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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, the development of remodeling, left ventricular (LV) dysfunction, and ischemic events, both when administered alone as long-term treatment in patients with impaired LV function and/or heart failure (HF) and as short-term treatment, early after acute myocardial infarction (AMI) and/or HF. The few data available on the use of ACE inhibitors in the elderly after AMI are conflicting. Nothing is known about the effects of ACE inhibitors in elderly postinfarction patients with preserved LV function: these patients have a remarkable medium- to long-term mortality and HF incidence after infarction. The aim of this study is to evaluate, in patients with AMI aged > or =65 years, the effects of Perindopril on the combined outcome of death, hospitalization for HF, and heart remodeling, considered to be a > or =8% increase in LV end-diastolic volume (LVEDV). Secondary objectives include the same factors listed in the primary end points but considered separately. In addition, safety of the drug, ventricular remodeling, and adaptation are being evaluated. A total of 1100 patients with AMI (first episode or reinfarction), aged > or =65 years, and preserved or only moderately depressed LV (LV ejection fraction > or =40%), are to be enrolled and randomly assigned to treatment (8 mg for 12 months of Perindopril or placebo, in double-blind conditions). Clinical assessment is performed at fixed times, and periodic evaluations of (1) ventricular shape, dimensions, and function by quantitative 2-D echocardiography, and (2) heart rate variability and arrhythmias by ambulatory electrocardiographic monitoring are anticipated. The results and conclusions will be available by 2002 year.
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PMID:PREAMI: Perindopril and Remodelling in Elderly with Acute Myocardial Infarction: study rationale and design. 1130 Mar 69

Abundant evidence has accumulated showing that angiotensin converting enzyme (ACE) inhibitors reduce long-term cardiovascular morbidity and mortality rates in patients with heart failure and myocardial infarction. Fewer completed trials have assessed their potential benefits in this regard in hypertensive subjects, but evidence of benefit is beginning to accrue from studies examining patients with hypertension, particularly in the presence of diabetes and after infarction. Ongoing trials of blood pressure (BP) lowering using ACE inhibition fall into three main categories: 1) those comparing ACE inhibitors with older drugs such as diuretics and beta blockers; 2) those examining more aggressive versus less aggressive lowering of BP; and 3) those investigating BP lowering in patients at high risk for a cardiac event. Among those in the last group is the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), which examines the effects of perindopril-based ACE inhibitor therapy in both normotensive and hypertensive patients who have survived a stroke. This trial is particularly important because it serves as a model for studies of BP lowering across a wide range of BP and BP-related conditions.
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PMID:Ongoing trials of angiotensin-converting enzyme inhibition: what they can tell us. 1149 8

Congestive heart failure (CHF) is the most common and lethal consequence of atherosclerotic cardiovascular disease, with a prevalence estimated between 1% and 10%, and very high associated mortality. Preventing the continued progression of established heart failure and improving the prognosis for patients with this disease is difficult, but angiotensin-converting enzyme (ACE) inhibitors have been shown to be effective in reducing mortality in patients with CHF. In a review of the worldwide literature of the efficacy and safety of perindopril erbumine for the treatment of patients with CHF, once-daily treatment with this ACE inhibitor was shown to be effective in patients with CHF of all severities. Its use is associated with a low risk of first-dose hypotension and no unwanted effects on blood pressure in normotensive patients. Perindopril also improves arterial compliance and reverses left ventricular hypertrophy in patients with hypertension. It is well tolerated and has no significant effects on heart rate, indexes of renal function, or plasma lipid profile. It also has no clinically significant interactions with other drugs, including digoxin, likely to be taken by patients with CHF.
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PMID:Perindopril treatment for congestive heart failure. 1159 57

