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Journal of the... Sep 2011Candesartan is a relatively novel antihypertensive agent of the angiotensin receptor blocker (ARB). Several clinical trials have compared candesartan with losartan in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Candesartan is a relatively novel antihypertensive agent of the angiotensin receptor blocker (ARB). Several clinical trials have compared candesartan with losartan in the management of essential hypertension. However, systematic assessment of efficacy and safety between candesartan and losartan is still lacking.
METHODS
We reviewed randomised controlled trials (RCTs) comparing candesartan with losartan for net reduction in blood pressure from baseline, response and control rates, and incidences of common and serious adverse events.Weighted mean differences (WMD), and relative risk (RR) with 95% confidence intervals (CI) were calculated for continuous and dichotomous data, respectively.
RESULTS
A total of 12 RCTs with 3644 patients were included in this meta-analysis. When comparing the efficacy of candesartan and losartan in reducing systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the end of the follow-up period, results with candesartan were superior to losartan in the reduction SBP and DBP (WMD, -2.97; 95% CI, -4.18 - -1.77; p < 0.001; WMD, -1.76; 95% CI, -2.57 - -0.96; p < 0.001; respectively). Candesartan had better response and control rates than losartan. (RR, 1.12; 95% CI, 1.06-1.18; p < 0.01; RR, 1.26; 95% CI, 1.06-1.50; p = 0.008). Reported common adverse events for the two agents were not significantly different (RR, 0.98; 95% CI, 0.86-1.12; p = 0.78). The incidence of serious adverse events for candesartan was lower than for losartan (RR, 0.48; 95% CI, 0.25-0.92; p = 0.03). The net reduction of DBP showed negative correlation with baseline DBP in both candesartan and losartan groups (regression coefficient -1.81, p = 0.03 and regression coefficient -1.56, p = 0.02, respectively).
CONCLUSIONS
Candesartan is superior to losartan in reducing blood pressure. Candesartan also causes fewer serious adverse events than losartan.
Topics: Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Humans; Hypertension; Losartan; Publication Bias; Regression Analysis; Tetrazoles; Treatment Outcome
PubMed: 21421652
DOI: 10.1177/1470320310391503 -
Basic & Clinical Pharmacology &... Oct 2019The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety.... (Clinical Trial)
Clinical Trial
The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety. Amlodipine is mainly metabolized by cytochrome P450 (CYP) 3A4, whereas losartan is metabolized by CYP2C9 and CYP3A4. The potential pharmacokinetic interactions between amlodipine and losartan were assessed. An open-label, three-period, fixed-sequence trial was conducted. Amlodipine, losartan and combined amlodipine and losartan were administered to 24 healthy male participants during periods 1, 2 and 3, respectively, for 9 days each. The pharmacokinetics of amlodipine, losartan and EXP-3174, an active metabolite of losartan, were assessed at steady-state. Twenty participants completed the study without serious adverse events. Losartan did not influence the exposure of amlodipine at steady-state (AUC , 165.15 ng h/mL [amlodipine alone] vs 172.36 ng h/mL [combination], P = 0.389) [geometric mean ratio (GMR) (90% confidence interval [CI]), 1.060 (0.954-1.178)]. In addition, the exposure of EXP-3174 was not affected by amlodipine (AUC , 1159.46 ng h/mL vs 1105.10 ng h/mL, P = 0.295) (GMR [90% CI], 0.957 [0.891-1.027]). However, amlodipine significantly decreased the exposure of losartan at steady-state (AUC , 1241.50 ng h/mL vs 1082.02 ng h/mL, P = 0.006) (GMR [90% CI], 0.875 [0.813-0.942]) and increased oral clearance of losartan (84.65 L/h vs 97.26 L/h, P = 0.002). Combination use of two drugs caused additive haemodynamic changes compared to treatment of amlodipine or losartan alone. The co-administration of amlodipine and losartan was tolerable and did not cause substantial pharmacokinetic interaction, even though losartan disposition was affected. Combination use of the two drugs caused additive haemodynamic changes compared to monotherapy of amlodipine or losartan.
Topics: Administration, Oral; Adult; Amlodipine; Angiotensin Receptor Antagonists; Antihypertensive Agents; Calcium Channel Blockers; Drug Interactions; Drug Therapy, Combination; Healthy Volunteers; Hemodynamics; Humans; Hypertension; Losartan; Male; Middle Aged; Republic of Korea; Young Adult
PubMed: 31058419
DOI: 10.1111/bcpt.13244 -
Annals of the Rheumatic Diseases Apr 2004
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Losartan; Uricosuric Agents
PubMed: 15020353
DOI: No ID Found -
Indian Journal of Pharmacology 2021The presence of comorbidities such as cardiovascular disease, peripheral vascular disease, and chronic renal disease, or and the prevention of these ailments in...
