ramipril and Diabetes-Mellitus

Antagonism of renin-angiotensin-aldosterone system is exerted through angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, renin inhibitors and mineralocorticoid receptor antagonists. These drugs have been successfully tested in numerous trials and in different clinical settings. The original indications of renin-angiotensin-aldosterone system blockers have progressively expanded from the advanced stages to the earlier stages of cardiorenal continuum. To optimize the degree of blockade of renin-angiotensin-aldosterone system, dose uptitrations of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists or the use of a dual blockade, initially identified with the combination of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, have been proposed. The data from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) study do not support this specific dual blockade approach. However, the dual blockade of angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists with direct renin inhibitors is currently under investigation while that based on an aldosterone blocker with any of the previous three drugs requires more evidence beyond heart failure. In this review, we revisited potential advantages of dual blockade of renin-angiotensin-aldosterone system in arterial hypertension and diabetes.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Diabetes Complications; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Hypertension; Mineralocorticoid Receptor Antagonists; Ramipril; Renin; Renin-Angiotensin System; Telmisartan

Increasing attention is being devoted to the use of combination therapy with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in order to achieve maximal blockade of the renin-angiotensin system (RAS) in patients at high risk of cardiovascular events. This approach has been adopted in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), which compared the effects of the ARB telmisartan and the ACE inhibitor ramipril, alone and in combination, on cardiovascular mortality and morbidity in high-risk patients with vascular disease or diabetes mellitus and end-organ damage. The results showed that telmisartan was as effective as ramipril for the primary cardiovascular outcome during a 56-month follow-up but was better tolerated. However, dual RAS blockade was not associated with any additional benefits, and the incidence of adverse events was greater with the combination. Based on these findings, optimal cardioprotective strategies in high-risk patients are likely to involve the addition of either telmisartan or ramipril on top of the patient's usual care, but not both. The choice of agent to be used in the long term could be based on other considerations, such as compliance and safety. Both cough and angioedema were higher with ramipril than telmisartan during the 56-month follow-up period in ONTARGET.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Diabetes Mellitus; Humans; Kidney Diseases; Ramipril; Risk Factors; Telmisartan

The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of a variety of clinical conditions, including atherosclerosis, hypertension, left ventricular hypertrophy, myocardial infarction, and heart failure. Inhibition of the RAAS with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ARBs) has been shown to be effective in lowering blood pressure and reducing cardiovascular mortality and morbidity in various at-risk patient populations. A number of studies have shown that these 2 classes are effective in reducing the rate of renal disease progression in patients with diabetic nephropathy, although more long-term vascular outcome studies are needed in patients with chronic kidney disease. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) was the first study to show comparable reno- and cardioprotective effects between an ARB (telmisartan) and ramipril in a broad section of at-risk patients, on top of usual standard care. However, telmisartan showed better tolerability than ramipril in ONTARGET, with less cough and angioedema. This difference was obtained despite patients having been selected for tolerability to both drugs at study entry.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Diabetes Mellitus; Drug Therapy, Combination; Humans; Kidney Diseases; Ramipril; Telmisartan

The investigators review the evidence of the potential role of renin-angiotensin system (RAS) blockers in delaying or preventing the onset and progression of diabetes mellitus (DM) and cardiovascular disease and the suggested mechanisms by which these agents exert their favorable metabolic and cardiovascular effects. Data from clinical trials suggest that RAS blockade not only reduces cardiovascular risk in patients with DM but also may prevent or delay DM onset in at-risk subjects. These observations set the stage for further studies evaluating the risk for developing DM as a primary end point: the Diabetes Reduction Approaches With Ramipril And Rosiglitazone Medications (DREAM) trial, in which ramipril significantly increased regression to normoglycemia (although it did not reduce the primary end point of new-onset DM or death), and the ongoing Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, the only DM prevention trial also powered to evaluate whether a reduced risk for DM is associated with a reduction in cardiovascular disease events. In conclusion, overwhelming evidence suggests that the RAS plays an important role in the pathogenesis of DM and its associated cardiovascular risks.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus; Diabetes Mellitus, Type 2; Disease Progression; Endothelium, Vascular; Humans; Ramipril; Renin-Angiotensin System; Rosiglitazone; Tetrazoles; Thiazolidinediones; Valine; Valsartan; Vasodilation; Ventricular Function

Despite extensive documentation of their insulin-sensitizing and antihyperglycemic effects, the importance and place of the thiazolidinediones in diabetes management remain unclear. Three new controlled clinical trials of thiazolidinediones offer new information on the clinical utility of these agents.. During the past year, three new trials of thiazolidinediones were reported. In Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication, rosiglitazone reduced progression to diabetes in prediabetic patients by 60%. A Diabetes Outcome Progression Trial found rosiglitazone to have greater antihyperglycemic durability than metformin and glyburide in patients with recently diagnosed type 2 diabetes. Finally, in the Carotid Intima-media Thickness in Atherosclerosis using Pioglitazone, treatment with pioglitazone in patients with type 2 diabetes slowed progression of carotid wall thickness compared with the sulfonylurea glimepiride.. These trials support the contention that thiazolidinediones have superior efficacy in improving and stabilizing glycemic control than older antihyperglycemic agents, especially early in the course of type 2 diabetes. Findings from the Carotid Intima-media Thickness in Atherosclerosis using Pioglitazone add to the evidence that these agents have clinically meaningful vasculoprotective effects. Although generally well tolerated, they promote weight gain, limiting their acceptability to some extent, and occasionally lead to a diagnosis of heart failure, mostly in susceptible individuals.

