Axel Müller

Short- and long-term results of abciximab versus aspirin in conjunction with thrombolysis for patients with peripheral occlusive arterial disease and arterial thrombosis

Acute peripheral occlusive arterial disease is an important cause of morbidity and mortality, particularly among older persons. Catheter-directed thrombolytic therapy is the treatment of choice but has limitations: long lytic times, occlusions refractory to throm bolysis, and a high rate of restenosis. We conducted a pilot study to evaluate the use of the platelet GP IIb/IIIa receptor antagonist abciximab versus aspirin in conjunction with thrombolysis in patients with acute peripheral occlusive arterial disease associated with arterial thrombosis. A total of 84 patients were randomized into two equal groups to receive 5 mg recom binant tissue plasminogen activator intravenously and 500 IU heparin/hour along with either 500 mg acetylsalicylic acid or a bolus of 0.25 mg/kg abciximab followed by 10 μg/min abciximab over 12 hours (heparin reduced to 250 IU/hour). Primary efficacy criteria included the number of rehospitalizations, reinterventions, and amputations during the following 6 months. Secondary endpoints were the changes in the Fontaine stage, Bollinger index (vessel occlusion), ankle-to-brachial ratios, distance to claudication after 6 months, and the duration of the initial local lysis treatment. Adjunctive use of abciximab reduced the rates of rehospitalization, reinterventions, and amputations versus results with the use of aspirin (10 vs 14 occurrences, respec tively ; 9 vs 11; 3 vs 5; when summed, intergroup difference p < 0.05). Secondary periph eral occlusive arterial disease variables became highly significant versus aspirin (p < 0.001 or greater) at 3 and 6 months after treatment. The duration of lysis was markedly shorter upon addition of abciximab versus aspirin (75 vs 110 min; p < 0.001). No major bleeding complications or embolisms occurred. These preliminary results indicate that abciximab may have a useful role when used adjunctively with a thrombolytic agent in older persons with acute peripheral occlusive arterial disease and arterial thrombosis.

Potential use of a low-molecular-weight heparin to prevent restenosis in patients with extensive wall damage following peripheral angioplasty.

The long-term outcome of primary successful percutaneous transluminal angioplasty (PTA) for patients with peripheral occlusive arterial disease (POAD) is frequently compromised by the development of restenosis, especially when extensive dissections result from the angioplastic procedure. Unfortunately, prevention of the occlusive process by means of drugs such as antithrombotics, anticoagulants, thrombolytics, corticosteroids, lipid reducers, or cytostatics has not been demonstrated convincingly. The authors sought to clarify whether such patients could benefit from the postsurgical administration of low-molecular-weight heparin. A total of 172 POAD patients with extensive dissections after PTA in the pelvic or upper leg regions were randomized for 7-day post-PTA intravenous treatment with either full heparinization or nadroparin calcium followed by adjunctive oral aspirin for 6 months. The primary outcome measure was the degree of stenosis (normal findings; stenosis <50%, > 50%, >80%, occlusion) before and after angioplasty, as well as 3 weeks and 3 and 6 months after dilation; secondary efficacy criteria included changes in the Fontaine stage and in the cruro brachial ratio. No significant treatment-related differences were found at the 3 post-PTA follow-up exam inations with regard to the degree of stenosis. This was also the case for the subgroup of patients (n = 62) who had undergone angioplasty in the pelvic region. By contrast, when angio plasty was performed in the superficial femoral artery (n = 110), the degree of restenosis was significantly lower (p<0.01) among patients receiving nadroparin calcium compared to those given heparin at week 3, month 3, and month 6. No intergroup differences emerged for secondary outcome measures in the long term or for safety parameters. These preliminary results indicate that patients with extensive dissections after PTA treatment for POAD in the upper leg region might benefit from a reduction in the rate of restenosis by administration of 7-day weight-adjusted nadroparin calcium.

Telemedical support in patients with chronic heart failure: experience from different projects in Germany

The great epidemiological significance and costs associated with chronic heart failure pose a challenge to health systems in Western industrial countries. In the past few years, controlled randomised studies have shown that patients with chronic heart failure benefit from telemedical monitoring; specifically, telemonitoring of various vital parameters combined with a review of the symptoms, drug compliance and patient education. In Germany, various telemedical monitoring projects for patients with chronic heart failure have been initiated in the past few years; seven of them are presented here. Currently 7220 patients are being monitored in the seven selected projects. Most patients (51.1%) are in NYHA stage II, 26.3% in NYHA stage III, 14.5% in NYHA stage I and only 6.6% in NYHA stage IV respectively. Most projects are primarily regional. Their structure of telemedical monitoring tends to be modular and uses stratification according to the NYHA stages. All projects include medical or health economics assessments. The future of telemedical monitoring projects for patients with chronic heart failure will depend on the outcome of these assessments. Only of there is statistical evidence for medical benefit to the individual patient as well as cost savings will these projects continue.

