Prognostic markers of all-cause mortality in patients with atrial fibrillation: data from the prospective long-term registry of the German Atrial Fibrillation NETwork (AFNET).

AIMS: Atrial fibrillation (AF) is associated with a high risk of cardiovascular and non-cardiovascular death, even on anticoagulation. It is controversial, which conditions-including concomitant diseases and AF itself-contribute to this mortality. To further clarify these questions, major determinants of long-term mortality and their contribution to death were quantified in an unselected cohort of AF patients. METHODS AND RESULTS: We established a large nationwide registry comprising 8833 AF-patients with a median follow-up of 6.5 years (45 345 patient-years) and central adjudication of adverse events. Baseline characteristics of the patients were evaluated as predictors of mortality using Cox regression and C-indices for determination of predictive power. Annualized mortality was highest in the first year (6.2%) and remained high thereafter (5.2% in men and 5.5% in women). Thirty-eight percent of all deaths were cardiovascular, mainly due to heart failure or sudden death. Sex-specific age was the strongest predictor of mortality, followed by concomitant cardiovascular and non-cardiovascular conditions. These factors accounted for 25% of the total mortality beyond age and sex and for 84% of the mortality differences between AF types. Thus, the electrical phenotype of the disease at baseline contributed only marginally to prediction of mortality. CONCLUSION: Mortality is high in AF patients and arises primarily from heart failure, peripheral artery disease, chronic obstructive lung disease, chronic kidney disease, and diabetes mellitus, which, therefore, should be targeted to lower mortality. Parameters related to the electrical manifestation of AF did not have an independent impact on long-term mortality in our representative cohort.

Intracoronary autologous bone marrow cell transfer after myocardial infarction: the BOOST-2 randomised placebo-controlled clinical trial.

AIMS: Intracoronary infusion of autologous nucleated bone marrow cells (BMCs) enhanced the recovery of left ventricular ejection fraction (LVEF) after ST-segment elevation myocardial infarction (STEMI) in the randomised-controlled, open-label BOOST trial. We reassessed the therapeutic potential of nucleated BMCs in the randomised placebo-controlled, double-blind BOOST-2 trial conducted in 10 centres in Germany and Norway. METHODS AND RESULTS: Using a multiple arm design, we investigated the dose-response relationship and explored whether γ-irradiation which eliminates the clonogenic potential of stem and progenitor cells has an impact on BMC efficacy. Between 9 March 2006 and 16 July 2013, 153 patients with large STEMI were randomly assigned to receive a single intracoronary infusion of placebo (control group), high-dose (hi)BMCs, low-dose (lo)BMCs, irradiated hiBMCs, or irradiated loBMCs 8.1 ± 2.6 days after percutaneous coronary intervention (PCI) in addition to guideline-recommended medical treatment. Change in LVEF from baseline (before cell infusion) to 6 months as determined by MRI was the primary endpoint. The trial is registered at Current Controlled Trials (ISRCTN17457407). Baseline LVEF was 45.0 ± 8.5% in the overall population. At 6 months, LVEF had increased by 3.3 percentage points in the control group and 4.3 percentage points in the hiBMC group. The estimated treatment effect was 1.0 percentage points (95% confidence interval, -2.6 to 4.7; P = 0.57). The treatment effect of loBMCs was 0.5 percentage points (-3.0 to 4.1; P = 0.76). Likewise, irradiated BMCs did not have significant treatment effects. BMC transfer was safe and not associated with adverse clinical events. CONCLUSION: The BOOST-2 trial does not support the use of nucleated BMCs in patients with STEMI and moderately reduced LVEF treated according to current standards of early PCI and drug therapy.

Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism.

