6 research outputs found
PERTINENT - PERindopril-Thrombosis, InflammatioN, endothelial dysfunction and neurohormonal activation trial: A sub-study of the EUROPA study
BACKGROUND: Markers of thrombosis, inflammation, endothelial dysfunction and neurohumoral activation such as fibrinogen, D-dimer, C-reactive protein, von Willebrand factor, tumour necrosis factor-alpha and chromogranin-A are reported to be linked to the increase of cardiovascular risk for atherosclerosis progression and events in patients with cardiovascular diseases. METHODS: EUROPA is a double blind, placebo-controlled trial on 12,231 patients that evaluates the effect of an angiotensin converting enzyme inhibitor--perindopril--on prevention of cardiovascular events in patients with coronary artery disease. PERTINENT is a sub-study of EUROPA that evaluates (a) in Part A (300 patients): the influence of perindopril vs. placebo on fibrinogen, D-dimer, C-reactive protein, von Willebrand factor, tumour necrosis factor-alpha and chromogranin-A. In addition, NOS expression and induction of apoptosis on human umbilical vein endothelial cells and angiotensin converting enzyme levels are also studied; (b) in Part B (about 1200 patients): the predictive role of plasma levels of C-reactive protein and von Willebrand factor on the occurrence of cardiovascular events. To this end, matched case-control analyses are planned (patients with vs. patients without events). STATUS OF PERTINENT: Blood analyses are in progress in four specialised laboratories: (a) Gaubius Laboratory, Leiden, TNO-PG, The Netherlands; (b) University Department of Medicine, Birmingham, UK; (c) University of Pavia, Italy; (d) Fondazione Salvatore Maugeri, Cardiovascular Research Centre, Gussago, Italy. CONCLUSIONS: The PERTINENT sub-study might help elucidating the phenomena contributing to the pathophysiology of cardiovascular events in patients with coronary artery disease and the role of perindopril in such context
Effects of angiotensin-converting enzyme inhibition with perindopril on left ventricular remodeling and clinical outcome - Results of the randomized Perindopril and Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) study
Background: Angiotensin-converting enzyme inhibitors
reduce mortality and remodeling after myocardial
infarction in patients with left ventricular dysfunction.
Methods: Perindopril and Remodeling in Elderly With
Acute Myocardial Infarction (PREAMI), a doubleblind,
randomized, parallel-group, multicenter, placebocontrolled
study, determined whether similar benefits occur
in elderly postinfarction patients with preserved left
ventricular function. A total of 1252 patients 65 years or
older with a left ventricular ejection fraction of 40% or
higher and recent acute myocardial infarction were randomized
to receive perindopril erbumine or placebo (8
mg/d) for 12 months. The combined primary end point
was death, hospitalization for heart failure, or left ventricular
remodeling. Secondary end points included cardiovascular
death, hospitalization for reinfarction or angina,
and revascularization.
Results: The primary end point occurred in 181 patients
(35%) taking perindopril and 290 patients (57%)
taking placebo, with a significant absolute risk reduction
of 0.22 (95% confidence interval, 0.16 to 0.28;
P.001). A total of 126 patients (28%) and 226 patients
(51%) in the perindopril and placebo groups, respectively,
experienced remodeling. The mean increase in left
ventricle end-diastolic volume was 0.7 mL with perindopril
compared with 4.0 mL with placebo (P.001). In
the perindopril group, 40 deaths (6%) and 22 hospitalizations
(4%) for heart failure occurred, whereas 37 deaths
(6%) and 30 hospitalizations (5%) occurred in the placebo
group. Treatment did not affect death, whereas the
hospitalization rate for heart failure was slightly reduced
(absolute risk reduction, 0.01; 95% confidence interval,
−0.01 to 0.02). No treatment effect on other secondary
end points was detected.
Conclusion:Wefound that 1-year treatment with 8mg/d
of perindopril reduces progressive left ventricular remodeling
that can occur even in the presence of small
infarct size, but it was not associated with better clinical
outcomes
PREAMI: Perindopril and remodelling in elderly with acute myocardial infarction: Study rationale and design
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 ≥65 years, the effects of Perindopril on the combined outcome of death, hospitalization for HF, and heart remodeling, considered to be a ≥8% increase in LV end-diastolic volume (LVEDV). Secondary objectives include the same factors listed in the primary end points hut 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 ≥65 years, and preserved or only moderately depressed LV (LV ejection fraction ≥40%), are to he 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
the European trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA trial).
Background 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. 13 655 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, 12 218 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% 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
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)
BACKGROUND: 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