DE19503995C2 - Use of carvedilol to reduce mortality in patients with myocardial impairment - Google Patents
Use of carvedilol to reduce mortality in patients with myocardial impairmentInfo
- Publication number
- DE19503995C2 DE19503995C2 DE1995103995 DE19503995A DE19503995C2 DE 19503995 C2 DE19503995 C2 DE 19503995C2 DE 1995103995 DE1995103995 DE 1995103995 DE 19503995 A DE19503995 A DE 19503995A DE 19503995 C2 DE19503995 C2 DE 19503995C2
- Authority
- DE
- Germany
- Prior art keywords
- patients
- carvedilol
- mortality
- reduce mortality
- studies
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
Description
Carvedilol (chem. Name: 1-(4-Carbazolyloxy)-3-[2-(2-methoxyphenoxy)-ethyl amino]-2-propanol) ist Gegenstand des europäischen Patentes Nr. 0 004 920 und wird als Arzneimittel zur Behandlung der Hypertonie und Angina Pectoris beschrieben. Die pharmakologische Wirkung ist auf eine β-rezeptorenblockie rende Aktivität mit vasolilatierenden Eigenschaften zurückzuführen. Die Sub stanz ist zwischenzeitlich unter der Bezeichnung Dilatrend® in Deutschland auf dem Markt (vgl. Rote Liste 1994). Als Indikation ist die Behandlung der essentiellen Hypertonie angegeben in einer Dosierung von 25 mg Carvedilol pro Tag, beginnend mit 12,5 mg an den ersten beiden Tagen.Carvedilol (chemical name: 1- (4-carbazolyloxy) -3- [2- (2-methoxyphenoxy) ethyl amino] -2-propanol) is the subject of European Patent No. 0 004 920 and is used as a medicine to treat hypertension and angina pectoris described. The pharmacological effect is on a β-receptor block activity with vasolilating properties. The sub stanz is now known as Dilatrend® in Germany on the market (see Red List 1994). Treatment is the indication essential hypertension indicated in a dosage of 25 mg carvedilol per day, starting with 12.5 mg on the first two days.
Obwohl β-Rezeptorenblocker generell bei herzinsuffizienten Patienten kontra indiziert sind, gibt es Hinweise dafür, daß einzelne Patienten von einer Be handlung mit β-Rezeptorenblockern profitieren (z. B. durch Erhöhung der Ejektions-Fraktion).Although β-receptor blockers are generally contraindicated in heart failure patients are indicated, there is evidence that individual patients from a Be action with β-receptor blockers benefit (e.g. by increasing the Ejection fraction).
In J. Cardiovasc. Pharmacol. 19 (Suppl.), 138-141(1992); Cardiology 82 (Suppl.), 24-28 (1993); and J. Hypertension 11 (Suppl. 4), 41-48 (1993) wird gezeigt, daß Carvedilol bei akuter Anwendung in der Lage ist, die Größe eines experimentell erzeugten Herzinfarktes bei Versuchstieren zu vermindern.In J. Cardiovasc. Pharmacol. 19 (Suppl.), 138-141 (1992); Cardiology 82 (Suppl.), 24-28 (1993); and J. Hypertension 11 (Suppl. 4), 41-48 (1993) shown that Carvedilol is capable of the size of an acute application to reduce experimentally generated heart attacks in experimental animals.
In Drugs 45 (2), Seiten 232-258 (1993) wird erwähnt, daß Carvedilol bei Patienten mit einer ischämischen Herzinsuffizienz die Auswurfleistung des Herzens erhöht. Keine dieser Publikationen weist auf den Nutzen einer Langzeitbehandlung von Carvedilol zur Vermeidung der Mortalität bei verschiedenen Formen der eingeschränkten myocardialen Funktion hin.In Drugs 45 (2), pages 232-258 (1993) it is mentioned that Carvedilol in Patients with ischemic heart failure have an ejection performance of Heart raised. None of these publications indicate the benefit of one Long-term treatment of carvedilol to avoid mortality various forms of restricted myocardial function.
