Background: Treatment with the dipeptidyl peptidase-4 inhibitors (DPP4i) and angiotensin receptor blockers (ARBs) in patients with type 2 diabetic nephropathy (DN) has not been well characterized. This study aimed to assess the renoprotection of this combined treatment in DN patients. Methods: A total of 159 type 2 DN patients from 2013 to 2015 were enrolled retrospectively from a prospective DN cohort at the National Clinical Research Center of Kidney Diseases, Jinling Hospital (China). Fifty-seven patients received DPP4i and ARB treatment, and 102 patients were treated with ARBs alone. All patients were followed up for at least 12 months. Statistical analyses were performed using Stata version 12.0. Results: There were no significant differences at baseline for age, sex, body mass index, duration of diabetes, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and estimated glomerular filtration rate (eGFR) between the two groups. Antihypertensive and antidiabetic medication use was similar in each group except calcium channel antagonists (P = 0.032). No significant changes in FBG and HbA1c were observed in the two groups after treatment. The eGFR decreased slower in the DPP4i + ARB group than in the ARB group at 12 months (Δ12 months: -2.48 ± 13.86 vs. -6.81 ± 12.52 ml·min·1.73m, P = 0.044). In addition, proteinuria was decreased further in the DPP4i + ARB group than in the ARB group after 24 months of treatment (Δ24 months: -0.18 [-1.00, 0.17] vs. 0.32 [-0.35, 0.88], P = 0.031). There were 36 patients with an eGFR decrease of more than 30% over 24 months. After adjusting for FBG, HbA1c, and other risk factors, DPP4i + ARB treatment was still associated with a reduced incidence of an eGFR decrease of 20% or 30%. Conclusions The combined treatment of DPP4i and ARBs is superior to ARBs alone, as evidenced by the greater proteinuria reduction and lower eGFR decline. In addition, the renoprotection of DPP4i combined with ARBs was independent of glycemic control.
Aged ; Angiotensin Receptor Antagonists ; therapeutic use ; Diabetic Nephropathies ; drug therapy ; Dipeptidyl-Peptidase IV Inhibitors ; therapeutic use ; Female ; Humans ; Losartan ; therapeutic use ; Male ; Middle Aged ; Prospective Studies ; Retrospective Studies

The effects of angiotensin II receptor antagonist losartan on elastic properties of aorta in patients with mild to moderate essential hypertension were assessed. The ascending aortic distensibility in 26 patients (48 +/- 3 years) with mild to moderate essential hypertension before and after 12 weeks of treatment with losartan (50 mg/day) was evaluated by using two-dimensional echocardiography. M-mode measurements of aortic systolic (Ds) and diastolic diameter (Dd) were taken at a level approximately 3 cm above the aortic valve. Simultaneously, cuff brachial artery systolic (SBP) and diastolic (DBP) pressures were measured. Aortic pressure-strain elastic modulus (Ep) was calculated as Dd x (SBP-DBP)/(Ds-Dd) x 1333 and stiffness index beta (beta) was defined as Dd x Ln (SBP/DBP)/(Ds-Dd). Blood pressure significantly decreased from 148 +/- 13/95 +/- 9 mmHg to 138 +/- 12/88 +/- 8 mmHg (systolic blood pressure, P = 0.001; diastolic blood pressure, P = 0.003). There was no significant difference in pulse pressure before and after treatment with losartan (53 +/- 10 mmHg vs 50 +/- 7 mmHg). The distensibility of ascending aorta increased significantly as showed by the significant decrease in pressure-strain elastic modulus from 4.42 +/- 5.79 x 10(6) dynes/cm2 to 1.99 +/- 1.49 x 10(6) dynes/cm2 (P = 0.02) and stiffness index beta from 27.4 +/- 32.9 to 13.3 +/- 9.9 (P = 0.02). Although there was a weak correlation between the percent changes in pressure-strain elastic modulus and stiffness index beta and that in diastolic blood pressure after losartan treatment (r = 0.40, P = 0.04 and r = 0.55, P = 0.004, respectively), no correlation was found between the percent changes in pressure-strain elastic modulus and stiffness index beta and that in systolic blood pressure (r = 0.04, P = 0.8 and r = 0.24, P = 0.2, respectively). Our study demonstrated that angiotensin II receptor antagonist losartan has a beneficial effect on aortic distensibility in patients with mild to moderate essential hypertension and this effect is partly independent of blood pressure reduction.
Aorta/*physiopathology ; Aorta/ultrasonography ; Echocardiography ; Elasticity ; Hypertension/*drug therapy ; Hypertension/*physiopathology ; Hypertension/ultrasonography ; Losartan/*therapeutic use ; Receptors, Angiotensin/*antagonists & inhibitors

