Birgit Frilling

Antibiotic Therapy After Acute Myocardial Infarction

Background—Infection with Chlamydia pneumoniae is suspected to contribute to the pathogenesis of human atherosclerosis. We investigated whether treatment with the macrolide antibiotic roxithromycin would reduce mortality or morbidity in patients with an acute myocardial infarction. Methods and Results—Eight hundred seventy-two patients with an acute myocardial infarction (AMI) were randomly assigned to receive double-blind treatment with either 300 mg roxithromycin or placebo daily for 6 weeks. Primary end point was total mortality during 12-month follow-up. Four hundred thirty-three patients were treated with roxithromycin and 439 with placebo. With the exception of a higher proportion of patients suffering an anterior wall AMI (48.1% in the roxithromycin group versus 40.2% in the placebo group;P =0.027) and a lower prevalence of chronic obstructive pulmonary disease in the roxithromycin group (3.5% versus 6.9%, P =0.028), baseline characteristics, reperfusion therapy, and medical treatment were well balanced between the two groups. More patients in the roxithromycin group interrupted their study medication before completion of at least 4 weeks of treatment (78 of 433 [18%] versus 48 of 439 [11%];P =0.003; odds ratio, 1.8; 95% CI, 1.2 to 2.6). Follow-up at 12 months was achieved in 868 of 872 (99.5%) patients. Total mortality at 12 months was 6.5% (28 of 431) in the roxithromycin group compared with 6.0% (26 of 437) in the placebo group (odds ratio, 1.1; 95% CI, 0.6 to 1.9;P =0.739). There were also no differences in the secondary combined end points at 12 months. Conclusions—Treatment of AMI patients with roxithromycin did not reduce event rates during 12 months of follow-up. Therefore, our findings do not support the routine use of antibiotic treatment with a macrolide in patients with AMI.

Comparison of efficacy and complication rates after percutaneous coronary interventions in patients with and without renal insufficiency treated with abciximab.

Risk factors for bleeding were found in varying rates in both groups of patients. Neither adjunctive heparin therapy nor risk factors for bleeding complications could sufficiently explain the significantly higher rates of peri-interventional bleeding among patients with impaired renal function. Multivariate analysis of the registry data showed an independent association of renal insufficiency with bleeding complications under abciximab (odds ratio 5.1; 95% confidence interval 1.9 to 13.8). Success rates after PCI under abciximab were comparable in patients with normal and impaired renal function. These data suggest that the effects of abciximab are not entirely independent of renal function. Further investigation of this subject is necessary to find the optimal regimen for patients with impaired renal funtion receiving this highly effective drug.

Reperfusion therapy for acute ST-elevation and non ST-elevation myocardial infarction: what can be achieved in daily clinical practice in unselected patients at an interventional center?

Background: In the year 2000 a new definition of acute myocardial infarction (AMI) was introduced, now differentiating ST segment elevation AMI (STEMI) from non-ST segment elevation AMI (NSTEMI). The characterization of AMI patients according to this definition is still incomplete. Methods and results: 888 consecutive AMI patients at a single interventional center were included: 493 (55.5%) STEMI and 395 (44.5%) NSTEMI patients. Median age of STEMI patients was four years lower compared to NSTEMI patients (62.8 versus 66.6 years, P<0.001). STEMI patients more often presented in cardiogenic shock (11.0% versus 2.0%, P<0.001) and after pre-hospital resuscitation (4.9% versus 0.8%, P<0.001). Catheterization was performed in 98.4% of STEMI and in 95.9% of NSTEMI patients (P<0.001). The circumflex artery was more often the culprit lesion in NSTEMI patients compared to STEMI patients (58.3% versus 48%, P=0.003). They also showed significantly more often a 3 vessel disease (41.4% versus 29.9%, P=0.002). Out of STEMI patients 10.1% were treated with medical therapy only compared to 27.2% of NSTEMI patients (P<0.001). Whereas PCI was performed more often in STEMI patients (84.3% versus 57.8%, P<0.001), CABG was used more often in NSTEMI patients (21.6% versus 9.1%, P<0.001). In-hospital death was 8.7% in STEMI compared to 4.8% in NSTEMI patients (P<0.001). Conclusions: In clinical practice STEMI and NSTEMI seem to occur with similar frequency. Invasive strategies were applied in a high percentage in both groups, however with different therapeutic consequences. In-hospital mortality was twice as high in STEMI compared to NSTEMI patients.

