Disease relevance of Altace

• CONCLUSIONS: 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 [1].
• 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 [1].
• METHODS: 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 [1].
• However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001) [2].
• Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial [2].

Psychiatry related information on Altace

• RESULTS: Ramipril reduced the incidence of the triple-composite end point of cardiac death, acute myocardial infarction or clinical heart failure (risk reduction 58%; 95% confidence interval 7% to 80%, p = 0.031) [3].
• In consideration of patient compliance, once-daily administration of ramipril seems to be optimal for the treatment of essential hypertension [4].
• Mean Physical Health Component (PHC) and Mental Health Component (MHC) scores had a significantly smaller decrease in the ramipril than metoprolol group in both the initial period from baseline to year 1 (PHC, 2.08 +/- 0.56; MHC, 1.89 +/- 0.62) and during the first 4 years of follow-up (PHC, 1.60 +/- 0.44; MHC, 1.48 +/- 0.48) [5].

High impact information on Altace

• Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators [1].
• ACE inhibition with ramipril, in the antihypertensive dose of 1 mg/kg/day for 6 weeks, prevented the increase in blood pressure and the development of LVH [6].
• Renal renin mRNA levels both under stimulatory (low-salt diet plus ramipril) and inhibitory (high-salt diet) conditions were not different between wild-type and cGKI-/- mice, but were significantly elevated in cGKII-/- mice under all experimental conditions [7].
• In this well treated and largely normotensive population with coronary disease, but good left-ventricular function, the benefits from ramipril were additive to other proven therapies in normotensive patients and in those with higher baseline blood pressure [8].
• Follow-up study of patients randomly allocated ramipril or placebo for heart failure after acute myocardial infarction: AIRE Extension (AIREX) Study. Acute Infarction Ramipril Efficacy [9].

Chemical compound and disease context of Altace

• Postinfarction survival and inducibility of ventricular arrhythmias in the spontaneously hypertensive rat : effects of ramipril and hydralazine [10].
• Prevention of albuminuria by aminoguanidine or ramipril in streptozotocin-induced diabetic rats is associated with the normalization of glomerular protein kinase C [11].
• Arteriolar wall thickening, capillary rarefaction and interstitial fibrosis in the heart of rats with renal failure:the effects of ramipril, nifedipine and moxonidine [12].
• Nitric oxide and prostaglandins in the prolonged effects of losartan and ramipril in hypertension [13].
• The development of hypertension and left ventricular hypertrophy was prevented by high- but not low-dose ramipril and was not affected by chronic bradykinin B2-receptor blockade [14].

Biological context of Altace

• In this study, we purified brush border membrane vesicles enriched in ACE, and characterized the ACE with regard to (a) its stability in the membrane, (b) substrate hydrolysis kinetics compared with pulmonary endothelial ACE, and (c) pharmacologic interaction with Ramipril [15].
• Thus, a reduction in MVO2 coupled with unchanged total vascular mechanical power suggests improved efficiency of ventriculoarterial coupling with ramipril and with nifedipine in the subset of patients in whom heart rate remained unchanged [16].
• During normoglycemia, the hemodynamic changes induced by ramipril were similar in both genotypes [17].
• During hyperglycemia, the changes induced by ramipril were accentuated in the II genotype group and attenuated dose dependently in the D allele group (treatment-genotype interaction P values for ERPF, 0.018; MAP, 0.018; and total renal resistances, 0.055) [17].
• Effects of ramipril on left ventricular mass and function in cardiovascular patients with controlled blood pressure and with preserved left ventricular ejection fraction: a substudy of the Heart Outcomes Prevention Evaluation (HOPE) Trial [18].

Anatomical context of Altace

• Brush border ACE was inhibited by Ramipril, one of the most specific and potent orally administered ACE inhibitors indicated for hypertension [15].
• The importance of an intact endothelium that continuously generates kinins is supported by observations that basal and ramipril-induced release of kinins and PGI2 is markedly reduced after deendothelialization of isolated hearts [19].
• Aminoguanidine and ramipril, known for their different mechanism of action, seem to prevent diabetes-induced changes in lysosomal processing either through their effects on enzyme activity within the lysosome or through their effects on the trafficking of molecules to and from the lysosome [20].
• In aortas isolated from rats orally treated for 6 weeks with 10 mg/kg ramipril (group 1) or 1 mg/kg ramipril (group 2), this toxic effect of oxidized LDL was also markedly attenuated [21].
• The effects of ramipril on sympathetic nervous system function in older patients with hypertension [22].

