Early Renin-angiotensin System Blockade Improved Short-term and Longterm Renal Outcomes in Systemic Lupus Erythematosus Patients with Antiphospholipid-associated Nephropathy.

OBJECTIVE: To investigate the renal protective effects of early renin-angiotensin-aldosterone system (RAAS) blockade with renin-angiotensin system inhibitors (RASI) in systemic lupus erythematosus (SLE) patients with antiphospholipid-associated nephropathy (aPLN). METHODS: Medical data of 57 SLE patients with biopsy-proven aPLN were analyzed. Early RAAS blockade was defined as administration of RASI within 3 months after kidney biopsy and continued for ≥ 12 months. RESULTS: There was no significant difference in demographic data, laboratory findings, and renal histology by the time of kidney biopsy, except that the RASI group had higher proteinuria levels vs the non-RASI group [5.2 (2.8-8.8) vs 1.9 (0.6-2.8) g/d, p = 0.005, respectively] and higher prevalence of hypertension (75% vs 29%, p = 0.001, respectively). No significant difference between the 2 groups was observed in estimated glomerular filtration rate (eGFR), mean arterial pressure, and proteinuria level at 12 months after kidney biopsy. The improvement ratio of eGFR at 12 months was significantly higher in the RASI group versus the non-RASI group [26% (-5 to 86) vs -2% (-20 to 20), p = 0.028, respectively], and the rate of change in eGFR beyond 12 months was similar between the 2 groups. During a mean followup of 80 months, 4 (23%) patients in the non-RASI group and 3 (8%) patients in the RASI group developed kidney disease progression. Early RAAS blockade significantly decreased the risk of kidney disease progression [HR = 0.11 (0.02-0.59); p = 0.010]. Proteinuria and hypertension controls were similar between the 2 groups. CONCLUSION: Early RAAS blockade improved the short-term and longterm renal outcomes in SLE patients with aPLN. The renal protective effect of RASI was independent of its antihypertensive and antiproteinuric effects.

Comparison of efficacy and safety between benidipine and hydrochlorothiazide in fosinopril-treated hypertensive patients with chronic kidney disease: protocol for a randomised controlled trial.

INTRODUCTION: Co-administration of a diuretic or calcium channel blocker with an ACE inhibitor are both preferred combinations in patients with hypertensive chronic kidney disease (CKD). According to the available evidence, it is still unknown which combination plays a more active role in renal protection. We hypothesised that a combination of fosinopril and benidipine may delay the progression of CKD more effectively than a combination of fosinopril and hydrochlorothiazide (HCTZ). METHODS AND ANALYSIS: This study will be a multicentred, prospective, double-blind, randomised parallel controlled trial for hypertensive CKD patients in China. Patients will be randomised to one of two treatment groups: a combination of benidipine 4-8 mg/day and fosinopril 20 mg/day; or a combination of HCTZ 12.5-25 mg/day and fosinopril 20 mg/day. Patients will be followed up for 24 months after a month's fosinopril run-in. There will be dose-titration after 1 and 2 months. The primary endpoint is changes in estimated glomerular filtration rate (eGFR) from baseline to month 24. Secondary endpoints include changes in home blood pressure (BP), ambulatory BP, proteinuria, urinary albumin/creatinine ratio, and composite renal events in 24 months. Inclusion criteria are: age 18-80 years, non-dialysis CKD patients with eGFR >30 mL/min/1.73 m2, home BP >130 mm Hg systolic or BP >80 mm Hg diastolic at the screening and randomisation, and 24 hour proteinuria <3.5 g. Principal exclusions are hypertensive crisis, transplantation, cancer, severe diabetes complications, hyperkalaemia and severe allergy. The required sample size was 511 patients for detecting a difference in the change of eGFR (one sided α=0.025, power 1-ß=0.90). ETHICS AND DISSEMINATION: BEAHIT (Benidipine and Hydrochlorothiazide in Fosinopril Treated Chronic Kidney Disease Patients with Hypertension) was approved by Changzheng Hospital Ethics Committee (CZ-20160504-16). The outcomes will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02646397.

Comparative Efficacy and Safety of Antihypertensive Agents for Adult Diabetic Patients with Microalbuminuric Kidney Disease: A Network Meta-Analysis.

