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Am Heart J. 2007 Apr;153(4):629-35.
Fox KM, Bertrand ME, Remme WJ, Ferrari R, Simoons ML, Deckers JW; EUROPA Investigators.
Cardiology Department, Royal Brompton Hospital, Sydney Street, London, UK.
Efficacy of perindopril in reducing risk of cardiac events in patients with revascularized coronary artery disease.
Perindopril can reduce the risk of cardiac events in patients with revascularized coronary artery disease.
BACKGROUND: The aim of the study was to assess the effect on cardiac events of adding perindopril 8 mg once daily
to standard preventive therapy in the subgroup of EUROPA patients with previous revascularization and without
previous myocardial infarction (MI). METHODS: We conducted a subgroup analysis of the EUROPA study patients
according to their revascularization and previous MI history. Among the 12,218 patients of EUROPA, we identified
6709 (54.9%) patients who had a previous revascularization. Approximately equal proportions had undergone
percutaneous coronary intervention (3122) or coronary artery bypass grafting (3136). Of the revascularized
patients, 3047 (24.9%) patients had not experienced a previous MI. RESULTS: Out of the 6709 revascularized
patients, 3340 were treated with perindopril and 3369 with placebo. Baseline characteristics were similar to the
whole EUROPA population in terms of demographics, medical history, physical examination (heart rate, blood
pressure), and medications at screening. The mean patient age was 60 years, and 85% were men. The relative risk
reduction with perindopril 8 mg was 17.3% (95% CI 1.3%-30.8%, P = .035) for the composite primary end point of
cardiovascular death, nonfatal MI, and resuscitated cardiac arrest and was 23% (95% CI 4.9%-37.6%, P = .015) for
fatal and nonfatal MI. In the 3047 revascularized patients without a history of MI, perindopril was associated with
a relative risk reduction of 31.7% for fatal and nonfatal MI (95% CI 4.4%-51.2%, P = .026). CONCLUSION: Perindopril
8 mg daily is beneficial for primary and secondary prevention of cardiac events in patients with coronary artery
disease without clinical evidence of heart failure including those with previous revascularization.
Vasc Health Risk Manag. 2006;2(2):117-24.
Campbell DJ.
Hospital, Fitzroy, Victoria, Australia.
A review of Perindopril in the reduction of cardiovascular events.
Perindopril is capable to reduce cardiovascular events: a review BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEI) have a well-established role in the prevention of
cardiovascular events in hypertension, left ventricular dysfunction, and heart failure. More recently, ACEI have
been shown to prevent cardiovascular events in individuals with increased cardiovascular risk, where hypertension,
left ventricular dysfunction, or heart failure was not the primary indication for ACEI therapy. OBJECTIVE: To
review studies of the effects of the ACEI perindopril on cardiovascular events. METHOD: The EUROPA (European Trial
on Reduction of Cardiac Events with Perindopril in Patients with Stable Coronary Artery Disease Study), PROGRESS
(Perindopril Protection Against Recurrent Stroke Study), and ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes
Trial--Blood Pressure Lowering Arm) trials are reviewed. RESULTS: Perindopril alone reduced cardiovascular events
in subjects with stable coronary heart disease. Perindopril in combination with indapamide reduced cardiovascular
events in subjects with cerebrovascular disease. Perindopril in combination with amlodipine reduced cardiovascular
events in subjects with hypertension. CONCLUSION: Perindopril reduced cardiovascular events. The reduction of
cardiovascular events by perindopril was in large part associated with reduction of blood pressure, and greater
reduction in cardiovascular events was associated with greater reduction of blood pressure. Perindopril may need to
be combined with other antihypertensive agents to maximize reduction of cardiovascular events.
Expert Opin Pharmacother. 2007 Apr;8(6):881-9.
Metra M, Nodari S, Bordonali T, Milani P, Dei Cas L.
University of Brescia c/o Spedali Civili, Section of Cardiovascular Diseases, Department of Experimental and Applied Medicine, P.zza Spedali Civili 1, 25123 Brescia, Italy.
