Rudolf Schiele

Comparison of clinical benefits of Clopidogrel therapy in patients with acute coronary syndromes taking Atorvastatin versus other statin therapies

In clinical practice, we found no significant difference between atorvastatin therapy or other statin therapies in the clinical outcomes of patients with acute coronary syndromes receiving clopidogrel therapy. In patients receiving atorvastatin therapy, clopidogrel therapy was associated with a significant decrease in mortality and stroke during univariate analysis and a moderate trend of reduced mortality and stroke without statistical significance in the multivariate analysis.

Comparison of primary angioplasty with conservative therapy in patients with acute myocardial infarction and contraindications for thrombolytic therapy

The benefit of primary angioplasty in patients with acute myocardial infarction (AMI) and contraindications for thrombolysis compared to a conservative regimen is still unclear. Out of 5,869 patients with AMI registered by the MITRA trial, 337 (5.7%) patients had at least one strong contraindication for thrombolytic therapy. Out of these 337 patients 46 (13.6%) were treated with primary angioplasty and 276 (86.4%) were treated conservatively. Patients treated conservatively were older (70 years vs. 60 years; P = 0.001), had a higher rate of a history with chronic heart failure (14.8% vs. 4.4%; P = 0.053), a higher heart rate at admission (86 beats/min vs. 74 beats/min; P = 0.001), and a higher prevalence of diabetes mellitus (27.1% vs. 12.8%; P = 0.056). Patients treated with primary angioplasty received more often aspirin (91.3% vs. 74.6%; P = 0.012), β‐blockers (60.9% vs. 46.1%; P = 0.062), angiotensin converting enzyme (ACE) inhibitors (71.7% vs. 44%; P = 0.001), and the so‐called optimal adjunctive medication (54.4% vs. 32.3%; P = 0.004). Hospital mortality was significantly lower in patients who received primary angioplasty (univariate: 2.2% vs. 24.7%; P = 0.001; multivariate: OR = 0.46; P = 0.0230). In patients with AMI and contraindications for thrombolytic therapy, primary angioplasty was associated with a significantly lower mortality compared to conservative treatment. Therefore, hospitals without the facilities to perform primary angioplasty should try to refer such patients to centers with the facilities for such a service, if this is possible in an acceptable time.Cathet. Cardiovasc. Intervent. 46:127–133, 1999.

Akuter Myokardinfarkt in Deutschland im Zeitraum zwischen 1996 und 1998: Therapie und hospitaler Verlauf Ergebnisse des Myokardinfarktregisters (MIR) in Deutschland