BACKGROUND: Antihypertensive treatment mitigates the progression of chronic kidney disease. Here, we comparatively assessed the effects of antihypertensive agents in normotensive and hypertensive diabetic patients with microalbuminuric kidney disease. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) comparing oral antihypertensive agents in adult diabetic patients with microalbuminuria. The primary efficacy outcome was reduction in albuminuria, and the primary safety outcomes were dry cough, presyncope, and edema. Random-effects pairwise and Bayesian network meta-analyses were performed to produce outcome estimates for all RCTs, only hypertensive RCTs, or only normotensive RCTs. Surface under the cumulative ranking (SUCRA) probability rankings were calculated for all outcomes. Sensitivity analyses on type 2 diabetes status, age, or follow-up duration were also performed. RESULTS: A total of 38 RCTs were included in the meta-analyses. The angiotensin-converting enzyme inhibitor-calcium channel blocker (ACEI-CCB) combination therapy of captopril+diltiazem was most efficacious in reducing albuminuria irrespective of blood pressure status. However, the ACEI-angiotensin receptor blocker (ACEI-ARB) combination therapy of trandolapril+candesartan was the most efficacious in reducing albuminuria for normotensive patients, while the ACEI-CCB combination therapy of fosinopril+amlodipine was the most efficacious in reducing albuminuria for hypertensive patients. The foregoing combination therapies displayed inferior safety profiles relative to ACEI monotherapy with respect to dry cough, presyncope, and edema. With respect to type 2 diabetic patients with microalbuminuria, the Chinese herbal medicine Tangshen formula followed by the ACEI ramipril were the most efficacious in reducing albuminuria. CONCLUSIONS: Trandolapril+candesartan appears to be the most efficacious intervention for reducing albuminuria for normotensive patients, while fosinopril+amlodipine appears to be the most efficacious intervention for reducing albuminuria for hypertensive patients. For practitioners opting for monotherapy, our SUCRA analysis supports the use of trandolapril and fosinopril in normotensive and hypertensive adult diabetic patients with microalbuminuria, respectively.

Effects of antihypertensive treatment on cardiovascular autonomic control: a prospective study.

OBJECTIVE: The aim of study was to propose an approach to the control of dynamics of autonomic dysfunction in cardiovascular system (CVS) under antihypertensive treatment (AT) in patients with arterial hypertension (AH), based on individual features of synchronization of 0.1-Hz rhythms in heart rate (HR) and photoplethysmogram (PPG) and spectral indices of heart rate variability (HRV). METHODS: We designed prospective cohort diagnostic accuracy and studied 105 AH patients (66 females) aged 47±8 years during 8 weeks. The HRV spectral indices and the index S of synchronization between the 0.1-Hz rhythms in HR and PPG during a tilt test are compared in their ability to control the AT with angiotensin-converting enzyme inhibitors (ACE-Is) (fosinopril or enalapril) and ß-blockers (atenolol or metoprolol). We apply Shapiro-Wilk, Mann-Whitney U and Wilcoxon tests. RESULTS: It is shown that the power of low-frequency (LF) band in HRV spectrum and index S can be used as criteria for initial assessment of the status of autonomic regulation in AH patients. The patients with S<25% in vertical body's position and LF>250 ms2 in horizontal body's position require ACE-Is treatment. The AH patients with LF<350 ms2 and S<30% in vertical body's position require ß-blocker treatment. The AH patients with S>25% and LF>250 ms2 in horizontal body's position do not require any ACE-Is or ß-blocker treatment. Both drug groups can be used in patients with low values of index S and low power of LF band in HRV spectrum. CONCLUSION: The control of AT can be carried out in AH patients taking into account the individual features of autonomic dysfunction in CVS. Sensitivity and specificity of our approach were 65% and 73%, respectively.

Mitigation of experimental radiation nephropathy by renin-equivalent doses of angiotensin converting enzyme inhibitors.

PURPOSE: We tested five different angiotensin converting enzyme inhibitors (ACEI) as mitigators of experimental radiation nephropathy at drug doses calibrated to the plasma renin activity (PRA). This was done to determine whether all ACEI had the same efficacy as mitigators of radiation nephropathy when used at drug doses that gave equivalent suppression of the renin angiotensin system. METHOD: 10 Gy total body irradiation with bone marrow transplantation was used to cause radiation nephropathy in barrier-maintained rats. Equivalent ACEI doses were determined based on their effect to inhibit angiotensin converting enzyme (ACE) and raise the PRA in unirradiated animals. RESULTS: PRA-equivalent doses were found for captopril, lisinopril, enalapril, ramipril and fosinopril. These doses overlap the human doses of these drugs on a body surface area basis. All ACE inhibitors, except fosinopril, mitigated radiation nephropathy; captopril was a somewhat better mitigator than lisinopril, enalapril or ramipril. CONCLUSIONS: Most, but not all, ACEI mitigate radiation nephropathy at doses that overlap their clinically-used doses (on a body surface area basis). Fosinopril is known to be an ineffective mitigator of radiation pneumonitis, and it also does not mitigate radiation nephropathy. These pre-clinical data are critical in planning human studies of the mitigation of normal tissue radiation injury.