Approximately 25% of US adults have high blood pressure (BP). Selection of effective and safe antihypertensive therapy for these individuals is an important health-care priority. High BP can be treated with a wide range of antihypertensive agents from a number of different classes. These drugs may differ in their suitability for administration to different subpopulations of patients. Results from both clinical trials and postmarketing surveillance indicate that the angiotensin-converting enzyme (ACE) inhibitor perindopril erbumine is safe and well tolerated in a wide range of patients with hypertension. Cough, the most common ACE inhibitor-associated side effect, is also the most common clinical adverse event reported for perindopril, but <2% of perindopril-treated patients discontinue therapy because of cough. Other adverse events often associated with ACE inhibitors, first-dose hypotension and hyperkalemia, appear to occur less often with perindopril than with other agents in this class. The favorable safety profile for perindopril extends to a wide range of patients, including the elderly and those with either heart failure or renal disease. Perindopril has no negative effects on lipids in patients with hyperlipidemia or on glycemic control in patients with type 2 diabetes mellitus, and it reduces proteinuria in patients with renal disease. Perindopril has no known clinically significant drug-drug interactions. Thus, perindopril is a safe BP-lowering agent with documented tolerability in a wide range of patients with hypertension.
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PMID:Safety profile of perindopril. 1159 59

Angiotensin-converting enzyme inhibitors (ACEi) reduce cardiovascular morbidity and mortality by improving coronary perfusion, reducing ventricular hypertrophy and remodeling, and preventing progression of coronary atherosclerosis. However, the cellular mechanisms underlying the beneficial effects of ACEi are not fully understood. We studied the in vivo effects of ACE inhibition with perindopril on cellular expression of ACE, AT(1) receptors and 2 nitric oxide synthase (NOS) isoforms, endothelial (eNOS) and inducible NOS (iNOS), in human blood vessels using quantitative in vitro autoradiography and immunocytochemistry. Seven patients with ischemic heart disease were treated with perindopril (4 mg/d) for up to 5 weeks before elective coronary bypass surgery, whereas controls did not receive the ACEi (n=7). Perindopril decreased plasma ACE by 70% and the plasma angiotensin II to angiotensin I ratio by 57% and reduced vascular ACE to approximately 65% of control levels in both endothelium and adventitia. By contrast, AT(1) receptor binding in vascular smooth muscle cells was increased by 80% in patients treated with perindopril as confirmed by immunocytochemistry. eNOS was expressed primarily in endothelial cells, whereas little iNOS expression occurred in vascular smooth muscle cells of untreated patients. Both eNOS and iNOS expression seemed to increase during perindopril treatment. These results suggest that suppression of angiotensin II formation in the vascular wall and increased expression of eNOS and iNOS during ACE inhibition may be beneficial in reversing endothelial dysfunction in patients with cardiovascular disease. Because vascular AT(1) receptor expression is increased during chronic ACE inhibition, more clinical studies are required to determine whether it is necessary to combine ACE inhibitors and AT(1) receptor antagonists in clinical management of heart failure, coronary heart disease, and hypertension
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PMID:Perindopril alters vascular angiotensin-converting enzyme, AT(1) receptor, and nitric oxide synthase expression in patients with coronary heart disease. 1236 66

