the gonadotropin levels were high. CT scan showed bilateral adrenal hyperplasia. Besides, this patient had hyperglycemia, hyperinsulinism and negative diabetes type 1 related antibodies. A homozygous mutation c. 985 to 987delinsAA in exon 6 was found in the patient which caused the missense mutation (p.Y329fs).
DIAGNOSES
17α-hydroxylase/17, 20-lyase deficiency combined with T2DM was considered.
INTERVENTIONS
The patient received dexamethasone, estradiol valerate, metformin, amlodipine besylate and D3 calcium carbonate tablets. The doses of dexamethasone was changed according to her blood potassium levels.
OUTCOMES
After treatment, the blood pressure, blood potassium and blood glucose returned to normal range. Besides, she had restored her menstrual cycle.
LESSONS
For patients with hypertension, hypokalemia and lack of pubertal development, the possibility of 17OHD should be considered. The subsequent treatment would be challenging in patients with combined 17OHD and T2DM, considering the potential contribution of glucocorticoids to diabetic balance and osteoporosis.
Topics: Female; Humans; Young Adult; Adrenal Hyperplasia, Congenital; Dexamethasone; Diabetes Mellitus, Type 2; Hydrocortisone; Hypertension; Hypokalemia; Lyases; Mixed Function Oxygenases; Mutation; Potassium; Steroid 17-alpha-Hydroxylase
PubMed: 38206738
DOI: 10.1097/MD.0000000000036727 -
Scientific Reports Jan 2024Given possible involvement of the central and peripheral angiotensin system in pain processing, we conducted clinical and preclinical studies to test whether...
Given possible involvement of the central and peripheral angiotensin system in pain processing, we conducted clinical and preclinical studies to test whether pharmacological inhibition of the angiotensin system would prevent diabetic peripheral neuropathy (DPN) accompanying type 2 diabetes mellitus (T2DM). In the preclinical study, the nociceptive sensitivity was determined in leptin-deficient ob/ob mice, a T2DM model. A clinical retrospective cohort study was conducted, using the medical records of T2DM patients receiving antihypertensives at three hospitals for nearly a decade. In the ob/ob mice, daily treatment with perindopril, an angiotensin-converting enzyme inhibitor (ACEI), or telmisartan, an angiotensin receptor blocker (ARB), but not amlodipine, an L-type calcium channel blocker (CaB), significantly inhibited DPN development without affecting the hyperglycemia. In the clinical study, the enrolled 7464 patients were divided into three groups receiving ACEIs, ARBs and the others (non-ACEI, non-ARB antihypertensives). Bonferroni's test indicated significantly later DPN development in the ARB and ACEI groups than the others group. The multivariate Cox proportional analysis detected significant negative association of the prescription of ACEIs or ARBs and β-blockers, but not CaBs or diuretics, with DPN development. Thus, our study suggests that pharmacological inhibition of the angiotensin system is beneficial to prevent DPN accompanying T2DM.
Topics: Animals; Mice; Humans; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Antihypertensive Agents; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Retrospective Studies; Antiviral Agents
PubMed: 38200077
DOI: 10.1038/s41598-024-51572-z -
Cureus Nov 2023Objective Hypertension (HTN) is among the most common causes of chronic disease burden, along with dyslipidemia. It is a prominent risk factor for cardiovascular and...