The “Myocardial Infarction Registry” in Germany (MIR) is a multicenter and prospective registry of consecutively included, unselected patients with acute myocardial infarction. The purpose of MIR is to document the actual praxis of decision making and prescribing of an optimized infarction therapy in AMI patients. Optimized infarction therapy is defined as the combination of reperfusion therapy and ASS, betablocker, and ACE inhibitor. 14,598 patients with acute myocardial infarction were included between 12/96 and 5/98 in 217 hospitals throughout Germany. 68% of the patients were male; mean age was 67 years. The prehospital delay time was 195 minutes in median, the first ECG was diagnostic in 66% of the patients. A reperfusion therapy was applied in 46.1% of the patients (thrombolysis 36.2%, primary PTCA 9.9%). During the acute phase, the following adjunctive therapy was used: ASS in 90.3%, betablockers in 53.8%, and ACE inhibitors in 52.5%. Intrahospital mortality was 15.4%. Compared to hospitals without cardiologists, the hospitals with cardiologist had a lower intrahospital mortality (13.8% versus 16.1%; p < 0.001). Reasons are the more frequent use of a reperfusion therapy by cardiologists (54.3% versus 42.3%; p < 0.001) and the availability of a catheter laboratory with PTCA facilities. A lower intrahospital mortality was associated with each therapy of the optimized infarction therapy: reperfusion therapy (odds ratio 0.7; 95% CI: 0.5–0.8), ASS (odds ratio 0.6; 95% CI: 0.5–0.8), betablocker (odds ratio 0.6; 95% CI: 0.5–0.7) and ACE inhibitor (odds ratio: 0.5; 95% CI: 0.4–0.7). However, patients with poor initial prognosis – such as cardiogenic shock, hypotension and/or bradycardia – could not benefit from the orally adjunctive therapy. This fact may have led to an overestimation of the influence on intrahospital mortality. In representative communal German hospitals, a reperfusion therapy in combination with an optimized adjunctive therapy in patients with acute myocardial infarction is associated with a reduction in intrahospital mortality. Compared to previous registries, the application of betablockers and ACE inhibitors was clearly increased. Reasons could be the participation in a quality registry, the obligation to document why a therapy has not been given and repeated and intensified education of the treating physicians. Thus, the mainly communal hospitals in Germany are increasingly following recommendations about the early treatment of acute myocardial infarction. Myocardial infarction registries such as MIR reflect daily prescribing habits in hospitals and describe the implementation of the results of randomized trials into daily routine. Das Myokardinfarktregister in Deutschland (MIR) ist ein multizentrisch und prospektiv angelegtes Register von konsekutiv eingeschlossenen, unselektierten Patienten mit akutem Myokardinfarkt. Ziel des MIR ist eine Dokumentation der Entscheidungs- und Verordnungspraxis einer optimierten Infarkttherapie, bestehend aus rekanalisierender Therapie, ASS, Betablocker und ACE-Hemmer-Gabe. Von 12/96–5/98 wurden bundesweit 14598 Patienten mit akutem Myokardinfarkt in 217 Krankenhäusern eingeschlossen. Von diesen nahmen 68 Kliniken aus den neuen Bundesländern teil. 65% der Patienten waren männlich, das mittlere Alter betrug 67 Jahre. Die Prähospitalzeit lag im Median bei 195 min, das Erst-EKG war bei 66% der Patienten diagnostisch. Eine rekanalisierende Therapie erhielten 46,1% der Patienten (hospitale Thrombolyse 36,2%; Primär-PTCA 9,9%). Als Begleitmedikation in der Akutphase wurden verordnet: ASS bei 90,3%, Betablocker bei 53,8% und ACE-Hemmer bei 52,5%. Die intrahospitale Gesamtmortalität betrug 15,4%. Im Vergleich zeigte sich in kardiologischen Fachabteilungen eine niedrigere Gesamtmortalität (13,8%) gegenüber den Krankenhäusern der Regelversorgung (16,1%). Als mögliche Gründe fanden sich der häufigere Gebrauch einer rekanalisierenden Therapie in Krankenhäusern mit kardiologischer Fachabteilung (54,3% versus 42,3%; p < 0,001) und das Vorhandensein eines Katheterlabors mit PTCA-Möglichkeit. Eine niedrigere intrahospitale Mortalität im Gesamtkollektiv war mit allen Therapiebausteinen der optimierten Infarkttherapie assoziiert: rekanalisierende Therapie (odds ratio 0,7; 95%-KI: 0,5–0,8), Gabe von ASS (odds ratio 0,6; 95%-KI: 0,5–0,8), Betablocker (odds ratio 0,6; 95%-KI: 0,5–0,7) und ACE-Hemmer (odds ratio 0,5, 95%-KI: 0,4–0,7). In dieser Analyse konnten Patienten mit schlechter Prognose – z. B. kardiogener Schock, Hypotension und/oder Bradykardie bei Aufnahme und Frühverstorbene –, die nicht der oralen adjuvanten Infarkttherapie zugeführt werden konnten, nicht berücksichtigt werden. Der Einfluß der adjuvanten Therapie auf die Senkung der intrahospitalen Mortalität wird dadurch möglicherweise überschätzt. Im Klinikalltag ist einem repräsentativen Anteil von Krankenhäusern Deutschlands eine rekanalisierende Therapie in Kombination mit einer optimierten adjuvanten Therapie beim akuten Myokardinfarkt assoziiert mit einer Senkung der intrahospitalen Mortalität. Im Vergleich zu vorausgegangenen ähnliche Registern ließ sich der Therapieanteil der Betablocker und ACE-Hemmer deutlich steigern. Dies läßt sich mit der Teilnahme an einem Qualitätsregister, der Verpflichtung der Dokumentation, warum eine Therapie nicht gegeben wurde, und einer wiederholten und intensivierten Aufklärungsaktion der behandelnden Ärzte begründen. Den Empfehlungen zur Frühbehandlung des akuten Myokardinfarktes wird somit im Klinikalltag der überwiegend kommunalen Krankenhäuser zunehmend entsprochen. Myokardinfarktregister wie MIR reflektieren die tägliche Verordnungspraxis im Krankenhaus und beschreiben die Umsetzung der Ergebnisse großer randomisierter Studien in den Klinikalltag.

