Event rates and risk factors for venous thromboembolism and major bleeding in a population of hospitalized adult patients with acute medical illness receiving enoxaparin thromboprophylaxis.

BACKGROUND: We aimed to describe the event rates and risk-factors for symptomatic venous thromboembolism (VTE) and major bleeding in a population of hospitalized acutely ill medical patients. METHODS: Patients ≥40 years old and hospitalized for acute medical illness who initiated enoxaparin prophylaxis were selected from the US Optum research database. Rates of symptomatic VTE and major bleeding at 90-days were estimated via the Kaplan-Meier (KM) method. Risk factors were identified via the Cox proportional hazards model. RESULTS: A total of 123,022 patients met the selection criteria. The KM rates of VTE and major bleeding at 90-days were 3.5 % and 2.2 %, respectively. Among subgroups, the risk of VTE varied from 3.0 % in patients with ischemic stroke to 6.9 % in patients with a cancer-related hospitalization, and the risk of major bleeding varied from 1.9 % in patients with inflammatory conditions to 3.6 % in patients with ischemic stroke. Key risk factors for VTE were prior VTE (HR=4.15, 95 % confidence interval [CI] 3.80-4.53), cancer-related hospitalization (HR=2.35, 95 % CI 2.10-2.64), and thrombophilia (HR=1.64, 95 % CI 1.29-2.08). Key risk factors for major bleeding were history of major bleeding (HR=2.17, 95 % CI 1.72-2.74), history of non-major bleeding (HR=2.46, 95 % CI 2.24-2.70), and hospitalization for ischemic stroke (2.42, 95 % CI 2.11-2.78). CONCLUSION: There is substantial heterogeneity in the event rates for VTE and major bleeding in acute medically ill patients. History of VTE and cancer related hospitalization represent profiles with a high risk of VTE, where continued VTE prophylaxis may be warranted.

Imaging Predictors of Left Ventricular Functional Recovery after Reperfusion Therapy of ST-Elevation Myocardial Infarction Assessed by Cardiac Magnetic Resonance.

BACKGROUND: Left ventricular global longitudinal strain (LV GLS) is a superior predictor of adverse cardiac events in patients with myocardial infarction and heart failure. We investigated the ability of morphological features of infarcted myocardium to detect acute left ventricular (LV) dysfunction and predict LV functional recovery after three months in patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: Sixty-six STEMI patients were included in the C-reactive protein (CRP) apheresis in Acute Myocardial Infarction Study (CAMI-1). LV ejection fraction (LVEF), LV GLS, LV global circumferential strain (LV GCS), infarct size (IS), area-at-risk (AAR), and myocardial salvage index (MSI) were assessed by CMR 5 ± 3 days (baseline) and 12 ± 2 weeks after (follow-up) the diagnosis of first acute STEMI. RESULTS: Significant changes in myocardial injury parameters were identified after 12 weeks of STEMI diagnosis. IS decreased from 23.59 ± 11.69% at baseline to 18.29 ± 8.32% at follow-up (p < 0.001). AAR and MVO also significantly reduced after 12 weeks. At baseline, there were reasonably moderate correlations between IS and LVEF (r = -0.479, p < 0.001), LV GLS (r = 0.441, p < 0.001) and LV GCS (r = 0.396, p = 0.001) as well as between AAR and LVEF (r = -0.430, p = 0.003), LV GLS (r = 0.501, p < 0.001) and weak with LV GCS (r = 0.342, p = 0.020). At follow-up, only MSI and change in LV GCS over time showed a weak but significant correlation (r = -0.347, p = 0.021). Patients with larger AAR at baseline improved more in LVEF (p = 0.019) and LV GLS (p = 0.020) but not in LV GCS. CONCLUSION: The CMR tissue characteristics of myocardial injury correlate with the magnitude of LV dysfunction during the acute stage of STEMI. AAR predicts improvement in LVEF and LV GLS, while MSI is a sensitive marker of LV GCS recovery at three months follow-up after STEMI.