Zwei Mortalitätsuntersuchungen mit den β-Blockern Metoprolol und mit Biso prolol haben folgendes ergeben: In der Studie mit Metoprolol (Waagstein et al. 1993) wurden nur Patienten mit eingeschränkter myocardialer Funktion auf der Grundlage nicht-ischämischer Herzerkrankungen eingeschlossen. Es wurden keine signifikanten Unterschiede in der Mortalität im Vergleich zu einer Place bo-Gruppe gefunden. In der Bisoprolol-Studie (CIBIS investigators, 1994) wur den auch Patienten mit eingeschränkter myocardialer Funktion auf der Grund lage ischämischer Herzerkrankungen (z. B. nach Myocard-Infarkt) eingeschlos sen. In dieser Studie ergab sich ebenfalls im Gesamtkollektiv kein signifikanter Unterschied in der Mortalität zwischen Bisoprolol- und Placebo-Behandlung.Two mortality studies with the beta-blockers metoprolol and with biso prolol have shown the following: In the study with metoprolol (Waagstein et al. 1993), only patients with impaired myocardial function on the Basis of non-ischemic heart disease included. There were no significant differences in mortality compared to a place bo group found. In the bisoprolol study (CIBIS investigators, 1994) to the bottom of patients with impaired myocardial function location of ischemic heart disease (e.g. after myocardial infarction) included sen. In this study, there was also no significant result in the overall collective Difference in mortality between bisoprolol and placebo treatment.
Die Senkung des Mortalitätsrisikos in solchen Patientenkollektiven ist ein medizinischer Behandlungszweck, weil es - unabhängig von den β-Blockern - mehrere andere Medikamente gibt, die eine vorübergehende Verbesserung der Befindlichkeit der Patienten bewirken, aber das Mortalitätsrisiko sogar eher erhöhen (z. B. Phosphodiesterase-Hemmer wie Milrinon, milde β-Sympa tho-mimetica wie Xamoterol oder Flosequinan).The reduction in mortality risk in such patient populations is one medical treatment purpose because - regardless of the β-blockers - several other medications out there that are a temporary improvement of the patient's condition, but even the mortality risk rather increase (e.g. phosphodiesterase inhibitors such as milrinone, mild β-sympa tho-mimetica such as xamoterol or flosequinan).
Überraschenderweise wurde nun in mehreren Studien mit Carvedilol bei Pati enten mit eingeschränkter myocardialer Funktion gefunden, daß die Mortali tätsrate deutlich gesenkt wird (im Mittel um 60% gegenüber einer Placebo- Behandlung).Surprisingly, in several studies with Carvedilol at Pati ducks with reduced myocardial function found that the Mortali rate is significantly reduced (on average by 60% compared to a placebo Treatment).
Die Studien wurden folgendermaßen durchgeführt:The studies were carried out as follows:
Alle Patienten waren mit den z. Zt. in der Therapie zur Behandlung einer eingeschränkten myocardialen Funktion etablierten Medikamenten vorbehan delt (Digitalis-Glykoside + Diuretica + ACE-Hemmer). Trotz dieser intensiven Therapie war der Therapieerfolg unzureichend. In dem doppelblinden Studien design erhielten die Patienten zusätzlich Carvedilol oder ein Placebo. Alle Pa tienten wurden über einen Zeitraum von ca. 6 Monaten behandelt. Im Gegen satz zu den Dosen bei der Behandlung der Hypertonie wurden die Patienten mit Eingangsdosen von 3,125 mg oder 6,25 mg Carvedilol pro Tag über 14 Tage behandelt. Danach waren Dosissteigerungen jeweils im Abstand von 14 Tagen möglich bis zu einer Maximal-Dosis von 2 × 25 mg Carvedilol/Tag.All patients were with the z. Currently in therapy for the treatment of a Restricted myocardial function to established drugs delt (digitalis glycosides + diuretics + ACE inhibitors). Despite this intense Therapy was insufficient therapy success. In the double-blind studies design, the patients also received Carvedilol or a placebo. All pa patients were treated over a period of about 6 months. In the opposite Patients were treated with doses in the treatment of hypertension with intakes of 3.125 mg or 6.25 mg carvedilol per day over 14 Days treated. Thereafter, dose increases were at intervals of 14 days possible up to a maximum dose of 2 × 25 mg carvedilol / day.
Die nachfolgende Tabelle zeigt die Mortalitätsraten in vier repräsentativen Studien. Aus den Daten kann eine überraschende Verminderung des Mortali tätsrisikos abgeleitet werden. The table below shows the mortality rates in four representative Studies. A surprising reduction in Mortali can be derived from the data incidence risks are derived.