Topics: Adult; Aged; Carotid Arteries; Clinical Trials as Topic; Diabetes Mellitus; Disease Progression; Female; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Ramipril; Rosiglitazone; Thiazolidinediones

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus; Diabetic Angiopathies; Humans; Premedication; Ramipril; Rosiglitazone; Thiazolidinediones; Treatment Outcome

Diabetes has long been recognized as a risk factor for heart disease. Recent evidence has brought to light complex interactions that seem to influence both the renal and the vascular complications of diabetes. The use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers has been shown to ameliorate renal and cardiac risks in both type 1 and type 2 diabetes to a degree that is disproportionate to blood pressure-lowering effects. The judicious use of these agents can materially improve the prognosis for patients with diabetes.

Topics: Albuminuria; Amlodipine; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biphenyl Compounds; Calcium Channel Blockers; Captopril; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathies; Humans; Irbesartan; Kidney Diseases; Losartan; Prognosis; Ramipril; Tetrazoles

Ramipril is a long-acting, lipophylic angiotensin converting enzyme inhibitor, its principle action is to inhibit the conversion of angiotensin I to the active angiotensin II. Ramipril is indicated in the treatment of hypertension, congestive cardiac failure (including that following acute myocardial infarction), nephropathy (with and without diabetes mellitus) and now, following the findings of the HOPE study, in the prevention of cardiovascular events (including myocardial infarction) in high risk individuals. This article concentrates on reviewing the evidence supporting ramipril's use in these indications.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Diabetes Mellitus; Heart Failure; Humans; Hypertension; Myocardial Infarction; Proteinuria; Ramipril

Studies have shown a non-linear relationship between systolic blood pressure (SBP) and diastolic blood pressure (DBP) and outcomes, with increased risk observed at both low and high blood pressure (BP) levels. We hypothesized that the BP-risk association is different in individuals with and without diabetes at high cardiovascular risk.. We identified patients with (N = 11 487) or without diabetes (N = 19 450), from 30 937 patients, from 133 centres in 44 countries with a median follow-up of 56 months in the ONTARGET/TRANSCEND studies. Patients had a prior history of stroke, myocardial infarction (MI), peripheral artery disease, or were high-risk diabetics. Patients in ONTARGET had been randomized to ramipril 10 mg daily, telmisartan 80 mg daily, or the combination of both. Patients in TRANSCEND were ACE intolerant and randomized to telmisartan 80 mg daily or matching placebo. We analysed the association of mean achieved in-trial SBP and DBP with the composite outcome of cardiovascular death, MI, stroke and hospitalization for congestive heart failure (CHF), the components of the composite, and all-cause death. Data were analysed by Cox regression and restricted cubic splines, adjusting for risk markers including treatment allocation and accompanying cardiovascular treatments. In patients with diabetes, event rates were higher across the whole spectrum of SBP and DBP compared with those without diabetes (P < 0.0001 for the primary composite outcome, P < 0.01 for all other endpoints). Mean achieved in-trial SBP ≥160 mmHg was associated with increased risk for the primary outcome [diabetes/no diabetes: adjusted hazard ratio (HR) 2.31 (1.93-2.76)/1.66 (1.36-2.02) compared with non-diabetics with SBP 120 to <140 mmHg], with similar findings for all other endpoints in patients with diabetes, and for MI and stroke in patients without diabetes. In-trial SBP <120 mmHg was associated with increased risk for the combined outcome in patients with diabetes [HR 1.53 (1.27-1.85)], and for cardiovascular death and all-cause death in all patients. In-trial DBP ≥90 mmHg was associated with increased risk for the primary outcome [diabetes/no diabetes: HR 2.32 (1.91-2.82)/1.61 (1.35-1.93) compared with non-diabetics with DBP 70 to <80 mmHg], with similar findings for all other endpoints, but not for CHF hospitalizations in patients without diabetes. In-trial DBP <70 mmHg was associated with increased risk for the combined outcome in all patients [diabetes/no diabetes: HR 1.77 (1.51-2.06)/1.30 (1.16-1.46)], and also for all other endpoints except stroke.. High on treatment BP levels (≥160 or ≥90 mmHg) are associated with increased risk of cardiovascular outcomes and death. Also low levels (<120 or <70 mmHg) are associated with increased cardiovascular outcomes (except stroke) and death. Patients with diabetes have consistently higher risks over the whole BP range, indicating that achieving optimal BP goals is most impactful in this group. These data favour guidelines taking lower BP boundaries into consideration, in particular in diabetes.. http://clinicaltrials.gov.Unique identifier: NCT00153101.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Blood Pressure Determination; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus; Diastole; Drug Therapy, Combination; Heart Failure; Hospitalization; Humans; Hypertension; Myocardial Infarction; Peripheral Arterial Disease; Ramipril; Retrospective Studies; Risk Factors; Stroke; Systole; Telmisartan