[CLINICAL PERSPECTIVES OF COMPLEX APPLICATION OF PERCUTANEOUS CORONARY INTERVENTION AND DRUG REVASCULARIZATION IN ACUTE CORONARY SYNDROME].

The article presents the evaluation of the influence of complex application of monopril, propranolol and heparin and percutaneous coronary intervention (PCI); monopril, propranolol with methylase in combination with PCI and PCI only on hemddynamics, cardiohemodynamics and clinical course in acute myocardial infarction (MI), as well as the monitoring of these patients. A comparison of the results of the complex medical and mechanical revascularization. The study involved 63 patients with acute coronary syndrome (ACS): anterior MI with Q wave and ST-segment with the rise in age from 30 to 70 years, the average age (56.7 +/- 1.2) years old, who were randomly divided into three groups with 21 in each. Patients in group I received heparin, propranolol with monopril and PCI; II--methylase (tenakteplaza) and propranolol, monopril and after 1 day they performed PCI; group III patients performed only PCI. With the help of echocardiography and Doppler echocardiometry values studied endsystolic (ESV) and end-diastolic (EDV) volume, ejection fraction (EF), stroke (SI) and heart (HI) index, index of local contractility disturbance of the left ventricle (LV ILCD) as well as the dynamics of systolic, (SBP) and diastolic (PBP) blood pressure, clinical features of myocardial infarction during follow-up. Injection of methylase, infusion of propranolol, receiving per os of monopril and conduct after 1 day of PCI accelerate the stabilization of central hemodynamics. ESV, EDV and ILCD reduce, systolic function of LV improves, ejection fraction increases. When there was no restenosis, myocardial infarction relapse and mortality 1 patient on 5th day was recorded acute heart failure (AHF). When treating by monopril, propranolol and heparin and conduct of PCI also stabilize central hemodynamics. ESV, EDV and ILCD reduce, EF increases and systolic function of LV improves (I group). However, in one patient on the 3rd day were recorded acute heart failure (AHF). Restenosis, recurrent myocardial infarction, and mortality were not observed. During the PCI only treatment 4 patients relapsed MI, 4 patients had restenosis, 2 patients had AHF and 2 patients died. Observations have shown that the combined application of drug therapy with PCI provides a positive predictive as opposed to using only PCI.

Effect of pravastatin and fosinopril on recurrent urinary tract infections.

OBJECTIVES: Recurrent urinary tract infections (UTIs) are a problem affecting both women and men. Animal experiments and in vitro studies indicate that statins might prevent recurrent UTIs. We assessed the effects of pravastatin on UTI antibiotic prescribing among adults. METHODS: A post hoc analysis was conducted with data from PREVEND IT, a trial among participants randomized to receive pravastatin, fosinopril or placebo in a 2 × 2 factorial design over 4 years. Trial data were linked to the pharmacy prescription database IADB.nl. The primary outcome was the number of prescriptions with a nitrofuran derivate, a sulphonamide or trimethoprim as a proxy for UTI antibiotic prescribing. Generalized estimating equations were used to estimate the effect on the number of UTI antibiotic prescriptions. Cox regression was used to determine the effect on first and second (recurrent) UTI antibiotic prescriptions. RESULTS: Of the 864 trial participants, 655 were eligible for analysis. During an average follow-up of 3.8 years, 112 (17%) participants received at least one UTI antibiotic prescription. Intention-to-treat analyses showed that pravastatin was associated with a reduced total number of UTI antibiotic prescriptions (relative risk, 0.43; 95% CI, 0.21-0.88) and occurrence of second UTI antibiotic prescriptions [hazard ratio (HR), 0.25; 95% CI, 0.08-0.77]. No significant effect on occurrence of first UTI antibiotic prescriptions was found (HR, 0.83; 95% CI, 0.57-1.20). Fosinopril was associated with an increased occurrence of first UTI antibiotic prescriptions (HR, 1.82; 95% CI, 1.16-2.88). Combination therapy with fosinopril and pravastatin did not significantly influence the number of UTI antibiotic prescriptions. CONCLUSIONS: This study suggests that pravastatin can reduce the occurrence of recurrent UTIs. Larger studies among patients with recurrent UTIs are warranted.