221 ist eine in den USA durchgeführte Studie und ist im Protokoll ähnlich wie die anderen US-Studien (220, 239, 240). Die Studie 223 wurde in Australien und Neuseeland durchgeführt. Auf den beiden Zusammenfassungen gibt es den Absatz "Prior and Concomitant Medications". Es geht daraus hervor, daß in der US-Studie über 90% der Patienten mit der Dreierkombination Digoxin + Diuretikum + ACE-Hemmer vorbehandelt waren. Anders war es in der Australien/Neuseeland-Studie. Dort bekamen weit weniger Patienten Digitalis- Glykoside und auch Diuretika wurden nur bei rund 75% eingesetzt. Daraus läßt sich ableiten, daß Carvedilol in verschiedenen Kombinationen mit den einzelnen anderen Substanzen eingesetzt worden ist. Die Ergebnisse dieser Studien 221 und 223 sind auch kurz erläutert.221 is a study conducted in the United States and is similar in protocol to the other US studies (220, 239, 240). Study 223 was in Australia and New Zealand. On the two summaries there are the paragraph "Prior and Concomitant Medications". It follows that in the US study, over 90% of patients with the triple digoxin + Diuretic + ACE inhibitors were pretreated. It was different in the Australia / New Zealand study. There, far fewer patients got digitalis Glycosides and diuretics were only used in around 75%. Out of it can be deduced that Carvedilol in various combinations with the individual other substances has been used. The results of this Studies 221 and 223 are also briefly explained.
Überraschend war ferner, daß die Mortalitätsrate bei Patienten mit einge schränkter myocardialer Funktion auf der Grundlage ischämischer Herzerkran kungen im gleichen Umfang zu beobachten war wie die auf der Grundlage ei ner nicht ischämischen Herzerkrankung. Außerdem ist anzumerken, daß die Senkung der Mortalitätsrate höher ist als die in den bisherigen mit ACE-Hem mern durchgeführten Studien (Anmerkung: In der CONSENSUS-Studie waren nur Patienten mit schwerer Herzinsuffizienz eingeschlossen).It was also surprising that the mortality rate in patients with impaired myocardial function based on ischemic heart crane was observed to the same extent as that based on egg a non-ischemic heart disease. It should also be noted that the Lowering the mortality rate is higher than that in previous ACE-Hem studies carried out (note: in the CONSENSUS study only patients with severe heart failure included).
Zum Vergleich des mortalitätsmindernden Effektes bei Patienten mit einge schränkter myocardialer Funktion wird auf die nachfolgenden verschiedenen Studien hingewiesen:To compare the mortality-reducing effect in patients with restricted myocardial function is different on the following Studies noted:
Von besonderer Bedeutung ist, daß der Nutzen von Carvedilol zusätzlich zu den der ACE-Hemmer eintritt, da alle Patienten in den Carvedilol-Studien mit ACE-Hemmern während der gesamten Studiendauer behandelt waren.Of particular importance is that the benefits of Carvedilol are additional which the ACE inhibitor occurs because all patients in the Carvedilol studies with ACE inhibitors were treated throughout the study period.
Claims (1)
Priority Applications (34)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE1995103995 DE19503995C2 (en) | 1995-02-08 | 1995-02-08 | Use of carvedilol to reduce mortality in patients with myocardial impairment |
US08/483,635 US5760069A (en) | 1995-02-08 | 1995-06-07 | Method of treatment for decreasing mortality resulting from congestive heart failure |
DE69602424T DE69602424T2 (en) | 1995-02-08 | 1996-02-07 | USE OF CARBAZOLIC COMPOUNDS FOR PRODUCING A MEDICINAL PRODUCT FOR TREATING CONGESTIVE HEART FAILURE |
PCT/EP1996/000498 WO1996024348A2 (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds for the treatment of congestive heart failure |
BR9607111A BR9607111A (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds for the treatment of congestive heart failure |
DK96902984T DK0808162T3 (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds to treat congestive heart failure |
SI9630081T SI0808162T1 (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds for the manufacture of a medicament for the treatment of congestive heart failure |
RO97-01454A RO121629B1 (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds for preparing a medicine for congestive cardiac failure treatment |
US10/721,022 USRE40707E1 (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds for the treatment of congestive heart failure |
CN96192902A CN1093760C (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds for treating congestive heart failure |
AU47181/96A AU702106C (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds for the treatment of congestive heart failure |
SK1068-97A SK106897A3 (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds for the treatment of congestive heart failure |
RU97114836/14A RU2197242C2 (en) | 1995-02-08 | 1996-02-07 | Method for decreasing a lethality rate as a result of a static heart failure by using carvedilol |
