EUROPA-Studie (Perindopril) (60 Abbildungen)
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FÜR ÖSTERREICH: Weitere Informationen: Servier, Mariahilfer Straße 20/5, 1070 Wien, Tel. 01/524 39
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Abbildung 0
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EUROPA-Studie
Abbildung 1: EUROPA (EUropean trial on Reduction Of cardiac events with Perindopril in stable Artery coronary disease) is
the largest and longest study ever conducted in patients with stable coronary disease. It was announced at ESC in Vienna
on the 31st of August 2003 during an official hotline session. EUROPA is considered as a reference study for the
initiation of the ACEI perindopril 8 mg once daily as chronic treatment in all patients with stable coronary artery
disease.
Keywords: Coversum, EUROPA-Studie, kardiales
Ereignis, KHK, Koronare
Herzkrankheit, Perindopril, Servier Austria
GmbH, Stabile Angina
pectoris
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Studientrends - ACE-Hemmer
Abbildung 2: The clinical trials with ACE inhibitors in coronary artery disease patients over the years have proved their
benefits in the "treatment" of patients right after the ischemic event (CONSENSUS, SOLVD, AIRE, SAVE, TRACE) and it was
less proved on the "prevention" of secondary events (EUROPA, HOPE, PEACE), or even failed to prove (QUIET).
Keywords: ACE-Hemmer,
Coversum, Perindopril, Prävention, Schema, Servier Austria
GmbH, Studie, Therapie
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ACE-Hemmung - Benefit
Abbildung 3: So far, the benefit of ACE inhibitors were extensively investigated in large cohort of ishemic heart disease
patients: post MI, LVSD with EF < 40 %, HF. The difference between these trials lies in the type of patients selected
for each respective trial, which are actually patients of high risk. Coronary artery disease is a progressive condition
involving patients with lower and higher risk levels. For cardiologists, according to the investigators from the EUROPA
trial, patients involved presented all-risk coronary patients in comparison to other trials conducted in this area, which
were patients considered as high risk patients. So, EUROPA was aiming to resolve the question on the benefits of ACE
inhibition in the treatment of all risk stable coronary artery disease patients.
Keywords: ACE-Hemmung, Coversum, KHK, Koronare
Herzkrankheit, Perindopril, Schema, Servier Austria
GmbH, Studie
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KHK - Sekundärprävention
Abbildung 4: The rationale of the possible benefits of an ACEI in the treatment of coronary artery disease is based on
their anti ischemic properties linked to their mode of action. Angiotensin II (A II) plays a significant role in the
mechanisms which underlie the atherosclerotic process: vasoconstriction and cell proliferation. Angiotensin-converting
enzyme (ACE) inhibitors, such as perindopril, interrupt the production of A II, leading to antiproliferative and anti
atherogenic effect. On the other hand, ACE inhibitors counteract the breakdown of bradykinin. A substance, which is
responsible for the improvement in endothelial function, leading to vasodilation and growth inhibition. Bradykinin
stimulates nitric oxide (NO) production and prostaglandin release from the endothelium. NO production and prostaglandin
release yield beneficial vasodilatory, growth-inhibitory, antiatherogenic, antithrombotic, anti-inflammatory, and
antioxidant effects.
Keywords: ACE-Hemmer,
Angiotensin, Coversum, KHK, Kininogen, Koronare
Herzkrankheit, Perindopril, Schema, Sekundärprävention,
Servier Austria
GmbH
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KHK - Sekundärprävention
Abbildung 5: Indeed, looking more closely at the very important formation of bradykinin and pharmacological mode of
action of ACEIs, we can conclude that bradykinin is one of the most important consequence of ACE inhibition. Bradykinin
stimulates the release of NO from the endothelium, which not only dilates the vessel but also reduces platelet
aggregation, the activity of white cells, and smooth muscle cell hypertrophy, all of which result from the activities of
angiotensin II. Damage to the endothelium by smoking, hypercholesterolemia, diabetes, hypertension, or superoxides
inhibits NO release, allowing angiotensin II to exert the harmful effects, as represented on the left side of the figure.
SMC = glatte Muskelzellen FGF = Fibroblasten Growth Factor PDGF = Platelet Derived Growth Factor
Keywords: ACE-Hemmer,
Angiotensin, bradykinin, Coversum, KHK, Koronare
Herzkrankheit, Perindopril, Schema, Sekundärprävention,
Servier Austria
GmbH
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Endotheliale Dysfunktion
Abbildung 6: The earliest changes that occur within the dysfunctional endothelium include: Increase of the permeability
of the endothelium to lipoproteins and plasma constituents. This alteration is mediated by nitric oxide, angiotensin II,
endothelin and other compounds. Leukocyte adhesion molecules are produced in greater quantity, thus increasing the uptake
of leukocytes and their adhesion to the vessel wall.