Antibody levels against Chlamydia pneumoniae and outcome of roxithromycin therapy in patients with acute myocardial infarction. Results from a sub-study of the randomised Antibiotic Therapy in Acute Myocardial Infarction (ANTIBIO) trial.

Die Ergebnisse verschiedener Studien zur Prävention kardiovaskulärer Ereignisse mittels Behandlung durch Makrolid-Antibiotika die gegen eine C. pneumoniae Infektion gerichtet sind, waren kontrovers. Die vorliegende Arbeit untersucht verschiedene Testsysteme zum Nachweis einer C. pneumoniae Infektion sowie den Effekt einer Behandlung mit Roxithromycin bei Patienten nach einem akuten Myokardinfarkt (AMI) in Abhängigkeit von ihrem Serostatus gegen C. pneumoniae. Wir analysierten das Blut von 160 Patienten der prospektiven randomisierten doppelblinden ANTIBIO-tische Therapie beim AMI (ANTIBIO-) Studie, die den Effekt einer Therapie mit Roxithromycin 300 mg/die über 6 Wochen bei Patienten mit AMI untersuchte. Anti-Chlamydia IgG-, IgA-, and IgM-Antikörper wurden mittels verschiedener Testsysteme bestimmt. Wir fanden eine gute Korrelation zwischen den beiden IgG und IgA Bestimmungsmethoden (r = 0,900, p < 0,001 und r = 0,878, p < 0,001), wobei es jedoch starke Unterschiede in der Prävalenz positiver Testergebnisse gab. Das führte zu nur moderaten Werten in der Konkordanzanalyse, ausgedrückt durch den Kappa Koeffizienten, für IgG κ = 0,611 (95% CI = 0,498– 0,724, p < 0,001) und für IgA κ = 0,431 (95% CI: 0,322–0,540, p < 0,001). Wir fanden keine Assoziation zwischen positiven C. pneumoniae Titern und der klinischen Ereignisrate während der 12-Monats-Nachbeobachtungsphase. Auch Patienten mit positiven C. pneumoniae Titern profitierten nicht von einer Roxithromycin Therapie (p = ns). In Abhängigkeit vom verwendeten Testsystem ergeben sich deutliche Unterschiede in der Prävalenz C. pneumoniae seropositiver Patienten. Die klinische Ereignisrate während der Nachbeobachtungszeit wurde weder durch den Serostatus gegen C. pneumoniae der Patienten, noch durch eine Behandlung mit Roxithromycin, unabhängig vom Serostatus, beeinflusst. Results of studies concerning prevention of cardiovascular disease by treatment with macrolide antibiotics targeting C. pneumoniae infection are still controversial. This study describes the results of different tests for infection with C. pneumoniae as well as the effect of treatment with roxithromycin in patients with acute myocardial infarction (AMI) in relation to their serostatus against C. pneumoniae. We analysed blood of 160 patients who came from the ANTIBIOtic therapy after an AMI (ANTIBIO-) study, a prospective, randomised, placebo-controlled, double-blind study to investigate the effect of roxithromycin 300 mg/OD for 6 weeks in patients with an AMI. Anti-Chlamydia IgG-, IgA-, and IgM-antibodies of these patients were analysed by means of different test systems. There was a good correlation between the two IgG and IgA methods (r = 0.900, p < 0.001 and r = 0.878, p < 0.001, respectively), but marked differences in the prevalence of positive tests. This resulted in only moderate concordance values, as expressed by the Kappa coefficients, for IgG κ = 0.611 (95% CI = 0.498–0.724, p < 0.001) and for IgA κ = 0.431 (95% CI: 0.322–0.540, p < 0.001). No significant association between positive C. pneumonia titers and the combined clinical endpoint during the 12 month follow-up could be found. In all test systems used, patients with positive anti-C. pneumoniae titers did not benefit from roxithromycin therapy (p = ns). Depending on the test system used, there are large differences in the prevalence of anti-C. pneumoniae seropositive patients. Clinical events during the 12 month follow-up after AMI did not depend on serostatus against C. pneumoniae and treatment with roxithromycin did not influence these events, independently of the serostatus against C. pneumoniae. However, the power of this subgroup analysis was low to detect small but significant differences.