OBJECTIVES
The presence of comorbidities such as cardiovascular disease, peripheral vascular disease, and chronic renal disease, or and the prevention of these ailments in diabetics, frequently demands multiple drug treatments, increasing the risk of drug-drug interactions (DDIs). The current study was focused on identifying possible DDIs on concomitant administration of losartan, a drug used to regulate hypertension along with a combination of glimepiride + metformin, widely used to treat diabetes mellitus. Possible pharmacodynamic and pharmacokinetic interactions were observed for, following single-dose as well as multiple-dose treatment protocols in normal and alloxan-induced diabetes in albino Wistar rats and rabbits.
MATERIALS AND METHODS
Blood samples from surviving rats/rabbits obtained through orbital venous sinus bleeding/marginal ear vein bleeding, respectively, at predetermined intervals and put through to biochemical estimations of sugar level in the blood by Glucose oxidase/peroxidase method; insulin levels in serum using the enzyme-linked immunosorbent assay and serum glimepiride levels using the high-performance liquid chromatography.
RESULTS AND DISCUSSION
Losartan, when treated as a single drug, resulted in a slight lowering of blood glucose levels in normal rats, diabetic rats and normal rabbits. Hypoglycemic activity of a combination of glimepiride + metformin was enhanced when losartan was co-administered as a single dosage schedule as well as a multiple dose schedule as indicated by a reduced blood glucose level and enhanced levels of insulin in rats as well as in rabbits. Serum glimepiride levels were also higher and pharmacokinetic parameters of glimepiride including mean residence time, C, T, AUMC, AUMC, and AUC, were significantly higher, whereas its clearance was decreased in the two regimens of losartan that was followed.
CONCLUSION
It can therefore be concluded, that in diabetics with hypertension as a comorbidity condition, co-administration of losartan with glimepiride + metformin should be avoided or the dosage of a combination of glimepiride + metformin needs to be tittered to avoid recurrence of hypoglycemic episodes.
Topics: Alloxan; Animals; Antihypertensive Agents; Blood Glucose; Diabetes Mellitus, Experimental; Disease Models, Animal; Drug Interactions; Drug Therapy, Combination; Hypoglycemic Agents; Losartan; Metformin; Rabbits; Rats; Rats, Wistar; Sulfonylurea Compounds
PubMed: 34975134
DOI: 10.4103/ijp.IJP_845_19 -
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 -
Annals of the Rheumatic Diseases Jun 2003
Topics: Drug Therapy, Combination; Fenofibrate; Gout Suppressants; Humans; Hypertension; Hyperuricemia; Losartan
PubMed: 12759281
DOI: 10.1136/ard.62.6.497 -
Molecules (Basel, Switzerland) Apr 2022Losartan potassium salt (LSR) is a well-known antihypertensive drug with proven beneficial effects on human health. Its formulation with the non-toxic...
Losartan potassium salt (LSR) is a well-known antihypertensive drug with proven beneficial effects on human health. Its formulation with the non-toxic 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) could improve its pharmacological profile. Thus, its molecular interactions are studied using a combination of Differential Scanning Calorimetry (DSC), Nuclear Magnetic Resonance (NMR) and Molecular Dynamics (MD). First, its complexation is shown through Differential Scanning Calorimetry as lyophilization provided distinct thermal properties in comparison to the mixture. The complexation is further proved by utilizing the chemical shift changes in the complexation and T1 values. Furthermore, the reversible favorable complexation was shown by MD calculations. Such physical chemical properties provide evidence that this formulation must be further explored through biological experiments.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Antihypertensive Agents; Calorimetry, Differential Scanning; Freeze Drying; Humans; Hypromellose Derivatives; Losartan; Solubility
PubMed: 35458617
DOI: 10.3390/molecules27082421 -
International Journal of Clinical... Jun 2021Controversy exists regarding the drug selection in hypertension (HTN) management in patients with COVID-19. This study aimed to compare the effects of losartan and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Controversy exists regarding the drug selection in hypertension (HTN) management in patients with COVID-19. This study aimed to compare the effects of losartan and amlodipine in patients with primary HTN and COVID-19.