Keywords: Atherosklerose, Coversum, Dysfunktion, Endothel, Graphische
Darstellung, Perindopril, Plaque, Servier Austria
GmbH
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Endotheliale Dysfunktion
Abbildung 7: As the dysfunctional endothelium progresses from early to more mature stages of atherosclerotic lesions,
abnormal activity within the blood vessel continues: A fatty streak is formed within the vessel wall (lipid
accumulation). Later, smooth muscle cells begin to migrate into the developing plaque. Leukocytes continue to adhere to
the endothelium and after penetration move into the vessel wall. Inflammatory response in the atherosclerotic lesion
starts. Platelets adhere to the dysfunctional endothelium contributing to the migration and proliferation of smooth
muscle cells and monocytes, but also to platelet aggregation. Platelets accumulating on the vessel wall contribute to
thrombus formation. As the atherosclerotic plaque progresses to late stages, a fibrous cap forms over the plaque and
walls of the lesion from the vessel lumen. This fibrous cap may then become unstable and rupture causing thrombus
formation, and often, CV events.
Keywords: Atherosklerose, Coversum, Dysfunktion, Endothel, Graphische
Darstellung, Perindopril, Plaque, Servier Austria
GmbH
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KHK - Sekundärprävention
Abbildung 8: So, ACEIs, by both decreasing A II and increasing bradykinin levels offer possible anti ischemic effects,
which could lead to secondary prevention of cardiovascular events in the treatment of coronary artery disease patients.
inhibition in secondary prevention, comes directly from the following properties of perindopril, as demonstrated in human
or experimental models: anti-atherosclerotic action, action on plaque rupture reduction, improvement of vascular
endothelium, enhanced fibrinolysis, modulation of the neurohormonoally-induced arterial vasoconstriction, blood pressure
lowering action in reducing left ventricular hypertrophy.
Keywords: ACE-Hemmer,
KHK, Koronare
Herzkrankheit, Sekundärprävention
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EUROPA-Studie - Hypothese
Abbildung 9: Based on the hypothesis that ACE inhibition affects atherosclerotic process in multiple ways, benefits in
all patients with coronary artery disease, can be anticipated.
Keywords: ACE-Hemmer,
Atherosklerose, Coversum, EUROPA-Studie, Ischämie, KHK, Koronare
Herzkrankheit, Perindopril, Sekundärprävention,
Servier Austria
GmbH
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EUROPA-Studie - Perindopril
Abbildung 10: EUROPA is investigators led study, where perindopril 8 mg once daily is the ACEI of choice due to its
actions ideally suitable for investigating this hypothesis. Looking more specifically at the main reasons why perindopril
was chosen for the EUROPA trial, the following properties came under consideration: - Reliable 24-hour efficacy in BP
reduction following a single tablet daily taken in the morning (as confirmed by its high TPR), with exceptional
hemodynamic tolerance, proven when initiated and maintained in all patient types (in heart failure, post MI, as well as
in patients with a history of stroke). - High tissue affinity. - Unique increase of bradykinin. - Its anti-ischemic
properties proven to: - correct coronary endothelial dysfunction, - normalize the structure of resistance arteries, -
normalize fibrinolitic balance and structure of resistance arteries. - Anti atherosclerotic effect - Anti ischemic
efficacy - Good tolerance even in fragile patients with previous heart failure and strokes.
Keywords: ACE-Hemmer,
Atherosklerose, Coversum, EUROPA-Studie, Ischämie, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Blutdruck
Abbildung 11: The blood pressure reduction over 24 h minimizes the risk of stroke and myocardial infarction in the early
morning hours. In the randomized, parallel study, 293 mild-to-moderate essential hypertensive patients were treated with
perindopril 4 to 8 mg once daily or placebo for 12 weeks. Trough-to-peak ratio (TPR) in placebo-corrected diastolic blood
pressure at 24 h versus 6 h was 100 %, and 97 % for 4 mg and 8 mg, respectively. A linear relationship in efficacy
between the dose of perindopril and the reduction in blood pressure was demonstrated over the range of 4 mg to 8 mg once
daily over the 24 h.