OBJECTIVETo study the effects of angiotensin II receptor blockers (ARB), losartan and irbesartan, on blood pressure and serum uric acid (SUA) level in mild to moderate essential hypertensive patients complicating hyperuricaemia.

METHODSA total of 351 eligible patients were recruited in this multi-center, randomized, double-blind parallel clinical trial. After 1 week screening and a 2 week single-blinded placebo wash-out period, patients were randomly assigned to receive losartan 50 mg (n=76) or irbesartan 150 mg (n=175) once daily for 4 weeks, followed by a double-dose for another 4 weeks in patients whose seated DBP were >or=90 mm Hg or SBP>or=140 mm Hg at the end of 4 weeks. The SUA concentration and blood pressure were measured at baseline, 4 and 8 weeks post therapy.

RESULTSThree hundred and twenty-five patients completed the study (162 in the losartan group and 163 in the irbesartan group). Both groups were well matched for baseline clinical characteristics and demographics. SUA was significant reduced in losartan group (430.93 micromol/L vs 372.35 micromol/L, P<0.0001), but not in Irbesartan group (430.46 micromol/L vs 420.67 micromol/L, P>0.05) 8 weeks post therapy compared to baseline level. Blood pressure was significantly and equally reduced in both groups after 8 weeks treatment compared to baseline level (P<0.0001).

CONCLUSIONLosartan is an optimum choice of medication for patients with mild-to-moderate hypertension complicating hyperuricemia.

Adult ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Biphenyl Compounds ; therapeutic use ; Double-Blind Method ; Female ; Follow-Up Studies ; Humans ; Hypertension ; drug therapy ; metabolism ; Losartan ; therapeutic use ; Male ; Middle Aged ; Tetrazoles ; therapeutic use ; Uric Acid ; metabolism

OBJECTIVEThe purpose of the present study was to evaluate the clinical efficacy of perindopril or losartan in combination with low-dose amiodarone on maintenance of sinus rhythm in patients with idiopathic paroxysmal atrial fibrillation (PAF).

METHODSOne hundred and eighty-one patients with idiopathic PAF were included in the study and randomly divided into three groups: group 1 (amiodarone group, n = 61) was treated with amiodarone alone, group 2 (amiodarone plus losartan, n = 59) was treated with amiodarone and perindopril in combination, and group 3 (amiodarone plus perindopril group, n = 61) was treated with amiodarone and perindopril in combination. The left atrial diameter (LAD) was measured with transthoracic echocardiogram at before and after 6, 12, 18 and 24-month of treatment. The duration of observation was up to two years and the primary end point of the study was the first recurrence of AF.

RESULTSDuring the 6 month following up, there was no difference in LAD among the three groups. After 12 months, LAD in group 1 was significantly larger than group 2 and group 3 (P < 0.05). At 7th-month, the sinus rhythm maintenance of group 1 was lower significantly than group 2 and group 3. At the end of the study, the maintenance of sinus rhythm in group 2 and group 3 was higher significantly than in group 1 (83.05% and 80.33% vs 59.01%, P < 0.05), nevertheless, there was no significant difference between group 2 and group 3.

CONCLUSIONSThe results of this study suggest that the combination of amiodarone with angiotensin converting enzyme inhibitor perindopril or with angiotensin II receptor antagonist losartan are more effective than amiodarone alone in sinus rhythm maintenance for idiopathic PAF. ACEI and ARB can inhibit the enlargement of left atrium and reduce recurrence rate in patients with idiopathic PAF.