BACKGROUND: In patients with acute pulmonary embolism, systemic thrombolysis improves right ventricular (RV) dilatation, is associated with major bleeding, and is withheld in many patients at risk. This multicenter randomized, controlled trial investigated whether ultrasound-assisted catheter-directed thrombolysis (USAT) is superior to anticoagulation alone in the reversal of RV dilatation in intermediate-risk patients. METHODS AND RESULTS: Fifty-nine patients (63±14 years) with acute main or lower lobe pulmonary embolism and echocardiographic RV to left ventricular dimension (RV/LV) ratio ≥1.0 were randomized to receive unfractionated heparin and an USAT regimen of 10 to 20 mg recombinant tissue plasminogen activator over 15 hours (n=30; USAT group) or unfractionated heparin alone (n=29; heparin group). Primary outcome was the difference in the RV/LV ratio from baseline to 24 hours. Safety outcomes included death, major and minor bleeding, and recurrent venous thromboembolism at 90 days. In the USAT group, the mean RV/LV ratio was reduced from 1.28±0.19 at baseline to 0.99±0.17 at 24 hours (P<0.001); in the heparin group, mean RV/LV ratios were 1.20±0.14 and 1.17±0.20, respectively (P=0.31). The mean decrease in RV/LV ratio from baseline to 24 hours was 0.30±0.20 versus 0.03±0.16 (P<0.001), respectively. At 90 days, there was 1 death (in the heparin group), no major bleeding, 4 minor bleeding episodes (3 in the USAT group and 1 in the heparin group; P=0.61), and no recurrent venous thromboembolism. CONCLUSIONS: In patients with pulmonary embolism at intermediate risk, a standardized USAT regimen was superior to anticoagulation with heparin alone in reversing RV dilatation at 24 hours, without an increase in bleeding complications. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01166997.

A real-world perspective on the prevalence and treatment of heart failure with a reduced ejection fraction but no specific or only mild symptoms.

Heart failure (HF) is commonly described according to the severity of symptoms, using the New York Heart Association (NYHA) classification, and the assessment of ventricular function, by measuring the left ventricular ejection fraction (LVEF). It is important to acknowledge, however, that the severity of symptoms does not systematically correlate with the level of ventricular systolic dysfunction. Patients with no or only mild symptoms are still at high risk of HF-related morbidity and mortality. The objective of this review was to summarize the prevalence, characteristics, and treatment of patients with chronic HF and mild or no symptoms and to review epidemiological data from three recent registries conducted in Europe. From a clinical practice perspective, patients with a reduced ejection fraction who have only mild symptoms appear to represent a group of patients for whom the provision of adequate medical care is yet to be optimized. While prescription of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers appears to be consistently high, the use of mineralocorticoid receptor antagonists is more variable and does not appear to be in accordance with the latest clinical guidelines. As approximately half of patients with HF and a reduced LVEF have NYHA class II symptoms, significant reductions in morbidity and mortality could be achieved by more comprehensive treatment of this population.

Use of vitamin K antagonists for secondary stroke prevention depends on the treating healthcare provider in Germany - results from the German AFNET registry.

BACKGROUND: Anticoagulation using vitamin K antagonists (VKAs) significantly reduces the risk of recurrent stroke in stroke patients with atrial fibrillation (AF) and is recommended by guidelines. METHODS: The German Competence NETwork on Atrial Fibrillation established a nationwide prospective registry including 9,574 AF patients, providing the opportunity to analyse AF management according to German healthcare providers. RESULTS: On enrolment, 896 (9.4 %) patients reported a prior ischaemic stroke or transient ischaemic attack. Stroke patients were significantly older, more likely to be female, had a higher rate of cardiovascular risk factors, and more frequently received anticoagulation (almost exclusively VKA) than patients without prior stroke history. Following enrolment, 76.4 % of all stroke patients without VKA contraindications received anticoagulation, which inversely associated with age (OR 0.95 per year; 95 % CI 0.92-0.97). General practitioners/internists (OR 0.40; 95 % CI 0.21-0.77) and physicians working in regional hospitals (OR 0.47; 95 % CI 0.29-0.77) prescribed anticoagulation for secondary stroke prevention less frequently than physicians working at university hospitals (reference) and office-based cardiologists (OR 1.40; 95 % CI 0.76-2.60). The impact of the treating healthcare provider was less evident in registry patients without prior stroke. CONCLUSIONS: In the AFNET registry, anticoagulation for secondary stroke prevention was prescribed in roughly three-quarters of AF patients, a significantly higher rate than in primary prevention. We identified two factors associated with withholding oral anticoagulation in stroke survivors, namely higher age and-most prominently-treatment by a general practitioner/internist or physicians working at regional hospitals.