Outcomes After Left Main Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock (from the German ALKK PCI Registry).

Early revascularization therapy with percutaneous coronary intervention (PCI) has been shown to improve outcomes in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). Data from consecutive patients with AMI and CS treated with PCI enrolled into the prospective Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte-PCI registry were centrally collected and analyzed. Patients were divided into 4 groups with PCI for left main (LM), 1-vessel, 2-vessel, and 3-vessel diseases. Patients' characteristics, procedural features, antithrombotic therapies, and in-hospital complications were compared between the 4 groups. Between 2010 and 2015 a total of 2,348 consecutive patients with AMI and CS were treated by PCI in 51 hospitals, 295 for LM (15 for protected, 280 for unprotected) and single-vessel (n = 491), 2-vessel (n = 524), and 3-vessel disease (n = 1,038). Thrombolysis in myocardial infarction 3 patency of the culprit lesion after PCI was 84.3%, 84.0%, 80.8%, and 84.6% in single-vessel, 2-vessel, 3-vessel disease, and LM PCI, respectively, whereas in-hospital mortality was 27.9%, 33.9%, 46.5%, and 55.9%. Bleeding rates were low (2.0%-2.3 %) and not different between groups. In a multivariate analysis a higher age, thrombolysis in myocardial infarction flow <3 after PCI, 3-vessel disease, and LM PCI were independent predictors of mortality. In conclusion, PCI of the LM is performed in about 12.5% of patients with AMI and CS and was associated with a high procedural success rate, whereas mortality is increased with LM PCI.

Left atrial appendage closure with the watchman device reduces atrial fibrillation management costs.

AIMS: To report hospitalization costs of patients with non-valvular atrial fibrillation (AF) submitted to percutaneous left atrial appendage closure (LAAC) with the Watchman device. METHODS: Pre- and post-procedural hospitalization AF-related costs were calculated using the DRG system (diagnosis-related groups) and compared. RESULTS: Between 2012 and 2016, 677 non-valvular AF patients underwent LAAC. Median time from first cardiac hospitalization to LAAC was 5.9 years (IQR 1.6-9.1) and median follow-up after LAAC was 4.8 years (IQR 3.6-5.6). LAAC mortality was 1.3% and follow-up mortality 16.9%. Median pre-LAAC hospitalization cost was € 17,867 (IQR € 7512-35,08) and post-LAAC € 8772 (IQR € 1183-25,159) (p < 0.0001). Annualized cost pre-LAAC was 3773 € (IQR € 1644-8,493) and post-LAAC 2,001 € (IQR € 260-6913) (p < 0.0001). Follow-up survivors had significantly lower post-LAAC costs (p < 0.0001) and after a survival cut-off time of 4.6 years LAAC procedural and post-procedural hospitalization costs achieved parity with pre-LACC costs (AUC 0.64; p = 0.02). CHA2DS2-VASc score (B = 0.04; p = 0.02; 95% CI 0.006-0.08), and HAS-BLED score (B = 0.08; p = 0.004; 95% CI 0.02-0.14) were independent determinants for annualized hospitalization costs post-LAAC. At Cox-regression analysis the DRG mean clinical complexity level (CCL) was the only independent determinant for follow-up mortality (OR = 2.2; p < 0.0001; 95% CI 1.6-2.8) with a cut-off value of 2.25 to predict follow-up mortality (AUC 0.72; p < 0.0001; Spec. 70%; Sens. 70%). CONCLUSION: Hospitalization costs pre-LAAC are consistent, and after LAAC, they are significantly reduced. Costs seem related to the patient's risk profile at the time of the procedure. With the increase in post-LAAC survival time, the procedure becomes economically more profitable.

[Dual antiplatelet therapy after acute coronary syndrome or percutaneous coronary intervention: with what and for how long?] / Duale Thrombozytenhemmung nach akutem Koronarsyndrom oder perkutaner Koronarintervention ­ womit und wie lange?

