Claus Juenger

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.

Osteopontin, a New Prognostic Biomarker in Patients With Chronic Heart Failure

Background—Osteopontin, a glycoprotein that can be detected in plasma, was found to be upregulated in several animal models of cardiac failure and may thus represent a new biomarker that facilitates risk stratification in patients with heart failure. We therefore tested whether osteopontin plasma levels are elevated in patients with chronic heart failure and whether they provide independent prognostic information. Methods and Results—We analyzed osteopontin plasma levels in 420 patients with chronic heart failure due to significantly impaired left ventricular systolic function and correlated the results with disease stage and prognostic information (median follow-up of 43 months). We found that osteopontin plasma levels were significantly elevated in patients with heart failure as compared with healthy control subjects (532 versus 382 ng/mL, P=0.008), irrespective of heart failure origin (ischemic versus dilated cardiomyopathy). Furthermore, osteopontin levels were higher in patients with moderate to severe heart failure than in patients with no or mild symptoms (672 ng/mL for New York Heart Association class III/IV versus 479 ng/mL for class I/II, P<0.0001). Estimated 4-year death rates in patients with osteopontin levels above or below a cutoff value derived from receiver operating characteristic analyses were 56.5% and 28.4%, respectively (hazard ratio 3.4, 95% confidence interval 2.2 to 5.3, P<0.0001). In a multivariable model that included demographic, clinical, and biochemical parameters such as N-terminal prohormone brain natriuretic peptide, osteopontin emerged as an independent predictor of death (hazard ratio 2.3, 95% confidence interval 1.4 to 3.5, P<0.001). Conclusion—Our findings suggest that osteopontin might be useful as a novel prognostic biomarker in patients with chronic heart failure.

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.

Impact of Ramipril versus other angiotensin-converting enzyme inhibitors on outcome of unselected patients with ST-elevation Acute Myocardial Infarction

We examined the impact of treatment with ramipril versus other angiotensin-converting enzyme (ACE) inhibitors on clinical outcome in unselected patients of the prospective multicenter registry Maximal Individual Therapy of Acute Myocardial Infarction PLUS registry (MITRA PLUS). Of 14,608 consecutive patients with ST-elevation acute myocardial infarction, 4.7% received acute therapy with ramipril, 39.0% received other ACE inhibitor therapy, and 56.3% received no ACE inhibitor therapy. In a multivariate analysis, the treatment with ramipril compared with the treatment without ACE inhibitors was associated with a significantly lower hospital mortality and a lower rate of nonfatal major adverse coronary and cerebrovascular events. Compared with other generic ACE inhibitors, ramipril therapy was independently associated with a significantly lower hospital mortality (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.32 to 0.90) and a lower rate of nonfatal major adverse coronary and cerebrovascular events (OR 0.65, 95% CI 0.46 to 0.93), but not with a lower rate of heart failure at discharge (OR 0.79, 95% CI 0.50 to 1.27).

Beneficial effects of abciximab in patients with primary percutaneous intervention for acute st segment elevation myocardial infarction in clinical practice

Objectives: To assess the safety and effectiveness of abciximab in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) in clinical practice. Methods: Data were analysed of 2184 consecutive patients treated with primary PCI for acute STEMI and either concomitant abciximab or no glycoprotein IIb/IIIa inhibitor (control group), who were prospectively enrolled in the Acute Coronary Syndromes (ACOS) registry between July 2000 and November 2002. Results: Patients who were treated with abciximab were younger than the control group, and fewer of them had a history of stroke/transient ischaemic attack and systemic hypertension, but more of them had three-vessel coronary artery disease and cardiogenic shock. Cumulated mid-term survival for patients treated with abciximab was significantly higher than in the control group (91% v 79%, log rank p < 0.05, median observational time 375 days, range 12–34 months). The Cox proportional hazards model of mid-term mortality after admission with adjustment for baseline characteristics showed that mortality was significantly lower in the abciximab group than in the control group (hazard ratio 0.68, 95% confidence interval 0.49 to 0.95). Whereas overall there was no difference in bleeding complications, patients older than 75 years had more major bleeding events with abciximab (12.5% v 3.4%, p  =  0.03). Conclusion: In clinical practice adjunctive treatment with abciximab in patients with primary PCI for acute STEMI was associated with a reduction in mid-term mortality. The subgroup of patients older than 75 years who were treated with abciximab had more major bleeding complications.

