Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rationale, design, organization, and outcome definitions of the Acute Infarction Ramipril Efficacy (AIRE) Study are described prospectively. A total of 2,000 patients (1,000 per treatment group) will be recruited to this multicenter, multinational, double-blind, randomized, placebo-controlled study investigating the effect of oral treatment with ramipril (2.5 or 5 mg twice daily) on the total mortality of survivors of an acute myocardial infarction (AMI) with early clinical evidence of heart failure. Secondary outcomes of the study include progression to severe/resistant heart failure (at which time the patient will be withdrawn from the study treatment), reinfarction, and stroke. Treatment will be initiated in hospital between day 3 and day 10 following AMI, and follow-up continued for an average of 15 months and a minimum of 6 months. The study data will be analyzed on an intention-to-treat basis: a single formal interim analysis will be conducted after 175 deaths. An Independent Adjudicating Panel will act as the overall ethical supervisory body for the study and will retain the randomization code. An International Steering Committee will be responsible for the clinical definitions of the secondary study outcomes, and will regularly review progress of the study. We believe that early treatment with ramipril may reduce the total mortality of patients surviving an AMI with clinical evidence of heart failure.
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PMID:The Acute Infarction Ramipril Efficacy (AIRE) Study: rationale, design, organization, and outcome definitions. 172 16

The active diacids of the new converting enzyme (CE) inhibitors ramipril and perindopril proved to possess a similar inhibitory potency against rat plasma CE in vitro. Both diacids were more active than enalaprilic acid or captopril. In stroke-prone spontaneously hypertensive rats (SHRSP) chronic oral treatment for 2 weeks with enalapril (30 mg/kg per day), ramipril or perindopril (each 1 mg/kg normalized blood pressure. The CE inhibitor-induced changes in parameters of the plasma renin-angiotensin system [angiotensin I (ANG I), angiotensin II (ANG II), PRC and CE activity] followed the expected pattern, but were not quantitatively related to the antihypertensive action of the three CE inhibitors. Four weeks of oral equi-dose treatment with the three CE inhibitors (10 mg/kg per day) inhibited tissue CE activity in various organs including kidney, heart, vascular wall and brain. Ramipril and perindopril lowered blood pressure and tissue CE activity more potently than enalapril did. These results are consistent with the hypothesis that CE inhibition in tissue with subsequent local reduction of ANG II synthesis may contribute to the antihypertensive mechanisms of CE inhibitors.
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PMID:Antihypertensive action and inhibition of tissue converting enzyme (CE) by three prodrug CE inhibitors, enalapril, ramipril and perindopril in stroke-prone spontaneously hypertensive rats. 302 91

Ramipril and perindopril, the active diacids of two new converting enzyme (CE) inhibitors proved to possess a similar inhibitory potency against rat plasma CE in vitro. These diacid compounds were more active than enalaprilic acid or captopril. In stroke-prone spontaneously hypertensive rats (SHRSP) chronic oral treatment for two weeks with enalapril (30 mg/kg per day), ramipril or perindopril (each 1 mg/kg per day) normalized blood pressure. The CE inhibitor-induced changes in parameters of the plasma renin-angiotensin system (angiotensin I, angiotensin II, PRC, CE activity) followed the expected pattern, but were not quantitatively related to the antihypertensive action of the three inhibitors. Four weeks of oral equi-dose treatment with the three CE inhibitors (10 mg/kg per day) inhibited tissue CE activity in various organs including kidney, heart, vascular wall and brain. Ramipril and perindopril lowered blood pressure and tissue CE activity more potently than enalapril. These results confirm the hypothesis that CE inhibition in tissue with subsequent local reduction of ANG II synthesis may contribute to the antihypertensive mechanisms of CE inhibitors.
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PMID:[Antihypertensive action and inhibition of tissue conversion enzyme by ramipril, perindopril and enalapril in the spontaneously hypertensive rat (SHRSP)]. 302 75