Thrombotic complications following coronary interventions (PCI) used to be frequent specifically in acute coronary syndrome (ACS) patients. In recent years complication rates have significantly fallen due to improved stent technology, catheterisation techniques and intravascular visualisation. Therefore, the shortest necessary duration of dual antiplatelet therapy (DAPT) comprising aspirin and a P2Y12 inhibitor is constantly the subject of scientific investigations in order to avoid bleeding complications without allowing ischemic complications to occur. A DAPT duration of 12 months after PCI and ACS was accepted as a standard. Meanwhile a highly individualized approach in terms of therapy duration and choice of drugs that takes the patient's individual bleeding and ischemic risk into account is being practised. Prolonged DAPT (>12 months) is currently recommended for patients post myocardial infarction with a low bleeding risk, at high ischemic risk due to coronary triple vessel disease, following a high risk coronary intervention with an unsatisfactory result or a personal history of prior stent thrombosis. Alternatively, instead of prolonged DAPT, dual-pathway antithrombotic therapy of aspirin plus rivaroxaban (2.5 mg bid) is recommended to prevent future strokes, critical limb ischemia and to reduce mortality in cases with multiregional atherosclerosis. In the meantime, reduced-duration DAPT of 3-6 months is being recommended for most patients. Recent data show that in patients with a high bleeding risk, a DAPT treatment period of 4 weeks may be sufficient with a markedly reduced rate of bleeding and without evidence for more ischemic events. Following the early termination of DAPT, continuing antithrombotic monotherapy with the P2Y12 inhibitor ticagrelor may be indicated to prevent further ischemic events without the risk of bleeding complications comparable to DAPT.

C-Reactive Protein Apheresis as Anti-inflammatory Therapy in Acute Myocardial Infarction: Results of the CAMI-1 Study.

Background: C-reactive protein (CRP) is a well-known marker of inflammation. It is less known that CRP mediates tissue damage in acute myocardial infarction (AMI) thus potentially worsening prognosis. A newly developed specific CRP adsorber allows efficient lowering of CRP levels and may improve survival. Objectives: Aim of this multi-center, controlled, non-randomized first-in-man CRP apheresis in Acute Myocardial Infarction study (CAMI-1) was to investigate the relationship between CRP levels (CRP gradient), myocardial infarct size and function as well as safety and efficacy of CRP apheresis in the setting of acute ST-segment Elevation Myocardial Infarction (STEMI) in humans. Methods: Eighty-three patients (45 apheresis, 38 controls) were recruited. CRP apheresis was performed 24 ± 12, 48 ± 12, and optionally 72 ± 12 h after onset of symptoms. First aphereses were performed at a median CRP concentration of 23.0 mg/L (range 9-279). In each apheresis session, 5,900 ± 400 mL plasma was processed via peripheral venous access. Primary study endpoint was a reduction in myocardial infarct size after STEMI as determined by cardiovascular magnetic resonance (CMR). Results: In controls, the CRP concentration significantly correlated with infarct size (p = 0.002) and decreased myocardial function (p ≤ 0.001). The CRP concentration in apheresis patients did not correlate with infarct size (p = 0.66) or left ventricular (LV) function (p = 0.79) and global strains and therefore significantly differed from controls (p = 0.03 and p = 0.002). Three major adverse cardiac events occurred in the control group after 12 months, none occurred in the apheresis group. Mean CRP depletion achieved over all apheresis procedures was 53.0 ± 15.1%. Apheresis sessions were well-tolerated. Reduced infarct size in the apheresis group compared to the control group (primary endpoint) was not achieved according to the original statistical analysis plan. Taking into account the individual CRP levels, however, revealed significant results. Modifications of the analysis plan were introduced in order to recruit a sufficient number of patients. Conclusions: This pilot study in humans reveals a correlation between CRP concentration and myocardial infarct size. CRP concentrations in STEMI can effectively be reduced by CRP apheresis without relevant side effects. CRP apheresis has the potential to interfere with deleterious aspects of STEMI. By lowering CRP levels, it resulted in the loss of correlation of CRP concentrations with myocardial infarct sizes as well as LV function. These results encourage a larger, randomized clinical trial. Clinical Trial Registration: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00008988, DRKS00008988.