Clinical trials update from the World Congress of Cardiology 2006.
Information on trials clinical trials update from the World Congress of Cardiology held in 2006. This article provides information on trials presented at the World Congress of Cardiology 2006 (WCC-2006). This was
a joint meeting of the European Society of Cardiology and the World Heart Federation. Heart failure trials dealing
with understudied patient populations (e.g., the elderly), trials of new treatments (i.e., immune modulation
therapy) and new intervention strategies (i.e., the Cardiac Insufficiency Bisoprol-III study) or patient monitoring
(the Home or Hospital Heart Failure study) were presented at this meeting. Among the studies about coronary artery
disease treatment, WCC-2006 saw the presentation of the landmark meta-analyses regarding the incidence of late
events in patients receiving drug-eluting stents. The main results of these meta-analyses, and the associated
debate, are summarised in this article. Finally, the results of other trials of percutaneous patent foramen ovale
closure and atrial fibrillation treatment in elderly patients are summarised.
J Renin Angiotensin Aldosterone Syst. 2007 Mar;8(1):13-22.
Donnelly R, Manning G.
Derby City General Hospital, Derby, DE22 3DT, UK.
Angiotensin-converting enzyme inhibitors and coronary heart disease prevention.
Prevention of coronary heart disease and the Angiotensin-converting enzyme inhibitors. A number of large randomised controlled trials have shown that angiotensin-converting enzyme (ACE) inhibitors,
compared with placebo or other blood pressure-lowering drugs, improve coronary heart disease outcomes (fatal and
non-fatal myocardial infarction, and coronary revascularisation) in diverse patient groups, e.g. in primary and
secondary prevention, those with and without left ventricular dysfunction, and among hypertensive and
non-hypertensive subjects. An updated meta-regression analysis which included five major trials in patients with
established coronary artery disease (CAD) (EUROPA, INVEST, ACTION, PEACE and CAMELOT) concluded that ACE inhibitor
(ACE-I) therapy has clear benefits in secondary prevention, but there are important and unexplained differences
between trials in clinical outcome, baseline cardiovascular risk, blood pressure changes and trial design which
deserve further discussion of the underlying mechanisms and clinical interpretation. For example, in
placebo-controlled trials the biggest (2022%) reductions in primary end points (including mortality) have been
observed with perindopril and ramipril, whereas trials using trandolapril and quinapril had no effect on survival
or recurrent CAD events. This review summarises and compares the major findings of these recent trials, and
provides further analysis of the underlying mechanisms and clinical significance of secondary CAD prevention with
ACE-I therapy.
Neurobiol Learn Mem. 2006 Sep 29;
Jenkins TA, Chai SY.
Division of Psychiatry and Neuroscience, Queen's University, Belfast BT9 7BL, Northern Ireland, UK; Howard Florey Institute of Experimental Physiology and Medicine, The University of Melbourne, Parkville, Vic. 3010, Australia.
Effect of chronic angiotensin converting enzyme inhibition on spatial memory and anxiety-like behaviours in rats.
Efficacy on spatial memory and anxiety-like behaviours in rats due to the chronic angiotensin converting enzyme inhibition. Angiotensin converting enzyme inhibitors (ACEis) are widely used anti-hypertensive agents that are also reported to have positive effects on mood and cognition. The present study examined the influence of the ACEi, perindopril, on cognitive performance and anxiety measures in rats. Two groups of rats were treated orally for one week with the ACEi, perindopril, at doses of 0.1 and 1.0mg/kg/day. Learning was assessed by the reference memory task in the water maze, comparing treated to control rats. Over five training days both perindopril-treated groups learnt the location of the submerged platform in the water maze task significantly faster than control rats. A 60s probe trial on day 6 showed that the 1.0mg/kg/day group spent significantly longer time in the training quadrant than control rats. This improved performance in the swim maze task was not due to the effect of perindopril on motor activity or the anxiety levels of the rats as perindopril-treated and control animals behaved similarly in activity boxes and on the elevated+maze. These results confirm the anecdotal human studies that ACEis have a positive influence on cognition and provide possibilities for ACEis to be developed into therapies for memory loss.