Use of Abciximab and Tirofiban in Patients with Peripheral Arterial Occlusive Disease and Arterial Thrombosis

Acute peripheral arterial occlusive disease is an important factor affecting the mobility and mortality rate of elderly patients. Catheter-guided arterial thrombolysis in these patients has its limitations: long lysis times, early occlusions, and high restenosis rates. The study investi gated whether the use of tirofiban has the same favorable effect as the glycoprotein (GP) IIb/IIIa receptor antagonist abciximab and whether lysis times can be shortened and the disease course positively influenced by these substances. Sixty patients were randomly assigned to 2 groups. Each group received 5 mg recombinant tissue-type (rt-PA) plasminogen activator by slow intra-arterial injection for 10 minutes followed by 5 mg rt-PA per hour and 500 IU heparin per hour IV. After randomization 1 group received a bolus of 0.25 mg abciximab per kg body weight followed by 10 mg per minute IV for 12 hours (heparin was reduced to 250 IU/hr). The other group received a bolus of 0.4 μg tirofiban per kg body weight as well as postinterventional medication with 0.1 μg tirofiban per minute and kg body weight for 24 hours. During medication with GP IIb/IIIa inhibitor, the patients received a reduced heparin dosage for 24 hours. After 24 hours both groups received 200 mg aspirin orally and full heparinization controlled on the basis of the partial thromboplastin time. The following efficacy criteria were analyzed: rehospitalization events, reintervention events, and amputations within 6 months. Secondary endpoints were changes in the Fontaine stage, the crurobrachial index, the distance to claudication, and the duration of local arterial lysis. No significant differences were found between the abciximab and tirofiban groups in terms of the rehospitalization, rein tervention, or amputation rates, nor were there any group differences in the total number of events. The secondary parameters, such as the crurobrachial index, distance to claudication, and Fontaine stage, also showed no significant differences between the 2 groups within 6 months. The duration of lysis was significantly shorter in the abciximab group. Major bleeding events did not occur in either group. With regard to the adverse effect rate, there were no significant differences between the 2 groups. Both abciximab and tirofiban can be used successfully in patients with peripheral arterial occlusive disease and arterial thrombosis.

Remote Monitoring in Patients with Pacemakers and Implantable Cardioverter-Defibrillators: New Perspectives for Complex Therapeutic Management

Axel Muller1, Thomas M. Helms2, Hans-Jurgen Wildau3, Jorg Otto Schwab4 and Christian Zugck5 1Klinik fur Innere Medizin I der Klinikum Chemnitz gGmbH Burgerstr. 2, D-09113 Chemnitz, 2Deutsche Stiftung fur chronisch Kranke, Alexanderstrase 26, D-90762 Furth, 3BIOTRONIK SE Co,Woermannkehre 1, D-12359 Berlin, 4Universitatsklinikum Bonn, Medizinische Klinik und Poliklinik II, Sigmund-Freud-Str. 25, D-53105 Bonn, 5Universitatsklinikum Heidelberg, Innere Medizin III (Kardiologie, Angiologie und Pulmologie), Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany

Current status of antihypertensive drug treatment in primary care practice at launch of the new renin inhibitor aliskiren (RASANT)