Frühbehandlung des akuten Myokardinfarktes: Umsetzung von Therapierichtlinien in den klinischen Alltag, MITRA-Pilotphase

MITRA (Maximale Individuelle TheRapie beim Akuten Myokardinfarkt) ist eine Anwendungsbeobachtung für den stationären und poststationären Verlauf eines nicht selektierten Patientenkollektivs mit akutem transmuralem Infarkt. Es sollen die Praktikabilität, der optimale Einsatz und die Sicherheit einer „individuell optimierten” Infarkttherapie untersucht werden. Zusätzlich soll die Qualität der Infarkttherapie in bezug auf jeden einzelnen Therapiebaustein abgeschätzt werden. An der multizentrischen Studie beteiligen sich fast flächendeckend 54 Kliniken einer umschriebenen Region im Südwesten Deutschlands. In der Pilotphase wurden konsekutiv 1303 Patienten mit akutem transmuralem Infarkt eingeschlossen. Im Median betrug das Alter 66 Jahre, ⅔ waren Männer. Die Prähospitalzeit war 2,7 Stunden, 64% erreichten die Klinik innerhalb der ersten 4 Stunden nach Symptombeginn. Bei 47% bestand ein Vorderwandinfarkt. In den Subgruppen der Patienten, die keine absolute Kontraindikationen hatten, erhielten: 53,4% das Thrombolytikum, 87,6% ASS, 37,1% den Betablocker und 17,4% der Patienten den ACE-Hemmer. In einer gesonderten Betrachtung wurden Patienten als „optimal behandelt” definiert, wenn sie in der Akutphase Thrombolyse, ASS und Betablocker nur dann erhielten, wenn sie absolute Kontraindikationen hatten. Bekamen die Patienten mindestens eines dieser drei Therapeutika nicht, obwohl absolute Kontraindikationen nicht vorlagen, wurden sie als „suboptimal behandelt” klassifiziert. Nur 29% (n = 383) der Patienten wurden „optimal”, während 71% (n = 775) suboptimal behandelt wurden. Die univariate Analyse ergab, daß die optimal therapierten Patienten jünger waren, sie hatten häufiger ein eindeutiges EKG oder einen Linksschenkelblock, einen Vorderwandinfarkt, eine manifeste Herzinsuffizienz, AV-Block, Bradykardie oder eine fortgeschrittene COLD. Die Prähospitalzeit war häufiger verfügbar. Im optimal behandelten Kollektiv betrug die 48-h-Mortalität 5,0% vs. 9,3% im suboptimal behandelten Kollektiv und die Krankenhausmortalität 10,9% vs. 17,7%. Die multivariate Analyse zeigte, daß die Variable „optimale Therapie” ein unabhängiger Prädiktor sowohl für die Früh- als auch für die Krankenhausmortalität ist. Intrahospitale Komplikationen traten auf: Apoplex 2,8%, Reinfarkt 12,9%, Herzinsuffizienz 21,5%, kardiogener Schock 10,4% und Krankenhaussterblichkeit 18,1% (Letalität < 48 h 9,5%). Zwischen den Erkenntnissen und Empfehlungen aus großen randomisierten Therapiestudien und der klinischen Praxis besteht zum jetzigen Zeitpunkt eine deutliche Diskrepanz. Nach den vorliegenden Daten sollte die Qualität der derzeitigen medikamentösen Infarkttherapie noch deutlich verbessert werden, denn „optimale Therapie” ist ein günstiger Prädiktor für die Früh- und Klinikmortalität. The prognostic value of thrombolytics, aspirin, beta-blockers and ACE-inhibitors has been well documented in large clinical trials, but the application of these drugs in clinical practice is not known. MITRA is a multicenter study of 54 hospitals in a defined region in southwest Germany. The aim is to document actual clinical practice (pilot phase) and to establish an individually optimised prognostic therapy for acute myocardial infarction, considering only the absolute contraindications for each drug. In the pilot phase, 1303 consecutive patients with acute transmural myocardial infarction were enrolled. The median age was 66 years, the prehospital time was 2.7 hours. 47 % had an anterior infarction. In the subgroup of patients without absolute contraindications, only 53.4% were treated with thrombolytics, 87.6% with aspirin, 37.1% with beta-blocker, and 17.4% with ACE-inhibitor. Out of these, patients were classified as “optimally treated” if they received thrombolysis, aspirin as well as beta-blocker. Patients were also included if any of these medications was withheld in the presence of absolute contraindications. Treatment was defined suboptimal, if the patients did not receive any of these three medications despite the absence of absolute contraindications. Only 29% (n = 383) received an optimal postinfarction therapy and 71% (n = 775) a suboptimal treatment. The univariate analysis revealed 10 variables influencing optimal therapy. In this subgroup patients were younger, they more often had clear ECG-findings or left bundle branch block, an anterior infarction, acute cardiac failure, AV-block, bradycardia, recent trauma or surgery (less then 2 weeks) and a severe chronic obstructive lung disease. The prehospital time was more often available. Early mortality after 2 days was 5.0% versus 9.3% in the suboptimal treated patients (OR: 0.5, CI: 0.30–0.86) the total inhospital mortality was 10.9% in the optimal versus 17.7% in the suboptimal group (OR: 0.6, CI: 0.38–0.84). In a multivariate analysis the parameter “optimal treatment” was found to be an independent predictor of the early (OR = 0.4; CI: 0.20–0.69) and the inhospital mortality (OR = 0.4; CI: 0.25–0.64). The following in-hospital events occurred: stroke 2.8%, reinfarction 12.9%, cardiac failure 21.5%, cardiogenic shock 10.4% and in-hospital mortality 18.1% (2-days mortality 9.5%). Pharmacological therapy for acute myocardial infarction is inconsistent with the recommendations suggested in recent clinical trials and needs to be individually optimised. Optimal treatment is an independent predictor of early and inhospital mortality.

