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JAMA Apr 2023Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure-lowering therapies are available but the potential for maximizing benefit... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure-lowering therapies are available but the potential for maximizing benefit by personalized targeting of drug classes is unknown.
OBJECTIVE
To investigate and quantify the potential for targeting specific drugs to specific individuals to maximize blood pressure effects.
DESIGN, SETTING, AND PARTICIPANTS
A randomized, double-blind, repeated crossover trial in men and women with grade 1 hypertension at low risk for cardiovascular events at an outpatient research clinic in Sweden. Mixed-effects models were used to assess the extent to which individuals responded better to one treatment than another and to estimate the additional blood pressure lowering achievable by personalized treatment.
INTERVENTIONS
Each participant was scheduled for treatment in random order with 4 different classes of blood pressure-lowering drugs (lisinopril [angiotensin-converting enzyme inhibitor], candesartan [angiotensin-receptor blocker], hydrochlorothiazide [thiazide], and amlodipine [calcium channel blocker]), with repeated treatments for 2 classes.
MAIN OUTCOMES AND MEASURES
Ambulatory daytime systolic blood pressure, measured at the end of each treatment period.
RESULTS
There were 1468 completed treatment periods (median length, 56 days) recorded in 270 of the 280 randomized participants (54% men; mean age, 64 years). The blood pressure response to different treatments varied considerably between individuals (P < .001), specifically for the choices of lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Large differences were excluded for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine. On average, personalized treatment had the potential to provide an additional 4.4 mm Hg-lower systolic blood pressure.
CONCLUSIONS AND RELEVANCE
These data reveal substantial heterogeneity in blood pressure response to drug therapy for hypertension, findings that may have implications for personalized therapy.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02774460.
Topics: Female; Humans; Male; Middle Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Hydrochlorothiazide; Hypertension; Lisinopril; Double-Blind Method; Cross-Over Studies; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Diuretics; Calcium Channel Blockers; Precision Medicine
PubMed: 37039792
DOI: 10.1001/jama.2023.3322 -
American Family Physician Nov 2020Drugs are being prescribed with more frequency and in higher quantities. A serious adverse drug event from prescribed medications constitutes 2.4% to 16.2% of all...
Drugs are being prescribed with more frequency and in higher quantities. A serious adverse drug event from prescribed medications constitutes 2.4% to 16.2% of all hospital admissions. Many of the adverse drug events present intraorally or periorally in isolation or as a clinical symptom of a systemic effect. Clinical recognition and treatment of adverse drug events are important to increase patient adherence, manage drug therapy, or detect early signs of potentially serious outcomes. Oral manifestations of commonly prescribed medications include gingival enlargement, oral hyperpigmentation, oral hypersensitivity reaction, medication-related osteonecrosis, xerostomia, and other oral or perioral conditions. To prevent dose-dependent adverse drug reactions, physicians should prescribe medications judiciously using the lowest effective dose with minimal duration. Alternatively, for oral hypersensitivity reactions that are not dose dependent, quick recognition of clinical symptoms associated with time-dependent drug onset can allow for immediate discontinuation of the medication without discontinuation of other medications. Physicians can manage oral adverse drug events in the office through oral hygiene instructions for gingival enlargement, medication discontinuation for oral pigmentation, and prescription of higher fluoride toothpastes for xerostomia.
Topics: Albuterol; Amlodipine; Anticonvulsants; Antihypertensive Agents; Atorvastatin; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bronchodilator Agents; Deprescriptions; Drug Hypersensitivity; Fluorides; Gingival Overgrowth; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperpigmentation; Hypoglycemic Agents; Lisinopril; Losartan; Metformin; Metoprolol; Mouth Diseases; Omeprazole; Oral Hygiene; Proton Pump Inhibitors; Simvastatin; Thyroxine; Toothpastes; Xerostomia
PubMed: 33179891
DOI: No ID Found -
The Cochrane Database of Systematic... Oct 2018Dysphagia (swallowing problems), which is common after stroke, is associated with increased risk of death or dependency, occurrence of pneumonia, poor quality of life,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dysphagia (swallowing problems), which is common after stroke, is associated with increased risk of death or dependency, occurrence of pneumonia, poor quality of life, and longer hospital stay. Treatments provided to improve dysphagia are aimed at accelerating recovery of swallowing function and reducing these risks. This is an update of the review first published in 1999 and updated in 2012.