Clinical Benefit of Early Reperfusion Therapy in Patients With ST-Elevation Myocardial Infarction Usually Excluded from Randomized Clinical Trials (Results from the Maximal Individual Therapy in Acute Myocardial Infarction Plus [MITRA Plus] Registry)

Randomized clinical trials (RCTs) usually enroll selected patient populations that may not be representative for patients seen in everyday practice. Therefore, concerns have been raised regarding their external validity. For the present study we evaluated the MITRA Plus registry and included 20,175 patients with ST-elevation myocardial infarction. We defined RCT-ineligible patients as patients fulfilling >or=1 of the following criteria: age >or=75 years, prehospital delay >12 hours, prehospital cardiopulmonary resuscitation, cardiogenic shock, impaired renal function, and previous stroke. Those patients (n = 9,369, 46.4%) were compared to patients eligible for enrollment in RCTs (n = 11,806, 53.6%). Ineligible patients were older (p <0.0001), more often were women (p <0.0001), and more often had concomitant diseases (p <0.0001). Ineligible patients less often received early reperfusion therapy (p <0.0001), aspirin (p <0.0001), clopidogrel (p <0.0001), and statins (p <0.0001). Ineligible patients had a higher hospital mortality (20.1% vs 4.9%; p <0.0001) and a higher rate of nonfatal strokes (1.5% vs 0.4%, p <0.0001) compared to eligible patients. Early reperfusion therapy (thrombolysis and/or percutaneous coronary intervention [PCI]) in ineligible patients was associated with a significant decrease of hospital mortality (odds ratio 0.62, 95% confidence interval 0.49 to 0.79), with primary PCI being more effective than thrombolytic therapy (odds ratio 0.52, 95% confidence interval 0.41 to 0.65). In conclusion, about 50% of patients with ST-elevation myocardial infarction seen in clinical practice are usually excluded from RCTs. Hospital mortality in those patients is very high. Primary PCI improves the prognosis and is therefore the preferred reperfusion strategy in these patients.

Guideline-oriented ambulatory lipid-lowering therapy of patients at high risk for cardiovascular events by cardiologists in clinical practice: the 2L cardio registry.

Background Lipid-lowering treatment has been proven to decrease the rate of cardiovascular events in high-risk patients with manifest coronary artery disease (CAD) or CAD equivalent risk profile. Current treatment guidelines recommend low-density lipoprotein-cholesterol (LDL-C) less than 100 mg/dl (optional < 70 mg/dl) as the target level for this high-risk population. Little is known about the ambulatory treatment of high-risk patients in clinical practice and the achievement of guideline recommended target values. Methods and results In the ‘2L cardio’ registry in Germany, 295 cardiologists enrolled 6711 consecutive patients with known CAD, and/or diabetes mellitus, peripheral arterial disease (summarized as ‘coronary risk equivalent’, CE), on chronic statin treatment. They recorded actual LDL-C values at entry, probable changes in therapy, and the expected LDL-C values using a lipid calculator based on an earlier observational study in a similar setting. The three groups comprised 2618 patients with CAD plus CE (39.0%; median LDL-C 112 mg/dl), 3436 patients with CAD only (51.2%; median LDL-C 108 mg/dl), and 657 with CE only (9.8%; median LDL-C 124 mg/dl). They had LDL-C levels less than 100 mg/dl in 36.2% [95% confidence intervals (CI): 34.3–38.1], 39.7% (CI: 38.0–41.4), and 27.2% (CI: 23.7–30.7), respectively. Statin doses at entry were usually in the lower to intermediate range (e.g. simvastatin median 25 mg/day). Cardiologists switched to another statin in 10.1% (9.4–10.8), increased the dose of statins (if same drug) in 22.2% (CI: 21.1–23.2) and/or added a cholesterol absorption inhibitor in 23.7% (CI: 22.7–24.7) of the patients. The cardiologists’ intervention improved expected LDL-C levels in the total cohort by a mean of 9.0 mg/dl, but the 100 mg/dl LDL-C target was only reached in 51.3% (CI: 50.0–52.5) of the total cohort. CE patients appeared undertreated in terms of antiplatelet drugs. Discussion Through infrequent increases in statin doses and mainly through add-on of a cholesterol absorption inhibitor, cardiologists improved target level attainment. Compared with earlier studies in the outpatient setting, the treatment to target for LDL-C of high-risk CAD patients has improved, but is not satisfactory.

