Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
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Perindopril is a long-acting, once-daily lipophilic angiotensin-converting enzyme inhibitor with high tissue angiotensin-converting enzyme affinity, lowering angiotensin II and potentiating bradykinin. Its efficacy, safety and tolerability are well established in the treatment of hypertension and heart failure. Moreover, large morbidity-mortality trials, such as the EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) and Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), have shown that antihypertensive treatment with perindopril reduces and prevents cardiovascular disease in a large range of patients with vascular diseases, whether hypertensive or not. Thus, the outcome of these and other trials support the concept of cardiovascular protective properties of angiotensin-converting enzyme inhibition with perindopril in addition to the obvious blood-pressure-lowering effect. Considering its properties and the gathered clinical evidence on efficacy and tolerability, perindopril fulfils the criteria of the latest guidelines for hypertension and cardiovascular disease management and should therefore be considered as a first-line antihypertensive agent, forming a consistent part of the comprehensive strategy against hypertension and related cardiovascular complications.
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PMID:Angiotensin-converting enzyme inhibition in cardiovascular disease: evidence with perindopril. 1572 72

Angiotensin-converting enzyme inhibitors are widely-prescribed drugs for hypertension and are supported by clinical trials in which they reduce cardiovascular events. In the high-risk patients in the Heart Outcomes Prevention Evaluation, the Perindopril Protection Against Recurrent Stroke Study, and European Trial of Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease, ramipril and perindopril showed impressive benefits. One reason trandolapril did somewhat less well in the Prevention of Events With Angiotensin-Converting Enzyme Inhibition trial may be that its patients were very well treated with other effective modalities. In the Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial, lisinopril-treated patients had a slightly lower incidence of myocardial infarction, despite much poorer control of blood pressure, perhaps because a second-line diuretic was prohibited by protocol. Although angiotensin-converting enzyme inhibitors can cause cough and angioedema (more common among blacks), angiotensin receptor blockers are currently more expensive and have fewer outcome trials to support their use.
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PMID:Cardiovascular events in hypertension trials of Angiotensin-converting enzyme inhibitors. 1610 30

Perindopril is a long-acting, once-daily lipophilic angiotensin-converting enzyme inhibitor with high tissue angiotensin-converting enzyme affinity, lowering angiotensin II and potentiating bradykinin. Its efficacy, safety, and tolerability are well established in the treatment of hypertension and heart failure. Moreover, large morbidity-mortality trials, such as the EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) and Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), have shown that antihypertensive treatment with perindopril reduces and prevents cardiovascular disease in a large range of patients with vascular diseases, whether or not they are hypertensive. Thus, the outcomes of these and other trials support the concept of cardiovascular protective properties of angiotensin-converting enzyme inhibition with perindopril in addition to the obvious blood-pressure-lowering effect. Considering its properties and the clinical evidence on efficacy and tolerability that has been gathered, perindopril fulfils the criteria of the latest guidelines for hypertension and cardiovascular disease management and should therefore be considered as a first-line antihypertensive agent, forming a consistent part of the comprehensive strategy against hypertension and related cardiovascular complications.
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PMID:Specific properties and effect of perindopril in controlling the renin-angiotensin system. 1612 51

Structural and functional changes in large and small arteries in hypertension, even at early stages, may affect one or several end organs such as the brain, heart, and kidneys, contributing to cardiovascular morbidity and mortality. Therefore, modern treatment strategies should not only target blood pressure (BP) reduction but also normalize vascular structure and function. The purpose of this article is to review the large body of evidence, from randomized double-blind clinical trials, that has been gathered in regard to the angiotensin-converting enzyme (ACE) inhibitor perindopril, demonstrating its efficacy in reducing BP, reversing abnormalities of vascular structure and function in patients with essential hypertension, and ultimately preventing cardiovascular events. At the site of small resistance arteries, long-term treatment with perindopril, but not atenolol, reduced arterial wall hypertrophy for a given BP reduction. The improvement in small artery function in response to structural changes is exemplified at the site of the coronary circulation. Perindopril increased coronary blood flow and coronary reserve, in parallel with the regression of periarteriolar and interstitial collagen of coronary arterioles. At the site of large arteries, long-term treatment with perindopril reduced carotid and radial artery wall hypertrophy, and reduced carotid artery internal diameter. In response to these structural changes, large artery function improved at the site of the carotid and brachial arteries, showing a higher arterial distensibility, and at the site of the coronary circulation, showing a normalized arterial dilation in response to a cold pressor test or an increase in blood flow. Moreover, in patients with end-stage renal disease, perindopril decreased pulse wave velocity independently of BP changes, resulting in a highly significant relative risk reduction in all-cause and cardiovascular mortality. The multifactorial antiatherosclerotic profile of perindopril suggests a beneficial effect not only in patients with uncomplicated hypertension but also in patients with established coronary heart disease or previous stroke, as exemplified by the EUropean trial on Reduction Of coronary events with Perindopril in stable coronary Artery disease (EUROPA) and the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS).
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PMID:Evidence for benefits of perindopril in hypertension and its complications. 1612 52