Keywords: Blutdruck, Coversum, Diagramm, EUROPA-Studie, Perindopril, Servier Austria
GmbH
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Perindopril - Gewebs-ACE
Abbildung 12: Perindopril has a very high tissue and plasma ACE affinity, as proven for the first time ever with an ACEI
in humans suffering from coronary artery disease. Zhuo et al. studied the in vivo effects of ACE inhibition with
perindopril on cellular expression of ACE, in human blood vessels using quantitative in vitro autoradiography and
immunocytochemistry. 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. Perindopril
inhibits both endothelial and advential ACE, this being further proof for reversing endothelial dysfunction, a key role
player in the manifestation of cardiovascular diseases and their complications. This is one of the main reasons
supporting its choice in the EUROPA study.
Keywords: ACE, ACE-Hemmung, Coversum, Perindopril, Servier Austria
GmbH
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Perindopril - Bradykinin
Abbildung 13: The long term treatment of patients with coronary artery disease, with perindopril 8 mg once daily,
significantly decreases serum ACE activities (p < 0.01) and increases plasma bradykinin concentrations (p < 0.05).
These results provide the first evidence that long-term treatment with perindopril exerts anti ischemic effects on the
myocardial ishemia induced by increased myocardial oxygen demand in patients with.
Keywords: ACE-Hemmung, bradykinin, Coversum, Diagramm, KHK, Koronare
Herzkrankheit, Perindopril, Servier Austria
GmbH
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Perindopril - Endotheliale Dysfunktion
Abbildung 14: Perindopril corrects endothelial function as observed in this study, not accomplished by different
antihypertensive therapies (ACEI, ARB, CCB and Beta-blockers) in essential hypertensive patients. Only perindopril
managed to significantly increase flow mediated dilation after 6 months. AT1 receptor antagonist did not improve
endothelial dysfunction leading to the conclusion that the beneficial effect of perindopril is related to bradykinin
dependant mechanisms.
Keywords: Coversum, Diagramm, Dysfunktion, Endothel, Perindopril, Servier Austria
GmbH
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Perindopril - Endothliale Dysfunktion
Abbildung 15: Perindopril, due to its high tissue affinity, corrects endothelial function at the level of the coronary
arteries, which is altered in patients suffering from hypertension. This leads to improvement in coronary vasodilatation
and heart perfusion. As shown in this study, perindopril restores flow-dependent and cold pressor test-induced dilations
in the coronary arteries of hypertensive patients. Coronary blood flow was significantly increased by perindopril from
33.7 + 10.0 to 57.9 + 20.5 mL/min (p < 0.01) and coronary resistance decreased from 4.28 + 1.27 to 2.96 + 0.84 mm
Hg.mL-1 .min-1 (p < 0.001).3
Keywords: Cold-pressure-Test,
Coversum, Diagramm, Dysfunktion, Endothel, Perindopril, Servier Austria
GmbH, Vasodilatation, Vasokonstriktion
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Perindopril - Widerstandsarterien
Abbildung 16: Effect of antihypertensive treatment on small arteries of patients with previously untreated essential
hypertension was evaluated with perindopril and atenolol. Gluteal biopsies were taken before and after treatment under
local anesthetic. A significant change in the media:lumen ratio after the treatment with perindopril was obvious, in
contrast to atenolol and besides the similar BP reduction obtained.
Keywords: Coversum, Diagramm, Hypertonie, Lumen, Perindopril, Servier Austria
GmbH, Widerstandsarterie
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Perindopril - Widerstandsarterien
Abbildung 17: Perindopril normalises structure of coronary resistance arteries in patients with hypertensive heart
disease. In the study where hypertensive patients with LVH and microvascular angina, were treated with perindopril 4 mg
to 8 mg for 1 year, after the treatment period, perindopril had significantly decreased coronary resistance. Perindopril
induced the regression of periarteriolar fibrosis of resistance vessels and of the interstitial collagen. This was
accompanied by marked improvement in coronary reserve. These findings indicate the beneficial reparative effects of ACE
inhibition with perindopril on coronary microcirculation in hypertensive heart disease, beyond BP control.
Keywords: Coversum, Diagramm, Kollagen, Perindopril, Servier Austria
GmbH, Widerstandsarterie
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Perindopril - Koronarreserve
Abbildung 18: As a result, the coronary reserve increased by 67 %. Also, the LV muscle mass index significantly decreased
by 11 % after a 12-month perindopril treatment. Percent of increase in coronary reserve was more than expected by
regression of LVH alone. Regression of fibrosis was demonstrated by perindopril in the non-pressure overloaded right
ventricle and independently from local myocyte size. It seems to be due to direct/chronic effects of perindopril on
collagen metabolism. Perindopril 4 to 8 mg, once daily, reverses both interstitial fibrosis and LV mass in patients with
LVH and significantly restores coronary flow reserve in the long term treatment independently of its anti-hypertensive
efficacy.