METHODS
In this randomised clinical trial, hospitalised patients with COVID-19 and primary HTN were enrolled in the study. One arm received losartan, 25 mg, twice a day and the other arm received amlodipine, 5 mg per day for 2 weeks. The main outcomes were compare 30-day mortality rate and length of hospital stay.
RESULTS
The mean age of patients treated with losartan (N = 41) and amlodipine (N = 39) was 67.3 ± 14.8 and 60.1 ± 17.3 years, respectively (P value = .068). The length of hospital stay in losartan and amlodipine groups was 4.57 ± 2.59 and 7.30 ± 8.70 days, respectively (P value = .085). Also, the length of ICU admission in losartan and amlodipine group was 7.13 ± 5.99 and 7.15 ± 9.95 days, respectively (P value = .994). The 30-day mortality was two and five patients in losartan and amlodipine groups, respectively (P value = .241).
CONCLUSIONS
There was no priority in losartan or amlodipine administration in COVID-19 patients with primary HTN in decreasing mortality rate, hospital and ICU length stay. Further studies need to clarify the first-line anti-HTN medications in COVID-19.
Topics: Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Blood Pressure; COVID-19; Double-Blind Method; Humans; Hypertension; Losartan; Middle Aged; SARS-CoV-2; Treatment Outcome
PubMed: 33650197
DOI: 10.1111/ijcp.14124 -
Proceedings of the National Academy of... Feb 2023Immune checkpoint blockers (ICBs) have failed in all phase III glioblastoma trials. Here, we found that ICBs induce cerebral edema in some patients and mice with...
Immune checkpoint blockers (ICBs) have failed in all phase III glioblastoma trials. Here, we found that ICBs induce cerebral edema in some patients and mice with glioblastoma. Through single-cell RNA sequencing, intravital imaging, and CD8 T cell blocking studies in mice, we demonstrated that this edema results from an inflammatory response following antiprogrammed death 1 (PD1) antibody treatment that disrupts the blood-tumor barrier. Used in lieu of immunosuppressive corticosteroids, the angiotensin receptor blocker losartan prevented this ICB-induced edema and reprogrammed the tumor microenvironment, curing 20% of mice which increased to 40% in combination with standard of care treatment. Using a bihemispheric tumor model, we identified a "hot" tumor immune signature prior to losartan+anti-PD1 therapy that predicted long-term survival. Our findings provide the rationale and associated biomarkers to test losartan with ICBs in glioblastoma patients.
Topics: Animals; Mice; Glioblastoma; Losartan; Immune Checkpoint Inhibitors; CD8-Positive T-Lymphocytes; Edema; Tumor Microenvironment
PubMed: 36724255
DOI: 10.1073/pnas.2219199120 -
Molecules (Basel, Switzerland) Jan 2023Many studies have shown that alterations in the gut microbiota are associated with hypertension. Our study aimed to observe the characteristics of the gut microbiota in...
Many studies have shown that alterations in the gut microbiota are associated with hypertension. Our study aimed to observe the characteristics of the gut microbiota in hypertension and to further explore whether drug molecules can play a therapeutic role in hypertension by interfering with the gut microbiota. We evaluated the differences in the composition of the gut microbiota in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Meanwhile, three first-line cardiovascular disease (CVD) drugs, losartan, atorvastatin, and aspirin, were used to treat the SHR in order to observe their effects on the gut microbiota in SHR. The 16S rDNA results showed that the diversity and richness of the gut microbiota in SHR were significantly reduced compared with that of the WKY, the Firmicutes/Bacteroidetes ratio was increased, the abundances of and short chain fatty acids (SCFAs)-producing bacteria decreased, and the abundance of lactate-producing bacteria increased. In addition to lowering the blood pressure, losartan increased the abundances of , and in SHR, reduced the abundances of , and , reduced the Firmicutes/Bacteroidetes ratio, and rebalanced the gut microbiota. Losartan also increased the abundances of and SCFAs-producing bacteria and reduced the abundance of lactate-producing bacteria. However, atorvastatin and aspirin had no significant effect on the gut microbiota in SHR. The above results showed that losartan could change the characteristics of the gut microbiota in hypertension and rebalance the gut microbiota, which may be related to lowering the blood pressure. Atorvastatin and aspirin have no significant influence on the gut microbiota in SHR.
Topics: Rats; Animals; Losartan; Blood Pressure; Rats, Inbred SHR; Atorvastatin; Gastrointestinal Microbiome; Aspirin; Hypertension; Rats, Inbred WKY
PubMed: 36677668
DOI: 10.3390/molecules28020612