Adult ; Aged ; Amiodarone ; therapeutic use ; Anti-Arrhythmia Agents ; therapeutic use ; Atrial Fibrillation ; drug therapy ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Losartan ; therapeutic use ; Male ; Middle Aged ; Perindopril ; therapeutic use ; Prospective Studies

OBJECTIVETo observe the effect of Compound Fructus Arctii Mixture (FAM, consisted of Fructus Arctii and ethanol extract of Radix Astragalus membranaceus) in treating diabetic nephropathy.

METHODSUsing FAM to treat 31 patients with diabetic nephropathy and controlled by 23 patients treated with Losartan, the therapeutic course was 3 months for both groups, changes of clinical symptoms, blood glucose, lipid metabolism and urinary albumin were observed and compared.

RESULTSThe total effective rate in the treated group was 80.6% while in the control group 65.2%. The symptoms, urinary protein and albumin as well as lipid metabolism in the treated group all significantly improved after treatment (P<0.05), but in the control group improvement only showed in urinary albumin level (P<0.05).

CONCLUSIONFAM has the effects of reducing urinary protein in 24 hrs, lowering urinary albumin, improving blood glucose after meal and lipid metabolism.

Adult ; Albuminuria ; drug therapy ; Astragalus membranaceus ; Diabetic Nephropathies ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Female ; Furans ; therapeutic use ; Glucosides ; therapeutic use ; Humans ; Losartan ; therapeutic use ; Male ; Middle Aged ; Phytotherapy

OBJECTIVETo investigate the different effects of an angiotensin II type 1 (AT(1)) receptor antagonist, losartan, and an angiotensin converting enzyme (ACE) inhibitor, fosinopril, on cardiomyocyte apoptosis, myocardial fibrosis, and angiotensin II (Ang II) in the left ventricle of spontaneously hypertensive rats (SHRs).

METHODSSHRs of 16-week-old were randomly divided into 3 groups: SHR-L (treated with losartan, 30 mg.kg(-1) x d(-1)), SHR-F (treated with fosinopril, 10 mg x kg(-1) x d(-1)), and SHR-C (treated with placebo). Each group consisted of 10 rats. Five rats, randomly selected from each group, were killed at the 8th and 16th week after treatment. Cardiomyocyte apoptosis, collagen volume fraction (CVF), perivascular collagen area (PVCA) and Ang II concentrations of plasma and myocardium were examined.

RESULTSCompared with the controls at the 8th and 16th week, systolic blood pressures were similarly decreased in both treatment groups. Left ventricular weight and left ventricular mass indexes were significantly lower in both treatment groups. However, the latter parameter at the 16th week was reduced to a less extent in the fosinopril group than that in the losartan group. Compared with the controls, cardiomycyte apoptotic index was significantly reduced at the 8th week only in the fosinopril group, and at the 16th week in both treatment groups. The index of the fosinopril group was lower than that of the losartan group at the latter endpoint examined. Compared with the controls, the left ventricular collagen volume fraction and perivascular collagen area at the 8th and 16th weeks were significantly reduced in the SHRs treated with either fosinopril or losartan. However, the collagen volume fraction at the latter endpoint in the fosinopril group was lower than that in the losartan group. Compared with the controls at endpoints, plasma and myocardium Ang II levels were significantly increased in the losartan group. However, plasma Ang II concentrations were not altered, and myocardium Ang II concentrations at the 8th and 16th weeks were significantly reduced in the fosinopril group.

CONCLUSIONSBoth losartan and fosinopril could effectively inhibit cardiomyocyte apoptosis and myocardial fibrosis and reverse heart hypertrophy. Fosinopril may be more effective in these cardioprotective effects, suggesting that the effects of both drugs are related to the inhibition of myocardium renin-angiotension-aldsterone system.

