BACKGROUNDCongestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin converting-enzyme inhibitor (ACEI) is the cornerstone in its treatment. However, CHF continues to progress despite this therapy, perhaps because of production of angiotensin II (Ang II) by alternative pathways. The present study was conducted to examine the combined effects of a chronic ACEI, ramipril, and a chronic Ang II type 1 receptor blocker, TCV116, on rat CHF after myocardial infarction (MI).

METHODSCongestive heart failure was caused by MI in rats, which was induced by ligating the left anterior descending coronary artery. The experiment protocol included sham-operated rats (Sham), MI-control rats (MI-control), MI rats treated with ramipril 3 mg/kg (MI-ramipril) or TCV116 2 mg/kg (MI-TCV116) per day, half dosage (MI-1/2R&T) or full dosage (MI-R&T) combination of the two. At 22 weeks, cardiac hemodynamic parameters such as mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), maximal rate of left ventricule pressure development and decline (LV dP/dtmax) and left ventricular end diastolic pressure (LVEDP), and cardiac morphometric parameters such as heart weight (HW), left ventricular weight (LVW) and left ventricular cavity area (LVCA) were measured, mRNA expressions of cardiac molecule genes such as beta myosin heavy chain (betaMHC), B-type natriuretic peptide (BNP), transforming growth factor-beta1 (TGF-beta1), collagen I and III were quantified with reverse transcription polymerase chain reaction (RT-PCR) in the surviving septum myocardium, and survival rates were calculated.

RESULTSThere were no significant differences in MI sizes (%) among each MI related experimental groups (33 +/- 13, 34 +/- 14, 33 +/- 13, 35 +/- 13 and 33 +/- 14 for MI-control, MI-ramipril, MI-TCV116, MI-1/2R&T and MI-R&T, respectively, no statistical significance for all). Compared with sham-operated rats, MI rats without therapy showed significant increases in morphometric parameters as well as in mRNA expressions of cardiac molecule genes (P < 0.01); while their hemodynamic parameters were significantly impaired (P < 0.01), and in terms of spontaneous deaths survival rate shortened (P < 0.05). Compared with MI rats without therapy, MI rats treated with each single drug showed significant attenuation of mRNA expressions of cardiac molecule genes (P < 0.01); while their hemodynamic parameters were significantly improved (P < 0.05 or P < 0.01), and in terms of spontaneous deaths survival rate prolonged (P < 0.05). Both half and full dosage combined treatments exerted more powerful effects on improvement of cardiac phenotypic changes and on attenuation of betaMHC, BNP mRNA expressions (P < 0.05 vs monotherapy); while LVEDP was further lowered (P < 0.05 vs monotherapy). However, the total death in MI rats with full dosage combined treatment was more though there were no significant differences when compared with other treatments.

CONCLUSIONSThe results suggest that treatment with appropriate dosage combination of a chronic ACEI and a chronic ARB may further improve cardiac remodeling and cardiac function after MI.

Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; Animals ; Benzimidazoles ; administration & dosage ; Biphenyl Compounds ; administration & dosage ; Blood Pressure ; drug effects ; Drug Therapy, Combination ; Heart Failure ; drug therapy ; pathology ; physiopathology ; Male ; Myocardial Infarction ; complications ; Myocardium ; pathology ; Ramipril ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 ; drug effects ; Tetrazoles ; administration & dosage ; Ventricular Function, Left ; drug effects

BACKGROUNDCombination of angiotensin-converting enzyme inhibitors and calcium channel blockers has been successfully used in the antihypertensive therapy for many years. Fixed dose combinations of ramipril/amlodipine have a benefit effect for patients to achieve target blood pressure (BP). This study aimed to assess the efficacy and safety of fixed dose combinations of ramipril and amlodipine (Egiramlon®) in hypertensive diabetic patients.

METHODSHypertensive diabetic patients who were enrolled into the RAMONA trial were included in this open, prospective, Phase IV observational clinical study. Patients had mild-to-moderate hypertension and failed to reach target BP levels through their previous therapy. During the four months of observation, patients took part in three visits (1st day = visit 1, 1st month = visit 2, and 4th month = visit 3) where they received a fixed dose combination of 5/5, 5/10, 10/5, or 10/10 mg ramipril/amlodipine, respectively, with the possibly required dose titrations, based on the decision of their attending physician. Target BP for diabetic patients was <140/85 mmHg. BP levels were measured in all visits, by taking two readings at 2-min interval. Laboratory tests including full blood count, renal function test, electrolytes, blood glucose, serum cholesterol, uric acid, triglycerides, liver function test, creatinine kinase, and midstream urinalysis were performed at visit 1 and visit 3.

RESULTSThe 6423 patients completed the study. Among these patients, 1276 (19.9%) patients suffered from type 2 diabetes mellitus. The mean age of these diabetic patients was 64.2 ± 10.0 years; 707 (55.4%) patients were males. Target BP was achieved by 891 (69.8%) of diabetic patients at visit 3 (primary endpoint). BP decreased from 157.5/91.3 ± 9.6/7.6 mmHg (visit 1) to 130.9/79.6 ± 7.4/5.8 mmHg (visit 3). As for the secondary endpoint of the study, total cholesterol decreased from 5.50 ± 1.13 mmol/L (visit 1) to 5.20 ± 0.95 mmol/L (P = 0.000), low-density lipoprotein cholesterol decreased from 3.20 ± 0.93 mmol/L to 3.00 ± 0.77 mmol/L (P = 0.000), triglyceride decreased from 2.20 ± 1.14 mmol/L to 2.00 ± 1.97 mmol/L (P = 0.000), while high-density lipoprotein cholesterol increased from 1.30 ± 0.42 to 1.35 ± 0.30 mmol/L (P = 0.001) until the end of the 4th month (visit 3). Fasting blood glucose of the hypertensive diabetic patients decreased from 7.20 ± 1.88 mmol/L to 6.70 ± 1.38 mmol/L (P = 0.000), while HbA1c decreased from 7.90 ± 1.78% to 7.60 ± 1.83% (P = 0.000). Various fixed dose combinations of ramipril/amlodipine were well tolerated and no adverse event related to the use of the medicine has appeared.