Improving care coordination for patients with cardiac disease: Study protocol of the randomised controlled new healthcare programme (Cardiolotse).

INTRODUCTION: A lack of effective coordination and communication between ambulatory care physicians and hospitals, including the lack of follow-up care, poses a challenge to the recovery process of patients suffering from cardiac disease, often resulting in rehospitalisation and adverse outcomes. This innovative care programme aims to bridge the gap between ambulatory and hospital care. A key element of this programme is specifically trained care managers (Cardiolotse) who provide post-discharge support, access to additional resources and help the patient to navigate successfully through the healthcare system. MATERIAL AND METHODS: The study is set up as a prospective, randomised, controlled trial. Allocation to intervention group (support of care managers) and control group (usual care) follows an allocation ratio of 1:1 using block randomisation. Sample size calculations resulted in 1454patients per group after adjusting for potential non-compliance. All participants are surveyed at discharge, after 3 and 12 months. The primary outcome of the study is the 12-month rehospitalisation rate. Secondary outcomes include differences in length of hospital stay, mortality, quality-adjusted life years, costs and patient satisfaction. Statistical analysis and economic evaluation will be complemented by a process evaluation. DISCUSSION: The new healthcare programme is designed to support patients when leaving hospital with cardiac conditions by easing the transition between sectors through access to Cardiolotses and individualised care plans. We hypothesise that the programme reduces rehospitalisation and improves clinically relevant patient outcomes. TRIAL REGISTRATION: German Clinical Trial Register, DRKS00020424. Registered 2020-06-18, http://www.drks.de/DRKS00020424.

Apixaban or Vitamin K Antagonists and Aspirin or Placebo According to Kidney Function in Patients With Atrial Fibrillation After Acute Coronary Syndrome or Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.

BACKGROUND: In the AUGUSTUS trial (An Open-Label, 2×2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban Versus Vitamin K Antagonist and Aspirin Versus Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention), apixaban resulted in less bleeding and fewer hospitalizations than vitamin K antagonists, and aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention treated with a P2Y12 inhibitor. We evaluated the risk-benefit balance of antithrombotic therapy according to kidney function. METHODS: In 4456 patients, the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula was used to calculate baseline estimated glomerular filtration rate (eGFR). The effect of apixaban versus vitamin K antagonists and aspirin versus placebo was assessed across kidney function categories by using Cox models. The primary outcome was International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and ischemic events (death, stroke, myocardial infarction, stent thrombosis [definite or probable], or urgent revascularization). Creatinine clearance <30 mL/min was an exclusion criterion in the AUGUSTUS trial. RESULTS: Overall, 30%, 52%, and 19% had an eGFR of >80, >50 to 80, and 30 to 50 mL·min-1·1.73 m-2, respectively. At the 6-month follow-up, a total of 543 primary outcomes of bleeding, 1125 death or hospitalizations, and 282 ischemic events occurred. Compared with vitamin K antagonists, patients assigned apixaban had lower rates for all 3 outcomes across most eGFR categories without significant interaction. The absolute risk reduction with apixaban was most pronounced in those with an eGFR of 30 to 50 mL·min-1·1.73 m-2 for bleeding events with rates of 13.1% versus 21.3% (hazard ratio, 0.59; 95% CI, 0.41-0.84). Patients assigned aspirin had a higher risk of bleeding in all eGFR categories with an even greater increase among those with eGFR >80 mL·min-1·1.73 m-2: 16.6% versus 5.6% (hazard ratio, 3.22; 95% CI, 2.19-4.74; P for interaction=0.007). The risk of death or hospitalization and ischemic events were comparable to aspirin and placebo across eGFR categories with hazard ratios ranging from 0.97 (95% CI, 0.76-1.23) to 1.28 (95% CI, 1.02-1.59) and from 0.75 (95% CI, 0.48-1.17) to 1.34 (95% CI, 0.81-2.22), respectively. CONCLUSIONS: The safety and efficacy of apixaban was consistent irrespective of kidney function, compared with warfarin, and in accordance with the overall trial results. The risk of bleeding with aspirin was consistently higher across all kidney function categories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.