OBJECTIVES
To assess the effects of swallowing therapy on death or dependency among stroke survivors with dysphagia within six months of stroke onset.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (26 June 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library (searched 26 June 2018), MEDLINE (26 June 2018), Embase (26 June 2018), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (26 June 2018), Web of Science Core Collection (26 June 2018), SpeechBITE (28 June 2016), ClinicalTrials.Gov (26 June 2018), and the World Health Organization International Clinical Trials Registry Platform (26 June 2018). We also searched Google Scholar (7 June 2018) and the reference lists of relevant trials and review articles.
SELECTION CRITERIA
We sought to include randomised controlled trials (RCTs) of interventions for people with dysphagia and recent stroke (within six months).
DATA COLLECTION AND ANALYSIS
Two review authors independently applied the inclusion criteria, extracted data, assessed risk of bias, used the GRADE approach to assess the quality of evidence, and resolved disagreements through discussion with the third review author (PB). We used random-effects models to calculate odds ratios (ORs), mean differences (MDs), and standardised mean differences (SMDs), and provided 95% confidence intervals (CIs) for each.The primary outcome was functional outcome, defined as death or dependency (or death or disability), at the end of the trial. Secondary outcomes were case fatality at the end of the trial, length of inpatient stay, proportion of participants with dysphagia at the end of the trial, swallowing ability, penetration aspiration score, or pneumonia, pharyngeal transit time, institutionalisation, and nutrition.
MAIN RESULTS
We added 27 new studies (1777 participants) to this update to include a total of 41 trials (2660 participants).We assessed the efficacy of swallowing therapy overall and in subgroups by type of intervention: acupuncture (11 studies), behavioural interventions (nine studies), drug therapy (three studies), neuromuscular electrical stimulation (NMES; six studies), pharyngeal electrical stimulation (PES; four studies), physical stimulation (three studies), transcranial direct current stimulation (tDCS; two studies), and transcranial magnetic stimulation (TMS; nine studies).Swallowing therapy had no effect on the primary outcome (death or dependency/disability at the end of the trial) based on data from one trial (two data sets) (OR 1.05, 95% CI 0.63 to 1.75; 306 participants; 2 studies; I² = 0%; P = 0.86; moderate-quality evidence). Swallowing therapy had no effect on case fatality at the end of the trial (OR 1.00, 95% CI 0.66 to 1.52; 766 participants; 14 studies; I² = 6%; P = 0.99; moderate-quality evidence). Swallowing therapy probably reduced length of inpatient stay (MD -2.9, 95% CI -5.65 to -0.15; 577 participants; 8 studies; I² = 11%; P = 0.04; moderate-quality evidence). Researchers found no evidence of a subgroup effect based on testing for subgroup differences (P = 0.54). Swallowing therapy may have reduced the proportion of participants with dysphagia at the end of the trial (OR 0.42, 95% CI 0.32 to 0.55; 1487 participants; 23 studies; I² = 0%; P = 0.00001; low-quality evidence). Trial results show no evidence of a subgroup effect based on testing for subgroup differences (P = 0.91). Swallowing therapy may improve swallowing ability (SMD -0.66, 95% CI -1.01 to -0.32; 1173 participants; 26 studies; I² = 86%; P = 0.0002; very low-quality evidence). We found no evidence of a subgroup effect based on testing for subgroup differences (P = 0.09). We noted moderate to substantial heterogeneity between trials for these interventions. Swallowing therapy did not reduce the penetration aspiration score (i.e. it did not reduce radiological aspiration) (SMD -0.37, 95% CI -0.74 to -0.00; 303 participants; 11 studies; I² = 46%; P = 0.05; low-quality evidence). Swallowing therapy may reduce the incidence of chest infection or pneumonia (OR 0.36, 95% CI 0.16 to 0.78; 618 participants; 9 studies; I² = 59%; P = 0.009; very low-quality evidence).
