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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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
Hypertension 2002 Feb
PMID:Perindopril alters vascular angiotensin-converting enzyme, AT(1) receptor, and nitric oxide synthase expression in patients with coronary heart disease. 1236 66

Blood pressure levels are strongly predictive of the risks of first-ever and recurrent stroke. The benefits of blood pressure-lowering therapy for the prevention of fatal and non-fatal stroke in middle-aged individuals are well established. However, until recently, there has been uncertainty about the consistency of such benefits across different patient groups and in particular, for older people and in those with a history of stroke. This paper discusses the evidence surrounding the effectiveness of blood pressure-lowering therapy, specifically in older patients with a history of stroke, with particular attention paid to the results from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). PROGRESS was a randomised, double-blind, placebo-controlled trial of 6105 individuals with a history of cerebrovascular disease recruited from 172 hospital outpatient clinics in ten countries. Participants (mean age 64 years; range 26-91 years) were randomly assigned to receive active treatment with an ACE inhibitor-based blood pressure-lowering regimen (perindopril) with or without addition of the diuretic indapamide, or matched placebo. At the end of follow up (mean of 4 years), active treatment reduced the incidence of total stroke by 28% (95% CI 17-38%) and the rate of major vascular events by 26% (95% CI 16-34%). Importantly, benefits of treatment were consistent across key patient subgroups, including those with and without hypertension, patients who were Asian and non-Asian, and for both ischaemic and haemorrhagic strokes subtypes. Current evidence is now strong for clinicians to consider blood pressure-lowering therapy as pivotal in the prevention of stroke, especially in patients with a known history of cerebrovascular disease (and vascular disease, in general), irrespective of blood pressure levels, as soon as patients are clinically stable after an acute stroke or other vascular event. Additional age-specific analyses of the PROGRESS data, together with those from other completed trials, will provide more reliable information about the size of the benefits of blood pressure-lowering therapy, specifically for different age groups, and particularly in the oldest old (those aged >80 years). In the meantime though, an ACE inhibitor plus diuretic treatment regimen that maximises the degree of blood pressure reduction has a good safety profile and is an effective treatment that should be considered in all patients with stroke, including the elderly.
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PMID:The Perindopril Protection Against Recurrent Stroke Study (PROGRESS): clinical implications for older patients with cerebrovascular disease. 1264 80

Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.
Hypertension 2003 May
PMID:Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER. 1265 6

To compare the effect of antihypertensive drugs on endothelium-dependent vasodilation in the peripheral conduit arteries of patients with essential hypertension, in a prospective, randomized, parallel group study, endothelial function was assessed in 168 hypertensive patients before and after 6-month treatment with randomly assigned nifedipine GITS (30 to 60 mg, n=28), amlodipine (5 to 10 mg, n=28), atenolol (50 to 100 mg, n=29), nebivolol (5 to 10 mg, n=28), telmisartan (80 to 160 mg, n=29), and perindopril (2 to 4 mg, n=28). If necessary, hydrochlorothiazide (25 mg) was added to each compound. We evaluated brachial artery flow-mediated, endothelium-dependent dilation (high-resolution ultrasound) compared with endothelium-independent response to glyceryl trinitrate (25 microg/s). Brachial artery diameter was measured by automatic computerized analysis. Forty healthy subjects were evaluated as a control group. Oxidative stress production was evaluated by measuring plasma malondialdehyde and plasma lipoperoxides; plasma antioxidant capacity was assessed as ferric-reducing antioxidant power. Hypertensive patients showed a significantly (P<0.01) lower flow-mediated dilation (5.2+/-1.9%) as compared with healthy control subjects (7.1+/-2.6%). Response to glyceryl trinitrate was similar in control subjects and patients. At baseline, blood pressure, diameter, flow-mediated dilation, and response to glyceryl trinitrate were similar in the different treatment groups. All treatments similarly reduced blood pressure, but only perindopril increased flow mediated dilation (from 5.1+/-2 to 6.4+/-2.4%; P<0.01) without modifying the response to glyceryl trinitrate. Perindopril but also telmisartan nifedipine and amlodipine reduced oxidative stress and increased plasma antioxidant capacity. In patients with essential hypertension, ACE inhibitors appear to be the only compounds able to improve conduit artery endothelium-dependent vasodilation.
Hypertension 2003 Jun
PMID:Different effect of antihypertensive drugs on conduit artery endothelial function. 1271 41