Impact of the body mass index on occurrence and outcome of acute ST-elevation myocardial infarction

Obesity is a traditional risk factor for the development of cardiovascular disease. However, recent studies have described a better outcome of obese patients in the clinical course of acute coronary syndromes.We investigated the impact of the body mass index (BMI) on occurrence and outcome of acute ST-elevation myocardial infarction (STEMI). Data of 10 534 consecutive patients with STEMI of the German MITRA PLUS registry were analyzed, comparing international classes of the BMI (obesity: BMI ≥ 30 kg/m2, overweight: 25–29.9 kg/m2, normal weight: 18.5–24.9 kg/m2).STEMI occurred at a younger age in obese patients. The obese patients with first STEMI were 3 years younger than the normal weight patients with first STEMI (62.5 vs 65.7 years, p <0.0001).After STEMI has occurred, the obese patients had the lowest hospital (6.0%) and long-term mortality (4.8%) of all compared BMI-groups. In a multivariate analysis, obesity compared to normal weight was associated with a trend of a reduced mortality without significance during the hospital course (OR 0.81, 95% CI 0.60–1.08) and with significance during follow-up (OR 0.56, 95% CI 0.40–0.79).In conclusion, our data show that obesity is a risk factor of a manifestation of STEMI at a younger age compared to normal weight patients. After STEMI has occurred, obesity is associated with a trend of a lower mortality during the following clinical course. Therefore, the focus of prevention should be the reduction of obesity and metabolic syndrome in young people, to avoid the early occurrence of STEMI by primary prevention.

Short-term comprehensive cardiac rehabilitation after AMI is associated with reduced 1-year mortality: results from the OMEGA study

Background The prognostic effect of early, comprehensive short-term cardiac rehabilitation on top of current, guideline-adjusted treatment of acute myocardial infarction has not sufficiently been evaluated. Design Prospective cohort study. Methods Within the OMEGA study population, the clinical course of 3560 patients still alive 3 months after acute myocardial infarction were evaluated by comparing patients who had attended to cardiac rehabilitation (70.6%) with those who did not. Total mortality and major adverse cerebrovascular and cardiovascular events, as well as non-fatal events, were evaluated within the time period of 4–12 months after hospital admission for acute myocardial infarction. The effect of cardiac rehabilitation on clinical events was estimated by using the propensity score method to adjust for confounding parameters in multivariate analysis. Results Patients participating in cardiac rehabilitation were younger, more often had acute revascularization, less often experienced non-ST-elevation myocardial infarction, and less often had a history of diabetes or cardiovascular events. Total mortality (OR 0.46, 95% CI 0.27–0.77) and major adverse cerebrovascular and cardiovascular events (OR 0.53, 95% CI 0.38–0.75) were significantly lower in the rehabilitation group. Subgroup analysis including major clinical characteristics also revealed significantly reduced rates of total death and major adverse cerebrovascular and cardiovascular events in the rehabilitation group. Conclusions Attendance to early, comprehensive short-term cardiac rehabilitation programmes on top of current guideline-adjusted treatment of acute myocardial infarction is associated with a significantly improved 1-year prognosis.