Fosinopril and zofenopril, two angiotensin-converting enzyme (ACE) inhibitors, potentiate the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice.

The renin-angiotensin system (RAS) exists in the brain and it may be involved in pathogenesis of neurological and psychiatric disorders including seizures. The aim of the present research was to evaluate the effects of some angiotensin-converting enzyme inhibitors (ACEi; captopril, enalapril, fosinopril and zofenopril), commonly used as antihypertensive agents, in the DBA/2 mice animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive interactions in the same model. All ACEi were able to decrease the severity of audiogenic seizures with the exception of enalapril up to the dose of 100mg/kg, the rank order of activity was as follows: fosinopril>zofenopril>captopril. The co-administration of ineffective doses of all ACE inhibitors with AEDs, generally increased the potency of the latter. Fosinopril was the most active in potentiating the activity of AEDs and the combination of ACEi with lamotrigine and valproate was the most favorable, whereas, the co-administrations with diazepam and phenobarbital seemed to be neutral. The increase in potency was generally associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of AEDs with ACEi was predominantly more favorable than control. ACEi administration did not influence plasma and brain concentrations of the AEDs studied excluding pharmacokinetic interactions and concluding that it is of pharmacodynamic nature. In conclusion, fosinopril, zofenopril, enalapril and captopril showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations.

Fosinopril-cyclodextrin inclusion complexes: phase solubility and physicochemical analysis.

Fosinopril is one of the most hydrophobic substances among the angiotensin-converting enzyme inhibitors, exhibiting low water solubility and poor bioavailability following oral administration. Inclusion complexes between the drug substance and cyclodextrins (CDs) were obtained in order to improve its solubility. The purpose of this study was to investigate the guest-host interaction of fosinopril sodium (FOS) with beta-cyclodextrin (beta-CD) and its derivative, randomly methylated beta-cyclodextrin (RAMEB) in solution by phase solubility diagrams (PSD) and in solid state by using thermal analysis, powder X-ray diffractometry (PXRD) and Fourier transform infrared spectroscopy (FTIR). The phase solubility analysis indicated that the solubility of FOS in simulated gastric fluid was increased in the presence of CDs and revealed for RAMEB an A(L)-type diagram, suggesting the formation of a 1:1 inclusion complex, and for beta-CD a B(s)-type phase diagram. The estimated apparent stability constant (K1:1), according to the Higuchi and Connors method, is 3209.99 M(-1) and 1770.34 M(-1) for RAMEB and beta-CD complexes respectively. The binary systems FOS/CDs were prepared using the kneading method in the molar ratio 1:1. The PXRD patterns and the thermograms indicated a drug amorphization process, higher for FOS/RAMEB binary system and the FTIR analysis suggested that the ester group of FOS is probably enclosed in the CD's cavity. The results of this study confirm the formation of inclusion complexes both in solution and in solid state and suggest that the complexes formation between FOS and CDs could improve the bioavailability of the drug due to the enhancing absorption expected from increased drug solubility.

Meta-analysis of randomized controlled trials on effect of angiotensin-converting enzyme inhibitors on cancer risk.

The renin-angiotensin system is an important mediator of tumor progression and metastasis. A recent meta-analysis of randomized controlled trials reported an increased risk of cancer with angiotensin receptor blockers. It is unknown whether angiotensin-converting enzyme (ACE) inhibitors may have a similar effect. Our primary objective was to determine the effect of ACE inhibitors on cancer occurrence and cancer death. Our secondary objective was to determine the effect of ACE inhibitors on occurrence of gastrointestinal (GI) cancers given previous concerns of increased risk. Systematic searches of SCOPUS (covering MEDLINE, EMBASE, and other databases) and the Food and Drug Administration official web site were conducted for all randomized controlled trials of ACE inhibitors. Trials with ≥1 year of follow-up and enrolling a minimum of 100 patients were included. Fourteen trials reported cancer data in 61,774 patients. This included 10 trials of 59,004 patients providing information on cancer occurrence, 7 trials of 37,515 patients for cancer death, and 5 trials including 23,291 patients for GI cancer. ACE inhibitor therapy did not have an effect on occurrence of cancer (I(2) 0%, risk ratio [RR] 1.01, 95% confidence interval [CI] 0.95 to 1.07, p = 0.78), cancer death (I(2) 0%, RR 1.00, 95% CI 0.88 to 1.13, p = 0.95), or GI cancer (RR 1.09, 95% CI 0.88 to 1.35, p = 0.43). In conclusion, ACE inhibitors did not significantly increase or decrease occurrence of cancer or cancer death. There was also no significant difference in risk of GI cancer.