The risk of stroke is strongly and persistently related to the usual level of both systolic blood pressure (SBP) and diastolic blood pressure (DBP). This relation holds for primary and secondary stroke, both ischemic and hemorrhagic. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) has now provided definitive evidence that lowering the blood pressure of patients with preexisting cerebrovascular disease (prior stroke or transient ischemic attack [TIA]) also reduces the incidence of secondary stroke. PROGRESS showed that a flexible blood pressure-lowering regimen involving an angiotensin-converting enzyme inhibitor (perindopril) and a diuretic (indapamide) reduces the incidence of stroke, major coronary events, and major vascular events by 28%, 26%, and 26%, respectively. These benefits were associated with an average reduction of 9.0 mm Hg (SBP) and 4.0 mm Hg (DBP). The 28% reduction in stroke incidence translated into a 24% reduction in ischemic stroke and a 50% reduction in hemorrhagic stroke. Combination therapy with perindopril and indapamide decreased blood pressure more effectively than did perindopril monotherapy (mean reduction of 12.3 mm Hg [SBP] and 5.0 mm Hg [DBP] vs 4.9 mm Hg [SBP] and 2.8 mm Hg [DBP], respectively) and was equally effective in reducing stroke risk in patients with and without hypertension. In conclusion, blood pressure-lowering therapy is now established as the most important measure for primary and secondary stroke prevention. Results of PROGRESS suggest that antihypertensive treatment with a combination of perindopril plus indapamide should now be routinely considered for all patients with previous stroke or TIA.
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PMID:Trials on blood pressure-lowering and secondary stroke prevention. 1278 2

High blood pressure is a known risk factor for stroke and dementia. However, very little is known about the prevention of dementia by lowering blood pressure. Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) was designed to determine the effects of an angiotensin-converting enzyme (ACE) inhibitor-based blood pressure-lowering regimen on the risk of stroke among individuals with a prior stroke or transient ischaemic attack (TIA). One of the important aims of the study was to test the hypothesis that treatment would reduce the incidence of dementia and cognitive decline. A total of 6105 patients were randomized to active treatment or placebo. Active treatment comprised perindopril for all participants, and indapamide for those with neither a specific indication for, nor a contraindication to, a diuretic. Dementia was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Cognitive decline was defined as a drop of 3 points or more on the Mini-Mental State Examination (MMSE) between baseline and final follow-up. During a median follow-up of 3.9 years, dementia was diagnosed in 410 patients and cognitive decline in 610. Active treatment reduced the risk of cognitive decline (risk reduction [RR] 19%; 95% confidence interval [CI], 4-32; P = 0.01] but there was no clear reduction in the risk of dementia (RR, 12%; 95% CI, -8-28; P = 0.2]). The RR for cognitive outcomes preceded by a recurrent stroke was 34% (95% CI, 3-55; P = 0.03) for dementia and 45% (95% CI, 21-61; P = <0.001) for cognitive decline. Among individuals with a history of stroke or TIA, blood pressure-lowering treatment reduced the risk of cognitive decline by about one fifth. Cognitive decline and dementia associated with recurrent stroke during follow-up were each reduced by between one third and one half. These findings provide further support for the recommendation that blood pressure lowering with perindopril and indapamide be considered for all patients with cerebrovascular disease.
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PMID:Vascular factors and cognition: toward a prevention of dementia? 1295 51

The authors evaluated, in a community-based open-label trial, the effectiveness and safety of perindopril in 13,220 US hypertensive patients and studied how physicians adhere to hypertension treatment guidelines. Patients received perindopril 4 mg q.d. for 6 weeks. Based on physicians perception of blood pressure response, the patient was either maintained on 4 mg or the dose was increased to 8 mg for an additional 6 weeks. From baseline to week 12, the mean sitting blood pressure significantly declined from 156.9/94.5 mm Hg to 139.2/84.0 mm Hg. Further dose titration resulted in a clinically significant reduction in blood pressure in all patients with inadequate response on 4 mg at week 6. Blood pressure control (<140/<90 mm Hg) was achieved at 12 weeks in 48.8% patients. The subpopulation analyses demonstrated that perindopril monotherapy was effective in both men and women, in patients of all ethnicities, and in patients <65 and > or =65 years of age. Perindopril was safe and well tolerated in all hypertensive subgroups including high-risk patients. Physicians were more attuned to controlling diastolic than systolic blood pressure, and their adherence to the treatment guidelines was found to be not optimal.
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PMID:Antihypertensive utility of perindopril in a large, general practice-based clinical trial. 1472 19

High blood pressure is a major risk factor for stroke and is also closely correlated with cognitive decline and dementia. Indeed, most longitudinal studies showed that cognitive functioning is often inversely proportional to blood pressure values measured 15 or 20 years previously. Because of the aging of the population, the frequency of stroke and dementia will dramatically increase in the coming years. Therefore, the prevention of cerebrovascular and cognitive disorders represents a major challenge. Antihypertensive drugs have shown clinical benefits in both primary and secondary prevention of strokes. Consensus is generally that blood-pressure lowering represents the major determinant of the benefit conferred by the antihypertensive treatment for stroke prevention; however, recent studies have suggested some differences between classes of antihypertensive drugs. The results of therapeutic trials (Systolic Hypertension in Europe, Perindopril Protection Against Recurrent Stroke Study [PROGRESS]) open the way to the prevention of dementia (vascular or Alzheimer's type) by antihypertensive treatments. These two studies suggest different mechanisms for the prevention of cognitive decline using antihypertensive drugs. In this context, reduced incidence of dementia should be the primary outcome of future trials comparing different classes of antihypertensive drugs.
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PMID:Prevention of dementia and cerebroprotection with antihypertensive drugs. 1512 72


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