Efficacy of the long-acting nitro vasodilator pentaerithrityl tetranitrate in patients with chronic stable angina pectoris receiving anti-anginal background therapy with beta-blockers: a 12-week, randomized, double-blind, placebo-controlled trial.

BACKGROUND: The organic nitrate pentaerithrityl tetranitrate (PETN) has been shown to have ancillary properties that prevent the development of tolerance and endothelial dysfunction. This randomized, double-blind, placebo-controlled, multicentre study ('CLEOPATRA' study) was designed to investigate the anti-ischaemic efficacy of PETN 80 mg b.i.d. (morning and mid-day) over placebo in patients with chronic stable angina pectoris. METHODS AND RESULTS: A total of 655 patients were evaluated in the intention-to-treat population, randomized to PETN (80 mg b.i.d., n = 328) or placebo (n = 327) and completed the study. Patients underwent treadmill exercise tests at randomization, after 6 and 12 weeks of treatment. Treatment with PETN over 12 weeks did not modify the primary endpoint total exercise duration (TED, P = 0.423). In a pre-specified sub-analysis of patients with reduced exercise capacity (TED at baseline ≤9 min, n = 257), PETN appeared more effective than placebo treatment (P = 0.054). Superiority of PETN over placebo was evident in patients who were symptomatic at low exercise levels (n = 120; P = 0.017). Pentaerithrityl tetranitrate 80 mg b.i.d. was well tolerated, and the overall safety profile was comparable with placebo. CONCLUSION: Although providing no additional benefit in unselected patients with known coronary artery disease, PETN therapy, administered in addition to modern anti-ischaemic therapy, could increase exercise tolerance in symptomatic patients with reduced exercise capacity.

[Atrial fibrillation in Germany--epidemiology, diagnosis, treatment and costs]. / Vorhofflimmern in Deutschland-- Epidemiologie, Diagnostik, Therapie und Kosten.

Atrial fibrillation is the most common cardiac arrhythmia. It is an independent risk factor for cardiovascular complications and stroke. The treatment options for atrial fibrillation have changed significantly in recent years by new drugs and ablative procedures. It is based on the principal strategies of anticoagulation, rhythm and rate control. Goal is to reduce symptoms and subsequent events. Although the costs of about 700 to pound 800 per patient per year are rather high, new treatment options might be associated with a reduction in event rates and an increase in quality adjusted life years (QALYs). The aim of this review is to give a practical overview of the epidemiology, diagnosis, treatment and costs to pharmacists who have a key role in the implementation of pharmacotherapy of atrial fibrillation.

Treatment of coronary bifurcation lesions with drug-eluting stents: insights from the first phase of the prospective multicenter german drug-eluting stent registry.

BACKGROUND: Controversy exists about the impact of treating bifurcations on overall outcome of coronary interventions using drug-eluting stents (DES). We sought to investigate 1-year outcome of the treatment of bifurcation lesions using DES in a large "real-world" cohort. METHODS AND RESULTS: Among 5,126 patients enrolled in phase I of the multicenter German Drug-Eluting Stent Registry, 814 (16%) were treated for a bifurcation lesion. Patients with bifurcations were compared to those without bifurcations in terms of baseline characteristics, major adverse cardiac and cerebrovascular events (MACCE) and target vessel revascularization (TVR) at 1 year. Usage of sirolimus-eluting stents (SES) versus paclitaxel-eluting stents (PES) was also evaluated. In total, 1,021 and 5,189 stents were implanted in the bifurcation (1.25 stents/patient) and nonbifurcation (1.2 stents/patient) group, respectively, but 64.5% of bifurcation lesions were treated with a single stent. More complex lesion and procedural characteristics were observed in the bifurcation group. However, there was no difference in 1-year MACCE rates (a composite of death, myocardial infarction, and stroke) between the bifurcation group and nonbifurcation group (8.1% vs. 8.3%, P = 0.85). Rates of TVR (11.2% vs. 10.8%, P = 0.75) and Academic Research Consoritum-defined definite stent thrombosis (0.9% vs. 0.8%, P = 0.67) were also comparable. MACCE and TVR rates remained similar after adjustment for differences in baseline characteristics. MACCE and TVR in SES patients were 7.2% and 12.6% versus 8.7% and 10.2% in PES patients (P = 0.46 and P = 0.30, respectively). CONCLUSION: In this large multicenter registry, treatment of bifurcation lesions with DES appears effective and safe. The presence of bifurcations did not affect 1-year outcomes after DES implantation. The outcomes for SES and PES were similar.