Angiotensin II ; analysis ; Animals ; Antihypertensive Agents ; therapeutic use ; Apoptosis ; drug effects ; Blood Pressure ; drug effects ; Fibrosis ; Fosinopril ; therapeutic use ; Hypertension ; complications ; drug therapy ; Hypertrophy, Left Ventricular ; drug therapy ; Losartan ; therapeutic use ; Myocardium ; chemistry ; pathology ; Rats ; Rats, Inbred SHR

OBJECTIVE: To investigate the relationship between serum asymmetric dimethylarginine (ADMA) and blood pressure as well as target organ damage in essential hypertension, and to evaluate the effects of enalapril and losartan on them. METHODS: Forty-two newly diagnoszed patients with essential hypertension were randomly divided into enalapril-treated group and losartan-treated group. Serum ADMA, L-arginine, and nitric oxide( NO) were measured before and after the treatment for 8 weeks. Twenty-three healthy volunteers were included as control subjects. RESULTS: The concentrations of ADMA and L-arginine in serum were significantly higher but the level of nitric oxide was relatively lower ( P < 0.01 ) in hypertensive patients than those in control subjects. Serum ADMA was higher in different levels of blood pressure and target organ damage. Treatment with enalapril or losartan for 8 weeks not only reduced blood pressure but also decreased serum ADMA (P <0.01 ). Furthermore, treatment with these drugs also increased the level of serum nitric oxide but didn't change the level of L-arginine. CONCLUSION The concentrations of serum ADMA and L-arginine were increased, but the level of nitric oxide was decreased in the early stage of essential hypertension. Both enalapril and losartan could ameliorate the endothelial function by reducing the concentration of ADMA.
Adult ; Aged ; Antihypertensive Agents ; therapeutic use ; Arginine ; analogs & derivatives ; blood ; Enalapril ; therapeutic use ; Female ; Humans ; Hypertension ; blood ; drug therapy ; Losartan ; therapeutic use ; Male ; Middle Aged ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; antagonists & inhibitors

OBJECTIVE: To evaluate the effect of asymmetric dimethylarginine (ADMA) and the results of losartan intervention on platelet-aggregation in spontaneous hypertensive rats. METHODS: Spontaneous hypertensive rats (SHR) were randomly assigned into 3 groups: SHR control group, L-arginine treatment group (L-arg) and losartan (los) treatment group, each group consisting of 16 rats. Another 16 Wistar Kyoto rats (WKY) served as normal control group. The L-arginine and losartan treatment groups received 1.0 g/kg L-arginine or 30 mg/kg losartan in 10 mL/kg distilled water daily through gastric tube for 2 weeks respectively, while the SHR and WKY groups received distilled water alone. All the rats took tap water and standard feed freely during the experimental period. Systolic blood pressure (SBP) was monitored by the tail-cuff method. At the end of the 2-week intervention, all the rats were sacrificed and the blood samples were collected from the carotid artery. The platelet-aggregation-rate, NO levels, eNOS activity, and ADMA levels both in the plasma and the platelets were measured. We got other platelet samples from the SD rats and incubated the platelets with blood vascular endothelium from the above 4 groups of experimental rats and the platelet-aggregation-rate was monitored as well. RESULTS: (1) Systolic blood pressure of the SHR was significantly higher, compared with that of the WKY (P<0.01), which were significantly reduced both in the L-arginine and losartan groups (P<0.01). (2) Platelet-aggregation-rate of the SHR was significantly higher, compared with that of WKY (P<0.01), which was significantly reduced both in the L-arginine and losartan groups (P<0.01). (3) NO levels both in the plasma and the platelets of the SHR were lower, compared with those of the WKY (P<0.05); and were elevated significantly both in the L-arginine and losartan groups,compared with those of the SHR (P<0.05); (4) Both the plasma and the platelet eNOS activities of SHR followed the same pattern of the NO levels in these groups (P<0.01). (5) In contrast, the plasma and platelet ADMA levels showed a reverse pattern (P<0.05). (6) Platelets from the SD rats incubated with vascular endothelium of WKY exhibited lower platelet-aggregation-rate,compared with the platelets incubated with SHR vascular endothelium (P<0.05); Platelet-aggregation-rate of the SHR group increased, compared with that of the WKY group (P<0.05); Platelet-aggregation-rate both of L-arginine and losartan groups reduced, compared with that of the SHR group (P<0.05). CONCLUSION High levels of ADMA both in the plasma and in the platelets of SHR are associated with the decline of eNOS activity and NO levels, which might be an important reason for the increased platelet-aggregation-rate. Intervention with Losartan can reduce the platelet-aggregation-rate simultaneously with its known anti-hypertensive effect. The possible mechanism might be that losartan can enhance the eNOS activity and elevate NO levels through the suppression of ADMA.
Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Antihypertensive Agents ; therapeutic use ; Arginine ; analogs & derivatives ; blood ; Hypertension ; blood ; drug therapy ; Losartan ; therapeutic use ; Male ; Platelet Aggregation ; drug effects ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

OBJECTIVETo evaluate the efficacy and safety of olmesartan medoxomil compared with losartan potassium in patients with mild to moderate essential hypertension.