Angiotensin converting enzyme (ACE) inhibitors reduce morbidity and mortality in patients with heart failure and are a first-line therapy for chronic heart failure. However, the first-dose may be associated with asymptomatic or symptomatic hypotension. In previous small series with different ACE inhibitors, different blood pressure responses have been reported. We defined hypotension as a fall in mean blood pressure > or = 20 mm Hg and an absolute value of systolic blood pressure < or = 90 mm Hg and diastolic blood pressure <60 mm Hg. We studied the evolution of mean, systolic and diastolic blood pressure after initiation of perindopril and captopril treatments in a multicentre, double-blind, randomised, comparative, prospective study. One hundred seventy-six patients, mean age 64.9+/-12.1 years, 116 men, with symptomatic heart failure, NYHA class II-IV, and a left ventricular ejection fraction <40%, were randomised to receive a single dose of captopril 6.25 mg (n = 85) or perindopril 2 mg, (n = 91). Systolic and diastolic blood pressure were recorded with Dinamap every 15 minutes during a baseline period of 2 hours, every 30 minutes from 2 to 7 hours and at 8 hours after the drug administration. Baseline characteristics of both groups were similar (demography, heart failure aetiology, NYHA class and blood pressure). Throughout the study there were 23 asymptomatic episodes of hypotension in the captopril group and 6 in the perindopril group (p = 0.039). One patient in the captopril group had symptomatic episodes. Mean blood pressure falls were significantly higher in the captopril versus perindopril group at 60 minutes (-4.6 mm Hg vs+0.7 mm Hg; p=0.004), 75 minutes (-4.4 mm Hg vs -1.1 mm Hg; p = 0.042), and 180 minutes (-3.4 mm Hg vs +0.0 mm Hg; p= 0.042). When elderly patients (> or =70 years) were considered the same pattern of response was found. In summary, first-dose hypotension is not negligible on initiation of therapy with ACE inhibitors in heart failure patients with low ejection fraction. Perindopril results in significantly less reduction in blood pressure and a lower incidence of symptomatic or asymptomatic hypotensive episodes and allows a safer start of therapy than captopril in heart failure patients.
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PMID:A comparative study of the first dose hypotensive effects of captopril and perindopril in patients with heart failure. 1191 59

The present study was designed to examine whether the production of aldosterone from the heart is suppressed by angiotensin-converting enzyme (ACE) inhibition in patients with heart failure. Forty-one patients with left ventricular systolic dysfunction were randomly divided into either the perindopril group (n = 21, perindopril 4 mg/day) or the placebo group (n = 20). Plasma levels of aldosterone and ACE activity were measured in the anterior interventricular vein, coronary sinus, and aortic root during cardiac catheterization. The levels of aldosterone as well as ACE activity were significantly higher at the anterior interventricular vein and the coronary sinus than at the aortic root in the placebo group (aldosterone: 92.1 +/- 9.0 vs 70.6 +/- 8.3 pg/ml [p <0.001]; 90.3 +/- 9.2 vs 70.6 +/- 8.3 pg/ml [p <0.001], respectively; ACE activity: 13.6 +/- 0.8 vs 12.2 +/- 0.7 IU/L [p <0.001], 13.4 +/- 0.8 vs 12.2 +/- 0.7 IU/L [p <0.001], respectively). On the other hand, there were no differences in the levels of aldosterone or ACE activity between the anterior interventricular vein and aortic root or between the coronary sinus and aortic root (aldosterone: 68.1 +/- 8.4 vs 69.9 +/- 9.4 pg/ml [p = NS]; 67.3 +/- 8.9 vs 69.9 +/- 9.4 pg/ml [p = NS], respectively; ACE activity: 9.7 +/- 0.8 vs 9.9 +/- 0.8 IU/L [p = NS]; 9.8 +/- 0.8 vs 9.9 +/- 0.8 IU/L, respectively) in the perindopril group. The levels of aldosterone as well as ACE activity were significantly lower at the anterior interventricular vein and coronary sinus in the perindopril group than in the placebo group. The difference in the level of aldosterone between the anterior interventricular vein and aortic root (Delta aldosterone [anterior interventricular vein - aortic root]) had a significant positive correlation with that of ACE activity (Delta ACE [anterior interventricular vein - aortic root]) (r = 0.536, p <0.001), whereas ACE activity in the aortic root had no significant correlation with either the aldosterone levels in the aortic root or Delta aldosterone (anterior interventricular vein - aortic root). Perindopril suppressed cardiac aldosterone production by mainly suppressing cardiac ACE activity in patients with heart failure. Thus, aldosterone production is activated in the failing ventricle and is suppressed by perindopril mainly via the suppression of cardiac ACE activity in patients with heart failure.
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PMID:Effects of perindopril on aldosterone production in the failing human heart. 1200 75