PL96321737A PL321737A1 (en) | 1995-02-08 | 1996-02-07 | Application of carbazoles for treating haemostatic cardiac insufficiency |
JP52398296A JP3546058B2 (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds in the treatment of congestive heart failure |
EP96902984A EP0808162B1 (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds for the manufacture of a medicament for the treatment of congestive heart failure |
CZ19972463A CZ292002B6 (en) | 1995-02-08 | 1996-02-07 | Medicament for decreasing mortality resulting from congestive heart failure in mammals |
KR1019970705480A KR100295940B1 (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds for the treatment of congestive heart failure |
ES96902984T ES2134588T3 (en) | 1995-02-08 | 1996-02-07 | USE OF CARBAZOLE COMPOUNDS FOR THE PREPARATION OF A MEDICATION FOR THE TREATMENT OF CONGESTIVE HEART FAILURE. |
NZ301692A NZ301692A (en) | 1995-02-08 | 1996-02-07 | Use of a compound which is both a beta adrenoreceptor antagonist and a alpha-1 adrenoreceptor antagonist especially carvedilol to treat congestive heart failure either on its own or with an angiotensin converting enzyme inhibitor, diuretic and/or cardiac glycoside |
US08/875,603 US5902821A (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds for the treatment of congestive heart failure |
AT96902984T ATE179891T1 (en) | 1995-02-08 | 1996-02-07 | USE OF CARBAZOLE COMPOUNDS IN THE PRODUCTION OF A MEDICINAL PRODUCT FOR THE TREATMENT OF CONGESTIVE HEART FAILURE |
CA002212548A CA2212548C (en) | 1995-02-08 | 1996-02-07 | Use of carbazole compounds for the treatment of congestive heart failure |
HU9900773A HUP9900773A3 (en) | 1995-02-08 | 1996-02-07 | Use of carbazole derivatives for producing pharmaceutical compositions suitable for the treatment of congestive heart failure |
ZA9600994A ZA96994B (en) | 1995-02-08 | 1996-02-08 | Method of treatment for decreasing mortality resulting from congestive heart failure. |
UA97094498A UA55382C2 (en) | 1995-02-08 | 1996-07-02 | Active ingredient of drug used for decreasing mortality resulting from congestive heart failure and method for treatment employing carbasol compounds |
FI973255A FI973255A (en) | 1995-02-08 | 1997-08-07 | Use of carbazole compounds in the treatment of congestive heart failure |
MXPA/A/1997/006042A MXPA97006042A (en) | 1995-02-08 | 1997-08-07 | Use of carbazol compounds for the treatment of cardiac congest insufficiency |
NO19973667A NO314830B1 (en) | 1995-02-08 | 1997-08-08 | Use of carvedilol in the manufacture of a medicament for the treatment of congestive heart failure |
HK98112352A HK1014861A1 (en) | 1995-02-08 | 1998-11-26 | Use of carbazole compounds in the manufacture of a medicament for the treatment of congestive heart failure |
GR990402047T GR3030966T3 (en) | 1995-02-08 | 1999-08-11 | Use of carbazole compounds for the treatment of congestive heart failure |
US09/863,535 US20010044455A1 (en) | 1995-02-08 | 2001-05-23 | Method of treatment for decreasing mortality resulting from congestive heat failure |
US10/324,856 US20030105138A1 (en) | 1995-02-08 | 2002-12-19 | Method of treatment for decreasing mortality resulting from congestive heart failure |
US10/721,020 USRE40000E1 (en) | 1995-02-08 | 2003-11-25 | Method of treatment for decreasing mortality resulting from congestive heart failure |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE1995103995 DE19503995C2 (en) | 1995-02-08 | 1995-02-08 | Use of carvedilol to reduce mortality in patients with myocardial impairment |
Publications (2)
Publication Number | Publication Date |
---|---|
DE19503995A1 DE19503995A1 (en) | 1996-08-22 |
DE19503995C2 true DE19503995C2 (en) | 1997-07-03 |
Family
ID=7753368
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE1995103995 Expired - Lifetime DE19503995C2 (en) | 1995-02-08 | 1995-02-08 | Use of carvedilol to reduce mortality in patients with myocardial impairment |
Country Status (1)
Country | Link |
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DE (1) | DE19503995C2 (en) |
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1995
- 1995-02-08 DE DE1995103995 patent/DE19503995C2/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
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DE19503995A1 (en) | 1996-08-22 |
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Legal Events
Date | Code | Title | Description |
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OP8 | Request for examination as to paragraph 44 patent law | ||
D2 | Grant after examination | ||
8364 | No opposition during term of opposition | ||
8327 | Change in the person/name/address of the patent owner |
Owner name: ROCHE DIAGNOSTICS GMBH, 68305 MANNHEIM, DE |
|
8310 | Action for declaration of annulment | ||
8330 | Complete disclaimer | ||
8327 | Change in the person/name/address of the patent owner |
Owner name: F. HOFFMANN-LA ROCHE AG, BASEL, CH |