Associations of Altace with other chemical compounds

• Renin mRNA levels were reduced to 77 +/- 14% under basal conditions and ramipril- and losartan-induced increases in renin mRNA levels were completely blunted after addition of L-NAME [23].
• METHODS AND RESULTS: Twenty-four hours after DC shock, adult mongrel dogs were assigned to one of three groups: a control group; a group treated with ramipril 10 mg BID; and a group treated with ramipril 10 mg BID along with a continuous subcutaneous infusion of HOE 140, a bradykinin antagonist [24].
• In conclusion: 1-year treatment of NIDDM patients with ramipril or atenolol does not influence metabolic control, the changes in serum lipids were similar [25].
• Sham-operated and subtotally nephrectomized (SNX) 300-g male Sprague-Dawley rats (N = 7 to 11) were left untreated (N = 9) or treated with Ramipril (0.5 mg/kg body wt per day; N = 7), Nifedipine (30 mg/kg body wt per day; N = 9), or Moxonidine (10 mg/kg body wt per day; N = 8) for 8 wk [12].
• We evaluated the effect of ramipril (a pure ACE inhibitor) and AVE7688 (a dual inhibitor of ACE and neutral endopeptidase) on renal accumulation of the advanced glycation end-product (AGE) 3-deoxyglucosone-imidazolone, carboxymethyllysine (CML) and pentosidine, and on clearance of CML in type 2 diabetes [26].

Gene context of Altace

• Furthermore, CsA blunted the increase of renocortical COX-2 expression in response to low salt intake or a combination of low-salt diet with the ACE inhibitor ramipril (10 mg/kg per day), which strongly stimulates renocortical COX-2 expression [27].
• In contrast, ramipril had no effect on cardiac ACE2 mRNA, which remained elevated in all areas of the MI rat heart [28].
• Interestingly, down-regulation of MMP-9 mRNA, protein, and activity was not affected by ramipril, indicating that the protective effect of this compound is not attributable to restoration of MMP-9 in the glomerulus [29].
• For this purpose, male Sprague-Dawley rats were fed a low-salt diet (0.02% wt/wt) with or without additional treatment with the ANG I-converting enzyme (ACE) inhibitor ramipril (10 mg x kg body wt(-1) x day(-1)) for 1 wk, and renocortical renin, COX-2, and nNOS mRNAs were assayed [30].
• CONCLUSIONS: Dual ETA/ETB receptor blockade improves endothelial function and exerts direct vasodilator effects in patients with atherosclerosis, also on treatment with ramipril suggesting that ET receptor blockade may have important therapeutic effects when added to ACE inhibition in these patients [31].

Analytical, diagnostic and therapeutic context of Altace

• Our aim in this study was to assess the long-term (3 years after the AIRE Study closed) magnitude, duration, and reliability of the survival benefits observed after treatment with ramipril (target dose 5 mg twice a day) when compared with placebo [9].
• The increase in left ventricular mass (mean +/- SEM) in the control group was similar to that observed in the CEI-HOE 140 group (+0.73 +/- 0.19 versus +0.75 +/- 0.18 g/kg, P = NS), but both were greater than the change in mass in the ramipril group (-0.48 +/- 0.13 g/kg, P = .004 and P = .0005, respectively) [24].
• The more favorable effects on LV topography of the early use of full-dose ramipril support the results of the major clinical trials, which have demonstrated an early survival benefit of ACE inhibition [32].
• Treatment with ACE inhibitors such as ramipril increases cardiac kinin levels and reduces post-ischemic reperfusion injuries in isolated rat hearts and infarct size in anesthetized animals [19].
• METHODS: We compared the effects of single oral doses of AVE7688 (5 and 25 mg) with those of 10 mg ramipril (R10), a selective ACE inhibitor, in a placebo-controlled crossover study in sodium-depleted normotensive subjects [33].

References