[Effect of Astragalus and Salvia's effective components and their compatibility on JAK/STAT pathway].

OBJECTIVE: To study the effect of Astragalus and Salvia's effective components and their compatibility on JAK/STAT pathway of rats' renal fibrosis. METHODS: 66 SD rats were randomly divided into 7 groups: normal group,model group,fosinopril group, salvianolic acids group, astragalus saponins group, granules compatibility of Astragalus and Salvia group, components combination of Astragalus and Salvia group. The variation of beta2-microglobulin(beta2-MG), the changes of renal pathology and JAK/STAT pathway were observed. RESULTS: The changes in renal pathology of treatment groups had different degrees of improvement; Astragalus and Salvia could reduce the urinary beta2-MG of unilateral ureteral obstruction (UUO) rat (P < 0.05), which was equal with fosinopril group. The rest of the treatment groups decreased especially fosinopril group while the difference was not significant when compared with the model group. Astragalus and its effective components could reduce the expression of renal tissue JAK, STAT1, STAT3 protein, among which fosinopril group and granules compatibility of Astragalus decreased significantly. Astragalus saponins group was not obvious, and the rest of the treatment group had significantly minor effect. CONCLUSION: Astragalus and Salvia's effective components and their compatibility may protect renal tubular function in unilateral ureteral obstruction, which may interfere with UUO rat kidney with JAK/STAT signaling pathway.

Effects of combination therapy with amlodipine and fosinopril administered at different times on blood pressure and circadian blood pressure pattern in patients with essential hypertension.

OBJECTIVE: The objective of our study was to compare the effects of a combination therapy with amlodipine and fosinopril administered concomitantly or at different times on blood pressure and circadian blood pressure pattern in subjects with essential hypertension. METHODS: 40 subjects with grade 1-2 essential hypertension and uncontrolled blood pressure after amlodipine or fosinopril monotherapy were randomized to combination therapy with amlodipine and fosinopril given in the morning and at bedtime (group A), or given concomitantly in the morning (group B). Clinic blood pressure values and 24-hour ambulatory blood pressure measurements were obtained before and after 4 weeks of treatment. RESULTS: After treatment, a reduction of 24-hour mean systolic and diastolic blood pressure was found in both groups. Subjects in group A showed a significant reduction in mean nocturnal systolic and diastolic blood pressure compared with group B (22.38/17.39 mmHg vs. 7.61/6.32 mmHg; P < 0.001). In group A a significant increase (5.68% and 4.57%, respectively; P < 0.05) was found in the diurnal/nocturnal blood pressure ratios of systolic and diastolic blood pressure and a slight reduction in the prevalence of non-dipping (< 10% decline in mean nocturnal vs. diurnal BP) from 53.85% to 30.77% (P = 0.428). Group B showed a significant reduction (5.68% and 5.76%; P < 0.01) in the diurnal/nocturnal systolic and diastolic blood pressure ratios and a slight increase in the prevalence of non-dipping from 38.46% to 53.85% (P = 0.428). CONCLUSION: Compared to concomitant administration of amlodipine and fosinopril in the morning, administration of the drugs at different times significantly decreased nocturnal blood pressure, increased the diurnal/nocturnal blood pressure ratio, and normalized the circadian blood pressure pattern. These findings indicate that chronotherapy may be an important strategy for optimizing blood pressure control and restoring the circadian blood pressure pattern.

Statins, antihypertensive treatment, and blood pressure control in clinic and over 24 hours: evidence from PHYLLIS randomised double blind trial.