Antihypertensive therapy based on the angiotensin-converting enzyme (ACE) inhibitor perindopril reduced the incidence of recurrent stroke in the Perindopril Protection against Recurrent Stroke Study (PROGRESS). The present study assessed the effect of perindopril on the 24-h blood pressure (BP) in hypertensive patients with lacunar infarction using ambulatory BP monitoring (ABPM). There was a 4-week observation period, a 4-week treatment period 1 (perindopril at 2 mg/day), and a 4-week treatment period 2 (perindopril at 4 mg/day). Twenty-seven hypertensive patients with lacunar infarction (10 dippers and 17 non-dippers) were enrolled. The average 24-h BP values were significantly decreased after both treatment periods. When the patients were divided into dippers and non-dippers, perindopril exhibited a different BP-lowering effect in the groups with these two circadian BP patterns. In dippers, daytime BP was significantly decreased, whereas nighttime BP was not, so an excessive fall of nighttime BP was not observed. In non-dippers, both daytime and nighttime BP were decreased, with a stronger BP-lowering effect at night. There was a significant inverse correlation between the magnitude of the change in nighttime BP and the night/day ratio. These results suggested that perindopril could induce a sustained decrease of the 24-h BP in patients with lacunar infarction. In particular, a more pronounced nighttime BP-lowering effect was observed in non-dippers. As the incidence of non-dippers is reported to be high among patients with cerebrovascular disease, better nighttime BP control by perindopril might have helped to improve the outcome of such patients in PROGRESS.
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PMID:Effect of the angiotensin-converting enzyme inhibitor perindopril on 24-hour blood pressure in patients with lacunar infarction: comparison between dippers and non-dippers. 1633 85

Perindopril is a third-generation ACE inhibitor that is characterised as a small, lipophilic molecule with a therapeutically active carboxyl side group. These and other features combine to make this a unique member of a very well-established class of drugs that have proven efficacy in a wide range of cardiovascular diseases. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) demonstrated benefit in the secondary prevention of patients with stroke, whereas the Perindopril and Remodelling in Elderly with Acute Myocardial Infarction (PREAMI) trial supports extended routine use after myocardial infarction. The most recent evidence from the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) show that perindopril is able to improve the prognosis of patients with a relatively low global cardiovascular risk, denoted either by the presence of stable coronary artery disease or of essential hypertension in conjunction with at least three other risk factors. The fact that major relative risk reductions have been reported for these two studies is matched by the significance of the findings to modern clinical practice. Both studies were conducted in the context of advance concomitant care that is typically better in clinical trials than in routine practice. In particular, the benefits observed were seen to be of a similar magnitude, and also independent of those resulting from statin therapy. Of particular interest is the likely complimentary action of these treatment strategies with regard to the stabilisation of atheromatous plaques. Perindopril is a well-established drug, the full value of which is only now becoming fully apparent.
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PMID:Perindopril. 1637 Sep 23

Chronic kidney disease (CKD) is associated with a high risk of cardiovascular disease, but evidence regarding the effectiveness of interventions to reduce that risk is lacking. The Perindopril Protection against Recurrent Stroke Study (PROGRESS) study enrolled 6105 participants with cerebrovascular disease and randomly allocated them to perindopril-based blood pressure-lowering therapy or placebo. Individuals with CKD were at approximately 1.5-fold greater risk of major vascular events, stroke, and coronary heart disease, and were more than twice as likely to die (all P< or =0.002). Perindopril-based treatment reduced the risk of major vascular events by 30% and stroke by 35% among subjects with CKD, and the absolute effects of treatment were 1.7-fold greater for those with CKD than for those without. Considering patients with CKD and a history of cerebrovascular disease, perindopril prevented one stroke or other cardiovascular event among every 11 patients treated over five years. In conclusion, kidney function should be considered when determining the need for blood pressure lowering therapy in patients with cerebrovascular disease.
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PMID:Chronic kidney disease, cardiovascular events, and the effects of perindopril-based blood pressure lowering: data from the PROGRESS study. 1780 73