Certoparin versus unfractionated heparin to prevent venous thromboembolic events in patients hospitalized because of heart failure: a subgroup analysis of the randomized, controlled CERTIFY study.

BACKGROUND: Despite the elevated risk for developing venous thromboembolic events in patients with heart failure, there are no randomized, double-blind, controlled trial data on the comparison of low-molecular-weight heparin with unfractionated heparin (UFH) in this patient population. METHODS: This was a subgroup analysis of the CERTIFY trial, which included 3,239 nonsurgical, acutely ill medical patients 70 years or older. Patients were randomized to receive 3,000-U anti-Xa certoparin once daily or 5,000-IU UFH 3 times a day. The analysis was performed on a subgroup of 542 patients diagnosed with heart failure at hospital admission. RESULTS: Patients with heart failure differed from patients without heart failure in that they were more likely using antiplatelets (67.2% vs 48.9%; P < .0001) and had a lower glomerular filtration rate (8.0% vs 5.5%; ≤ 30 mL/min per 1.73 m²; P = .0232). Thromboembolic risk was comparable except for a higher incidence of distal deep venous thrombosis (DVT) in patients with heart failure (10.80% vs 7.26%; P = .0144). Within the heart failure population, patient characteristics were comparable between randomized treatment groups. The incidence of the primary end point (proximal DVT, symptomatic nonfatal pulmonary embolism, and venous thromboembolism-related death combined) was numerically, slightly smaller with certoparin (3.78% vs 4.74% with UFH; odds ratio 0.79, 95% CI 0.32-1.94), and the incidence of major bleeding was 0.72% with certoparin versus 0.38% with UFH. CONCLUSIONS: Patients hospitalized for heart failure are at high risk for developing distal DVT and bleeding complications compared with acutely ill medical patients without heart failure. Within the heart failure population, the observed differences in prophylactic efficacy between 3,000-U anti-Xa certoparin once daily and 5,000-IU UFH 3 times a day were similar to those observed in the overall study population; this suggests that certoparin might be at least as effective as UFH also in this subgroup. There were no relevant differences in bleeding risk or frequency of adverse events.

Heparin based prophylaxis to prevent venous thromboembolic events and death in patients with cancer - a subgroup analysis of CERTIFY.

BACKGROUND: Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1) cancer patients receiving LMWH or UFH and 2) patients with or without cancer. METHODS: Acutely-ill, non-surgical patients ≥ 70 years with (n = 274) or without cancer (n = 2,965) received certoparin 3,000 UaXa o.d. or UFH 5,000 IU t.i.d. for 8-20 days. RESULTS: 1) Thromboembolic events in cancer patients (proximal DVT, symptomatic non-fatal PE and VTE-related death) occurred at 4.50% with certoparin and 6.03% with UFH (OR 0.73; 95% CI 0.23-2.39). Major bleeding was comparable and minor bleedings (0.75 vs. 5.67%) were nominally less frequent. 7.5% of certoparin and 12.8% of UFH treated patients experienced serious adverse events. 2) Thromboembolic event rates were comparable in patients with or without cancer (5.29 vs. 4.13%) as were bleeding complications. All cause death was increased in cancer (OR 2.68; 95%CI 1.22-5.86). 10.2% of patients with and 5.81% of those without cancer experienced serious adverse events (OR 1.85; 95% CI 1.21-2.81). CONCLUSIONS: Certoparin 3,000 UaXa o.d. and 5,000 IU UFH t.i.d. were equally effective and safe with respect to bleeding complications in patients with cancer. There were no statistically significant differences in the risk of thromboembolic events in patients with or without cancer receiving adequate anticoagulation. TRIAL REGISTRATION: clinicaltrials.gov, NCT00451412.

Sirolimus-eluting stent treatment at high-volume centers confers lower mortality at 6-month follow-up: results from the prospective multicenter German Cypher Registry.