Incidence, determinants, and clinical course of reinfarction in-hospital after index acute myocardial infarction (results from the pooled data of the maximal individual therapy in acute myocardial infarction [mitra], and the myocardial infarction registry [MIR])☆

There are few data about the incidence, determinants, and clinical course of in-hospital repeat acute myocardial infarction (RE-AMI) after an index AMI. From June 1994 to June 1998, 22,613 patients with AMI as an index event were registered by the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) and Myocardial Infarction Registries (MIR). Of these, 1,071 (4.7%) had a RE-AMI. For the index event, 9,143 patients (40.5%) were treated with thrombolysis, 1,707 (7.5%) with primary angioplasty, and 443 (2.0%) with a combination of both. Multivariate analysis showed that previous AMI (odds ratio [OR] 1.59; 95% confidence intervals [CI] 1.35 to 1.86), age >70 years (OR 1.57; 95% CI 1.36 to 1.81), diagnostic first electrocardiogram (OR 1.37; 95% CI 1.19 to 1.59), and female gender (OR 1.14; 95% CI 1.05 to 1.32) were independently associated with a higher incidence of RE-AMI. The incidence of RE-AMI was higher when patients received thrombolysis (OR 1.36; 95% CI 1.15 to 1.61), and it was lower when they underwent primary angioplasty (OR 0.74; 95% CI 0.53 to 1.03) or received beta blockers (OR 0.84; 95% CI 0.72 to 0.97). Patients with RE-AMI had higher hospital mortality compared with those without RE-AMI (OR 4.35; 95% CI 3.83 to 4.95). Multivariate logistic regression analysis showed an independent association of RE-AMI with in-hospital death (OR 6.60; 95% CI 5.61 to 7.70), repeat revascularization (OR 2.91; 95% CI 2.42 to 3.50), low workload capacity on the bicycle ergometry test (OR 2.17; 95% CI 1.71 to 2.76), and ejection fraction <40% (OR 1.72; 95% CI 1.38 to 2.14) at discharge. Thus, RE-AMI occurs in 4.7% of patients after an AMI. Previous AMI, age >70 years, diagnostic first electrocardiogram, and female gender are independent determinants for RE-AMI. Thrombolysis is associated with a higher and beta blockers with a lower incidence of RE-AMI. Once a RE-AMI occurs, it is a strong predictor of in-hospital mortality and morbidity.

Incidence, risk factors, and clinical outcome of stroke after acute myocardial infarction in clinical practice☆

: In this analysis of ischemic and hemorrhagic strokes after acute myocardial infarction (AMI) in 21,330 consecutively included patients with AMI, we found an incidence of stroke after AMI of 1.2% and a very poor prognosis. Previous stroke, atrial fibrillation, and older age were the strongest predictors of stroke after AMI; thrombolysis was a borderline risk factor and early therapy with aspirin was associated with a reduction in stroke after AMI.

Severe aortic regurgitation after percutaneous transcatheter aortic valve implantation: on the importance to clarify the underlying pathophysiology

Severe symptomatic aortic stenosis in a 90-year-old man was treated with percutaneous aortic valve implantation (TAVI) with a 29-mm CoreValve Revalving™ system. Following implantation, severe aortic regurgitation occurred. Echocardiography showed a small paravalvular and a huge valvular leakage, probably due to one malfunctioning valve leaflet. Concerning this pathophysiology, a further TAVI was performed using a second 29-mm CoreValve Revalving™ system, as a “valve-in-valve” implantation.

Effect of Preinfarction Angina Pectoris on Outcome in Patients With Acute Myocardial Infarction Treated With Primary Angioplasty (Results from the Myocardial Infarction Registry (MIR))

Preinfarction angina is associated with better clinical outcome in patients with acute myocardial infarction (AMI) who receive intravenous thrombolysis. This has not been proved in patients with AMI treated with primary angioplasty. We analyzed the data of the prospective multicenter Myocardial Infarction Registry (MIR). Of 14,440 patients with AMI, 774 with a prehospital delay of < or =12 hours were treated with primary angioplasty. Five hundred thirty-two patients (68.7%) had preinfarction angina. Patients with preinfarction angina were slightly older than patients without (63 vs 62 years, p = 0.042), prehospital delay was 1 hour longer (180 vs 120 minutes, p = 0.001), and arterial hypertension was more prevalent (47.6% vs 32.2%, odds ratio [OR] 1.91, 95% confidence intervals [CI] 1.39 to 2.62). There was no significant difference in hospital mortality (5.6% vs 3.3%, OR 1.75, 95% CI 0.79 to 3.87), reinfarction, stroke, or the combined end point of death, reinfarction, or stroke between the 2 groups. Logistic regression analysis showed no association of preinfarction angina with the occurrence of either death (OR 2.21, 95% CI 0.91 to 6.08) or the combined end points (OR 1.10, 95% CI 0.55 to 2.31). There was also no significant difference in mortality (6% vs 5.1%, OR 1.19, 95% CI 0.56 to 2.52), reinfarction, stroke, postinfarction angina, or the combined end points between patients with preinfarction angina within 48 hours compared with patients with preinfarction angina between 49 hours and 4 weeks before the AMI. Thus, the MIR data showed no protective effects of preinfarction angina in patients with AMI treated with primary angioplasty.