Keywords: Coversum, Diagramm, Koronarreserve, Perindopril, Servier Austria
GmbH
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Perindopril - Fibrinolyse
Abbildung 19: It has been confirmed that in hypertensive and cardiovascular disease the reduced levels of tissue-type
plasminogen activator (t-PA), are contributing to thrombus formation. This plays a role in the pathogenesis of acute
myocardial infarction and stroke. In a recent trial which compared the effects of perindopril and losartan on
fibrinolytic balance in coronary artery circulation of the patients with atypical chest pain and hypertension,
perindopril increased t-PA enhanced by bradykinin significantly more than losartan.
Keywords: bradykinin,
Coversum, Diagramm, Fibrinolyse, Hypertonie, Losartan, Perindopril, Servier Austria
GmbH, Tissue-type
plasminogen activator, tPA
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Perindopril - Antiatheriosklerotischer Effekt
Abbildung 20: In a study on diabetic apoE-deficient mice, perindopril shows its ability to oppose the development of
atherosclerosis by inhibiting ACE tissue growth factor and vascular cell adhesion molecule-1 overexpression in the aorta.
This experimental study clearly proves perindopril’s efficacy on atherosclerosis in at-risk diabetic animal models.
Perindopril plays a pivotal role in the opposition of development and acceleration of atherosclerosis in diabetes.
Candido R, Jandeleit-Dahm KA, Cao Z, et al. Circulation. 2002; 106: 246-53.
Keywords: Atherosklerose, Coversum, Diabetes, Graphische
Darstellung, Perindopril, Servier Austria
GmbH
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Perindopril - Antiischämische Wirksamkeit
Abbildung 21: Finally and as a final proof of perindopril’s choice for EUROPA it is interesting to look after
its anti-ischemic efficacy, as recently proven in humans suffering from stable angina. After 3 months of treatment,
perindopril given at the same dosage as used in EUROPA, that is to say 8 mg significantly reduces the time to ST-segment
depression, as well as exercise-induced left ventricular systolic dysfunction. A linear relationship exists between the
inhibition of plasma ACE by perindopril and the increase in bradykinin concentration. This high concentration is thought
to be involved in the anti-ischaemic effects obtained with perindopril. This further emphazises its choice to conduct the
EUROPA trial.
Keywords: Belastung, Coversum, Diagramm, Dysfunktion, Ischämie, Perindopril, Servier Austria
GmbH, ST-Segment, Stabile Angina
pectoris, Systole
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Perindopril - Verträglichkeit
Abbildung 22: First dose hypotension in heart failure patients with the initiation of an ACEI may be symptomatic or
asymptomatic, which may lead to renal, cardiac, or cerebral hypoperfusion. In the double-blind, randomized,
placebo-controlled, parallel-group prospective study of elderly patients with stable chronic heart failure, perindopril
demonstrated an excellent hemodynamic tolerance minimizing the risk of hypotension. Perindopril 2 mg produces no more
decrease in blood pressure then placebo. On the contrary, enalapril and captopril induce significant and long-lasting
reduction in mean arterial pressure. Perindopril once daily provides an excellent hemodynamic profile even in fragile
patients. So, for all these reasons perindopril was chosen to conduct EUROPA study. Mc Fadyen J, Lees K R, Reid J L. Br
Heart J. 1991; 66: 206-11.
Keywords: Blutdruck, captopril, Coversum, Diagramm, Enalapril, Herzinsuffizienz, Hypotonie, Perindopril, Servier Austria
GmbH, Verträglichkeit
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Perindopril - Verträglichkeit
Abbildung 23: Coversyl once daily maintains cerebral blood flow in patients with acute ischemic stroke. There is an
obvious theoretical concern that Bp lowering agent may also cause an adverse reduction in cerebral blood flow. In
patients with already compromised cerebral circulation (ie, those who have had a stroke) this would clearly be highly
undesirable. However it appears Coversyl provides BP controls without any adverse effects on cerebral blood flow. In a
study of 28 patients with acute stroke and hypertension, between 48 hours and 7 days after a stroke, patients were
randomized to either Coversyl once daily or placebo. The comparison with the placebo curve is particularly important in
the context of a stroke because of the spontaneous wide variations of blood pressure in the acute phase ( first weeks).