1. The influence of salt (sodium chloride; NaCl) (an additional 6% in the diet) and that of a novel sodium-reduced, potassium-, magnesium-, and L-lysine-enriched salt alternative on the cardiovascular effects of ramipril was studied in stroke-prone spontaneously hypertensive rats in a 6-week study. The intake of sodium chloride was adjusted to the same level by adding the salt alternative at a 1.75 times higher amount than regular salt. 2. Salt produced a marked rise in blood pressure and induced cardiac hypertrophy and significant mortality, while the salt alternative neither increased blood pressure nor caused any mortality and produced less cardiac hypertrophy than salt. 3. Ramipril treatment at a daily dose of 3 mg kg-1 normalized blood pressure and prevented the development of cardiac hypertrophy of rats on control diet. These effects of ramipril were blocked by the addition of salt but were only slightly attenuated by the addition of the salt alternative. The mortality in the salt group was prevented by ramipril. 4. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Salt, but not the salt alternative, increased vascular contractile responses to noradrenaline. Ramipril treatment improved the arterial relaxation responses to acetylcholine and to sodium nitroprusside. The vascular relaxation enhancing effect of ramipril was blocked by salt but only slightly attenuated by the salt alternative. 5. Ramipril treatment did not significantly increase plasma renin activity in the presence or in the absence of salt supplementation. The salt alternative did not cause hyperkalaemia, either alone or in combination with ramipril treatment. 6. Both salt supplementations, irrespective of ramipril treatment, induced a six to eight fold increase in the urinary excretion of calcium. There was an expected 90 to 140% rise in the urinary excretion of magnesium and 200% rise in the urinary excretion of potassium in the salt alternative group. Salt also produced an approximately 50% increase in magnesuria.7. Our findings suggest that replacement of salt by the potassium-, magnesium- and L-lysine-enriched salt alternative improves the cardiovascular effects of ramipril. In the present study the beneficial effect was related to the increased intakes of potassium and/or magnesium and L-lysine from the salt alternative because the amount of sodium chloride was the same.
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PMID:Replacement of salt by a novel potassium- and magnesium-enriched salt alternative improves the cardiovascular effects of ramipril. 803 5

Recent studies indicate that norepinephrine-induced contractile oscillations in the tail artery from stroke-prone spontaneously hypertensive rats (SHRSP) may be a vascular phenomenon independent of blood pressure level. The objectives of this study were: (1) to characterize pharmacologically the alpha-adrenoceptor mediating norepinephrine-induced oscillations in tail artery; and (2) to investigate the relationship between blood pressure level, altered by treatments with hydralazine/hydrochlorothiazide or the angiotensin converting enzyme inhibitor ramipril, and the observation of norepinephrine-induced oscillations in tail artery. The alpha 2-adrenoceptor agonists clonidine and guanabenz potently stimulated oscillatory contractions in the tail artery while the alpha 1-adrenoceptor agonists phenylephrine and methoxamine were considerably less potent. Yohimbine, an alpha 2-adrenoceptor antagonist, but not the alpha 1-adrenoceptor antagonist prazosin demonstrated high affinity for the receptor mediating norepinephrine-induced oscillatory contractions. These results support the hypothesis that norepinephrine-induced oscillatory contractions in the tail artery from SHRSP occur primarily through stimulation of alpha 2-adrenoceptors. Ramipril lowered blood pressure in SHRSP after 4 weeks of treatment during 6-10 weeks of life but did not alter the ability of the alpha 2-adrenoceptor agonist clonidine (10(-5) M) to induce contractile oscillations in tail arteries from SHRSP, indicating these oscillations are not a secondary effect of high blood pressure. These studies suggest that norepinephrine-induced oscillations in tail artery from SHRSP may be a vascular trait separate and distinct from blood pressure level and angiotensin II expression early in life.
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PMID:Effect of ramipril on alpha-adrenoceptor-mediated oscillatory contractions in tail artery of hypertensive rats. 828 89