BACKGROUND: Studies continue to identify percutaneous coronary intervention procedural volume both at the institutional level and at the operator level as being strongly correlated with outcome. High-volume centers have been defined as those that perform >400 percutaneous coronary intervention procedures per year. The relationship between drug-eluting stent procedural volume and outcome is unknown. We investigated this relationship in the German Cypher Registry. METHODS AND RESULTS: The present analysis included 8201 patients treated with sirolimus-eluting stents between April 2002 and September 2005 in 51 centers. Centers that recruited >400 sirolimus-eluting stent patients in this time period were considered high-volume centers; those with 150 to 400 patients were considered intermediate-volume centers; and those with <150 patients were designated as low-volume centers. The primary end point was all death, myocardial infarction, and target-vessel revascularization at 6 months. This end point occurred in 11.3%, 12.1%, and 9.0% of patients in the low-, intermediate-, and high-volume center groups, respectively (P=0.0001). There was no difference between groups in the rate of target-vessel revascularization (P=0.2) or cerebrovascular accidents (P=0.5). The difference in death/myocardial infarction remained significant after adjustment for baseline factors (odds ratio 1.85, 95% confidence interval 1.31 to 2.59, P<0.001 for low-volume centers; odds ratio 1.69, 95% confidence interval 1.29 to 2.21, P<0.001 for intermediate-volume centers). Patient and lesion selection, procedural features, and postprocedural medications differed significantly between groups. CONCLUSIONS: The volume of sirolimus-eluting stent procedures performed on an institutional level was inversely related to death and myocardial infarction but not to target-vessel revascularization at 6-month follow-up. Safety issues are better considered in high-volume centers. These findings have important public health policy implications.

Coronary stenting with the sirolimus-eluting stent in clinical practice: final results from the prospective multicenter German Cypher Stent Registry.

AIMS: Drug-eluting coronary stents (DES) have gained widespread use for the treatment of coronary artery disease. However, because of safety concerns and frequent "off-label" use data from "real life," registries are necessary to monitor indications and outcome of DES in daily clinical practice. METHODS AND RESULTS: We evaluated data from the German Cypher Stent Registry. A total of 10,894 patients treated with at least one sirolimus-eluting stent (SES) at 152 hospitals were included. Follow-up at a median of 6.4 months was available in 10,006 patients (92%). Median age was 64.8 years and 75.5% were male. Per lesion a mean of 1.09 +/- 0.41 SES were implanted with a mean length of 21.1 +/- 11.5mm. During follow-up, death rate was 1.8% and the rates of myocardial infarction or stroke were 2.1% and 0.5%. Any target vessel revascularization (TVR) was performed in 8.0% of patients. Independent predictors for death, myocardial infarction, or stroke were: cardiogenic shock, acute coronary syndromes, reduced left ventricular function, renal insufficiency, diabetes mellitus, advanced age, three-vessel disease, degree of stenosis, and prior myocardial infarction. Predictors for a TVR were: two- or three-vessel disease, target vessel = coronary bypass, advanced age, stent diameter, ostial lesions, indication in-stent restenosis, renal failure, and target vessel = left anterior descended artery. CONCLUSIONS: These results demonstrate that SES use in clinical practice is safe and effective. The main predictors of clinical events during follow-up are clinical parameters whereas as predictors of TVR mainly are angiographic parameters.

[Troponin test in clinical daily practice - Differences in the quality criteria for the diagnosis of acute myocardial Infarction considering clinical leading symptoms: A cross-sectional study]. / Troponin-Test im Alltag ­ Unterschiede der Gütekriterien in der Diagnose des akuten Myokardinfarkts unter Berücksichtigung klinischer Leitsymptome: eine Querschnittsstudie.