The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial reported that 3 years of therapy with rosiglitazone reduced the primary outcome of diabetes or death by 60%. Here we investigated whether an effect on diabetes prevention persists more than 1.5 years after therapy has been discontinued.. The DREAM On passive follow-up study was conducted at 49 of the 191 DREAM sites. Consenting participants were invited to have a repeat OGTT 1-2 years after active therapy ended. A diagnosis of diabetes at that time was based on either a fasting or 2 h plasma glucose level of ≥7.0 mmol/l or ≥11.1 mmol/l, respectively, or a confirmed diagnosis by a non-study physician. Regression to normoglycaemia was defined as a fasting and 2 h plasma glucose level of <6.1 mmol/l and <7.8 mmol/l, respectively.. After a median of 1.6 years after the end of the trial and 4.3 years after randomisation, rosiglitazone participants had a 39% lower incidence of the primary outcome (hazard ratio [HR] 0.61, 95% CI 0.53-0.70; p < 0.0001) and 17% more regression to normoglycaemia (95% CI 1.01-1.34; p = 0.034). When the analysis was restricted to the passive follow-up period, a similar incidence of both the primary outcome and regression was observed in people from both treatment groups (HR 1.00, 95% CI 0.81-1.24 and HR 1.14, 95% CI 0.97-1.32, respectively). Similar effects were noted when new diabetes was analysed separately from death. Ramipril did not have any significant long-term effect.. Time-limited exposure to rosiglitazone reduces the longer term incidence of diabetes by delaying but not reversing the underlying disease process.

Topics: Aged; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Ramipril; Rosiglitazone; Thiazolidinediones

Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage.. The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101.. 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril.. In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Creatinine; Diabetes Mellitus; Double-Blind Method; Drug Therapy, Combination; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney; Middle Aged; Proteinuria; Ramipril; Telmisartan

In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes.. After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure.. Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P=0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001).. Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit. (ClinicalTrials.gov number, NCT00153101 [ClinicalTrials.gov].).

Topics: Aged; Angioedema; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Blood Pressure; Cardiovascular Diseases; Creatinine; Diabetes Mellitus; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Ramipril; Risk; Telmisartan

Ramipril has been used in twice daily dose of 5 mg in most heart failure trials, whereas the dose used in Heart Outcomes Prevention Evaluation (HOPE) study was 10 mg once at bedtime. The HOPE investigators in an ambulatory blood pressure (ABP) substudy observed a fall of nighttime but not daytime blood pressure (BP). We examined the effects of once daily ramipril 10 mg versus 5 mg twice a day. Twenty-nine patients were recruited based on the original criteria for the HOPE study and were given ramipril either in twice-daily dose (5 mg b.d.) or once daily (10 mg o.d.) each morning in randomized, prospective crossover trial. Twenty-four hour ABP recordings were taken just before commencement of ramipril therapy and after treatment with twice-daily and once-daily ramipril. Our results show that ramipril causes a significant reduction of BP over 24-h period as compared with baseline. The mean baseline ABP was 124/73 mm Hg, which reduced to 117/69 mm Hg for the twice-a-day regimen (P<0.001) and 115/68 mm Hg for the once a day regimen (P<0.001). Both regimes effectively lower BP to a similar extent. Ramipril causes significant BP reduction in both once- and twice-daily dosing. The fall in BP after daytime dosing is greater than that observed in the HOPE study (including ABP substudy). Once-daily dosing in the morning seems to be effective in causing a significant reduction in the ABP profile of patients at high-risk of a future vascular event.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Cross-Over Studies; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Prospective Studies; Ramipril

Previous studies have suggested that blockade of the renin-angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension.. In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we randomly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels (after an 8-hour fast) or impaired glucose tolerance to receive ramipril (up to 15 mg per day) or placebo (and rosiglitazone or placebo) and followed them for a median of 3 years. We studied the effects of ramipril on the development of diabetes or death, whichever came first (the primary outcome), and on secondary outcomes, including regression to normoglycemia.. The incidence of the primary outcome did not differ significantly between the ramipril group (18.1%) and the placebo group (19.5%; hazard ratio for the ramipril group, 0.91; 95% confidence interval [CI], 0.81 to 1.03; P=0.15). Participants receiving ramipril were more likely to have regression to normoglycemia than those receiving placebo (hazard ratio, 1.16; 95% CI, 1.07 to 1.27; P=0.001). At the end of the study, the median fasting plasma glucose level was not significantly lower in the ramipril group (102.7 mg per deciliter [5.70 mmol per liter]) than in the placebo group (103.4 mg per deciliter [5.74 mmol per liter], P=0.07), though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the ramipril group (135.1 mg per deciliter [7.50 mmol per liter] vs. 140.5 mg per deciliter [7.80 mmol per liter], P=0.01).. Among persons with impaired fasting glucose levels or impaired glucose tolerance, the use of ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia. (ClinicalTrials.gov number, NCT00095654 [ClinicalTrials.gov].).