ZusammenfassungZiel:Mit dem Versorgungsforschungsprojekt „Praxis-Screening zur medikamentösen Behandlung der essentiellen Hypertonie“ wurden zum Zeitpunkt der Einführung einer neuen Klasse von Antihypertensiva – dem ersten oral ausreichend bioverfügbaren direkten Renininhibitor Aliskiren – in Deutschland der Status quo der antihypertensiven Behandlung sowie der mögliche therapeutische Stellenwert dieses neuen Therapieprinzips evaluiert.Methodik:Mittels Praxisfragebögen wurden niedergelassene Allgemeinmediziner und Internisten in 1 431 Arztpraxen zur Bedeutung und therapeutischen Stellung einzelner Präparategruppen zur Behandlung der arteriellen Hypertonie im 3. und 4. Quartal 2007 befragt. Zusätzlich sollten die Ärzte mögliche Vorteile des pharmakologischen Prinzips der direkten Reninhemmung darlegen und geeignete Kombinationspartner benennen. Mit Hilfe eines zweiten Fragebogens (Patientenfragebogen) wurden epidemiologische Daten (Alter, Geschlecht, Komorbiditäten) zu einzelnen Patienten erhoben, die in der jeweiligen Praxis aufgrund unzureichenden Ansprechens der bisher durchgeführten antihypertensiven Pharmakotherapie für eine Therapie mit Aliskiren vorgesehen waren.Ergebnisse:In einer Skala von 1 (sehr wichtig) bis 6 (unwichtig) wurden von den Ärzten Angiotensin-converting-Enzym-(ACE-)Hemmer (98,8%), Angiotensin-(AT)1-Rezeptor-Blocker (87,4%), β-Rezeptoren-Blocker (71,2%), Calciumantagonisten (58,9%), Thiaziddiuretika (56,3%) und Schleifendiuretika (32,3%) mit den Noten 1 und 2 bewertet. Von insgesamt 14 358 Patienten wurden Alter, Geschlecht, Schweregrad und Dauer der arteriellen Hypertonie, Komplikationen und Begleiterkrankungen sowie detaillierte Angaben zur vorbestehenden medikamentösen Therapie der arteriellen Hypertonie erhoben. 50,3% der Patienten waren auf ACE-Hemmer und 27,9% auf AT1-Rezeptor-Blocker eingestellt. 45,7% der Patienten wurden mit einem β-Rezeptoren-Blocker und 37,5% mit einem Calciumantagonisten behandelt. 53,2% der Patienten erhielten ein Diuretikum. Bei den Komplikationen bzw. Begleiterkrankungen zum Zeitpunkt der Datenerhebung dominierten bei den Patienten in den teilnehmenden Praxen Diabetes mellitus (43,8%), koronare Herzkrankheit (37,3%) und chronische Herzinsuffizienz (20,7%). 89,4% aller Patienten mit Diabetes mellitus erhielten entweder einen ACE-Hemmer oder einen AT1-Rezeptor-Blocker im Vergleich zu 69,6% der Patienten ohne Diabetes mellitus.Schlussfolgerung:Die therapeutische Rolle in der antihypertensiven Behandlung wird für Aliskiren vor allem in der Ergänzung einer vorbestehenden antihypertensiven Therapie bei Patienten mit schweren Hypertonieformen, länger bestehender Hypertonie und bei Komplikationen oder Begleiterkrankungen (z.B. Diabetes mellitus) gesehen. Der hohe Anteil von Patienten, insbesondere von Patienten mit Diabetes mellitus, die mit ACE-Hemmern oder mit AT1-Rezeptor-Blockern behandelt werden, spricht für eine hohe Leitlinienadhärenz im niedergelassenen Bereich. Kritisch ist jedoch die Einstufung von Schleifendiuretika als wichtige Antihypertensiva durch 32,3% der befragten Ärzte zu bewerten.AbstractPurpose:The present drug utilization research project was conducted in order to evaluate the current status of antihypertensive drug treatment at launch of aliskiren – a drug targeting a completely new pharmacological mode of action – and to investigate the potential therapeutic value of this new therapeutic principle.Methods:In 1,431 primary care practices in Germany, general practitioners and internal specialists were requested to determine the therapeutic value of different antihypertensive drugs (3rd and 4th quarter of 2007). Physicians were also requested to expose potential advantages of the new therapeutic principle of direct renin inhibition. Additional epidemiologic data such as age, gender and comorbidities were collected for each antihypertensive patient considered an optimal candidate to receive aliskiren in the respective medical practice due to an unfavorable response to the current antihypertensive treatment by using a second questionnaire.Results:On a scale between 1 (very important) and 6 (unimportant), the therapeutic value of antihypertensive drugs was judged as follows: angiotensin-inhibiting enzyme (ACE) inhibitors (98.8%), angiotensin (AT)1 receptor blockers (87.4%), β-receptor blockers (71.2%), calcium channel blockers (58.9%), thiazide diuretics (56,3%), and loop diuretics (32.3%) were judged with the mark 1 (very important) and 2 (important). From a total of 14,358 patients included in the present survey, age, gender, severity and duration of arterial hypertension, complications and comorbidities, and a detailed drug history were collected. 50.3% of the patients received an ACE inhibitor, 27.9% an AT1 receptor blocker, 45.7% a β-receptor blocker, 37.5% a calcium channel blocker, and 53.2% a diuretic. Dominating comorbidities up to the time of data collection were diabetes mellitus (43.8%), coronary heart disease (37.3%), and chronic heart failure (20.7%). 89.4% of patients with diabetes received either an ACE inhibitor or an AT1 receptor blocker compared to 69.6% of patients not suffering from diabetes.Conclusion:According to the evaluation of primary care physicians participating in this study, aliskiren might be useful for antihypertensive treatment in patients with severe arterial hypertension, in patients with an already long-lasting course of disease, and in the presence of comorbidities such as diabetes mellitus. The high percentage of patients in this study cohort already treated with an ACE inhibitor or an AT1 receptor blocker represents good adherence of primary care physicians to current treatment guidelines. The evaluation of loop diuretics as important antihypertensive drugs by 32.3% of attending physicians in this study requires critical discussion.PURPOSE The present drug utilization research project was conducted in order to evaluate the current status of antihypertensive drug treatment at launch of aliskiren - a drug targeting a completely new pharmacological mode of action - and to investigate the potential therapeutic value of this new therapeutic principle. METHODS In 1,431 primary care practices in Germany, general practitioners and internal specialists were requested to determine the therapeutic value of different antihypertensive drugs (3rd and 4th quarter of 2007). Physicians were also requested to expose potential advantages of the new therapeutic principle of direct renin inhibition. Additional epidemiologic data such as age, gender and comorbidities were collected for each antihypertensive patient considered an optimal candidate to receive aliskiren in the respective medical practice due to an unfavorable response to the current antihypertensive treatment by using a second questionnaire. RESULTS On a scale between 1 (very important) and 6 (unimportant), the therapeutic value of antihypertensive drugs was judged as follows: angiotensin-inhibiting enzyme (ACE) inhibitors (98.8%), angiotensin (AT)(1) receptor blockers (87.4%), beta-receptor blockers (71.2%), calcium channel blockers (58.9%), thiazide diuretics (56,3%), and loop diuretics (32.3%) were judged with the mark 1 (very important) and 2 (important). From a total of 14,358 patients included in the present survey, age, gender, severity and duration of arterial hypertension, complications and comorbidities, and a detailed drug history were collected. 50.3% of the patients received an ACE inhibitor, 27.9% an AT(1) receptor blocker, 45.7% a beta-receptor blocker, 37.5% a calcium channel blocker, and 53.2% a diuretic. Dominating comorbidities up to the time of data collection were diabetes mellitus (43.8%), coronary heart disease (37.3%), and chronic heart failure (20.7%). 89.4% of patients with diabetes received either an ACE inhibitor or an AT(1) receptor blocker compared to 69.6% of patients not suffering from diabetes. CONCLUSION According to the evaluation of primary care physicians participating in this study, aliskiren might be useful for antihypertensive treatment in patients with severe arterial hypertension, in patients with an already long-lasting course of disease, and in the presence of comorbidities such as diabetes mellitus. The high percentage of patients in this study cohort already treated with an ACE inhibitor or an AT(1) receptor blocker represents good adherence of primary care physicians to current treatment guidelines. The evaluation of loop diuretics as important antihypertensive drugs by 32.3% of attending physicians in this study requires critical discussion.