Atherosclerotic cardiovascular disease remains a major cause of mortality and morbidity in most developed countries. Experimental and clinical evidence suggests that angiotensin-converting enzyme inhibitors and vitamin E therapy may retard the atherosclerotic process; however, definitive proof in humans is lacking. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) is designed to assess the effects of ramipril--an angiotensin-converting enzyme inhibitor, at 2 doses: 2.5 mg daily (which has little effect on lowering blood pressure) and 10 mg daily--and the antioxidant vitamin E, 400 IU daily, on atherosclerosis progression in 732 patients using a factorial 3 x 2 study design. High-risk patients with a documented history of significant cardiovascular disease or with diabetes and additional risk factors were enrolled and will be followed for 4 years. The extent and progression of atherosclerosis are assessed noninvasively by B-mode carotid ultrasonography. The SECURE trial is a substudy of the larger Heart Outcomes Prevention Evaluation (HOPE) study of 9,541 high-risk patients evaluating the effects of ramipril and vitamin E on major cardiovascular events (cardiovascular death, myocardial infarction, and stroke). The 2 studies are complementary. Whereas HOPE is expected to provide information on major clinical outcomes, SECURE will shed light on the mechanisms by which these effects may be mediated.
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PMID:Study design and baseline characteristics of the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E: SECURE. 888 65

Diuretic-based therapy is less effective in reducing the cardiac complications of hypertension than the risk of stroke and may be less effective in reducing left ventricular (LV) mass than is therapy with angiotensin converting enzyme (ACE) inhibition. In view of the strong association of LV hypertrophy with cardiovascular risk, this study was designed to compare the impact of therapy with a diuretic and ACE inhibition on cardiac and vascular structure. Fifty essential hypertensives (74% male, 88% nonwhite) participated in a double-blind study for 6 months and were randomized to either ramipril or hydrochlorothiazide (HCTZ). Echocardiography, carotid ultrasonography, and ambulatory blood pressure (BP) monitoring were performed at baseline and 3 and 6 months after initiation of therapy. The 22 ramipril patients were comparable to the 28 HCTZ patients at baseline in age, race, and 24-h BP. Although HCTZ resulted in a greater reduction in 24-h BP, only treatment with ramipril resulted in a decrease in LV mass (193 to 179 g, P < .005, v 184 to 182 g, P = NS), attributable to a reduction in wall thicknesses but not in chamber diameter. In multivariate analysis, both change in BP and treatment group were independent predictors of change in LV mass. Importantly, although neither drug reduced carotid artery cross-sectional area, relative wall thickness increased due to a tendency for vessel diameter to decrease and wall thickness to increase, particularly in the diuretic group. Ramipril caused a sustained fall in plasma angiotensin II, whereas HCTZ increased angiotensin II levels. Although diuretic therapy was more effective in lowering ambulatory BP in this predominantly nonwhite population, only therapy with ACE inhibition was associated with regression of LV mass. Vascular geometry was altered consistent with the reduction in distending pressure resulting in vascular remodelling.
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PMID:Differential effects of angiotensin converting enzyme inhibition and diuretic therapy on reductions in ambulatory blood pressure, left ventricular mass, and vascular hypertrophy. 960 75

The non-insulin-dependent DIABetes, HYpertension, microalbuminuria or proteinuria, CARdiovascular events, and Ramipril (DIABHYCAR) study is a randomized, prospective, double-blind, placebo-controlled, multicenter international trial of the ACE inhibitor ramipril (1.25 mg/day) in patients with type II diabetes and micro- or macroalbuminuria. The main outcome of the study is the time to first occurrence of either death from a cardiovascular origin, including sudden death, nonfatal myocardial infarction, stroke, or congestive heart failure, or requirement of hemodialysis or renal transplantation. The study was launched in France in early 1995 with the participation of general practitioners only, but had to be extended to 15 other countries in 1997 due to difficulties in recruitment. Since 2.5 years after the beginning of the trial the observed event rate was much less than anticipated, it was decided to increase recruitment and follow-up duration and to include congestive heart failure in the definition of the main outcome to keep the study power at a satisfactory level. Recruitment ended on April 1, 1998 with 4937 randomized patients. Following the early discontinuation for efficacy of another study of ramipril in high cardiovascular risk patients, the Heart Outcomes Prevention Evaluation study (HOPE), the second interim analysis of DIABHYCAR was performed early (when 406 instead of 500 patients presented a main outcome) and the Data Safety and Monitoring Board recommended that the study continue. Follow-up is planned to end on March 31, 2001.
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PMID:The non-insulin-dependent diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events, and ramipril (DIABHYCAR) study: design, organization, and patient recruitment. DIABHYCAR Study Group. 1091 14