Objective Hypertension (HTN) is among the most common causes of chronic disease burden, along with dyslipidemia. It is a prominent risk factor for cardiovascular and cerebrovascular morbidity and mortality. More often than not, HTN coexists with dyslipidemia. This study aimed to see the antihypertensive effect of statins (atorvastatin), as certain animal models have shown that statins have a voltage-gated calcium channel-blocking effect. Material and methods This was a randomized controlled trial done at the Ayub Hospital Complex in Abbottabad, Pakistan. After ethical approval, 120 patients with newly diagnosed hypertension belonging to either gender and aged 35 and above were enrolled in the trial. They were randomly divided into two groups, with each group comprising 60 patients. One group was administered amlodipine 5 mg per oral (PO) once a day, while the other group was given 5 mg of amlodipine PO plus 10 mg of atorvastatin PO. The patients were examined on a follow-up visit 14 days later, and blood pressure was recorded as per protocols. Results A total of 120 newly diagnosed patients were studied in this trial. The mean age was 51.07 years, with a standard deviation of ±6.15 years and a range of 41-60 years. There were 64 (53.3%) males and 56 (46.7%) females in the study. The mean systolic blood pressures (SBPs) and diastolic blood pressures (DBPs) in Group 2 (amlodipine 5 mg + atorvastatin 10 mg) were significantly lower than the patients in Group 1 (only amlodipine 5 mg) in the follow-up visit, which was 14 days after starting the medication (p≤0.05). Conclusion The addition of a lipid-lowering drug to an antihypertensive regimen results in a better lowering of blood pressure in hypertensive individuals.
PubMed: 38156151
DOI: 10.7759/cureus.49532 -
Electrolyte & Blood Pressure : E & BP Dec 2023As combination therapy, switching to single-pill combination (SPC) medication after a short period of monotherapy is helpful because reducing pill numbers can improve...
The Efficacy of Single-pill Combination of Olmesartan Medoxomil and Amlodipine Besylate on Office Blood Pressure in Hypertensive Patients who did not Respond to Amlodipine Besylate Monotherapy.
BACKGROUND
As combination therapy, switching to single-pill combination (SPC) medication after a short period of monotherapy is helpful because reducing pill numbers can improve patients' adherence to medications. This study was aimed to assess the effect of the single-pill combination (SPC) of olmesartan medoxomil 20 mg and amlodipine besylate 5mg (OLM 20 mg/AML 5 mg) on blood pressure (BP) reduction in hypertensive patients who did not respond to amlodipine besylate 5 mg (AML 5 mg) monotherapy for 4 weeks.
METHODS
This study was a prospective, open-label, multi-center, non-comparative study. Patients whose BP was not got the target BP (≥140 mmHg and if diabetic patients ≥130 mmHg) after 4 weeks treatment with AML 5 mg, were enrolled. AML 5 mg was switched to the SPC (OLM 20 mg/AML 5 mg) treatment for 8 weeks. The primary effectiveness endpoint was the reduction of seated systolic blood pressure (SeSBP) after SPC (OLM 20 mg/AML 5 mg) treatment for 8 weeks. The changes of brachial-ankle pulse wave velocity (baPWV), central BP (CBP), and augmentation index (AIx@75) were evaluated also.
RESULTS
Forty-seven patients were enrolled (mean age = 52±9 years, 36 men). After the SPC treatment for 8 weeks, SeSBP was reduced from 153±9 mmHg to 131±18 mmHg and seated diastolic BP (SeDBP) from 95±8 mmHg to 81±11 mmHg (p<0.001 and p<0.001, respectively). The reduction of SeSBP/SeDBP were 22 mmHg and 14 mmHg, respectively. The target goal BP achievement rate was 74.5%, and baPWV, CBP, and AIx@75 were improved.
CONCLUSION
SPC (OLM 20 mg/AML 5 mg) treatment for 8 weeks was effective in reducing BP, achieving target BP goal, and also improving arterial stiffness in uncontrolled hypertensive patients with AML 5 mg monotherapy.
PubMed: 38152599
DOI: 10.5049/EBP.2023.21.2.45 -
BMC Pharmacology & Toxicology Dec 2023Previously, observational studies showed that amlodipine can mitigate calcineurin inhibitor- and contrast-induced acute kidney injury (AKI). Herein, we aimed to measure...
BACKGROUND
Previously, observational studies showed that amlodipine can mitigate calcineurin inhibitor- and contrast-induced acute kidney injury (AKI). Herein, we aimed to measure the effect of amlodipine on renal ischemia/reperfusion (I/R) injury and find the underlying mechanisms.