Der Einfluss von Ursachenzuschreibungen auf Lebensqualität und Lebenszufriedenheit bei chronischen Erkrankungen: Ergebnisse einer Längsschnittuntersuchung

Die vorliegende Studie geht der Frage nach, welche Bedingungen Personen mit chronischen Erkrankungen ein moglichst hohes Ausmas und psychischem Wohlbefinden ermoglichen. Wir nehmen an, dass hierbei kognitiven Prozessen, insbesondere Ursachenzuschreibungen (Attributionen) eine Schlusselfunktion zukommt. Anhand eines langsschnittlichen Untersuchungsdesigns mit N = 129 Personen untersuchen wir die Auswirkungen von Attributionen auf subjektive Lebenszufriedenheit und Wohlbefinden bei Personen mit Diabetes mellitus und koronaren Herzerkrankungen. Attributionen, psychisches und physisches Wohlbefinden sowie die subjektive Lebenszufriedenheit wurden wahrend des Aufenthaltes der Patienten im Klinikum Chemnitz sowie nach einem durchschnittlichen Follow-up-Zeitraum von 3 Jahren erfasst. Patienten, die sich zur Baseline-Messung hohe Verantwortung fur ihre Erkrankung zuschreiben, berichten 3 Jahre spater uber signifikant geringere Lebensqualitat. Bei Patienten mit Diabetes mellitus zeigt sich zudem ein signifikanter Einfluss von Stress als wahrgenommener Ursache der Erkrankung auf ein geringeres physisches und psychisches Wohlbefinden. Attributionen auf Vererbung fuhren hingegen zu einer signifikant besseren subjektiven Lebenszufriedenheit dieser Patienten zum Zeitpunkt der Follow-up-Erhebung. Die Ergebnisse werden im Hinblick auf ihre Implikationen fur tertiar-praventive Masahmen diskutiert.