Kidney Int Suppl. 2003 Feb;(83):S66-73
Hoy WE, Wang Z, Baker PR, Kelly AM
Menzies School of Health Research, Darwin, Northern Territory, Australia
Reduction in natural death and renal failure from a systematic screening and treatment program in an Australian Aboriginal community
Reduce natural death and renal failure by taking part in the systematic screening and treatment program in an Australian Aboriginal community. BACKGROUND: Australian Aborigines in remote areas are experiencing an epidemic of renal and cardiovascular disease. In November 1995, we introduced a renal and cardiovascular treatment program into the Tiwi community, which has a three- to fivefold increase in death rates and a recent annual incidence of treated end-stage renal disease (ESRD) of 2760 per million. Our previous study described an estimated 50% reduction in renal failure and all-cause natural deaths in the treatment group through December 31, 1998. We now describe a reduction in these events through mid 2000. METHODS: People eligible for treatment were those with confirmed hypertension, diabetics with microalbuminuria or overt albuminuria, and people with overt albuminuria, regardless of blood pressure and diabetes. Treatment centered around the use of perindopril (Coversyl, Servier), with additional agents as needed to reach defined blood pressure goals, attempts at control of glucose and lipid levels, and health education. Two hundred and sixty-seven people, or 30% of the adult population, have been enrolled, with mean follow up of 3.39 years. Rates of terminal endpoints were compared on an intention-to-treat basis with those of 327 historical controls matched for baseline disease severity, who were followed for a mean of 3.18 years in the pre-treatment program era, against a background of no treatment or inconsistent changing treatment. RESULTS: Terminal events occurred in 38 controls and 23 people in the treatment group. The estimated rate of natural deaths in the treatment group was 50% that of the controls, (P=0.012); the rate of renal deaths was 47% (P=0.038) and the rate of non-renal deaths was 54% that of controls (P=0.085). Survival benefit in the treatment group was observed at all levels of overt albuminuria, in non-diabetics and diabetics, in normotensive as well as hypertensive people, and in people who had been taking angiotensin converting enzyme-inhibitors (ACEi) in the pre-program era, as well as those who had not. Benefit was absent among the low death rates of people without overt albuminuria, and questionable among people with glomerular filtration rates (GFRs) <60 mL/min. The number of people needed to treat (NNT) to avoid one terminal event of natural causes was calculated at only 11.6. CONCLUSIONS: Falling rates of deaths and renal failure in the whole community support marked benefit of the program. Millions of dollars have been saved, based on avoidance of dialysis alone, but the reduction in premature death is the greater benefit. Chronic disease programs like this are enormously effective, and should be introduced into to all high-risk communities as a matter of urgency.
Clin Ther. 2003 Jul;25(7):2006-21
Derosa G, Cicero AF, Ciccarelli L, Fogari R
Department of Internal Medicine and Therapeutics, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy.