AUTHORS' CONCLUSIONS
Moderate- and low-quality evidence suggests that swallowing therapy did not have a significant effect on the outcomes of death or dependency/disability, case fatality at the end of the trial, or penetration aspiration score. However, swallowing therapy may have reduced length of hospital stay, dysphagia, and chest infections, and may have improved swallowing ability. However, these results are based on evidence of variable quality, involving a variety of interventions. Further high-quality trials are needed to test whether specific interventions are effective.
Topics: Acupuncture Therapy; Acute Disease; Deglutition; Deglutition Disorders; Electric Stimulation Therapy; Gastrostomy; Humans; Intubation, Gastrointestinal; Length of Stay; Lisinopril; Metoclopramide; Nifedipine; Physical Stimulation; Pneumonia; Randomized Controlled Trials as Topic; Stroke; Stroke Rehabilitation; Time Factors; Transcranial Direct Current Stimulation
PubMed: 30376602
DOI: 10.1002/14651858.CD000323.pub3 -
Radiation Research Sep 2021Thrombocytopenia is a major complication in hematopoietic-acute radiation syndrome (H-ARS) that increases the risk of mortality from uncontrolled hemorrhage. There is a... (Comparative Study)
Comparative Study
Thrombocytopenia is a major complication in hematopoietic-acute radiation syndrome (H-ARS) that increases the risk of mortality from uncontrolled hemorrhage. There is a great demand for new therapies to improve survival and mitigate bleeding in H-ARS. Thrombopoiesis requires interactions between megakaryocytes (MKs) and endothelial cells. 16, 16-dimethyl prostaglandin E2 (dmPGE2), a longer-acting analogue of PGE2, promotes hematopoietic recovery after total-body irradiation (TBI), and various angiotensin-converting enzyme (ACE) inhibitors mitigate endothelial injury after radiation exposure. Here, we tested a combination therapy of dmPGE2 and lisinopril to mitigate thrombocytopenia in murine models of H-ARS following TBI. After 7.75 Gy TBI, dmPGE2 and lisinopril each increased survival relative to vehicle controls. Importantly, combined dmPGE2 and lisinopril therapy enhanced survival greater than either individual agent. Studies performed after 4 Gy TBI revealed reduced numbers of marrow MKs and circulating platelets. In addition, sublethal TBI induced abnormalities both in MK maturation and in in vitro and in vivo platelet function. dmPGE2, alone and in combination with lisinopril, improved recovery of marrow MKs and peripheral platelets. Finally, sublethal TBI transiently reduced the number of marrow Lin-CD45-CD31+Sca-1- sinusoidal endothelial cells, while combined dmPGE2 and lisinopril treatment, but not single-agent treatment, accelerated their recovery. Taken together, these data support the concept that combined dmPGE2 and lisinopril therapy improves thrombocytopenia and survival by promoting recovery of the MK lineage, as well as the MK niche, in the setting of H-ARS.
Topics: 16,16-Dimethylprostaglandin E2; Acute Radiation Syndrome; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Platelets; Bone Marrow; C-Reactive Protein; Cesium Radioisotopes; Drug Evaluation, Preclinical; Endothelial Cells; Endothelium, Vascular; Female; Gamma Rays; Hemorrhagic Disorders; Lisinopril; Megakaryocytes; Mice; Mice, Inbred C57BL; P-Selectin; Platelet Aggregation; Platelet Factor 4; Radiation Injuries, Experimental; Thrombocytopenia; Thrombopoiesis; Whole-Body Irradiation; von Willebrand Factor
PubMed: 34153091
DOI: 10.1667/RADE-20-00113.1 -
PloS One 2020Lisinopril and losartan manufacturer labels recommend twice-daily dosing (BID) if once-daily (QDay) is insufficient to lower blood pressure (BP).
BACKGROUND
Lisinopril and losartan manufacturer labels recommend twice-daily dosing (BID) if once-daily (QDay) is insufficient to lower blood pressure (BP).