Stroke is one of the leading causes of disability and death worldwide and is a more common cause of cardiovascular morbidity and mortality than myocardial infarction among patients with hypertension. Identifying and modifying key risk factors is crucial to reduce morbidity and mortality from stroke. Hypertension is the most important modifiable risk factor for ischemic stroke, and antihypertensive treatment is of paramount importance to reduce the incidence of stroke mortality and morbidity. Perindopril is a third-generation long acting, once-daily lipophilic angiotensin-converting enzyme inhibitor with high tissue angiotensin-converting enzyme affinity, lowering angiotensin II and potentiating bradykinin. Its efficacy, safety and tolerability are well established in the treatment of hypertension and heart failure. The purpose of this article is to review the evidence from clinical trials as well as from recent patents that has been gathered in regard to perindopril, demonstrating not only its efficacy in reducing blood pressure, but also to other cardiovascular protective properties that act in addition to the obvious blood-pressure-lowering effect in the prevention of stroke in patients with essential hypertension, with particular attention paid to the results from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS).
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PMID:Role of perindopril in the prevention of stroke. 1822 Oct 93

Recent epidemiological studies have shown a J-shaped association between the risk of stroke and systolic blood pressure (SBP) levels in people with chronic kidney disease (CKD). The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, placebo-controlled trial demonstrating that perindopril-based blood pressure (BP) lowering reduced the risk of stroke in 6105 participants with prior cerebrovascular disease. We estimated the effects of therapy on the risk of recurrent stroke in 1757 of these participants with stage 3 or greater CKD according to baseline BP and the relationship between achieved follow-up BP and the risk of stroke. Active therapy produced comparable and significant reductions in the risk of stroke across all baseline SBP levels. The age- and gender-adjusted incidence of stroke increased significantly in a log-linear relationship for achieved SBP levels and strokes per 1000 person-years. This association persisted after adjusting for potential confounding factors. We found that perindopril-based BP lowering effectively prevented recurrent stroke in people with CKD, across a wide range of BP levels, without evidence of an increased risk of stroke in people with low BP levels.
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PMID:Lower blood pressure and risk of recurrent stroke in patients with chronic kidney disease: PROGRESS trial. 1827 59

Dementia is a common and serious health problem that affects 33 million persons globally. With the increase in life expectancy, the prevalence of dementia is expected to reach 81.1 million persons by 2040. Dementia impairs quality of life and is associated with profound disease burden, morbidity, and mortality in both patients and caregivers. Therefore, identifying measures to prevent dementia is a research priority. Midlife hypertension has increased the risk of dementia in large prospective cohort studies. Researchers have investigated the blood pressure-lowering effects of antihypertensive drugs on the incidence of dementia. Although prospective cohort studies have shown that use of antihypertensive drugs was associated with a reduced rate of cognitive impairment and dementia, these studies were not placebo controlled. Four randomized, placebo-controlled studies-the Systolic Hypertension in Europe (Syst-Eur) study, Study on Cognition and Prognosis in the Elderly (SCOPE), Systolic Hypertension in the Elderly Program (SHEP), and Perindopril Protection Against Recurrent Stroke Study (PROGRESS)-investigated the effects of antihypertensive agents on the incidence of dementia. The Syst-Eur study found that active treatment with nitrendipine, enalapril, and/or hydrochlorothiazide reduced the rate of dementia by 50% compared with placebo (p=0.05). The PROGRESS study showed that active treatment with perindopril and indapamide was associated with reduced cognitive decline compared with placebo (risk ratio 19%, p=0.01). In contrast, the SCOPE study (candesartan or hydrochlorothiazide vs placebo) and the SHEP trial (chlorthalidone, atenolol, or reserpine vs placebo) found no significant difference between the active treatment and placebo groups on the incidence of dementia. Some researchers have suggested that certain antihypertensive drug classes, such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, diuretics, and calcium channel blockers, may offer benefit in reducing dementia risk in addition to their blood pressure-lowering effect. Further prospective randomized studies comparing different antihypertensive classes are needed to provide more evidence regarding the effects of antihypertensive drugs on dementia risk and to determine whether certain antihypertensive classes provide greater benefits than others.
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PMID:Effects of antihypertensive drug treatment on the risk of dementia and cognitive impairment. 1829 16


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