Over a 4.5 year follow-up period, the HOPE (Heart Outcomes Prevention Evaluation) trial, and the MICRO-HOPE (Microalbuminuria, Cardiovascular, and Renal Outcomes) and SECURE (Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E) substudies have all demonstrated a large benefit of ramipril versus placebo in patients over 55 years at high risk (by reason of a prior vascular event), or by being diabetic subjects with one additional risk factor. The baseline blood pressure on average was normal, at 139/79 mmHg, and was modestly reduced by 3.3/1.4 mmHg. Patients with known left ventricular dysfunction were excluded, as were those with uncontrolled hypertension. The incidence of stroke was reduced by 32%, myocardial infarction by 20% and cardiovascular death by 25%. The benefits conferred were in addition to, and largely independent of, other conventional treatments such as aspirin, lipid-lowering agents, beta-blockers, diuretics and calcium channel blockers. The relative risk reduction was very similar whether or not the patient was a known hypertensive at baseline. High dose ACE inhibition with ramipril is applicable to a far wider population of patients at high risk of cardiovascular events than the current indications of hypertension and left ventricular dysfunction.
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PMID:Future perspectives and implications. 1171 55

Diabetes is a major risk factor for cardiovascular events. Indeed, people with diabetes are 2-4 times more likely to die from cardiovascular causes than individuals without diabetes. Despite evidence to suggest that the burden of cardiovascular disease may be decreasing in Western populations, this trend has not been repeated in diabetic populations. Diabetes is also the most common cause of new-onset end-stage renal disease, blindness and amputations. The growing incidence of diabetes throughout the world, particularly in developing nations, suggests that diabetes-related cardiovascular disease and other chronic cardiovascular diseases will constitute a serious global threat to health and well-being. The HOPE (Heart Outcomes Prevention Evaluation) study was designed to determine if the angiotensin converting enzyme (ACE) inhibitor, ramipril, prevents cardiovascular events in high risk patients. As people with diabetes have a high risk of such events, this group was specified for inclusion and analysis in the HOPE study. The HOPE study was designed to include up to 4,000 people with diabetes and was designed with high power to detect an 18% risk reduction in the diabetic sub group alone. A total of 3,577 individuals with diabetes were randomised to receive either 10 mg of ramipril or placebo. After a period of 4.5 years of follow-up, the group of patients receiving ramipril had a statistically and clinically significant risk reduction of 25% in the primary outcome of myocardial infarction (MI), stroke or cardiovascular (CV) death. This comprises a 37% risk reduction in CV death, a 22% risk reduction in MI, a 33% reduction in stroke and a 24% reduction in all-cause mortality. The MICRO-HOPE (Microalbuminuria, Cardiovascular, and Renal Outcomes) sub study assessed the effect of ramipril on diabetic nephropathy. This was detected by a centrally measured urine albumin:creatinine ratio and confirmed by timed urine collection. Ramipril significantly reduced the risk of overt nephropathy by 22% (P = 0.045), and overt nephropathy, laser therapy or dialysis by 15% (P = 0.05). ACE inhibition with ramipril represents a new macrovascular and microvascular preventive therapy for people with diabetes.
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PMID:Diabetes and the HOPE study: implications for macrovascular and microvascular disease. 1171 57


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