Antithrombotic management and outcomes of patients with atrial fibrillation treated with NOACs early at the time of market introduction: Main results from the PREFER in AF Prolongation Registry.

The management of patients with atrial fibrillation (AF) has rapidly changed with increasing use of non-vitamin K antagonist oral anticoagulants (NOACs) and changes in the use of rhythm control therapy. The prevention of thromboembolic events European Registry in Atrial Fibrillation Prolongation Registry (PREFER Prolongation) enrolled consecutive patients with AF on NOACs between 2014 and 2016 in a multicentre, prospective, observational study with one-year follow-up, focusing on the time of introduction of NOACs. Overall, 3783 patients were enrolled, with follow-up information available in 3223 (85%). Mean age was 72.2 ± 9.4 years, 40% were women, mean CHA2DS2VASc score was 3.4 ± 1.6, and 2587 (88.6%) had a CHA2DS2VASc score ≥ 2. Rivaroxaban was used in half of patients, and dabigatran and apixaban were used in about a quarter of patients each; edoxaban was not available for use in Europe at the time. Major cardiovascular event rate was low: serious events occurred in 74 patients (84 events, 2%), including 24 strokes (1%), 62 major bleeds (2%), of which 30 were life-threatening (1%) and 3 intracranial (0.1%), and 28 acute coronary syndromes (1%). Mortality was 2%. Antiarrhythmic drugs were used in about 50% of patients, catheter ablation in 5%. Adverse events were low in this contemporary European cohort of unselected AF patients treated with NOACs already at the time of their first introduction, despite high thromboembolic risk.

[Antithrombotic Therapy in Patients with Acute Coronary Syndrome and Atrial Fibrillation]. / Antithrombotische Therapie bei akutem Koronarsyndrom und Vorhofflimmern.

The number of patients with atrial fibrillation (AF) is increasing due to the aging of the population. In addition, the number of patients with AF and an indication for oral anticoagulation (OAC) for the prevention of strokes increases, who are in need for a dual antiplatelet therapy (DAPT) with acetyl salicylic acid (ASA) plus a P2Y12-Inhibitor because of an acute coronary syndrome and/or coronary stent implantation. These patients did receive a triple therapy (TT) for 3-12 months in the past. Triple therapy never has been studied for efficacy or safety, however, the rate of bleeding complications in comparison to OAC or DAPT is significantly higher.Registries and smaller trials showed that dual therapy with an OAC plus a single platelet inhibitor may be sufficient to prevent strokes and stent thromboses/myocardial infarctions. Four prospective randomized trials involving all four NOACs (Non-Vitamin K oral anticoagulants) approved for stroke prevention in AF have been undertaken. The NOACs plus one antiplatelet agent were tested versus vitamin K-antagonists plus DAPT. In the meantime, the trials involving rivaroxaban (PIONEER AF-PCI), dabigatran (RE-DUAL PCI), apixaban (AUGUSTUS), and edoxaban (ENTRUST-AF-PCI) have been published. The current status is that a NOAC plus a single antiplatelet agent, mostly clopidogrel, is superior to TT with respect to the bleeding complications, without any obvious and statistically significant disadvantage for stroke rates or cardiac ischemic events. The international guidelines already recommend to treat with a NOAC and one antiplatelet agent instead of TT in case the patients bleeding risk is prevailing. Thus, TT seems not to be indicated anymore for most patients with AF and ACS or PCI.

Educational Impact on Apixaban Adherence in Atrial Fibrillation (the AEGEAN STUDY): A Randomized Clinical Trial.