INTRODUCTION: Cardiac troponins are the prefered cardial biomarker in the diagnosis of acute myocardial infarction. Because they are detectable by myocardial cell damage, no matter what pathophysiology, the interpretation of a positive test is difficult. The aim of this study is to assess the quality criteria of the troponin test in the diagnosis of acute myocardial infarction in everyday life and whether clinical leading symptoms have an influence on it. METHODS: This is a retrospective cross-sectional study, in which all patients who presented themselves in the emergency department of the Klinikum Lippe-Detmold between 01.01.2014 and 31.05.2014, and had a Troponin-I test were included. The diagnosis "acute myocardial infarction" referred to myocardial infarction type I and was made by the cardiologist on-duty. The patients were divided into four subgroups according to the leading symptoms. The quality criteria of the Troponin-test were calculated. RESULTS: 1046 patients were included. In 15 %, acute myocardial infarction was present, of which 97 % had thoracic pain. The sensitivities and the negative predictive values were over 90 %. The specificities ranged between 56 % and 81 %. The positive predictive values were modest and best in case of thoracic pain 58 %. CONCLUSION: The Troponin test had a good negative predictive value for all clinical symptoms. Thus, an acute myocardial infarction could be excluded with high precision. However, the positive predictive value was low. The only direct symptom that achieved acceptable levels was thoracic pain.

Ticagrelor-based antiplatelet regimens in patients treated with coronary artery bypass grafting: a meta-analysis of randomized controlled trials.

OBJECTIVES: The optimal antiplatelet strategy in patients undergoing CABG remains unclear. This is the first meta-analysis investigating the clinical outcomes associated with ticagrelor-based antiplatelet regimens in patients receiving CABG. METHODS: Relevant scientific databases were searched for studies investigating antiplatelet regimens after CABG from inception until April 1, 2019. Studies which randomly assigned CABG patients to either ticagrelor-based or control antiplatelet regimens were eligible. The primary outcome of this analysis was all-cause death. The main secondary outcome was MI. Other outcomes of interest were cardiac death, major adverse cardiac events, stroke and bleeding. This study is registered with PROSPERO, number CRD42019122192. RESULTS: Five trials comprising 3996 patients (2002 assigned to ticagrelor-based and 1994 to control antiplatelet regimens) were eligible for quantitative synthesis. The median follow-up was 12 months. Control antiplatelet regimens consisted of either aspirin or clopidogrel or both. As compared to control, ticagrelor-based regimens reduced the risk of all-cause death [0.61 (0.43-0.87); P = 0.007], cardiac death [0.58 (0.39-0.86); P = 0.007] and major adverse cardiac events [0.79 (0.63-0.98); P = 0.03], without difference in the risk of MI [0.76 (0.50-1.18); P = 0.22], stroke [0.99 (0.56-1.78); P = 0.98] or bleeding [1.04 (0.95-1.14); P = 0.41]. There was a treatment effect modification for the primary outcome associated with trials enrolling predominantly patients with acute coronary syndrome (P for interaction = 0.038). CONCLUSIONS: In patients receiving CABG, ticagrelor-based regimens reduce mortality and major adverse cardiac events without excess bleeding risk as compared with aspirin monotherapy or the combination of aspirin and clopidogrel. The benefit of ticagrelor-based regimens is more relevant in those studies enrolling predominantly patients with acute coronary syndrome. These findings require further confirmation in randomized trials focused on this subset of patients and powered for clinical outcomes.

Clinical outcomes of complete versus incomplete revascularization in patients treated with coronary artery bypass grafting: insights from the TiCAB trial.

OBJECTIVES: In this post hoc analysis of the Ticagrelor in coronary artery bypass grafting (CABG) trial, we aimed to analyse patients treated with CABG receiving either complete revascularization (CR) or incomplete revascularization (ICR) independent from random allocation to either ticagrelor or aspirin. METHODS: Of 1859 patients enrolled in the Ticagrelor in CABG trial, 1550 patients (83.4%) received CR and 309 patients (16.6%) ICR. Outcomes were evaluated regarding all-cause mortality, cardiovascular death, myocardial infarction (MI), repeat revascularization, stroke and bleeding within 12 months after CABG. RESULTS: Baseline parameters revealed significant differences regarding clinical presentation (stable angina pectoris: CR 68.9% vs ICR 71.2%, instable angina pectoris: 14.1% vs 7.8%, non-ST elevation MI: 17.0% vs 21.0%, P ˂ 0.01), lesion characteristics (chronic total occlusion: CR 91.3% vs ICR 96.8%, P ˂ 0.01), operative technique [off-pump coronary artery bypass surgery (OPCAB): CR 3.0% vs ICR 6.1%, P ˂ 0.01] and number of utilized grafts (total number of grafts: 2.69/patient vs 2.49/patient, P ˂ 0.001). ICR patients displayed a significantly increased risk of repeat revascularization [hazard ratio (HR) 1.91, 95% confidence interval (CI) 1.16-3.16; P < 0.01] and percutaneous coronary intervention (HR 1.95, 95% CI 1.13-3.35; P < 0.05) within 12 months after CABG. Higher risk for repeat revascularization in ICR patients was independent from random allocation to either ticagrelor or aspirin and persisted after adjustment for baseline imbalances. CONCLUSIONS: Patients with ICR presented more stable at the time of admission, but received less grafts, highly likely due to a higher rate of chronic total occlusion lesions and performed OPCAB. Although mortality presented no difference between groups, our results suggest that patients benefit from CR with regard to prevention of repeat revascularization.