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Diabetes Mellitus; Double-Blind Method; Fasting; Female; Glucose Intolerance; Humans; Incidence; Male; Middle Aged; Ramipril

Emerging data suggest that different indices of glycaemia are risk factors for clinical events. The aim of this analysis was to investigate the relationship between fasting plasma glucose or glycated haemoglobin (GHb) levels and incident cardiovascular (CV) outcomes, death, heart failure and overt nephropathy in diabetic and non-diabetic individuals enrolled in the Heart Outcomes Prevention Evaluation (HOPE) study.. The adjusted 4.5-year risk of CV events (myocardial infarction or stroke or CV death), heart failure, death and overt nephropathy was analysed in relation to baseline and updated GHb levels (in 3,529 diabetic HOPE study participants) and baseline fasting plasma glucose levels (in 1,937 non-diabetic and 1,013 diabetic participants).. In diabetic participants, a 1% absolute rise in the updated GHb predicted future CV events (relative risk [RR]=1.07, 95% CI 1.01-1.13; p=0.014), death (RR=1.12, 95% CI 1.05-1.19; p=0.0004), heart failure (RR=1.20, 95% CI 1.08-1.33; p=0.0008) and overt nephropathy (RR=1.26, 95% CI 1.17-1.36; p<0.0001) after adjusting for age, sex, diabetes duration, blood pressure, WHR, hyperlipidaemia and ramipril. Similarly, a 1 mmol/l rise in fasting plasma glucose was related to an increased risk of CV outcomes (RR=1.09, 95% CI 1.05-1.13; p<0.0001), death (RR=1.06, 95% CI 1.01-1.12; p=0.017), heart failure (RR=1.16, 95% CI 1.06-1.13; p=0.0007) and overt nephropathy (RR=1.34, 95% CI 1.23-1.45; p<0.0001) in the group composed of diabetic and non-diabetic individuals. The significant relationship between fasting plasma glucose and CV outcomes persisted after adjustment for diabetes status (RR=1.06, 95% CI 1.00-1.12; p=0.043).. There is an independent progressive relationship between indices of glycaemia and incident CV events, renal disease and death. Clinical trials of glucose lowering to prevent these outcomes in diabetic and non-diabetic individuals are indicated.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Fasting; Female; Glycated Hemoglobin; Humans; Kidney Diseases; Male; Placebos; Ramipril; Reference Values; Risk Factors; Vitamin E

We have previously demonstrated that ramipril reduces vascular events and new diagnoses of diabetes when given for a 4.5-year period. However, it is not known whether the benefits are observed in subgroups of patients at varying risk or on other proven therapies and whether the benefits are sustained beyond the current trial. The 2 aims of this investigation were to assess whether the benefits observed during the HOPE trial were (1) maintained after trial cessation during an additional 2.6 years of follow-up and (2) observed in subgroups based on risk and ancillary treatments.. Of the initial 267 study centers and 9297 patients, 174 centers and 4528 patients agreed to further follow-up. The rates of use of angiotensin-converting-enzyme inhibitors (ACEIs) in the 2 groups (72% ramipril versus 68% placebo) were similar after the end of the trial. During the posttrial follow-up, patients allocated to ramipril had a 19% further lower relative risk (RR) of myocardial infarction (95% confidence interval [CI], 0.65 to 1.01), a 16% lower RR (95% CI, 0.70 to 0.99) of revascularization, and a 34% lower RR of a new diagnosis of diabetes (95% CI, 0.46 to 0.95). Similar RR reductions in vascular events were observed during and after the active phase of the trial, regardless of baseline risk (RR of 0.76, 0.89, and 0.83 for low-, medium-, and high-risk patients, respectively) or ancillary treatments (RR of 0.90 for aspirin, 0.76 for beta-blockers, and 0.84 for lipid-lowering medication).. The benefits of ramipril observed during the active period of the HOPE trial were maintained during posttrial follow-up for cardiovascular death, stroke, and hospitalization for heart failure. Additional reductions in myocardial infarction, revascularization, and the development of diabetes were observed during the follow-up phase despite similar rates of ACEI use in the 2 randomized groups. These benefits were consistent regardless of patient risk or ancillary treatments.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Male; Ramipril; Treatment Outcome

To investigate the hypothesis that prior angina pectoris confers protection from remodeling occurring after myocardial infarction (MI), we analyzed echocardiograms from the Healing and Early Afterload Reducing Therapy (HEART) trial.. Ischemia occurring before MI has been shown to reduce infarct size in experimental models and to improve outcomes in patients. The extent to which ischemia occurring before MI influences subsequent changes in ventricular size and function is unclear.. We studied 283 patients enrolled in the HEART trial who had echocardiograms at days 1 and 90 after MI. Left ventricular (LV) dilation from days 1 to 90 was used as a measure of LV remodeling. We explored the relationship between symptomatic angina occurring before infarction and subsequent LV remodeling.. In patients who reported angina (n = 111) during the three months preceding MI, LV volume change was -0.73 +/- 2.6 ml over the 90-day post-MI period, compared with 6.8 +/- 2.6 ml for patients (n = 172) without angina (p = 0.017). In contrast, there were no differences in changes in ejection fraction based on prior angina. Maximal creatine kinase was significantly lower in patients with prior angina (2,119 +/- 1,729 vs. 2,701 +/- 2,088, p = 0.016). In a multivariate model, prior angina remained protective for ventricular remodeling after adjusting for age, gender, baseline ejection fraction, Killip class, baseline end-diastolic volume, and drug treatment group (p = 0.042). However, the protective effect of pre-infarction angina appeared to be attenuated in diabetic patients.. Ischemic symptoms occurring before MI may protect against LV remodeling. These protective effects may be secondary to recruitment of collaterals or ischemic preconditioning of the myocardium, and they appear to be attenuated in diabetic patients.