Cerebral blood flow was calculated from internal carotid artery Doppler ultrasound measurements. These measurements were
undertaken 3 times: before intake of Coversyl, during the first 24 hours, and then repeated after 2 weeks. The results
show that Coversyl reduces BP while maintaining cerebral blood flow.
Keywords: Blutdruck, Coversum, Diagramm, Hypertonie, Perindopril, Servier Austria
GmbH, Verträglichkeit
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EUROPA-Studie - Studienziel
Abbildung 24: The aim of EUROPA is clear and simple: that is to examine and investigate whether long-term administration
of the ACE inhibitor Perindopril added to standard therapy leads to secondary prevention of ischemic events in patients
with documented coronary artery disease, with or without signs of myocardial ischemia, and without heart failure.
Keywords: ACE-Hemmer,
Coversum, EUROPA-Studie, kardiovaskuläres
Ereignis, KHK, Koronare
Herzkrankheit, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Endpunkte
Abbildung 25: The EUROPA study was designed to determine whether adding perindopril to optimal therapy decreased the rate
of: CV mortality, non fatal MI, cardiac arrest – primary endpoint. In addition, selected secondary end points of
the study were: total mortality + non fatal MI + unstable angina + cardiac arrest; heart failure; revascularisation
(PCI/CABG) and stroke.
Keywords: Coversum, Endpunkt, EUROPA-Studie, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Studiendesign
Abbildung 26: After the run-in period of 2 weeks patients received 4 mg of perindopril once daily in the morning in
addition to their usual medication. At 4 weeks, the thrid visit, patients were randomized double-blind to perindopril 8
mg or placebo, and continued their treatment until the last patients included complete the 4-year follow-up period.
Keywords: Coversum, Diagramm, EUROPA-Studie, Perindopril, Servier Austria
GmbH, Studiendesign
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EUROPA-Studie - Patientenauswahl
Abbildung 27: According to these selection criteria, some important points can be highlighted: the patient profile is
very close to the general population met in clinical practice in terms of age and risk factors. Patients include were
older than 18 years, had documented coronary disease, were not scheduled for revascularisation and had no clinical signs
of heart failure.
Keywords: Coversum, EUROPA-Studie, KHK, Koronare
Herzkrankheit, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - KHK
Abbildung 28: EUROPA includes 100 % of patients with proven 100 % coronary artery disease. 12,218 patients aged 26 to 89
years (mean age 60 years) without heart failure were recruited and randomised if they had documented CAD, which was
defined as either: - A history of previous MI at least three months before selection - A history of PTCA or CABG at least
6 months old - Significant coronary stenosis on coronary angiogram - In males with a history of chest pain, by a positive
exercise test, stress echo or scintiography
Keywords: Angina
pectoris, CABG, Coversum, EUROPA-Studie, KHK, Koronare
Herzkrankheit, Myokardinfarkt, PCI, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Charakteristik
Abbildung 29
Keywords: Coversum, EUROPA-Studie, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Patientenrekrutierung
Abbildung 30: Patients were followed up at 3, 6, and 12 months, and every 6 months thereafter. After randomisation,
withdrawals from treatment were similar to those for placebo, and only 3 patients were lost to follow up amongst 12,218
patients.
Keywords: Coversum, EUROPA-Studie, Patient, Perindopril, Schema, Servier Austria
GmbH
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EUROPA-Studie - Zentren
Abbildung 31: EUROPA trail is a true pan-European trial. Therefore, the results were applicable across all Europe,
including 12,218 patients that were randomised from 424 centers in 24 Europeen countries, involving 525
investigators.
Keywords: Coversum, Europa, EUROPA-Studie, Graphische
Darstellung, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Ausschlußkriterien
Abbildung 32: Perindopril 8 mg once daily was well tolerated. Around 10 % of patients were not randomised after the
open-label dose-titration phase for various reasons.
Keywords: Ausschlußkriterien,
Coversum, EUROPA-Studie, Perindopril, Randomisierung, Servier Austria
GmbH
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EUROPA-Studie - Charakteristika
Abbildung 33: The analysis of the baseline characteristics of patients recruited into the study showed that: Patients
were at least 18 years without clinical evidence of heart failure and with evidence of coronary artery disease. In
average they were 60 years old which is not old for coronary artery disease. They were largely men: 86%, weight: 81 + 12,
heart rate: 68 + 10 and they had normal blood pressure. Importantly, there were no differences between these two groups,
perindpril and placebo, almost identically matched.