MATERIALS AND METHODS
Bilateral renal I/R was induced by clamping the hilum of both kidneys for 30 min. The first dose of amlodipine 10 mg/kg was gavaged before anesthesia. The second dose of amlodipine was administered 24 h after the first dose. Forty-eight hours after I/R, rats were anesthetized, and their blood and tissue specimens were collected.
RESULTS
Amlodipine significantly decreased the elevated serum levels of creatinine and blood urea nitrogen (BUN) and mitigated tissue damage in hematoxylin & eosin (H&E) staining. Amlodipine strongly reduced the tissue levels of malondialdehyde (MDA), interleukin 1β (IL1β), and tumor necrosis factor α (TNF-α). Amlodipine enhanced antioxidant defense by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) and Sestrin2. Furthermore, amlodipine significantly improved mitochondrial biogenesis by promoting Sestrin2/peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway. It also enhanced autophagy and attenuated apoptosis, evidenced by increased LC3-II/LC3-I and bcl2/bax ratios after renal I/R.
CONCLUSION
These findings suggest that amlodipine protects against renal I/R through Nrf2/Sestrin2/PGC-1α/TFAM Pathway.
Topics: Rats; Animals; NF-E2-Related Factor 2; Kidney; Reperfusion Injury; Ischemia; Apoptosis
PubMed: 38129888
DOI: 10.1186/s40360-023-00722-6 -
The Journal of International Medical... Dec 2023We evaluated the pharmacoeconomics of amlodipine combined with benazepril and hydrochlorothiazide combined with benazepril in the treatment of hypertension using a...
OBJECTIVE
We evaluated the pharmacoeconomics of amlodipine combined with benazepril and hydrochlorothiazide combined with benazepril in the treatment of hypertension using a Markov model to provide an evidence-based reference for clinical drug use.
METHODS
In this retrospective study, we constructed two types of Markov model using data from the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial to dynamically simulate the development of hypertension. The models were subjected to rollback analysis and cohort analysis to obtain the cost and effectiveness of the two drug regimens in preventing stroke and myocardial infarction in hypertensive patients. We conducted sensitivity analysis to determine the stability of the results.
RESULTS
The cost-effectiveness of amlodipine combined with benazepril was 66,196.97 RMB with 6.59 QALYs and that of hydrochlorothiazide combined with benazepril was 74,588.50 RMB with 6.46 QALYs. The incremental cost-effectiveness ratio of hydrochlorothiazide + benazepril was -64,550.23 compared with amlodipine + benazepril. The amlodipine + benazepril regimen was therefore more cost-effective than hydrochlorothiazide combined with benazepril. The sensitivity analysis results showed that the model was robust.
CONCLUSION
Compared with the hydrochlorothiazide + benazepril treatment regimen, the amlodipine + benazepril regimen showed greater economic benefits.
Topics: Humans; Amlodipine; Antihypertensive Agents; Benzazepines; Blood Pressure; Drug Therapy, Combination; Economics, Pharmaceutical; Hydrochlorothiazide; Hypertension; Myocardial Infarction; Retrospective Studies; Stroke; Clinical Trials as Topic
PubMed: 38114070
DOI: 10.1177/03000605231214921 -
The Journal of Extra-corporeal... Dec 2023Calcium channel blocker (CCB) toxicity carries a high mortality and is the sixth most fatal drug class reported to US poison centers. Amlodipine overdose is...
Calcium channel blocker (CCB) toxicity carries a high mortality and is the sixth most fatal drug class reported to US poison centers. Amlodipine overdose is characterized by a life-threatening arterial vasodilation that compromises organ perfusion. The management of CCB intoxication is focused on maintaining adequate organ perfusion. In cases refractory to medical therapies, hemodynamic support with extracorporeal membrane oxygenation (ECMO) is warranted necessitating higher flows than usual to compensate for the vasodilation and requiring central cannulation. We present a case of a 12-year-old with severe dihydropyridine CCB ingestion, refractory to medical management and successfully treated with central ECMO cannulation. The patient was discharged home with no significant disability. Central ECMO cannulation may be helpful to facilitate adequate flows in vasodilatory shock such as CCB overdose.