METHODThis is a randomized, double-blind, double-dummy, active-controlled, parallel, multi-center study. After a 2-week placebo run-in period, a total of 287 eligible subjects were randomized at 1:1 ratio to receive olmesartan medoxomil 20 mg or losartan potassium 50 mg, once daily for 8 weeks. The blood pressure was assessed after 4 weeks treatment. If the subject's seating diastolic blood pressure (SeDBP) was still >or=90 mm Hg, the dosage was doubled for another 4 weeks; for those subjects whose SeDBP was <90 mm Hg after 4-week treatment, the initial dosage remained unchanged and the treatment continued until completion of the study.

RESULTS(1) The mean trough reduction in SeDBP from baseline in olmesartan group was significantly greater than that in losartan group after 4 weeks (11.72 mm Hg vs 9.23 mm Hg, P=0.004) and 8 weeks treatment (12.94 mm Hg vs 11.01 mm Hg, P=0.035). (2) The number and percentage of responders in olmesartan group (81, 65.3%) were statistically higher than those (68, 52.7%) in losartan group (P=0.028) after 4 weeks treatment and were similar between the two groups after 8 weeks treatment (P>0.05). (3) Individual and overall trough/peak ratios of DBP and SBP in 24-hour ambulatory blood pressure monitoring were higher in olmesartan group than losartan group. The hypotensive effect of olmesartan was more durable than losartan at 24 hour interval. (4) The incidence of study drug-related adverse events (AEs) in olmesartan group (10.5%) was similar as that in losartan group (13.9%, P>0.05). Most of these AEs were mild and transient.

CONCLUSIONThis study shows that olmesartan medoxomil, at oral dose of 20 mg-40 mg once daily was effective and safe for hypertension treatment and the hypotensive effect was superior to losartan potassium (50 mg-100 mg once daily).

Adolescent ; Adult ; Aged ; Antihypertensive Agents ; administration & dosage ; China ; Double-Blind Method ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Imidazoles ; adverse effects ; therapeutic use ; Losartan ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Olmesartan Medoxomil ; Tetrazoles ; adverse effects ; therapeutic use

BACKGROUNDThere have been no mortality/morbidity endpoint studies with losartan in Chinese heart failure patients. The objective was to evaluate the effects of high-dose vs. low-dose losartan on clinical outcomes in Chinese subjects with heart failure.

METHODSThis study was a post hoc analysis of the Heart failure Endpoint evaluation of Angiotensin II Antagonist losartan (HEAAL) trial (n = 545). Chinese adults with symptomatic heart failure (New York Heart Association (NYHA) II-IV) intolerant of treatment with angiotensin converting enzyme (ACE) inhibitors were randomized to losartan 150 mg or 50 mg daily. The primary endpoint was the composite event rate of all-cause death or hospitalization for heart failure. Safety and tolerability were assessed.

RESULTSMedian follow-up was 4.8 years. Baseline characteristics were generally similar to the overall HEAAL cohort. Overall, 120 (44.1%) subjects in the losartan 150 mg group and 137 (50.2%) subjects in the losartan 50 mg group died (any cause) or were hospitalized for heart failure (hazard ratio (OR) 0.807, 95%CI 0.631 - 1.031). There were no notable differences between treatment groups in the proportion of subjects with adverse experiences.

CONCLUSIONThe results of this post hoc analysis in Chinese subjects, although not powered to show significance, were generally consistent with the main study results, which demonstrated a significantly reduced risk of all cause death or hospitalization for heart failure with daily losartan 150 mg vs. losartan 50 mg in subjects with symptomatic heart failure and intolerance to ACE inhibitors, supporting the use of the higher dose for optimum clinical benefit.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Double-Blind Method ; Female ; Heart Failure ; drug therapy ; Humans ; Losartan ; adverse effects ; therapeutic use ; Male ; Middle Aged