Keywords: Charakteristika, Coversum, EUROPA-Studie, Patient, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Anamnese
Abbildung 34: There were 65 % of patients with previous history of MI, 83 % of those with MI was more than 1 year in the
past, 1/3 of them had an MI 5 years before study started. Half of the patients randomised had revascularisation, and
small % of patients had peripheral vascular disease, history of stroke or TIA and 1.3 had heart failure as it was the
exclusion criteria, all equally balanced between perindopril and placebo group.
Keywords: Anamnese, Coversum, EUROPA-Studie, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Risikofaktoren
Abbildung 35: Patients randomised in EUROPA trial involved: hypertensive patients, which presented 27 % of the study
population, 11.8 % of patients had diabetes, 63.3 % were hypercholesterolemic and 15.4 % declared themselves as smokers.
Again, a very balanced population was maintained between perindopril and placebo groups of patients.
Keywords: Coversum, EUROPA-Studie, Perindopril, Risikofaktor, Servier Austria
GmbH
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EUROPA-Studie - Medikation
Abbildung 36: Of particular importance when it comes to interpretation of this study is the background treatment.
Demographic data clearly demonstrate that the EUROPA patients were receiving perindopril or placebo on top of optimal
preventive therapy. Most of the randomised coronary artery disease patients were treated with platelet inhibitors,
B-blockers, lipid lowering drugs, nitrates, Ca-blockers, diuretics and oral anticoagulants. Homogeneity was maintained
between these two groups of patients.
Keywords: Coversum, EUROPA-Studie, Medikament, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Primärer Endpunkt
Abbildung 38: RRR = relative Risikoreduktion. Perindopril reduced the combined primary endpoint of cardiovascular death,
myocardial infarction and cardiac arrest by 20 % (p = 0.0003) after 4 years follow up. Reduction of the primary end-point
reached significance even earlier and curves diverged after one year of treatment.
Keywords: Coversum, Diagramm, EUROPA-Studie, Herzstillstand, Myokardinfarkt, Perindopril, primärer
Endpunkt, Servier Austria
GmbH, Tod
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EUROPA-Studie - Endpunkte
Abbildung 39: All components of the primary end point were reduced in favour of perindopril. CV mortality was reduced by
14 %, non fatal MI by 22 % and cardiac arrest by 46 %. Composite of total mortality, non-fatal MI, unstable angina,
cardiac arrest was significantly reduced by 14 %.
Keywords: Coversum, Diagramm, Endpunkt, EUROPA-Studie, Herzstillstand, instabile Angina
pectoris, Mortalität, Myokardinfarkt, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Subgruppenanalyse
Abbildung 40: Sub-group analysis demonstrated that all patients benefited from perindopril 8 mg once daily. Regardless of
gender, age or history of MI, the cardiovascular death, MI or cardiac arrest was always in favor of perindopril
group.
Keywords: Alter, Coversum, Diagramm, EUROPA-Studie, Frau, Mann, Perindopril, Servier Austria
GmbH, Subgruppe
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EUROPA-Studie - Subgruppenanalyse
Abbildung 41: Sub-group analysis, also, showed that perindopril 8 mg once daily reduced morbidity and mortality in all
patients irrespective of previous history of hypertension, diabetes or stroke and/or TIA.
Keywords: Coversum, Diabetes
mellitus, Diagramm, EUROPA-Studie, Hypertonie, Perindopril, Schlaganfall, Servier Austria
GmbH, Subgruppe
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EUROPA-Studie - Subgruppenanalyse
Abbildung 42: Consistency of benefits with perindopril is shown in all patients whether they were using lipid lowering
drugs, b-blockers and Calcium-channel blockers, or not. Almost all patients were using platelet inhibitors and more than
half of them, lipid lowering drugs. By further analysis, no drug interaction was found meaning that benefits with
perindopril are independent of other drugs.
Keywords: Betablocker,
Coversum, Diagramm, EUROPA-Studie, Kalziumantagonist,
Lipidsenker, Perindopril, Servier Austria
GmbH, Subgruppe
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EUROPA-Studie - Sekundäre Endpunkte
Abbildung 43: Beneficial effect of treatment with perindopril on all prespecified secondary endpoints was shown in
EUROPA.