Der tragbare Kardioverter-Defibrillator

While the implantable cardioverter-defibrillator (ICD) has been proven to be the best choice for patients with long-term risk for sudden cardiac arrest/sudden cardiac death (SCA/SCD), the question is how to manage patients with only temporary risk, e.g., during the guidelines-recommended waiting period until the decision for an ICD can be made. These patient groups should be monitored around the clock to guarantee a lifesaving shock within a few minutes, if necessary.These conditions can be accomplished by the wearable cardioverter-defibrillator (WCD) in the outpatient sector. The WCD is worn on the skin and consists of four nonadhesive ECG electrodes as well as three defibrillation electrodes-two at the back and one at the front-embedded in a garment. The defibrillation unit is connected via a cord and can be worn over the shoulder or on a belt. Cardiac events can be recorded and retrospectively analyzed by the treating physician.The WCD is a safe and effective measure to terminate potentially lethal ventricular tachycardia and ventricular fibrillation. It may be used early after myocardial infarction with reduced left ventricular ejection fraction (LVEF), as well as for patients with acute heart failure in nonischemic cardiomyopathy with uncertain cause and prognosis. In addition, it may be used for patients waiting for heart transplantation, for patients who cannot be implanted an ICD due to comorbidities, and for patients after explantation of their ICD, e.g., because of infection until reimplantation.One may expect that risk stratification of patients with the WCD will lead to even better selection for ICD use.

[The Wearable Cardioverter-Defibrillator (WCD)].

While the implantable cardioverter-defibrillator (ICD) has been proven to be the best choice for patients with long-term risk for sudden cardiac arrest/sudden cardiac death (SCA/SCD), the question is how to manage patients with only temporary risk, e.g., during the guidelines-recommended waiting period until the decision for an ICD can be made. These patient groups should be monitored around the clock to guarantee a lifesaving shock within a few minutes, if necessary.These conditions can be accomplished by the wearable cardioverter-defibrillator (WCD) in the outpatient sector. The WCD is worn on the skin and consists of four nonadhesive ECG electrodes as well as three defibrillation electrodes-two at the back and one at the front-embedded in a garment. The defibrillation unit is connected via a cord and can be worn over the shoulder or on a belt. Cardiac events can be recorded and retrospectively analyzed by the treating physician.The WCD is a safe and effective measure to terminate potentially lethal ventricular tachycardia and ventricular fibrillation. It may be used early after myocardial infarction with reduced left ventricular ejection fraction (LVEF), as well as for patients with acute heart failure in nonischemic cardiomyopathy with uncertain cause and prognosis. In addition, it may be used for patients waiting for heart transplantation, for patients who cannot be implanted an ICD due to comorbidities, and for patients after explantation of their ICD, e.g., because of infection until reimplantation.One may expect that risk stratification of patients with the WCD will lead to even better selection for ICD use.

Der tragbare Kardioverter-Defibrillator@@@The Wearable Cardioverter-Defibrillator (WCD)

While the implantable cardioverter-defibrillator (ICD) has been proven to be the best choice for patients with long-term risk for sudden cardiac arrest/sudden cardiac death (SCA/SCD), the question is how to manage patients with only temporary risk, e.g., during the guidelines-recommended waiting period until the decision for an ICD can be made. These patient groups should be monitored around the clock to guarantee a lifesaving shock within a few minutes, if necessary.These conditions can be accomplished by the wearable cardioverter-defibrillator (WCD) in the outpatient sector. The WCD is worn on the skin and consists of four nonadhesive ECG electrodes as well as three defibrillation electrodes-two at the back and one at the front-embedded in a garment. The defibrillation unit is connected via a cord and can be worn over the shoulder or on a belt. Cardiac events can be recorded and retrospectively analyzed by the treating physician.The WCD is a safe and effective measure to terminate potentially lethal ventricular tachycardia and ventricular fibrillation. It may be used early after myocardial infarction with reduced left ventricular ejection fraction (LVEF), as well as for patients with acute heart failure in nonischemic cardiomyopathy with uncertain cause and prognosis. In addition, it may be used for patients waiting for heart transplantation, for patients who cannot be implanted an ICD due to comorbidities, and for patients after explantation of their ICD, e.g., because of infection until reimplantation.One may expect that risk stratification of patients with the WCD will lead to even better selection for ICD use.