Topics: Aged; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Creatine Kinase; Diabetes Mellitus; Double-Blind Method; Echocardiography; Female; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Predictive Value of Tests; Prevalence; Ramipril; Stroke Volume; Ventricular Remodeling

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, myocardial infarction, stroke, heart failure, need for revascularization, nephropathy, and diabetes and its complications. Although angiotensin-II receptor blockers (ARBs) have been less extensively evaluated, theoretically they may have "protective" effects similar to those of ACE inhibitors, but with better tolerability. Currently, there is uncertainty about the role of ARBs when used alone or in combination with an ACE inhibitor in high-risk populations with controlled hypertension.. Primary objectives of the ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) are to determine if the combination of the ARB telmisartan and the ACE inhibitor ramipril is more effective than ramipril alone, and if telmisartan is at least as effective as ramipril. The Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease (TRANSCEND) will determine if telmisartan is superior to placebo in patients who are intolerant of ACE inhibitors. The primary outcome for both trials is the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure.. High-risk patients with coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage are being recruited and followed for 3.5 to 5.5 years in 2 parallel, randomized, double-blind clinical trials.. Recruitment from 730 centers in 40 countries for ONTARGET (n = 25,620) was completed in July 2003. For TRANSCEND, 5776 patients (out of a projected total of 6000) have been recruited (by May 10, 2004). Baseline patient characteristics are comparable to the Heart Outcomes Prevention Evaluation (HOPE) trial, the basis of the design of the current study, confirming that patients are at high-risk.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Diabetes Mellitus; Double-Blind Method; Drug Therapy, Combination; Humans; Middle Aged; Patient Selection; Ramipril; Randomized Controlled Trials as Topic; Research Design; Telmisartan

Diabetes is a rapidly rising independent risk factor for atherosclerosis and serious illness. This risk can be reduced by lifestyle changes and/or various drugs. Novel therapies to prevent diabetes, as well as new risk factors for diabetes, atherosclerosis and obesity require testing and identification.. People with impaired fasting glucose or impaired glucose tolerance were randomised to ramipril (15 mg/day) or placebo and rosiglitazone (8 mg/day) or placebo with a 2x2 factorial design. They are assessed semi-annually for the primary outcome (diabetes or death). Diabetes is diagnosed if two consecutive plasma glucose levels exceed diagnostic thresholds (i.e. fasting >/=7.0 mmol/l or 2-h >/=11.1 mmol/l) within a 3-month period. Assuming an annual primary outcome incidence of 5%, there is more than 90% power to detect a 22% reduction. Approximately 20% of participants are having annual carotid ultrasounds to assess the effects on atherosclerosis. Patients screened but not randomised are being followed prospectively to identify determinants of obesity, diabetes and related disorders.. A total of 24,872 individuals in 21 countries were screened over 2 years and are eligible for follow-up. Of these, 5269 were randomised: 1835 (35%) had isolated impaired glucose tolerance, 739 (14%) had isolated impaired fasting glucose, and 2692 (51%) had both disorders. Annual carotid ultrasounds are currently being performed in 1406 randomised individuals.. The DREAM trial and related studies will determine if ramipril or rosiglitazone reduces the number of cases of diabetes and atherosclerosis, and will identify novel risk factors for diabetes.

Topics: Adult; Aged; Antihypertensive Agents; Body Mass Index; Body Size; Diabetes Mellitus; Diabetes, Gestational; Diabetic Angiopathies; Female; Humans; Hypoglycemic Agents; Life Style; Male; Middle Aged; Patient Selection; Pregnancy; Ramipril; Rosiglitazone; Thiazolidinediones

Type 2 diabetes is a growing clinical and public health problem. Preventive efforts related to lifestyle modification are not always successful; therefore, alternative prevention strategies need to be studied.. To investigate the effectiveness of ramipril, an angiotensin-converting enzyme inhibitor, in preventing diabetes among high-risk persons.. The randomized, controlled Heart Outcomes Prevention Evaluation trial of 5720 patients older than 55 years without known diabetes but with vascular disease who were followed up for a mean of 4.5 years. The study included 267 hospitals in 19 countries and was conducted between 1994 and 1999.. Patients were randomly assigned to receive ramipril, up to 10 mg/d (n = 2837), or placebo (n = 2883).. Diagnosis of diabetes determined from self-report at follow-up visits every 6 months, compared between the 2 groups.. One hundred and two individuals (3.6%) in the ramipril group developed diabetes compared with 155 (5.4%) in the placebo group (relative risk [RR], 0.66; 95% confidence interval [CI], 0.51-0.85, P<.001). Similar results were noted when different diagnostic criteria were used; in the ramipril group, the RR for diagnosis of diabetes and hemoglobin A(1c) greater than 110% was 0.60 (95% CI, 0.43-0.85), for initiation of glucose-lowering therapy, 0.56 (95% CI, 0.41-0.77), and for both, 0.51 (95% CI, 0.34-0.76). These effects were also consistently seen in several subgroups examined.. Ramipril is associated with lower rates of new diagnosis of diabetes in high-risk individuals. Because these results have important clinical and public health implications, this hypothesis requires prospective confirmation.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Proportional Hazards Models; Ramipril; Randomized Controlled Trials as Topic; Survival Analysis

Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction, whether or not they have heart failure. We assessed the role of an angiotensin-converting-enzyme inhibitor, ramipril, in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure.. A total of 9297 high-risk patients (55 years of age or older) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were randomly assigned to receive ramipril (10 mg once per day orally) or matching placebo for a mean of five years. The primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular causes. The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper.. A total of 651 patients who were assigned to receive ramipril (14.0 percent) reached the primary end point, as compared with 826 patients who were assigned to receive placebo (17.8 percent) (relative risk, 0.78; 95 percent confidence interval, 0.70 to 0.86; P<0.001). Treatment with ramipril reduced the rates of death from cardiovascular causes (6.1 percent, as compared with 8.1 percent in the placebo group; relative risk, 0.74; P<0.001), myocardial infarction (9.9 percent vs. 12.3 percent; relative risk, 0.80; P<0.001), stroke (3.4 percent vs. 4.9 percent; relative risk, 0.68; P<0.001), death from any cause (10.4 percent vs. 12.2 percent; relative risk, 0.84; P=0.005), revascularization procedures (16.3 percent vs. 18.8 percent; relative risk, 0.85; P<0.001), cardiac arrest (0.8 percent vs. 1.3 percent; relative risk, 0.62; P=0.02), [corrected] heart failure (9.1 percent vs. 11.6 percent; relative risk, 0.77; P<0.001), and complications related to diabetes (6.4 percent vs. 7.6 percent; relative risk, 0.84; P=0.03).. Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Double-Blind Method; Female; Humans; Male; Middle Aged; Myocardial Infarction; Ramipril; Risk Factors; Stroke; Treatment Outcome

Angiotensin-converting enzyme inhibitors reduce proteinuria in both normotensive and hypertensive patients with proteinuric renal disease. However, the mechanism of the antiproteinuric effect has not been clarified. We performed a prospective, double-blind, placebo-controlled, randomized crossover trial to test the hypothesis that the antiproteinuric effect of ramipril was due to an improvement in glomerular permselectivity independent of blood pressure and glomerular filtration rate. The effect of low-dose (1.25 mg/d) and high-dose (5 mg/d) ramipril was assessed in 15 normotensive nondiabetic patients with proteinuria (> 150 mg/d). The study was divided into four 12-week periods: placebo, high- or low-dose ramipril, crossover to low- or high-dose ramipril, and placebo. Blood pressure, glomerular filtration rate, renal plasma flow rate, urinary protein excretion rate, and plasma angiotensin II levels were measured at the end of each period. Mean arterial pressure, urine protein to creatinine ratio, and albumin excretion rate decreased significantly during low- and high-dose ramipril. Glomerular filtration rate and renal plasma flow rate were not changed significantly. Plasma angiotensin II levels decreased with both low- and high-dose ramipril. There were no episodes of hypotension and only one subject developed cough during ramipril that did not require discontinuation of the study drug. In conclusion, administration of ramipril in both low and high doses lowered blood pressure and reduced proteinuria in this cohort of normotensive patients with a variety of proteinuric renal diseases. The antiproteinuric effect of ramipril is probably mediated by a reduction in glomerular capillary pressure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuminuria; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Creatinine; Cross-Over Studies; Diabetes Mellitus; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Prospective Studies; Proteinuria; Ramipril; Renal Plasma Flow

Modification of gut-islet secretions after Roux-En-Y gastric bypass (RYBG) surgery contributes to its metabolic and anti-diabetic benefits. However, there is limited knowledge on tissue-specific hormone distribution post-RYGB surgery and how this compares with best medical treatment (BMT). In the present study, pancreatic and ileal tissues were excised from male Zucker-Diabetic Sprague Dawley (ZDSD) rats 8-weeks after RYGB, BMT (daily oral dosing with metformin 300mg/kg, fenofibrate 100mg/kg, ramipril 1mg/kg, rosuvastatin 10mg/kg and subcutaneous liraglutide 0.2mg/kg) or sham operation (laparotomy). Insulin, glucagon, somatostatin, PYY, GLP-1 and GIP expression patterns were assessed using immunocytochemistry and analyzed using ImageJ. After RYGB and BMT, body weight and plasma glucose were decreased. Intestinal morphometry was unaltered by RYGB, but crypt depth was decreased by BMT. Intestinal PYY cells were increased by both interventions. GLP-1- and GIP-cell counts were unchanged by RYGB but BMT increased ileal GLP-1-cells and decreased those expressing GIP. The intestinal contents of PYY and GLP-1 were significantly enhanced by RYGB, whereas BMT decreased ileal GLP-1. No changes of islet and beta-cell area or proliferation were observed, but the extent of beta-cell apoptosis and islet integrity calculated using circularity index were improved by both treatments. Significantly decreased islet alpha-cell areas were observed in both groups, while beta- and PYY-cell areas were unchanged. RYGB also induced a decrease in islet delta-cell area. PYY and GLP-1 colocalization with glucagon in islets was significantly decreased in both groups, while co-staining of PYY with glucagon was decreased and that with somatostatin increased. These data characterize significant cellular islet and intestinal adaptations following RYGB and BMT associated with amelioration of obesity-diabetes in ZDSD rats. The differential responses observed and particularly those within islets, may provide important clues to the unique ability of RYGB to cause diabetes remission.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Fenofibrate; Gastric Bypass; Glucagon; Glucagon-Like Peptide 1; Insulin; Liraglutide; Male; Metformin; Obesity; Ramipril; Rats; Rats, Sprague-Dawley; Rats, Zucker; Rosuvastatin Calcium; Somatostatin