OBJECTIVE: To investigate the possibility that statins reduce blood pressure as well as cholesterol concentrations through clinic and 24 hour ambulatory blood pressure monitoring. DESIGN: Randomised placebo controlled double blind trial. SETTING: 13 hospitals in Italy PARTICIPANTS: 508 patients with mild hypertension and hypercholesterolaemia, aged 45 to 70 years. INTERVENTION: Participants were randomised to antihypertensive treatment (hydrochlorothiazide 25 mg once daily or fosinopril 20 mg once daily) with or without the addition of a statin (pravastatin 40 mg once daily). Main outcome measures Clinic and ambulatory blood pressure measured every year throughout an average 2.6 year treatment period. RESULTS: Both the group receiving antihypertensive treatment without pravastatin (n=254) (with little change in total cholesterol) and the group receiving antihypertensive treatment with pravastatin (n=253) (with marked and sustained reduction in total cholesterol and low density lipoprotein cholesterol) had a clear cut sustained reduction in clinic measured systolic and diastolic blood pressure as well as in 24 hour, and day and night, systolic and diastolic blood pressure. Pravastatin performed slightly worse than placebo, and between group differences did not exceed 1.9 (95% confidence interval -0.6 to 4.3, P=0.13) mm Hg throughout the treatment period. This was also the case when participants who remained on monotherapy with hydrochlorothiazide or fosinopril throughout the study were considered separately. CONCLUSIONS: Administration of a statin in hypertensive patients in whom blood pressure is effectively reduced by concomitant antihypertensive treatment does not have an additional blood pressure lowering effect. Trial registration BRISQUI_*IV_2004_001 (registered at Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali-National Monitoring Centre on Clinical Research with Medicines).

Combination therapy with angiotensin-converting enzyme inhibitors and indapamide impairs glucose tolerance in Chinese hypertensive patients.

BACKGROUND: Elevated blood glucose (BG) induced by antihypertensive agents increases the risk of cardiovascular events. This study was designed to investigate whether fosinopril+indapamide combination therapy has any effect on glucose tolerance (GT), and if it did, whether conversion to fosinopril alone could reverse the impaired GT. METHODS: Included in the present study were 124 hypertensive patients, of whom 62 patients were treated with fosinopril plus indapamide (F/I group) and the remaining 62 patients were treated with fosinopril alone (F group). Of them, 89 patients completed a mean of 14-month follow-up. In the F/I group, 29 patients were converted to the use of fosinopril for 4-12 months after they completed the follow-up. RESULTS: In the F group, fasting BG decreased significantly from 5.1+/-0.5 to 4.8+/-0.7 mmol/l (p<0.01), and 2-h postprandial BG decreased significantly from 7.2+/-1.6 to 6.4+/-1.4 mmol/l (p<0.01), while in the F/I group, fasting BG increased significantly from 5.1 +/-0.6 to 5.3+/-0.9 mmol/l (p<0.05), and 2-h postprandial BG increased significantly from 7.2+/-1.7 to 7.7+/-1.8 mmol/l (p<0.05). In 29 patients of the F/I group who completed the follow-up and were converted to fosinopril, fasting BG decreased significantly from 5.5+/-1.0 to 5.3+/-1.0 mmol/l (p<0.05), and 2-h postprandial BG decreased significantly from 7.5+/-2.0 to 7.0+/-2.7 mmol/l (p<0.05). CONCLUSION: Fosinopril+indapamide combination therapy impaired GT in Chinese hypertensive patients, and fosinopril alone was able to reverse fosinopril+indapamide-induced GT impairment in part of these patients.

[Plasma tissue factor and serum angiotensin II and the therapeutic effect of different dosages of fosinopril on chronic heart failure].

OBJECTIVE: To determine the relation between plasma tissue factor (TF) and serum angiotensin II(AngII) and the effect of different dosages of fosinopril on chronic heart failure(CHF). METHODS: Thirty healthy controls and 35 CHF patients were recruited to observe AngII,TF, left ventricular ejection fractions(LVEF) and left ventricular end-systolic volume index (LVESVI) at baseline and 10 weeks after the treatment. The 35 patients were randomly assigned into 2 groups: A routine dosage fosinopril group received 10 mg once daily and a middle dosage group received 10 mg twice a day for 10 weeks. RESULTS: Compared with the healthy controls, AngII,TF,and LVESVI significantly increased (P<0.01) and LVEF significantly decreased (P<0.01) in CHF patients. The TF was positively correlated with AngII(r=0.2491, P<0.01) in the patients. After the 10-week treatment with different dosages of fosinopril, AngII,TF,and LVESVI obviously decreased(P<0.05 or P<0.01) and LVEF significantly increased in the 2 groups (P<0.05 or P<0.01). The middle dosage group changed more than the routine dosage group (P<0.01). CONCLUSION: TF is positively correlated with AngII in CHF patients. Fosinopril can greatly improve cardiac function and antagonize prethrobotic state,and the therapeutic effect improves with the dosage increase.