Laboratory Monitoring of Heparin and the Combination of Heparin and the Platelet Glycoprotein IIb/IIIa Receptor Antibody Fragment Abciximab (c7E3) in Patients Undergoing Percutaneous Transluminal Coronary Angioplasty (PTCA)

Background: Previous studies in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) have restricted laboratory monitoring to the activated clotting time (ACT). It remains unknown whether the ACT-prolonging effect of abciximab is clinically equivalent to a comparable degree of anticoagulation by heparin.Patients and Methods: 30 patients undergoing PTCA received 100 IU of heparin/kg body weight. Another 30 patients received an initial bolus of 70 IU of heparin/kg + abciximab. We determined ACT, laboratory and on-site activated partial thromboplastin time (APTT) and plasma heparin levels.Results: Despite markedly different preintervention heparin dosing, the ACTs were not significantly different between groups. After termination of PTCA, the median ACTs of both study groups were nearly equivalent (267 vs. 272 s; p = 0.79). The median ACT-prolonging effect of abciximab could be equated with 0.68 IU/ml heparin. Both APTT assays were not suitable for monitoring the anticoagulant effects during PTCA due to their high sensitivity. By contrast, the plasma heparin levels clearly reflected the different heparin doses. The weak correlation (r = 0.23) between ACTs and heparin levels in patients receiving heparin + abciximab was due to excessively prolonged ACTs in six patients (540–1,245 s). These data could be attributed to an unusually high response to abciximab. By contrast, the ACT was a reliable measure of the anticoagulant effect of heparin in patients receiving exclusively heparin.Conclusions: ACT reflects both heparin and abciximab therapy, whereas heparin levels reflect only heparin dose. The APTT assays were not suitable for monitoring the anticoagulant effects during PTCA.Hintergrund: Die „activated clotting time“ (ACT) ist der Standard zur patientennahen Kontrolle der Gerinnungssituation während der perkutanen transluminalen koronaren Ballonangioplastie (PTCA). Die Auswirkungen einer kombinierten Gabe von Heparin und dem Glykoprotein-IIb/IIIa-Antagonisten Abciximab auf die ACT ist jedoch nur unzureichend untersucht.Patienten und Methoden: 30 Patienten, bei denen eine PTCA durchgeführt wurde, erhielten 100 IU Heparin/kg Körpergewicht als Bolus. Weitere 30 Patienten erhielten einen initialen Bolus von 70 IU Heparin/kg + Abciximab. Wir bestimmten die ACT im Katheterlabor, die aktivierte partielle Thromboplastinzeit (APTT) im Labor und als „point-of-care“-Messung sowie die Plasmaheparinspiegel.Ergebnisse:Trotz der unterschiedlichen präinterventionellen Heparindosen war die maximale ACT statistisch nicht unterschiedlich zwischen den Gruppen. Nach der PTCA war die mediane ACT beider Gruppen fast identisch (267 vs. 272 Sekunden; p = 0,79). Der mediane ACT-verlängernde Effekt von Abciximab entsprach etwa 0,68 IU/ml Heparin. Beide APTT-Assays waren auf Grund ihrer hohen Sensitivität nicht geeignet die Gerinnungseffekte der Medikamente während der PTCA zu messen. Im Gegensatz dazu gelang dies mit der Bestimmung der Plasmaheparinspiegel sehr gut. Die schwache Korrelation (r=0.23) zwischen der ACT und dem Heparinspiegel bei Patienten, die eine Kombination von Heparin und Abciximab erhielten, konnte auf exzessiv verlängerte ACT-Werte (540–1245 s) bei sechs Patienten zurückgeführt werden, was durch ein ungewöhnlich starkes Ansprechen auf Abciximab zurückzuführen war. Im Gegensatz dazu korrelierte die ACT bei den nur mit Heparin behandelten Patienten gut mit den Heparinspiegeln.Schlussfolgerungen:Während die ACT sowohl die Heparin- als auch die Abciximab-Therapie widerspiegelt, zeigen die Heparinspiegel lediglich den Heparineffekt an. Die APTT-Assays sind nicht geeignet, die Gerinnungssituation von Patienten während einer PTCA zu kontrollieren.