Ticagrelor monotherapy versus aspirin in patients undergoing multiple arterial or single arterial coronary artery bypass grafting: insights from the TiCAB trial.

OBJECTIVES: We evaluated the effect of ticagrelor monotherapy on outcomes after multiple arterial grafting (MAG) or single arterial grafting (SAG) in coronary artery bypass grafting (CABG). METHODS: In a post hoc, non-randomized analysis of the TiCAB (Ticagrelor in CABG; ClinicalTrials.gov NCT01755520) trial, we compared event rates for ticagrelor versus aspirin in patients undergoing MAG and SAG. Primary outcome was the composite of cardiovascular death, non-fatal myocardial infarction (MI), stroke or repeat revascularization 1 year after CABG. Secondary outcomes included individual components of the primary end point, all-cause death and bleeding. RESULTS: Among 1753 patients, 998 patients underwent MAG and 755 patients underwent SAG. There was no significant difference in the 1-year primary composite outcome for ticagrelor versus aspirin with MAG [7.2% vs 7.9%; hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.57-1.43; P = 0.66] or SAG (12.3% vs 8.6%; HR 1.47, 95% CI 0.93-2.31; P = 0.10). Event rates for cardiovascular death, MI, stroke, repeat revascularization and all-cause death were similar for both treatment groups with MAG and SAG. No significant difference in major bleeding was observed for ticagrelor versus aspirin with MAG (2.6% vs 2.7%; HR 0.95, 95% CI 0.44-2.05; P = 0.90) or SAG (5.8% vs 4.0%; HR 1.49, 95% CI 0.77-2.89; P = 0.24). CONCLUSIONS: In patients undergoing either MAG or SAG in the TiCAB trial, ticagrelor monotherapy compared with aspirin did not affect the rate of cardiovascular death, non-fatal MI, stroke or repeat revascularization, or the rate of bleeding, at 1 year after CABG.

Desmoteplase in acute massive pulmonary thromboembolism.

Alteplase is standard therapy for patients with acute, massive pulmonary embolism. The novel plasminogen activator desmoteplase displays high fibrin specificity and selectivity for fibrinbound plasminogen. In a preclinical model desmoteplase was twice as potent with a shorter lysis time and lower reocclusion rate. We conducted a phase II study comparing 125, 180, and 250 microg/kg bodyweight desmoteplase with 100 mg alteplase. Efficacy criteria were total pulmonary resistance (TPR), mean pulmonary artery pressure (mPAP), and Miller Index. Intention to treat analysis of 34 patients. The reduction of TPR after 24 hours was comparable between desmoteplase 180 microg/kg and alteplase (-48.0 +/- 22.4 vs. -50.4 +/- 16.3%; p = n.s. vs. alteplase; p = 0.0002 and p<0.0001 vs. baseline). The greatest effect was achieved with desmoteplase 250 microg/kg (-56.0 +/- 29.4%; p = n.s. vs. alteplase, p = 0.0055 vs. baseline). Two hours after treatment PAP was reduced by 27.9 (p = 0.0004 vs. baseline) and 30.4% (p = 0.015 vs. baseline) with the higher doses of desmoteplase and 29.6% with alteplase (p = 0.0006 vs. baseline). Further PAP reduction after 6 hours was most pronounced in the desmoteplase 250 microg/kg group (-40.1 +/- 18.0%; p = 0.0028 vs. baseline). The reduction of the Miller Index was greatest using desmoteplase 250 microg/kg (-35.0 +/- 21.7%; p = 0.011 vs. baseline), and alteplase (-41.6 +/- 27.2%; p = 0.0003 vs. baseline). Safety did not differ among the 4 groups. The study results suggest that desmoteplase at doses of 180 and 250 microg/kg had similar or greater efficacy compared to alteplase 100 mg. Onset of action was faster, safety was comparable.