Keywords: Coversum, Diagramm, EUROPA-Studie, Perindopril, sekundärer
Endpunkt, Servier Austria
GmbH
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EUROPA-Studie - Myokardinfarkt
Abbildung 44: Perindopril 8 mg once daily reduced myocardial infarction (fatal or non-fatal) by 24 % (p < 0.001). This
is one of the most impressive results as curves separated early and there was a tendency for the gap between curves to
widen more in time even after the end of the study follow up. As Dr Harvey White, from Cardiology Dept. Green Lane
hospital, NZ commented in the EUROPA editorial: "Although the blood pressure reduction in EUROPA was small (5 mm Hg
systolic and 2 mm Hg diastolic), the systolic pressure reduction might be expected to translate into a 10 % reduction in
myocardial infarction, whereas the actual reduction in non-fatal MI was 24 %". This demonstrates that BP reduction should
not be the predominant mechanism of benefit with perindopril.
Keywords: Coversum, Diagramm, EUROPA-Studie, Myokardinfarkt, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Hospitalisierung
Abbildung 45: Another very significant result was reduction of hospitalisation for heart failure by 39 % (p = 0.002).
There is a clear evidence that the patients assigned to perindopril 8 mg once daily benefited right after the onset of
the study.
Keywords: Coversum, Diagramm, EUROPA-Studie, Herzinsuffizienz, Hospitalisierung, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Blutdruck
Abbildung 46: During the run-in period during where all patients received perindopril, blood pressure was reduced from
137/82 to 128/78 mm Hg. After randomisation, systolic and diastolic blood pressures among patients treated with
perindopril were maintained until the study end and the average blood pressure during double-blind treatment was 5/2 mm
Hg higher in the placebo group. Also, it was shown that reduction of fatal and non-fatal MI was reduced more then due to
the reduction of BP alone (ref. EUROPA editorial).
Keywords: Blutdruck, Coversum, Diagramm, EUROPA-Studie, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Compliance
Abbildung 47: After randomisation, study medication was well tolerated. At 3 years, 81 % of patients assigned perindopril
and 84 % of placebo patients, were taking study medication. Most of the patients assigned to perindopril continued on 8
mg, only 7 % had dropped to 4 mg at 3 years. The average use of study medication was 3.7 years of 4.2 years
follow-up.
Keywords: Compliance,
Coversum, Diagramm, EUROPA-Studie, Perindopril, Servier Austria
GmbH, Therapietreue
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EUROPA-Studie - Non Compliance
Abbildung 48: As perindopril 8 mg once daily was very well tolerated, the reasons for permanent withdrawal from treatment
were comparable to placebo.
Keywords: Abbruch, Coversum, EUROPA-Studie, Perindopril, Servier Austria
GmbH, Therapie
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EUROPA-Studie - Klinische Aussagen
Abbildung 49: Clinical implications from EUROPA trial are important for all at-risk coronary artery disease patients in
the clinical practice.
Keywords: Coversum, EUROPA-Studie, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - KHK
Abbildung 50: Out of 56 million deaths worldwide in 2001, burden of coronary disease is accounted for 29 % of them,
causing deaths in total for 16 million people. In 2020, 37 % of deaths are foreseen as CV deaths. In the European Union,
there are 20 million people at risk who have coronary artery disease. Prof. Kim Fox, at the EUROPA study presentation
commented that "investigators were particularly excited because the disease they are talking about is the most important
disease, and every improvement they can make will have a great impact on the health care in the western world."
Keywords: Coversum, Europa, EUROPA-Studie, KHK, Koronare
Herzkrankheit, Perindopril, Servier Austria
GmbH, Todesfall, Welt
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EUROPA-Studie - KHK
Abbildung 51: Coronary artery disease encompasses all major cardiovascular complications. Clinical expression of coronary
disease is presented through:silent ischemia, stable angina, unstable angina, MI, HF and sudden death.
Keywords: Coversum, EUROPA-Studie, KHK, Koronare
Herzkrankheit, Perindopril, Schema, Servier Austria
GmbH
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EUROPA-Studie - Perindopril - Benefit
Abbildung 52: In EUROPA study, all at-risk patients benefited, whether they were in low, medium or high risk group of
patients. Perindopril 8 mg once daily reduced primary end-point (CV death, MI or cardiac arrest) regardless of age,
gender, previous history of coronary artery disease (MI, CABG/PTCA, PVD, stroke), risk factors (smoking, diabetes) or
preventive therapy (platelet inhibitors, lipid lowering drugs or B-blockers).
Keywords: Benefit, Coversum, Diagramm, EUROPA-Studie, Herzstillstand, Myokardinfarkt, Perindopril, Servier Austria
GmbH, Tod
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EUROPA-Studie - Interaktionsanalyse
Abbildung 53: Although patients were treated with perindopril 8 mg once daily on top of standard, preventive therapy,
there were no significant interactions reported between the perindopril and all background medications.