[Fosinopril in the treatment of cardiorenal syndrome in chronic cardiac failure].

Renal dysfunction is an independent risk factor of chronic cardiac failure (CCF) and death due to this disease. CCF patients are elderly patients with diabetes mellitus, arterial hypertension and long-term chronic cardiac insufficiency. CCF patients do not often have left ventricular systolic dysfunction, renal affection is not associated with low ejection syndrome. Renal affection in CCF is primarily caused by activation of the system rennin-angiotensin, inflammation, disturbed bioavailability of nitric oxide, hyperactivation of the sympathetic nervous system. ACE inhibitors correct pathophysiological disorders of renal flow in CCF. Fosinopril shows the highest efficacy and safety in management of cardiorenal syndrome in CCF patients. Fosinopril can also prevent renal dysfunction in CCF patients.

[The use of monopril in elderly patients with arterial hypertension and coronary heart disease].

We examined 20 patients (mean age 69.4 yr) with stage II AH and CHD. 13 ones suffered CHD with stable FC II and III angina, two others had myocardial infarction. The patients were given monopril, 10 mg BID (08.00 & 20.00). Those with CHD were additionally treated with cardiket (20 mg BID) or monocinque (20 mg BID). If appropriate, hypothiazide or triampur compositum (25 mg each) was given in the morning. Usual clinical examination was supplemented by dynamic studies and evaluation of clinical symptoms on day 21 after therapy including systolic and diastolic AP, pulse and mean dynamic AD, double product, heart rate, ECG, echoCG, AP and ACG monitoring. The above treatment produced marked antihypertensive and antianginal effects in the absence of adverse events.

Simultaneous posterior ischemic optic neuropathy, cerebral border zone infarction, and spinal cord infarction after correction of malignant hypertension.

A 31-year-old woman developed bilateral posterior ischemic optic neuropathy and infarctions of the cerebral arterial border zones and spinal cord after correction of malignant hypertension. Although a few reports have described patients with neurologic abnormalities after treatment of malignant hypertension, full clinical and neuroimaging documentation of this combination of findings has not occurred. This case report suggests that the relative hypotension of autoregulatory failure induced by treatment of malignant hypertension may give rise to these neurologic complications.

Effects of a fixed-dose ACE inhibitor-diuretic combination on ambulatory blood pressure and arterial properties in isolated systolic hypertension.

The ideal therapy for patients with isolated systolic hypertension remains unclear; diuretics, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors are all used in clinical practice. The aim of this study was to determine whether a fixed-dose ACE inhibitor/diuretic combination would reduce ambulatory blood pressures (BP) and arterial stiffness in isolated systolic hypertension more than antihypertensive monotherapy. In this randomized, double-blind study, 8 weeks of fosinopril/hydrochlorothiazide combination (10/12.5 mg titrated up to 20/12.5 mg) was compared with the calcium channel blocker (amlodipine, 5 mg titrated up to 10 mg) and diuretic (indapamide, 2.5 mg) monotherapy in 28 patients with isolated systolic hypertension. Each patient received all 3 therapies. Assessments included 24-hour ambulatory BP, clinic BP, and applanation tonometry-derived augmentation index. At 8 weeks, the fall in average 24-hour systolic BP and night time systolic BP were significantly greater in the fosinopril-hydrochlorothiazide group, compared to amlodipine and indapamide. The decrease in augmentation index and central aortic systolic BP was also greater in the fosinopril-hydrochlorothiazide group, compared to either amlodipine or indapamide. There was no difference between therapies in decrease in clinic systolic or diastolic BP, or diastolic ABP (average 24-h, diurnal, or nocturnal). Compared with either calcium channel blocker or diuretic therapy, a fixed-dose ACE inhibitor-diuretic combination induces greater reductions in systolic ABP, particularly at night, favorable effects that may be related to a decrease in the intensity of or delay in arterial wave reflections. ACE inhibitor-diuretic combination therapy is a useful approach to cardiovascular risk reduction in isolated systolic hypertension.