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in the main study, ONTARGET, a double-blind, double-dummy, randomised controlled trial, the effects on cardiovascular outcomes of standard doses of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), an angiotensin-receptor blocker (telmisartan), and a combination of the drugs were evaluated in 25 620 participants. In the parallel TRANSCEND trial, the effects of telmisartan were compared with those of placebo in 5926 participants intolerant to ACE inhibitors. Secondary outcomes included cognitive impairment (defined by investigator-reported diagnosis of dementia or significant cognitive dysfunction, or a score of ≤ 23 on the Mini-Mental State Examination [MMSE]) and cognitive decline (a decrease of ≤ 3 points on the MMSE from baseline during follow-up). Analyses were by intention to treat. We pooled data from these studies to identify baseline predictors of cognitive impairment and its frequency according to mean systolic blood pressure during follow-up. These studies were registered with ClinicalTrials.gov, number NCT00153101.
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UK population using 1998 government actuary department data.
We recorded radial pressure pulse waveforms, using a commercially available system, in 30 subjects with >or=1 coronary risk factor in an acute study of ramipril at 10 mg and atenolol at 100 mg. Directly recorded radial and derived aortic pressure pulse waveforms were examined individually and were ensemble-averaged, and the difference between radial and aortic pressure responses was examined.
Objective To compare 1-year treatment adherence of ramipril + amlodipine and ramipril +hydroclorothiazide fixed-dose combination therapies in patients with hypertension. Methods Data were extracted from the database of the National Health Insurance Fund of Hungary. Treatment adherence was modelled using survival analysis. Results At 2 months after initiation of treatment, 42% of patients using ramipril +hydrochlorothiazide ( n = 28,800) had discontinued treatment, compared with 0% of patients using ramipril + amlodipine ( n = 10,295). At 1 year, treatment adherence was 29% in the ramipril + hydrochlorothiazide group and 54% in the ramipril + amlodipine group. The hazard ratio for discontinuing ramipril + hydrochlorothiazide vs ramipril + amlodipine was 2.318 (95% confidence intervals 2.246, 2.392). Conclusion Ramipril + amlodipine had significantly higher 1-year treatment adherence than ramipril + hydrochlorothiazide in patients with hypertension.
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We undertook a multicentre, randomised controlled trial of patients with non-diabetic proteinuric nephropathies receiving background treatment with the ACE inhibitor ramipril (2.5-5 mg/day). We randomly assigned participants either conventional (diastolic <90 mm Hg; n=169) or intensified (systolic/diastolic <130/80 mm Hg; n=169) blood-pressure control. To achieve the intensified blood-pressure level, patients received add-on therapy with the dihydropyridine calcium-channel blocker felodipine (5-10 mg/day). The primary outcome measure was time to end-stage renal disease over 36 months' follow-up, and analysis was by intention to treat.
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Among patients with intermittent claudication, 24-week treatment with ramipril resulted in significant increases in pain-free and maximum treadmill walking times compared with placebo. This was associated with a significant increase in the physical functioning component of the SF-36 score.
In patients with hypertension and diabetes, atherothrombosis is a leading cause of morbidity and mortality, and there is now compelling evidence demonstrating that lowering elevated blood pressure (BP) is one of the most beneficial aims of therapy in this high-risk population. Indeed, major international guidelines have set a target BP goal of 130/80 mmHg in high-risk patients and recommend combination treatment with two or more drug classes to help achieve this objective. Manidipine plus delapril is a fixed-dose combination of a third-generation dihydropyridine calcium antagonist and an angiotensin-converting enzyme inhibitor, which is effective in mild-to-moderately hypertensive patients with an inadequate response to monotherapy. It is also effective in the long-term (50 weeks) management of essential hypertension. Comparative studies have demonstrated that manidipine plus delapril is as effective as enalapril plus hydrochlorothiazide (HCTZ) in patients with hypertension that is unresponsive to monotherapy, and as effective as ramipril plus HCTZ, valsartan plus HCTZ, irbesartan plus HCTZ and olmesartan plus HCTZ in patients with essential hypertension and Type 2 diabetes. In addition, manidipine plus delapril exhibited renoprotective effects in normotensive Type 2 diabetic patients, and improved fibrinolytic function (significantly more than irbesartan plus HCTZ) in hypertensive patients with Type 2 diabetes. Manidipine 10 mg plus delapril 30 mg once daily was generally well tolerated, with no unexpected adverse effects and evidence of a low incidence of ankle edema. Thus, manidipine plus delapril is a fixed-dose combination treatment that significantly reduces elevated BP with once-daily administration. It is well tolerated and has ancillary properties, such as nephroprotective activity and improvement of fibrinolytic balance, which may help reduce cardiovascular morbidity and mortality, particularly in high-risk patients, such as those with Type 2 diabetes mellitus.
A metabolomic approach based on liquid chromatography coupled with quadrupole time-of-flight detector (LC-Q-TOF/MS) was developed to investigate the therapeutic mechanism of a traditional Chinese medicine (TCM) formula Shexiang Baoxin Pill (SBP) and a multi-component medicine polypill (consisting of simvastatin (Sim), atenolol (Ate), ramipril (Ram), hydrochlorthiazide (Hyd) and aspirin (Asp), named as SARHA). Twenty-seven biomarkers were identified in the serum of MI rats. Thirteen related pathways and 4 main pathological processes including oxidative injury, energy metabolism dysfunction, amino acid metabolism dysfunction and inflammation are involved in MI development. Our study revealed that SBP showed better therapeutic effectiveness than the polypill on MI through regulation of the energy metabolism dysfunction, oxidative injury and inflammation. The combination agent polypill had only certain therapeutic effects on inhibiting oxidative injury and inflammation induced by MI. The reverse effect of the polypill on biomarkers related to MI was much better than mono-therapy groups.
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One hundred and six patients were evaluable at the end of the study period and 21 different genotypes were observed among them. Seven of them were classified as responders after 8 weeks and at the end of 12 weeks, an additional 77 (72.64%) were deemed responders. 19/22 non-responders were treated with combination therapy and 7/19 (36.84%) showed a response to the same. There was a significant difference between the proportions of responders and non-responders among the genotypes of the ADD1 and β1-ADR genes (P=0.005 and 0.003, respectively). The best predictors of response to Ramipril 5 mg daily were the II/GG/SS, II/TG/SS, II/GG/SG, ID/GG/SS, ID/GG/SG and ID/TT/SS and DD/GG/SS; II/GG/GG, II/TT/SG, ID/TG/SG, ID/TT/SG, DD/GG/SG and DD/GG/GG were moderately predictive and II/TT/SS, II/TG/GG, ID/TG/GG, DD/TG/SG and DD/TG/GG were poorly predictive of response.