To assess the cross-sectional associations of the measures of glycemia and cognitive function in subjects at high cardiovascular risk.. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and concurrent Telmisartan Randomized Assessment Study in ACE intolerant Subjects with Cardiovascular Disease (TRANSCEND) are multi-center, randomized, controlled investigations of different approaches to angiotensin receptor blockade in over 30,000 high CV risk subjects. Baseline data in both trials was used to analyze relationships between measures of glycemic control and cognition.. The univariate and multivariate relationships between diabetes status, fasting plasma glucose (FPG), and scores on the Mini-Mental State Examination (MMSE) were assessed.. In subjects with diabetes, the mean MMSE score was 0.4 units lower than in those without diabetes (P<0.0001). In all subjects, a 1 mmol/L higher FPG value was associated with a MMSE score that was 0.06 units lower (P<0.0001). The association persisted after adjustment for several cardiovascular risk factors.. Dysglycemia is a risk factor for impaired cognitive function in this broadly representative, high-risk study population. Prospective studies can more reliably discern temporal associations, including the effects of glucose lowering in this clinical group.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Blood Glucose; Cardiovascular Diseases; Cognition; Cognition Disorders; Cross-Sectional Studies; Depression; Diabetes Mellitus; Diabetic Angiopathies; Drug Therapy, Combination; Female; Glucose Intolerance; Humans; Male; Middle Aged; Ramipril; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Telmisartan

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Creatinine; Diabetes Mellitus; Disease Progression; Drug Therapy, Combination; Glomerular Filtration Rate; Humans; Kidney; Multicenter Studies as Topic; Proteinuria; Ramipril; Randomized Controlled Trials as Topic; Telmisartan

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Cause of Death; Diabetes Mellitus; Drug Therapy, Combination; Humans; Ramipril; Telmisartan

A number of protected learning time schemes have been set up in primary care across the United Kingdom but there has been little published evidence of their impact on processes of care. We undertook a qualitative study to investigate the perceptions of practitioners involved in a specific educational intervention in diabetes as part of a protected learning time scheme for primary health care teams, relating to changing processes of diabetes care in general practice.. We undertook semistructured interviews of key informants from a sample of practices stratified according to the extent they had changed behaviour in prescribing of ramipril and diabetes care more generally, following a specific educational intervention in Lincolnshire, United Kingdom. Interviews sought information on facilitators and barriers to change in organisational behaviour for the care of diabetes.. An interprofessional protected learning time scheme event was perceived by some but not all participants as bringing about changes in processes for diabetes care. Participants cited examples of change introduced partly as a result of the educational session. This included using ACE inhibitors as first line for patients with diabetes who developed hypertension, increased use of aspirin, switching patients to glitazones, and conversion to insulin either directly or by referral to secondary care. Other reported factors for change, unrelated to the educational intervention, included financially driven performance targets, research evidence and national guidance. Facilitators for change linked to the educational session were peer support and teamworking supported by audit and comparative feedback.. This study has shown how a protected learning time scheme, using interprofessional learning, local opinion leaders and early implementers as change agents may have influenced changes in systems of diabetes care in selected practices but also how other confounding factors played an important part in changes that occurred in practice.

Topics: Diabetes Mellitus; Education, Medical, Continuing; Educational Measurement; Educational Status; Humans; Interviews as Topic; Learning; Models, Educational; Organizational Innovation; Perception; Physicians, Family; Primary Health Care; Program Evaluation; Qualitative Research; Ramipril; United Kingdom

Diabetes mellitus (DM) is a worldwide epidemic. Its prevalence is rapidly increasing in both developing and developed countries. Coronary heart disease (CHD) is highly prevalent and is the major cause of morbidity and mortality in patients with diabetes. Individuals with prediabetes states, with or without known CHD, should undergo lifestyle modifications aimed at preventing DM. In patients with CHD and DM, routine use of aspirin and an angiotensin-converting enzyme inhibitor, along with strict glycemic, blood pressure, and lipid control, is strongly recommended. Intense insulin therapy may be needed for glycemic control, and high-dose statin therapy may be needed for lipid control. For blood pressure control, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are considered first-line therapy. Noncompliance with medications and/or lifestyle measures and underprescription of evidence-based therapies remain important unsolved problems.