INTRODUCTION: Adherence to non-vitamin-K oral anticoagulants (NOACs) may be lower than to vitamin K antagonists because NOACs do not require routine monitoring. OBJECTIVE: We assessed the impact of an educational program on adherence and persistence with apixaban in patients with non-valvular atrial fibrillation (NVAF). METHODS: Patients with NVAF eligible for NOACs with one or more stroke risk factor (prior stroke/transient ischemic attack, age ≥ 75 years, hypertension, diabetes, or symptomatic heart failure) were randomized (1:1) to standard of care (SOC) or SOC with additional educational (information booklet, reminder tools, virtual clinic access). The primary outcome was adherence to apixaban (2.5 or 5 mg twice daily) at 24 weeks. Patients receiving the educational program were re-randomized (1:1) to continue the program for 24 further weeks or to switch to secondary SOC. Implementation adherence and persistence were reassessed at 48 weeks. RESULTS: In total, 1162 patients were randomized (SOC, 583; educational program, 579). Mean implementation adherence ± standard deviation (SD) at 24 weeks was 91.6% ± 17.1 for SOC and 91.9% ± 16.1 for the educational program arm; results did not differ significantly between groups at any time-point. At 48 weeks, implementation adherence was 90.4% ± 18.0, 90.1% ± 18.6, and 89.3% ± 18.1 for continued educational program, SOC, and secondary SOC, respectively; and corresponding persistence was 86.1% (95% confidence interval [CI] 81.3-89.7), 85.2% (95% CI 81.5-88.2), and 87.8% (95% CI 83.4-91.1). Serious adverse events were similar across groups. CONCLUSION: High implementation adherence and persistence with apixaban were observed in patients with NVAF receiving apixaban. The educational program did not show additional benefits. CLINICAL TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov [NCT01884350].

Guideline-adherence regarding critical time intervals in the German Chest Pain Unit registry.

BACKGROUND: Since 2008, the German Cardiac Society certified 256 Chest Pain Units (CPUs). Little is known about adherence to recommended performance measures in patients with suspected acute coronary syndrome (ACS) presenting to CPUs. We investigated guideline-adherence regarding critical time intervals and selected performance measures in German Chest Pain Units. METHODS: From 2008 to 2014, 23,804 consecutive patients with suspected ACS were prospectively enrolled in the Chest Pain Unit registry of the German Cardiac Society. RESULTS: Median time from symptom onset to first medical contact was 2 h in patients with ST-elevation myocardial infarction (STEMI) and 4 h in patients with unstable angina and non-STEMI (NSTEMI). In patients with STEMI, median time from hospital admission to percutaneous coronary intervention (PCI) was 40 min and median time from first medical contact to PCI was 1 h 35 min. Primary PCI was performed in 94.7% of patients with STEMI, 70.0% of patients with NSTEMI and 37.4% of patients with unstable angina. PCI was performed during the first 24 h in 79.5% of patients with NSTEMI and the first 72 h in 89.0% of patients with unstable angina. Electrocardiograms were performed in 99.5% after a median of 6 min after admission and obtained within 10 min in 71%. Interestingly, 56.1% of patients were found to have non-ACS diagnoses, underlining the importance of access to additional diagnostic modalities including echocardiography, stress testing or computed tomography. CONCLUSIONS: Guideline-adherence regarding critical time intervals and primary PCI rates is good in German Chest Pain Units. More than half of patients admitted with suspected ACS had non-ACS diagnoses. Improvements in pre-hospital time delays through public awareness programmes are warranted.

Antithrombotic Therapy in Patients With Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or With Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.

BACKGROUND: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.

Procedural Success Rates and Mortality in Elderly Patients With Percutaneous Coronary Intervention for Cardiogenic Shock.