Topics: Humans; Child; Calcium Channel Blockers; Extracorporeal Membrane Oxygenation; Perfusion; Dihydropyridines; Catheterization
PubMed: 38099637
DOI: 10.1051/ject/2023037 -
PloS One 2023Antihypertensive drug supply is sometimes inadequate in public sector health facilities in India. One of the core strategies of the India Hypertension Control Initiative...
BACKGROUND
Antihypertensive drug supply is sometimes inadequate in public sector health facilities in India. One of the core strategies of the India Hypertension Control Initiative (IHCI) is to improve the availability of antihypertensive drugs in primary and secondary care facilities. We quantified the availability of antihypertensive drugs in 2019-20 and described the practices in supply chain management in 22 districts across four states of India.
METHODS
Twenty-two districts from 4 states (Punjab, Madhya Pradesh, Telangana, and Maharashtra) were studied. We described the practices and challenges in supply chain management. We collected data on drug procurement from 2018 to 2020 and drug availability from April 2019 to March 2020. Quantity procured, the proportion of facilities with stockout at the end of each quarter, and availability of drugs in patient days were tabulated.
RESULTS
All states selected drug- and dose-specific protocols with Amlodipine as the initial drug and shifted to morbidity-based forecasting. The total number of antihypertensive tablets procured for the 22 districts increased from 16 million in 2017-2018 to 160 million in 2019-2020. The proportion of facilities with Amlodipine stock-out was below 5% during the study period. Amlodipine stock was available for at least 60 patient days from the third quarter of 2019 onward in all districts.
CONCLUSIONS
This study demonstrates that including best practices can gradually strengthen the procurement and supply chain for antihypertensives in a low-resource setting. As the program was rapidly growing, there were still gaps in the procurement and distribution system which needed to be addressed to ensure the adequacy of drugs. We recommend that best practices, including choosing a single protocol, basing supply on projected patient load rather than an increment from historical levels, and using simple stock management tools, be replicated in other districts in India to increase and sustain coverage of hypertension treatment.
Topics: Humans; Antihypertensive Agents; India; Hypertension; Amlodipine
PubMed: 38096180
DOI: 10.1371/journal.pone.0295338 -
PeerJ 2023Sporotrichosis caused by is a globally emerging infectious disease with limited therapeutic options. Thus, we aimed to evaluate the activity of amlodipine (AML) and...
BACKGROUND
Sporotrichosis caused by is a globally emerging infectious disease with limited therapeutic options. Thus, we aimed to evaluate the activity of amlodipine (AML) and lufenuron (LUF) alone and their interaction with itraconazole (ITZ), the first-choice drug against .
METHODS
Twenty clinical isolates of from two hyperendemic regions were tested through a microdilution assay to evaluate the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of AML and LUF. Checkerboard assay was performed with 10 isolates for both drug interactions with ITZ.
RESULTS
AML showed inhibitory and fungicidal activity against all isolates included, with MIC values ranging from 32 to 256 µg/mL, and MFC from 64 to 256 µg/mL. However, none of the isolates were inhibited by the highest soluble concentration of LUF (MIC >64 µg/mL for all strains). Synergic interaction of AML and LUF with ITZ occurred in 50% and 40% of the isolates tested, without any antagonistic effects.
CONCLUSION
Both repurposing drugs evaluated in our study showed a promising activity, especially in synergy with ITZ against , warranting future investigations regarding its activity.
Topics: Humans; Antifungal Agents; Amlodipine; Drug Repositioning; Itraconazole; Leukemia, Myeloid, Acute
PubMed: 38050607
DOI: 10.7717/peerj.16443