Reperfusion rate and inhospital mortality of patients with ST segment elevation myocardial infarction diagnosed already in the prehospital phase: results of the German Prehospital Myocardial Infarction Registry (PREMIR).

AIMS: We sought to evaluate the in-hospital fate of patients with ST segment elevation myocardial infarction (STEMI) diagnosed already in the prehospital phase by physican equipped ambulances. METHODS: A total of 2326 consecutive STEMI patients were included in PREMIR. For this analysis 218 patients with prehospital cardiopulmonary resuscitation were excluded. RESULTS: The median time between symptom onset and 12-lead ECG was 85 min. The median time intervals between the diagnostic 12-lead ECG and prehospital fibrinolysis were 10 min, until inhospital fibrinolysis 52 min and until primar PCI 86min, respectively. Reperfusion therapy with prehospital fibrinolysis (24%), inhospital fibrinolysis (13%) or primary PCI (45%) was performed in 82% of the patients. Inhospital mortality was 6.0% in patients with prehospital fibrinolysis (n = 504), 5.8% in patients with inhospital fibrinolysis (n = 278), 4.5% in patients with primary percutaneous coronary intervention (n = 962) and 16.2% in patients without early reperfusion therapy (n = 377), respectively. In the multivariate propensity score analysis comparing prehospital fibrinolysis and primary PCI we observed no significant difference in the odds for in-hospital mortality (odds ratio: 1.57, 95% CI: 0.94-2.63). The final discharge diagnosis was STEMI in 90% of the patients, in patients with prehospital fibrinolysis 95%. CONCLUSIONS: In patients with STEMI already diagnosed in the prehospital phase the ischemic time is short, accuracy of the diagnosis is high and reperfusion therapy is performed in over 82%. Inhospital mortality was not different between prehospital fibrinolysis and primary PCI.

Prevalence of microalbuminuria and its associated cardiovascular risk: German and Swiss results of the recent global i-SEARCH survey.

QUESTION UNDER STUDY: The aim of this study was to determine the prevalence of microalbuminuria (MAU) in hypertensive patients attending an office or hospital based cardiologist or internist. An additional aim was to describe associations between MAU and cardiovascular risk factors as well as to investigate the role of pharmacotherapy. METHODS: International, observational, cross-sectional study of 22282 patients with 5605 attendees in Germany and Switzerland at 444 cardiology centers. Inclusion criteria were male and female outpatients, aged > or =18 years with currently treated or newly diagnosed hypertension (> or =140/90 mm Hg at rest on the day of the study visit) and no reasons for false positive dip stick tests. The main outcome measures were the prevalence of MAU, co-morbid cardiovascular risk factors or disease and their association with the presence of MAU, and the role of pharmacotherapy in modulating prevalence of MAU. RESULTS: Prevalence of MAU in Germany and Switzerland (53.1%) was high, but lower when compared to the prevalence in "other countries" (OC, 60.2%). Routine MAU measurement was performed in 52.9% of the practices only (32.9% OC), although physicians regarded MAU to be important for risk assessment and therapeutic decisions. MAU is highly correlated with a wide variety of cardiovascular risk factors and co-morbid cardiovascular conditions including high waist circumference (55.1% [95%CI 56.0; 59.7]), diabetes (59.1% [56.8; 61.3]), atrial fibrillation (62.3% [57.4; 66.9]) and peripheral arterial disease (67.1% [61.6; 72.2]). Angiotensin receptor blockers (ARBs) appeared to be associated with the lowest risk of MAU (52.1%). Calcium channel blockers (CCBs) were used more frequent in patients with MAU (28.7%) than without (23.4%). CONCLUSIONS: Patients with MAU are common in clinical cardiology and its presence is associated with a wide variety of cardiovascular risk factors and co-morbid cardiovascular conditions. A more aggressive multi-factorial treatment might help to reduce this risk constellation.