Primary percutaneous coronary intervention and thrombolysis improve survival in patients with ST-elevation myocardial infarction and pre-hospital resuscitation☆☆☆

BACKGROUND Patients with ST-elevation myocardial infarction (STEMI) surviving pre-hospital resuscitation represent a selected subgroup of patients with a very high adverse event rate. Only few data on the outcome of primary percutaneous coronary intervention (primary PCI) and thrombolysis in such patients are available. METHODS We analysed the Maximal Individual Therapy of Acute Myocardial Infarction (MITRA) Plus registry. 1529 survivors of pre-hospital resuscitation with STEMI were included. 593 (38.8%) of those patients did not receive early reperfusion therapy, 793 (51.9%) patients received thrombolysis and 143 (9.4%) patients received primary PCI. Hospital mortality in patients receiving primary PCI or thrombolysis was adjusted for confounding factors with a propensity score analysis. RESULTS Primary PCI as well as thrombolysis in survivors of pre-hospital resuscitation with STEMI were associated with a significant reduction of hospital mortality (OR: 0.29, 95% CI 0.17-0.50; and 0.74, 95% CI 0.54-0.99, respectively), while primary PCI was superior compared to thrombolysis (OR 0.50, 95% CI 0.30-0.84). CONCLUSION Reperfusion therapy improves mortality of patients with STEMI surviving pre-hospital resuscitation, while primary PCI seems to be more effective than thrombolysis.

Actual clinical practice of exercise testing in consecutive patients after non-ST-elevation myocardial infarction: results of the acute coronary syndromes registry.

Background Exercise testing has been advocated for risk stratification and determination of therapeutic strategies after acute myocardial infarction. Frequency and therapeutic impact of exercise testing after non-ST-elevation myocardial infarction (NSTEMI) in actual clinical practice, however, is not known. Methods and results From the German acute coronary syndrome (ACOS) registry patients with acute NSTEMI (n = 5281) were evaluated: 20.8% of patients (1097/5281) had predischarge exercise testing, and from these tests 33.5% (367/1097) were positive. The strongest predictors for renunciation of predischarge exercise testing were ejection fraction under 40%, age over 70 years and stroke history. In-hospital coronary angiographies or percutaneous coronary interventions were not associated with a lower rate of exercise testing. During 1-year follow-up all-cause mortality was 13.6% in patients without and 5.1% in patients with exercise test respectively (P>0.0001). In patients with positive exercise test 1-year mortality was 6.5%, in patients with negative exercise test 4.4% (P=0.13). During follow-up no significant difference was found in the rate of coronary revascularizations between patients either with positive or negative exercise tests. Furthermore, no significant difference was found in the rate of death and revascularizations comparing different groups of exercise capacity. Conclusions After NSTEMI in Germany the majority of patients do not get predischarge exercise testing, although this group appears to be of special risk for fatality during follow-up. Furthermore, in actual clinical practice, neither exercise induced signs of ischemia nor exercise capacity have a significant impact on the rate of revascularization procedures during follow-up. Eur J Cardiovasc Prev Rehabil 13:457-463

Angioplasty within 24 h after thrombolysis in patients with acute ST-elevation myocardial infarction: current use, predictors and outcome

BackgroundPercutaneous coronary intervention (PCI) early after thrombolysis (early PCI) in patients with ST-elevation myocardial infarction (STEMI) is currently advised by clinical guidelines, but little is known about its use in clinical practice.MethodsWe analysed the MITRA (Maximal Individual Therapy of Acute Myocardial Infarction) plus registry.ResultsOut of a total of 34276 patients with STEMI, 10600 (30.9%) were treated with intravenous thrombolysis. Out of these patients, 487 (4.6%) patients received an angioplasty between 61 min and 24 hours after thrombolysis. They were compared to 10113 (95.4%) patients who received PCI either later than 24 hours after thrombolysis or not at all. A continuous increase in the frequency of early PCI between the years 1994 (2%)-2002 (16.7%) was observed. After adjusting for confounding variables independent predictors to use early PCI were the increasing year of inclusion, the facility of the hospital to perform PCI, younger age and male gender. Hospital mortality was 7.2% in patients receiving early PCI, compared to 11.2% in the other group (<0.01). Independent predictors for a higher hospital mortality were shock, age >65 years, female gender, an anterior STEMI and a prehospital delay of >3 hours. However, early PCI was not longer associated with a lower mortality (OR 0.95, 95% CI 0.64–1.14). ConclusionEarly PCI after thrombolysis is used infrequently in current clinical practice in Germany. Especially ‘low risk’ patients were treated with an early PCI, which may contribute to the missing effect on mortality compared to no or late PCI after thrombolysis.