CONCLUSIONSThe fixed dose combination of ramipril/amlodipine was effective in hypertensive diabetic patients who failed to reach target BP previously.

Aged ; Amlodipine ; administration & dosage ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; therapeutic use ; Antihypertensive Agents ; administration & dosage ; therapeutic use ; Blood Pressure ; drug effects ; Diabetes Mellitus, Type 2 ; drug therapy ; Female ; Humans ; Hypertension ; drug therapy ; Male ; Middle Aged ; Ramipril ; administration & dosage ; therapeutic use

PURPOSE: To evaluate the effects of angiotensin-converting enzyme inhibitors (ACE-I) in retarding progression of severe non-proliferative diabetic retinopathy (NPDR) in normotensive type 2 diabetic patients. METHODS: This was a retrospective case control study of 128 patients with normotensive type 2 diabetes with lower than +1 dipstick proteinuria and severe NPDR who were classified into either an ACE-I treated group (Enalapril maleate 10 mg, n=12 , Ramipril 5 mg, n=17) or an ACE-I untreated group (n=99). Medical records were reviewed for endpoints of (a) occurrence of proliferative diabetic retinopathy (PDR) or macular edema (ME) for which laser phototherapy was necessary or (b) development of proteinuria of higher than +1 level requiring medication of ACE-I. RESULTS: From the total of 128 patients, there were 29 ACE-I treated patients and 99 ACE-I untreated patients. There were no differences in the average age, duration of diabetes, body mass indices, blood pressure and levels of hyperglycemia or HbA1C between the two groups. Blood pressure and HbA1C levels in both groups remained unchanged during the study. The mean follow-up period was 41.6 months. In the ACE-I group, 6 patients progressed to PDR, 5 to ME and 6 developed proteinuria of greater than +1 over the follow-up period. In the control group, 30 patients progressed to PDR, 6 to ME and 9 developed proteinuria of greater than +1 over the follow-up period. CONCLUSIONS: Small doses of ACE-I did not yield any beneficial effects in retarding the progression of severe NPDR.
Treatment Failure ; Severity of Illness Index ; Retrospective Studies ; Ramipril/administration & dosage/*therapeutic use ; Middle Aged ; Male ; Humans ; Fundus Oculi ; Female ; Enalapril/administration & dosage/*therapeutic use ; Dose-Response Relationship, Drug ; Disease Progression ; Diabetic Retinopathy/*drug therapy/pathology ; Diabetes Mellitus, Type 2 ; Case-Control Studies ; Angiotensin-Converting Enzyme Inhibitors/administration & dosage/*therapeutic use ; Aged

BACKGROUNDThe results from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) indicated that the angiotensin-receptor blocker telmisartan was not inferior to the angiotensin-converting-enzyme inhibitor ramipril in reducing the composite endpoint of cardiovascular death, myocardial infarction, stroke or hospitalization for congestive heart failure in high-risk patients, and telmisartan was associated with slightly superior tolerability. The combination of the two drugs was associated with more adverse events without an increase in benefit. This study aimed to analyze the data from ONTARGET obtained from a subgroup of patients enrolled in China and to evaluate the demographic and baseline characteristics, the compliance, efficacy, and safety of the different treatment strategies in randomized patients in China.

METHODSA total of 1159 high-risk patients were randomized into three treatment groups: with 390 assigned to receive 80 mg of telmisartan, 385 assigned to receive 10 mg of ramipril and 384 assigned to receive both study medications. The median follow-up period was 4.3 years.

RESULTSThe mean age of Chinese patients was 65.6 years, 73.6% of patients were male. The proportion of patients with stroke/transient ischemic attacks at baseline in China was two times more than the entire study population (47.7% vs. 20.9%). In Chinese patients the proportion of permanent discontinuation of study medication due to cough was 0.5% in the telmisartan group, which was much less than that in the combination or the ramipril group. There were no significant differences in the incidence of primary outcome among three treatment groups of Chinese patients. More strokes occurred in Chinese patients than in the entire study population (8.5% vs. 4.5%). Greater systolic blood pressure reduction (-9.8 mmHg), and more renal function failure were noted in the combination treatment group than in the ramipril or telmisartan group (2.6% vs. 1.6% and 1.0%).

CONCLUSIONSThere was no evidence that the results of ONTARGET differed between Chinese patients and the entire study population with respect to the incidence of primary outcome, particularly safety. Compliance with study medications was good. The evidence from ONTARGET indicated that the treatment strategies in ONTARGET were applicable to patients in China.

Aged ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Benzimidazoles ; administration & dosage ; adverse effects ; therapeutic use ; Benzoates ; administration & dosage ; adverse effects ; therapeutic use ; China ; Drug Therapy, Combination ; Female ; Heart Failure ; drug therapy ; Humans ; Male ; Middle Aged ; Ramipril ; administration & dosage ; adverse effects ; therapeutic use