Topics: Antihypertensive Agents; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Diabetes Mellitus; Diabetic Angiopathies; Humans; Hyperglycemia; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Life Style; Myocardial Infarction; Obesity; Pioglitazone; Piperidines; Platelet Aggregation Inhibitors; Prediabetic State; Pyrazoles; Ramipril; Rimonabant; Risk Assessment; Thiazolidinediones; Triglycerides; Weight Loss

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Diabetes Mellitus; Humans; Hypertension; Incidence; Insulin Resistance; Ramipril

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Diabetes Mellitus; Humans; Incidence; Potassium; Ramipril

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Diabetes Mellitus; Humans; Hypertension; Incidence; Ramipril

This article summarizes an important study published in 2006 in the field of the prevention of diabetes mellitus. It is the DREAM study which evaluate the therapeutic effects of rosiglitazone and ramipril versus placebo in the prevention of type 2 diabetes in high risk patients: glucose intolerance or impaired fasting glucose. In this clinical study, more than 5000 patients were followed during 3 years. The risk of diabetes was reduced with rosiglitazone of 62% (NNT 9). In the field of negative effects the risk of cardiac insufficiency was multiplied by 7 (NNH 250) but stayed a rare event (to 0,5% of the treated subjects). The ramipril had no preventive effect for the prevention of type 2 diabetes but induced a higher frequency of return towards the normoglycaemia. This treatment can be recommended for these high risk subjects.

Topics: Antihypertensive Agents; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Ramipril; Randomized Controlled Trials as Topic; Rosiglitazone; Thiazolidinediones

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Diabetes Mellitus; Glucose Intolerance; Humans; Ramipril

Topics: Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus; Humans; Hypoglycemic Agents; India; Prediabetic State; Ramipril; Randomized Controlled Trials as Topic; Rosiglitazone; Thiazolidinediones

Albumin excretion is modulated post-filtration by lysosomal processing that produces a spectrum of albumin-derived material in urine, much of which is not detected by conventional immunoassays. This study aimed to determine the efficacy of ramipril treatment (+ RAM) after 24 weeks on total albumin excretion (intact plus albumin-derived peptides) in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with (d) and without (c) diabetes.. Intact albumin excretion was analysed by radioimmunoassay and total albumin excretion was analysed by measuring radioactivity derived from circulating [ C]albumin. Renal lysosomal activity was determined by urinary [ H]dextran sulphate desulphation. Renal transforming growth factor-beta 1 (TGF-beta 1), TGF-beta inducible gene-h3 (beta ig-h3) and angiotensinogen mRNA production were analysed by real time reverse transcriptase-polymerase chain reaction.. Hypertension (SHR-c and SHR-d) resulted in a significant increase in intact albumin excretion, which was significantly reduced by ramipril treatment (P < 0.05 for SHR-c + RAM and 0.001 for SHR-d + RAM compared to non-treated). This was accompanied by a significant decrease in blood pressure (P < 0.001 for SHR-c + RAM and SHR-d + RAM), renal beta ig-h3 mRNA production (P < 0.05 for SHR-c + RAM and SHR-d + RAM), and an increase in lysosomal activity. Diabetes (WKY-d and SHR-d) primarily caused a significant increase in total albumin excretion, predominantly in the form of albumin-derived fragments in the WKY-d group and intact albumin in the SHR-d group. Ramipril treatment reduced total albumin excretion in the WKY-d + RAM group (P < 0.001).. Ramipril prevents increases in both intact albumin and total albumin excretion in hypertensive and diabetic states, respectively.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Animals; Blood Pressure; Diabetes Mellitus; Extracellular Matrix Proteins; Hypertension; Lysosomes; Male; Ramipril; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Transforming Growth Factor beta; Transforming Growth Factor beta1

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus; Follow-Up Studies; Humans; Kidney Diseases; Placebos; Prospective Studies; Ramipril; Randomized Controlled Trials as Topic; Risk Factors; Time Factors

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Arteriosclerosis; Diabetes Mellitus; Disease Models, Animal; Humans; Hypertension; Imidazoles; Myocardial Infarction; Olmesartan Medoxomil; Rabbits; Ramipril; Rats; Tetrazoles; Time Factors

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Diabetes Mellitus; Humans; Ramipril; Risk

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Diabetes Mellitus; Humans; Ramipril; Risk

Topics: Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus; Humans; Ramipril

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Humans; Myocardial Infarction; Ramipril; Risk Factors; Stroke

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Diabetes Mellitus; Female; Humans; Incidence; Male; Middle Aged; Ramipril; Risk Factors; Treatment Outcome

20 patients with essential hypertension and diabetes mellitus (DM) type II were given Capoten (100-125 mg/day for 6 weeks) followed in a 2-week interval after its course termination by ramipril (10.0-12.5 mg/day). 50% of patients were sensitive to Capoten, 50% were resistance: 35 and 40% to ramipril, respectively. Ramipril was discontinued because of toxicity in 25% of patients. Hypotensive effects of ramipril were weaker than Capoten, though the former drug appeared more potent in lowering of peripheral vascular resistance at rest and at reactive hyperemia. Vasodilatation did not differ much.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Captopril; Diabetes Mellitus; Drug Evaluation; Drug Therapy, Combination; Female; Hemodynamics; Humans; Hypertension; Hypoglycemic Agents; Male; Middle Aged; Myocardial Ischemia; Ramipril