METHODS AND RESULTS
Retrospective cohort study of patients taking QDay lisinopril and losartan who experienced a dose-doubling (index date). A text-processing tool categorized BID and QDay groups at the index date based on administration instructions. We excluded: pregnant/hospice, regimens other than BID/QDay, and without BP measurements -6 months/+12 months of the index date. The most proximal BP measurements -6 months and +2 weeks to 12 months of the index date were used to evaluate BP differences. Propensity scores were generated, and differences in BP and adverse events (angioedema, acute kidney injury, hyperkalemia) between BID/QDay groups were analyzed within dosing cohorts using inverse propensity of treatment-weighted regression models. Of 11,210 and 6,051 patients who met all criteria for lisinopril and losartan, 784 (7.0%) and 453 (7.5%) were taking BID, respectively. BID patients were older and had higher comorbidity and medication burdens. There were no differences in systolic/diastolic BP between BID and QDay, with absolute differences in mean systolic BP ranging from -1.8 to 0.7 mmHg and diastolic BP ranging from -1.1 to 0.1 mmHg (all 95% confidence intervals [CI] cross 0). Lisinopril 10mg BID was associated with an increased odds of angioedema compared to lisinopril 20mg QDay (odds ratio 2.27, 95%CI 1.13-4.58).
CONCLUSIONS
Adjusted models do not support improved effectiveness or safety of BID lisinopril and losartan.
Topics: Aged; Aged, 80 and over; Angioedema; Antihypertensive Agents; Blood Pressure; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hypertension; Lisinopril; Losartan; Male; Middle Aged; Retrospective Studies; Treatment Outcome
PubMed: 33270787
DOI: 10.1371/journal.pone.0243371 -
BMC Pharmacology & Toxicology Jul 2022The combination of lisinopril and amlodipine has a marked additional effect on blood pressure and fewer side effects than individual monotherapy. This study was... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The combination of lisinopril and amlodipine has a marked additional effect on blood pressure and fewer side effects than individual monotherapy. This study was conducted to compare the pharmacokinetic parameters and evaluate the bioequivalence between two Lisinopril/amlodipine tablets in healthy Chinese subjects.
METHODS
A single center, randomized, open-label, single-dose, two-period crossover bioequivalence study was designed in healthy Chinese subjects under both fasting and fed conditions. Blood samples were collected before drug administration and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 24, 36, 48, 72, 96, 144, 168 h after administration. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentration of lisinopril and amlodipine. Maximum concentration (C) and area under the concentration-time curve (AUC) were used to evaluate bioequivalence. Adverse events were recorded.
RESULTS
Ninety-two healthy subjects were enrolled, and 75 completed the study. The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of C, AUC and AUC of lisinopril and amlodipine under both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80-1.25. A high-fat meal appeared to decrease the C and AUC of lisinopril. No severe adverse events were observed.
CONCLUSION
The trial demonstrated that the test and the reference lisinopril/amlodipine tablets were bioequivalent and well tolerated in Chinese people under fasting and fed conditions.
TRIAL REGISTRATION
Clinical Trails.gov identifier, NCT04885660 (retrospectively registered in 13/05/ 2021).
Topics: Amlodipine; China; Chromatography, Liquid; Fasting; Healthy Volunteers; Humans; Lisinopril; Tablets; Tandem Mass Spectrometry; Therapeutic Equivalency
PubMed: 35794660
DOI: 10.1186/s40360-022-00590-6 -
Langmuir : the ACS Journal of Surfaces... Aug 2021The peptide angiotensin-converting enzyme inhibitors captopril and lisinopril are unexpectedly shown to exhibit critical aggregation concentration (CAC) behavior through...
The peptide angiotensin-converting enzyme inhibitors captopril and lisinopril are unexpectedly shown to exhibit critical aggregation concentration (CAC) behavior through measurements of surface tension, electrical conductivity, and dye probe fluorescence. These three measurements provide similar values for the CAC, and there is also evidence from circular dichroism spectroscopy for a possible conformational change in the peptides at the same concentration. Cryogenic transmission electron microscopy indicates the formation of micelle-like aggregates above the CAC, which can thus be considered a critical micelle concentration, and the formation of aggregates with a hydrodynamic radius of ∼6-7 nm is also evidenced by dynamic light scattering. We also used synchrotron radiation X-ray diffraction to determine the single-crystal structure of captopril and lisinopril. Our results improve the accuracy of previous data reported in the literature, obtained using conventional X-ray sources. We also studied the structure of aqueous solutions containing captopril or lisinopril at high concentrations. The aggregation may be driven by intermolecular interactions between the proline moiety of captopril molecules or between the phenylalanine moiety of lisinopril molecules.
Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Lisinopril
PubMed: 34292730
DOI: 10.1021/acs.langmuir.1c01340 -
Journal of Clinical Hypertension... 2002Three separate randomized, double-blind, parallel-group, 12-week trials compared telmisartan with enalapril, lisinopril, and amlodipine for treating mild to moderate... (Comparative Study)
Comparative Study Review
Three separate randomized, double-blind, parallel-group, 12-week trials compared telmisartan with enalapril, lisinopril, and amlodipine for treating mild to moderate hypertension. Telmisartan 80 mg was associated with a significantly greater mean decrease in trough systolic and diastolic blood pressure than enalapril 20 mg (p<0.05). Mean decreases in trough systolic and diastolic blood pressure with telmisartan (40, 80, and 160 mg) and lisinopril (10, 20, and 40 mg) were similar. Telmisartan (40, 80, and 120 mg) provided greater decreases in mean hourly systolic and diastolic blood pressure throughout the 24-hour dosing interval, including the last 4 hours of the dosing period, than amlodipine (5 and 10 mg). Telmisartan was associated with a lower incidence of treatment-related cough than lisinopril and enalapril and less treatment-related angioedema than amlodipine. These data suggest that for treating mild to moderate hypertension, telmisartan has efficacy similar to lisinopril, greater efficacy than enalapril and amlodipine throughout the 24-hour dosing interval, and better tolerability than these angiotensin-converting enzyme inhibitors and amlodipine.
Topics: Amlodipine; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Blood Pressure; Enalapril; Humans; Hypertension; Lisinopril; Telmisartan; United States
PubMed: 12147925
DOI: 10.1111/j.1524-6175.2002.01585.x -
American Journal of Physiology. Renal... Aug 2021Hypertension is a critical comorbidity for progression of diabetic kidney disease (DKD). To facilitate the development of novel therapeutic interventions with the...
Hypertension is a critical comorbidity for progression of diabetic kidney disease (DKD). To facilitate the development of novel therapeutic interventions with the potential to control disease progression, there is a need to establish translational animal models that predict treatment effects in human DKD. The present study aimed to characterize renal disease and outcomes of standard of medical care in a model of advanced DKD facilitated by adeno-associated virus (AAV)-mediated renin overexpression in uninephrectomized (UNx) mice. Five weeks after single AAV administration and 4 wk after UNx, female UNx-ReninAAV mice received (PO, QD) vehicle, lisinopril (40 mg/kg), empagliflozin (20 mg/kg), or combination treatment for 12 wk ( = 17 mice/group). Untreated /+ mice ( = 8) and vehicle-dosed UNx-LacZAAV mice ( = 17) served as controls. End points included plasma, urine, and histomorphometric markers of kidney disease. Total glomerular numbers and individual glomerular volume were evaluated by whole kidney three-dimensional imaging analysis. UNx-ReninAAV mice developed hallmarks of progressive DKD characterized by severe albuminuria, advanced glomerulosclerosis, and glomerular hypertrophy. Lisinopril significantly improved albuminuria, glomerulosclerosis, tubulointerstitial injury, and inflammation. Although empagliflozin alone had no therapeutic effect on renal endpoints, lisinopril and empagliflozin exerted synergistic effects on renal histological outcomes. In conclusion, the UNx-ReninAAV mouse demonstrates good clinical translatability with respect to physiological and histological hallmarks of progressive DKD. The efficacy of standard of care to control hypertension and hyperglycemia provides a proof of concept for testing novel drug therapies in the model. Translational animal models of diabetic kidney disease (DKD) are important tools in preclinical research and drug discovery. Here, we show that the standard of care to control hypertension (lisinopril) and hyperglycemia (empagliflozin) improves physiological and histopathological hallmarks of kidney disease in a mouse model of hypertension-accelerated progressive DKD. The findings substantiate hypertension and type 2 diabetes as essential factors in driving DKD progression and provide a proof of concept for probing novel drugs for potential nephroprotective efficacy in this model.
Topics: Animals; Antihypertensive Agents; Benzhydryl Compounds; Blood Pressure; Diabetic Nephropathies; Disease Models, Animal; Female; Glucosides; Hypertension; Lisinopril; Mice; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome
PubMed: 34180715
DOI: 10.1152/ajprenal.00154.2021