Keywords: Behandlung,
Betablocker, Coversum, EUROPA-Studie, Interaktionsanalyse,
Kalziumantagonist,
Lipidsenker, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Benefits
Abbildung 54: EUROPA trial demonstrated benefit for all coronary artery disease patients including large cohort of low,
but also, medium and high risk patients randomised in the previous trials (I.e. HOPE, SOLVD, SAVE, AIRE, TRACE). Prof.
Kim Fox, the EUROPA chairman commented: "The results from the EUROPA trial demonstrate some of the largest benefits ever
seen in the prevention of chronic disease".
Keywords: Benefit, Coversum, EUROPA-Studie, KHK, Koronare
Herzkrankheit, Perindopril, Schema, Servier Austria
GmbH, Studie
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EUROPA-Studie - HOPE-Studie
Abbildung 55: EUROPA study with perindopril 8 mg once daily extends the observations of HOPE, in which cardiovascular
events were reduced with ACE inhibition in high-risk patients with coronary heart disease. The risk of patients in EUROPA
was lower than in HOPE, which selected older patients (66 vs 60), who had higher percentage of cardiovascular risk
disease PVD, hypertension), stroke or diabetes.
Keywords: Coversum, EUROPA-Studie, HOPE, Perindopril, Population, Servier Austria
GmbH
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EUROPA-Studie - HOPE-Studie
Abbildung 56: At baseline,patients randomised in EUROPA were using more extensive therapy. More patients in EUROPA used
optimal preventive therapy: aspirin, ß-blockers, and lipid-lowering drugs.
Keywords: Basistherapie, Coversum, EUROPA-Studie, HOPE, Medikament, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - HOPE-Studie
Abbildung 57: At a mean follow-up of 4.5 years, HOPE reported a placebo mortality of 12%, cardiovascular mortality of 8
%, and Q-wave myocardial infarction of 3 %, compared with 7 %, 4 %, and 2 %, respectively, in EUROPA study at 4.2 years
of follow-up. Thus, the major annual event rates in HOPE were 40 % to 80 % higher than those in EUROPA.
Keywords: Coversum, EUROPA-Studie, HOPE, Mortalität, Myokardinfarkt, Perindopril, Placebo, Servier Austria
GmbH
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EUROPA-Studie - Ergebnisse
Abbildung 58: As prof. Willem Remme, EUROPA Chairman added: "The EUROPA results are profound. Cardiovascular deaths,
myocardial infarction and heart failure were all significantly reduced in patients given treatment based on ACE inhibitor
perindopril, in addition to standard optimal therapy including aspirin, statins and ß -blockers". In this largest
and longest trial of stable CAD patients, perindopril 8 mg once daily reduced significantly: - CV mortality, non-fatal MI
and cardiac arrest by 20 % - CV mortality and non fatal MI by 19 % - Fatal and non fatal MI by 24 % - Heart failure by 39
%
Keywords: Coversum, Ergebnis, EUROPA-Studie, KHK, Koronare
Herzkrankheit, Perindopril, Risiko, Servier Austria
GmbH
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EUROPA-Studie - Benefit
Abbildung 59: Once again, the absolute benefits were achieved with perindopril 8 mg once daily in the EUROPA trial:
"Adding perindopril to standard optimal therapy over a four year period would stop 50,000 heart attacks or cardiovascular
deaths in a country with a population of 60 million" concluded prof. Kim Fox, the study chairman. "The EUROPA trial
provides clear evidence of major health gains for these patients. If the findings are applied worldwide then many
millions of lives could be saved" added prof. Willem Remme, the study chairman.
Keywords: Coversum, EUROPA-Studie, KHK, Koronare
Herzkrankheit, Nutzen, Perindopril, Servier Austria
GmbH
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EUROPA-Studie - Ergebnisse
Abbildung 60: Last but not least, all these benefits demonstrated with perindopril 8 mg once daily in EUROPA trial, were
achieved on top of standard optimal treatment (platelet inhibitors, lipid lowering drugs and ß -blockers) and are
consistent in all sub-groups of patients. Perindopril should be used in chronic therapy in all patients with coronary
disease: As prof. Willem Remme concluded: "We now have sufficient evidence to show that perindopril, due to its
anti-atherogenic effects and blood pressure lowering properties is beneficial and should be used in treating all patients
with coronary artery disease".
Keywords: Benefit, Coversum, EUROPA-Studie, KHK, Koronare
Herzkrankheit, Nutzen, Perindopril, Servier Austria
GmbH
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