Antibody levels against Chlamydia pneumoniae and outcome of roxithromycin therapy in patients with acute myocardial infarction

Die Ergebnisse verschiedener Studien zur Prävention kardiovaskulärer Ereignisse mittels Behandlung durch Makrolid-Antibiotika die gegen eine C. pneumoniae Infektion gerichtet sind, waren kontrovers. Die vorliegende Arbeit untersucht verschiedene Testsysteme zum Nachweis einer C. pneumoniae Infektion sowie den Effekt einer Behandlung mit Roxithromycin bei Patienten nach einem akuten Myokardinfarkt (AMI) in Abhängigkeit von ihrem Serostatus gegen C. pneumoniae. Wir analysierten das Blut von 160 Patienten der prospektiven randomisierten doppelblinden ANTIBIO-tische Therapie beim AMI (ANTIBIO-) Studie, die den Effekt einer Therapie mit Roxithromycin 300 mg/die über 6 Wochen bei Patienten mit AMI untersuchte. Anti-Chlamydia IgG-, IgA-, and IgM-Antikörper wurden mittels verschiedener Testsysteme bestimmt. Wir fanden eine gute Korrelation zwischen den beiden IgG und IgA Bestimmungsmethoden (r = 0,900, p < 0,001 und r = 0,878, p < 0,001), wobei es jedoch starke Unterschiede in der Prävalenz positiver Testergebnisse gab. Das führte zu nur moderaten Werten in der Konkordanzanalyse, ausgedrückt durch den Kappa Koeffizienten, für IgG κ = 0,611 (95% CI = 0,498– 0,724, p < 0,001) und für IgA κ = 0,431 (95% CI: 0,322–0,540, p < 0,001). Wir fanden keine Assoziation zwischen positiven C. pneumoniae Titern und der klinischen Ereignisrate während der 12-Monats-Nachbeobachtungsphase. Auch Patienten mit positiven C. pneumoniae Titern profitierten nicht von einer Roxithromycin Therapie (p = ns). In Abhängigkeit vom verwendeten Testsystem ergeben sich deutliche Unterschiede in der Prävalenz C. pneumoniae seropositiver Patienten. Die klinische Ereignisrate während der Nachbeobachtungszeit wurde weder durch den Serostatus gegen C. pneumoniae der Patienten, noch durch eine Behandlung mit Roxithromycin, unabhängig vom Serostatus, beeinflusst. Results of studies concerning prevention of cardiovascular disease by treatment with macrolide antibiotics targeting C. pneumoniae infection are still controversial. This study describes the results of different tests for infection with C. pneumoniae as well as the effect of treatment with roxithromycin in patients with acute myocardial infarction (AMI) in relation to their serostatus against C. pneumoniae. We analysed blood of 160 patients who came from the ANTIBIOtic therapy after an AMI (ANTIBIO-) study, a prospective, randomised, placebo-controlled, double-blind study to investigate the effect of roxithromycin 300 mg/OD for 6 weeks in patients with an AMI. Anti-Chlamydia IgG-, IgA-, and IgM-antibodies of these patients were analysed by means of different test systems. There was a good correlation between the two IgG and IgA methods (r = 0.900, p < 0.001 and r = 0.878, p < 0.001, respectively), but marked differences in the prevalence of positive tests. This resulted in only moderate concordance values, as expressed by the Kappa coefficients, for IgG κ = 0.611 (95% CI = 0.498–0.724, p < 0.001) and for IgA κ = 0.431 (95% CI: 0.322–0.540, p < 0.001). No significant association between positive C. pneumonia titers and the combined clinical endpoint during the 12 month follow-up could be found. In all test systems used, patients with positive anti-C. pneumoniae titers did not benefit from roxithromycin therapy (p = ns). Depending on the test system used, there are large differences in the prevalence of anti-C. pneumoniae seropositive patients. Clinical events during the 12 month follow-up after AMI did not depend on serostatus against C. pneumoniae and treatment with roxithromycin did not influence these events, independently of the serostatus against C. pneumoniae. However, the power of this subgroup analysis was low to detect small but significant differences.