OBJECTIVES: The aim of this study was to determine the impact of age on procedural and clinical outcomes in patients with cardiogenic shock (CS). BACKGROUND: The use of early revascularization therapy with percutaneous coronary intervention (PCI) has been shown to improve outcome in patients with acute myocardial infarction (AMI) complicated by CS. METHODS: Data from consecutive patients with AMI and CS treated with PCI enrolled into the prospective ALKK (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte) PCI registry were centrally collected and analyzed. Patients were divided into 4 groups according to their age (<65, 65 to 74, 75 to 84, and >85 years). Patients' characteristics, procedural features, antithrombotic therapies, and in-hospital complications were compared among the 4 groups. RESULTS: Between 2010 and 2015, a total of 2,323 consecutive patients with AMI and CS were treated by PCI in 51 hospitals. TIMI (Thrombolysis In Myocardial Infarction) flow grade 3 patency after PCI decreased with increasing age from 84% to 78%, while in-hospital mortality increased from 32% to 56%. Bleeding rates were low (2.0% to 2.3%) and not different among age groups. In the multivariate analysis, higher age, TIMI flow grade <3 after PCI, 3-vessel disease, and left main PCI were independent predictors of mortality. CONCLUSIONS: PCI in patients with AMI and CS is associated with a high procedural success rate and a low bleeding rate, even in very elderly patients, while mortality increases with increasing age. Because mortality in elderly patients with CS without revascularization therapy is very high, it seems justified to perform PCI in selected patients to reduce mortality.

Upper Extremity DVT versus Lower Extremity DVT: Perspectives from the GARFIELD-VTE Registry.

Upper extremity deep vein thrombosis (UEDVT) is less common than lower extremity DVT (LEDVT) and consequently less well characterized. This study compared clinical characteristics and 1-year outcomes between 438 UEDVT patients and 7,602 LEDVT patients recruited in the GARFIELD-VTE registry. UEDVT patients were significantly more likely to have a central venous catheter than those with LEDVT (11.5% vs. 0.5%; p < 0.0001), and had a higher rate of active cancer (16.2%) or recent hospitalization (19.4%) compared with LEDVT patients (8.7% and 11.2%, respectively). Nearly all patients with UEDVT and LEDVT were initiated on anticoagulant therapy, which was a direct oral anticoagulant in one-third individuals in both groups. At 3, 6, and 12 months, the proportion of UEDVT and LEDVT patients who were receiving anticoagulant therapy was 82.6 and 87.4%, 66.0 and 72.6%, and 45.7 and 54.6%, respectively. In the UEDVT and LEDVT groups, VTE recurrence rate was 4.0 (95% confidence interval [CI], 2.4-6.7) and 5.5 (95% CI, 4.9-6.1) per 100 person-years, respectively; major bleed was noted in 1.3 (95% CI, 0.6-3.2) and 1.6 (95% CI, 1.3-1.9) per 100 person-years and all-cause mortality in 9.7 (95% CI, 7.1-13.4) and 6.7 (95% CI, 6.1-7.3) per 100 person-years, respectively. Hence, risk of recurrence was similar in the two groups whereas all-cause mortality was significantly higher in the UEDVT group than the LEDVT group (p = 0.0338). This latter finding was likely due to the high prevalence of cancer in the UEDVT group.

Effect of renal insufficiency and diabetes mellitus on in-hospital mortality after acute coronary syndromes treated with primary PCI. Results from the ALKK PCI Registry.