A randomized, double-blind, controlled, parallel-group comparison of perindopril and candesartan in hypertensive patients with type 2 diabetes
Usage of perindopril vs candesartan in hypertensive patients with type 2 diabetes: a randomized, double-blind, controlled, parallel-group comparison study. BACKGROUND: When choosing an antihypertensive drug for patients with hypertension and diabetes mellitus (DM), the metabolic side effects, possibility of improving some metabolic parameters, and need for adequate blood pressure control must all be considered.OBJECTIVE: The goal of this study was to compare the impacts of perindopril and candesartan on blood pressure, glucose metabolism, serum lipid profile, and metabolic parameters in patients with mild hypertension and type 2 DM during therapy and after a 1-month washout period.METHODS: Type 2 DM patients with mild hypertension and good glucose control who were not taking hypercholesterolemic drugs were enrolled. Perindopril 4 mg QD or candesartan 16 mg QD was administered for 12 months in this randomized, double-blind, controlled, parallel-group clinical trial. Fasting plasma glucose (FPG), fasting plasma insulin (FPI), glycosylated hemoglobin, homeostasis model assessment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, lipoprotein(a) (Lp[a]), plasminogen activator inhibitor 1 (PAI-1), homocysteine, body mass index (BMI), and albumin excretion rate (AER) were assessed.RESULTS: Ninety-six patients (49 women and 47 men; mean [SD] ages, 53 [10] years [perindopril] and 55 [9] years [candesartan]) were enrolled. Mean (SD) body weight, height, and BMI were 78.2 (9.4) kg, 1.69 (0.05) m, and 27.2 (2.0) kg/m(2) in the perindopril group and 77.5 (8.6) kg, 1.70 (0.06) m, and 26.8 (2.5) kg/m(2) in the candesartan group. A significant change occurred from baseline to month 12 during treatment with perindopril in SBP and DBP (both P < 0.01), FPG (P < 0.05), FPI (P < 0.05), TC (P < 0.05), LDL-C (P < 0.05), Lp(a) (P < 0.05), PAM (P < 0.05), and AER (P < 0.05). Significant changes from baseline to month 12 occurred with candesartan in SBP and DBP (both P < 0.01) and AER (P < 0.05). The HOMA index was significantly lower at month 12 in the perindopril group than in the candesartan group (P < 0.05). When we interrupted perindopril and candesartan therapy for a 1-month washout period, changes in SBP and DBP values were significant compared with month 12 in both groups (all P < 0.05). Changes in TC and LDL-C from month 12 to the end of washout were significant only in the perindopril group (both P < 0.05).CONCLUSIONS: Perindopril and candesartan both effectively lowered blood pressure in this group of patients with mild hypertension and type 2 DM. Perindopril showed an improvement on some metabolic parameters compared with candesartan. However, the inclusion/exclusion criteria could limit the ability to extrapolate the results to a general population.
Lancet. 2003 Sep 6;362(9386):782-8.
Fox KM
Cardiology Department, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK.
Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study).
Perindopril is capable to reduce cardiovascular events in patients with stable coronary artery disease: a randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces the rate of cardiovascular events among patients with left-ventricular dysfunction and those at high risk of such events. We assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure. METHODS: We recruited patients from October, 1997, to June, 2000. 13655 patients were registered with previous myocardial infarction (64%), angiographic evidence of coronary artery disease (61%), coronary revascularisation (55%), or a positive stress test only (5%). After a run-in period of 4 weeks, in which all patients received perindopril, 12218 patients were randomly assigned perindopril 8 mg once daily (n=6110), or matching placebo (n=6108). The mean follow-up was 4.2 years, and the primary endpoint was cardiovascular death, myocardial infarction, or cardiac arrest. Analysis was by intention to treat. FINDINGS: Mean age of patients was 60 years (SD 9), 85% were male, 92% were taking platelet inhibitors, 62% beta blockers, and 58% lipid-lowering therapy. 603 (10%) placebo and 488 (8%) perindopril patients experienced the primary endpoint, which yields a 20% relative risk reduction (95% CI 9-29, p=0.0003) with perindopril. These benefits were consistent in all predefined subgroups and secondary endpoints. Perindopril was well tolerated. INTERPRETATION: Among patients with stable coronary heart disease without apparent heart failure, perindopril can significantly improve outcome. About 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event. Treatment with perindopril, on top of other preventive medications, should be considered in all patients with coronary heart disease.
Expert Rev Cardiovasc Ther. 2005 Jan;3(1):15-29.
Ferrari R.
University of Ferrara, Department of Cardiology, Arcispedale S Anna, Corso Giovecca 203, 44100 Ferrara, Italy.
Angiotensin-converting enzyme inhibition in cardiovascular disease: evidence with perindopril.
Evidence with perindopril on angiotensin-converting enzyme inhibition in patients with cardiovascular disease.
Perindopril is a long-acting, once-daily lipophilic angiotensin-converting enzyme inhibitor with high tissue angiotensin-converting enzyme affinity, lowering angiotensinII 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 [1] 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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