Antibody levels against Chlamydia pneumoniae and outcome of roxithromycin therapy in patients with acute myocardial infarction@@@Antikrper gegen Chlamydia pneumoniae und roxithromycin Therapie bei Patienten mit einem akuten Myokardinfarkt?Ergebnisse einer Substudie der randomisierten Antibiotischen Therapie beim Akuten Myokardinfarkt (ANTIBIO) Studie: Results from a sub-study of the randomised Antibiotic Therapy in Acute Myocardial Infarction (ANTIBIO) trial

Die Ergebnisse verschiedener Studien zur Prävention kardiovaskulärer Ereignisse mittels Behandlung durch Makrolid-Antibiotika die gegen eine C. pneumoniae Infektion gerichtet sind, waren kontrovers. Die vorliegende Arbeit untersucht verschiedene Testsysteme zum Nachweis einer C. pneumoniae Infektion sowie den Effekt einer Behandlung mit Roxithromycin bei Patienten nach einem akuten Myokardinfarkt (AMI) in Abhängigkeit von ihrem Serostatus gegen C. pneumoniae. Wir analysierten das Blut von 160 Patienten der prospektiven randomisierten doppelblinden ANTIBIO-tische Therapie beim AMI (ANTIBIO-) Studie, die den Effekt einer Therapie mit Roxithromycin 300 mg/die über 6 Wochen bei Patienten mit AMI untersuchte. Anti-Chlamydia IgG-, IgA-, and IgM-Antikörper wurden mittels verschiedener Testsysteme bestimmt. Wir fanden eine gute Korrelation zwischen den beiden IgG und IgA Bestimmungsmethoden (r = 0,900, p < 0,001 und r = 0,878, p < 0,001), wobei es jedoch starke Unterschiede in der Prävalenz positiver Testergebnisse gab. Das führte zu nur moderaten Werten in der Konkordanzanalyse, ausgedrückt durch den Kappa Koeffizienten, für IgG κ = 0,611 (95% CI = 0,498– 0,724, p < 0,001) und für IgA κ = 0,431 (95% CI: 0,322–0,540, p < 0,001). Wir fanden keine Assoziation zwischen positiven C. pneumoniae Titern und der klinischen Ereignisrate während der 12-Monats-Nachbeobachtungsphase. Auch Patienten mit positiven C. pneumoniae Titern profitierten nicht von einer Roxithromycin Therapie (p = ns). In Abhängigkeit vom verwendeten Testsystem ergeben sich deutliche Unterschiede in der Prävalenz C. pneumoniae seropositiver Patienten. Die klinische Ereignisrate während der Nachbeobachtungszeit wurde weder durch den Serostatus gegen C. pneumoniae der Patienten, noch durch eine Behandlung mit Roxithromycin, unabhängig vom Serostatus, beeinflusst. Results of studies concerning prevention of cardiovascular disease by treatment with macrolide antibiotics targeting C. pneumoniae infection are still controversial. This study describes the results of different tests for infection with C. pneumoniae as well as the effect of treatment with roxithromycin in patients with acute myocardial infarction (AMI) in relation to their serostatus against C. pneumoniae. We analysed blood of 160 patients who came from the ANTIBIOtic therapy after an AMI (ANTIBIO-) study, a prospective, randomised, placebo-controlled, double-blind study to investigate the effect of roxithromycin 300 mg/OD for 6 weeks in patients with an AMI. Anti-Chlamydia IgG-, IgA-, and IgM-antibodies of these patients were analysed by means of different test systems. There was a good correlation between the two IgG and IgA methods (r = 0.900, p < 0.001 and r = 0.878, p < 0.001, respectively), but marked differences in the prevalence of positive tests. This resulted in only moderate concordance values, as expressed by the Kappa coefficients, for IgG κ = 0.611 (95% CI = 0.498–0.724, p < 0.001) and for IgA κ = 0.431 (95% CI: 0.322–0.540, p < 0.001). No significant association between positive C. pneumonia titers and the combined clinical endpoint during the 12 month follow-up could be found. In all test systems used, patients with positive anti-C. pneumoniae titers did not benefit from roxithromycin therapy (p = ns). Depending on the test system used, there are large differences in the prevalence of anti-C. pneumoniae seropositive patients. Clinical events during the 12 month follow-up after AMI did not depend on serostatus against C. pneumoniae and treatment with roxithromycin did not influence these events, independently of the serostatus against C. pneumoniae. However, the power of this subgroup analysis was low to detect small but significant differences.