BACKGROUND: It is known that patients with acute coronary syndromes (ACS) and diabetes mellitus (DM) are at higher risk for in-hospital adverse events. However, we hypothesized that the higher event rate is due to the patients' subgroup with renal failure (RF), a common sequel of DM. METHODS AND RESULTS: We used data of the prospective ALKK-PCI registry including all consecutive percutaneous coronary interventions (PCI) for ACS of 48 hospitals between 2008 and 2013. We divided 69,651 patients in four groups according to their history of DM and RF (GFR < 60 ml/min). All-cause, in-hospital mortality of the following four groups: noDM/noRF, DM/noRF, DM/RF, RF/noDM, was: 3.5%, 6.6%, 21.9%, and 14.1% for STEMI and 1.5%, 2.1%, 7.2%, and 5.4% for NSTE-ACS. In a multivariate analysis we looked for independent mortality-predictors. Odds ratios with confidence intervals for the following variables: DM without RF, DM with RF, RF without DM were: 1.62 (1.37-1.90), 3.02 (2.43-3.76), and 2.13 (1.80-2.52) for STEMI and 1.20 (0.99-1.45), 2.72 (2.18-3.88), and 2.08 (1.69-2.56) for NSTE-ACS. We also calculated mortality in four groups (60-90, 45-60, 45-30, <30 ml/min) according to the estimated glomerular filtration rate (eGFR). Mortality rates were: 5.0%, 12.8%, 17.7%, and 31.5% for STEMI and 2.1%, 3.8%, 7.1%, and 12.0% for NSTE-ACS (p for trend <0.0001 for both). CONCLUSIONS: In-hospital death after PCI in patients with ACS and DM is mainly observed in the subgroup with co-existing RF. In a multivariate analysis, DM without RF was a significant mortality-predictor in STEMI, but not in NSTE-ACS. RF, irrespective of co-existent DM, was a stronger predictor than DM alone for both ACS-types (OR > 3) and mortality increased with decreasing eGFR.

Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation.

BACKGROUND: Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. METHODS: In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. RESULTS: Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. CONCLUSIONS: In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both. (Funded by Bristol-Myers Squibb and Pfizer; AUGUSTUS ClinicalTrials.gov number, NCT02415400.).

Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The use of aspirin in the primary prevention of cardiovascular events remains controversial. We aimed to assess the efficacy and safety of aspirin versus placebo in patients with a moderate estimated risk of a first cardiovascular event. METHODS: ARRIVE is a randomised, double-blind, placebo-controlled, multicentre study done in seven countries. Eligible patients were aged 55 years (men) or 60 years (women) and older and had an average cardiovascular risk, deemed to be moderate on the basis of the number of specific risk factors. We excluded patients at high risk of gastrointestinal bleeding or other bleeding, or diabetes. Patients were randomly assigned (1:1) with a computer-generated randomisation code to receive enteric-coated aspirin tablets (100 mg) or placebo tablets, once daily. Patients, investigators, and others involved in treatment or data analysis were masked to treatment allocation. The primary efficacy endpoint was a composite outcome of time to first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischaemic attack. Safety endpoints were haemorrhagic events and incidence of other adverse events, and were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00501059. FINDINGS: Between July 5, 2007, and Nov 15, 2016, 12 546 patients were enrolled and randomly assigned to receive aspirin (n=6270) or placebo (n=6276) at 501 study sites. Median follow-up was 60 months. In the intention-to-treat analysis, the primary endpoint occurred in 269 (4·29%) patients in the aspirin group versus 281 (4·48%) patients in the placebo group (hazard ratio [HR] 0·96; 95% CI 0·81-1·13; p=0·6038). Gastrointestinal bleeding events (mostly mild) occurred in 61 (0·97%) patients in the aspirin group versus 29 (0·46%) in the placebo group (HR 2·11; 95% CI 1·36-3·28; p=0·0007). The overall incidence rate of serious adverse events was similar in both treatment groups (n=1266 [20·19%] in the aspirin group vs n=1311 [20·89%] in the placebo group. The overall incidence of adverse events was similar in both treatment groups (n=5142 [82·01%] vs n=5129 [81·72%] in the placebo group). The overall incidence of treatment-related adverse events was low (n=1050 [16·75%] vs n=850 [13·54%] in the placebo group; p<0·0001). There were 321 documented deaths in the intention-to-treat population (n=160 [2·55%] vs n=161 [2·57%] of 6276 patients in the placebo group). INTERPRETATION: The event rate was much lower than expected, which is probably reflective of contemporary risk management strategies, making the study more representative of a low-risk population. The role of aspirin in primary prevention among patients at moderate risk could therefore not be addressed. Nonetheless, the findings with respect to aspirin's effects are consistent with those observed in the previously published low-risk primary prevention studies. FUNDING: Bayer.