Perindopril is a long-acting ACE inhibitor, acting through its only active metabolite perindoprilat. It inhibits the renin-angiotensin system by preventing both the conversion of angiotensin I to angiotensin II and the degradation of bradykinin, thereby reducing the vasoconstriction and left ventricular remodelling characteristic of heart failure. Perindopril 4mg significantly improved a range of haemodynamic parameters in single-dose and long-term (8 weeks and 3 months) studies involving patients with congestive heart failure (CHF), with little or no effect on blood pressure or heart rate. In randomised, double-blind, placebo-controlled clinical trials conducted over 3 months and a large noncomparative study (up to 30 months), perindopril 4mg once daily significantly increased exercise tolerance and reduced symptoms of heart failure in patients with mild to moderate CHF. Perindopril 4mg once daily is generally well tolerated in patients with mild to moderate CHF. In a large noncomparative study the most commonly reported adverse clinical event was cough, which led to 2.8% of patients discontinuing treatment. In short-term comparative trials there was a significantly lower incidence of first-dose hypotension following the recommended starting dose of perindopril 2mg than after the equivalent starting doses of captopril, enalapril and lisinopril.
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PMID:Perindopril: in congestive heart failure. 1207 91

Recently, we have demonstrated that heart failure in rats is associated with a myopathy altering energy metabolism in different muscles, but the origin of this myopathy is still unknown. Here, we studied the possible involvement of increased angiotensin II (Ang II) by treatment with perindopril, an inhibitor of angiotensin-converting enzyme (ACE). The beneficial effects of ACE inhibition could result either from vasodilatation-induced cardiac unloading or from inhibition of the direct angiotensin action on the muscle cells. The model of aortic banding with persisting left ventricular (LV) overload where the cardiac unloading does not occur allows to distinguish between the two effects of ACE inhibition. Four months after aortic clipping (just before the treatment), echocardiographic study showed an impairment of the systolic function (decrease of the LV shortening by 30% and ejection fraction by 21%). Ten-week treatment with perindopril dramatically decreased Ang II plasma level but did not reduce LV hypertrophy though a significant decrease in right ventricular (RV) hypertrophy occurred. Perindopril did not improve alterations in activities of energy metabolism enzymes (creatine kinase, citrate synthase, cytochrome c oxidase, lactate dehydrogenase) either in ventricular or in skeletal (gastrocnemius) muscle. Similarly, ACE inhibition did not improve the main parameters of mitochondrial respiration in permeabilized muscle fibers. These data suggest that the generalized metabolic myopathy induced by the hemodynamic abnormalities conditioned by the continuous LV overload (aorta clipping) does not result from the increase in Ang II level per se. Correction of hemodynamic parameters and LV unloading seem to be the prerequisite for the improvement of muscle energy metabolism abnormalities.
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PMID:Does angiotensin-converting enzyme inhibition improve the energetic status of cardiac and skeletal muscles in heart failure induced by aortic stenosis in rats? 1268 19

The multicentre placebo-controlled double-blind "EUropean trial on Reduction Of cardiac events with Perindopril in patients with stable coronary Artery disease" (EUROPA) assessed whether the angiotensin-converting-enzyme inhibitor perindopril reduces cardiovascular risk in a population with stable coronary heart disease and no apparent heart failure, whatever the associated cardiovascular risk. Patients were randomly assigned perindopril 8 mg once daily (n = 6110) or matching placebo (n = 6108). After a mean follow-up of 4.2 years, a relative risk reduction of 20% (95% CI 9-29, p = 0.0003) was observed in the combined primary endpoint (cardiovascular death, myocardial infarction, or cardiac arrest) in the group treated with perindopril as compared to placebo. About 50 patients needed to be treated for a period of 4 years to prevent one major cardiovascular event. This benefit was consistent in all predefined subgroups. According to these results, treatment with perindopril, on top of other preventive medications, should be considered in all patients with stable coronary heart disease.
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PMID:[Clinical study of the month. The EUROPA study: cardiovascular protection with perindopril in patients with stable coronary heart disease]. 1474 2


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