Integrated care for older multimorbid heart failure patients: protocol for the ESCAPE randomized trial and cohort study.

ESCAPE: Evaluation of a patient-centred biopsychosocial blended collaborative care pathway for the treatment of multimorbid elderly patients. THERAPEUTIC AREA: Healthcare interventions for the management of older patients with multiple morbidities. AIMS: Multi-morbidity treatment is an increasing challenge for healthcare systems in ageing societies. This comprehensive cohort study with embedded randomized controlled trial tests an integrated biopsychosocial care model for multimorbid elderly patients. HYPOTHESIS: A holistic, patient-centred pro-active 9-month intervention based on the blended collaborative care (BCC) approach and enhanced by information and communication technologies can improve health-related quality of life (HRQoL) and disease outcomes as compared with usual care at 9 months. METHODS: Across six European countries, ESCAPE is recruiting patients with heart failure, mental distress/disorder plus ≥2 medical co-morbidities into an observational cohort study. Within the cohort study, 300 patients will be included in a randomized controlled assessor-blinded two-arm parallel group interventional clinical trial (RCT). In the intervention, trained care managers (CMs) regularly support patients and informal carers in managing their multiple health problems. Supervised by a clinical specialist team, CMs remotely support patients in implementing the treatment plan-customized to the patients' individual needs and preferences-into their daily lives and liaise with patients' healthcare providers. An eHealth platform with an integrated patient registry guides the intervention and helps to empower patients and informal carers. HRQoL measured with the EQ-5D-5L as primary endpoint, and secondary outcomes, that is, medical and patient-reported outcomes, healthcare costs, cost-effectiveness, and informal carer burden, will be assessed at 9 and ≥18 months. CONCLUSIONS: If proven effective, the ESCAPE BCC intervention can be implemented in routine care for older patients with multiple morbidities across the participating countries and beyond.

In vitro thrombogenicity of drug-eluting and bare metal stents.

AIMS: We sought to investigate the thrombogenicity of different DES and BMS in an in vitro system of stent perfusion. MATERIAL AND METHODS: The experimental model consisted of a peristaltic pump connected to 4 parallel silicone tubes in which different stents were deployed. Blood was drawn from healthy volunteers and the amount of stent surfaced-induced thrombus deposition was determined using 125I-fibrinogen. RESULTS: Compared to Resolute, Biomatrix and Vision, Xience was associated with the lowest amount of stent surface-induced thrombus formation, with a significant difference compared to Vision (125I-fibrinogen median value deposition [IQ range]: 50 ng [25-98] versus 560 ng [320-1520], respectively, p < 0.05), but not to other DES. In the second set of experiments Fluoropolymer-coated BMS not eluting drug was associated with a significant 3-fold reduction in 125I-fibrinogen deposition (245 ng [80-300]) compared to Vision (625 ng [320-760], p < 0.05), but a 7-fold increase compared to Xience (35 ng [20-60], p < 0.05). Finally Xience was associated with a significantly greater absorption of albumin compared to BMS. CONCLUSIONS: In an in vitro system of stent perfusion, Xience was associated with the lowest amount of stent surface-induced thrombus formation compared with Resolute, Biomatrix and Vision, with a noted synergistic effect between the fluoropolymer and the drug.

Clinical outcomes with percutaneous coronary revascularization vs coronary artery bypass grafting surgery in patients with unprotected left main coronary artery disease: A meta-analysis of 6 randomized trials and 4,686 patients.

Some but not all randomized controlled trials (RCT) have suggested that percutaneous coronary intervention (PCI) with drug-eluting stents may be an acceptable alternative to coronary artery bypass grafting (CABG) surgery for the treatment of unprotected left main coronary artery disease (ULMCAD). We therefore aimed to compare the risk of all-cause mortality between PCI and CABG in patients with ULMCAD in a pairwise meta-analysis of RCT. METHODS: Randomized controlled trials comparing PCI vs CABG for the treatment of ULMCAD were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. RESULTS: Six trials including 4,686 randomized patients were identified. After a median follow-up of 39 months, there were no significant differences between PCI vs CABG in the risk of all-cause mortality (hazard ratio [HR] 0.99, 95% CI 0.76-1.30) or cardiac mortality. However, a significant interaction for cardiac mortality (Pinteraction= .03) was apparent between randomization arm and SYNTAX score, such that the relative risk for mortality tended to be lower with PCI compared with CABG among patients in the lower SYNTAX score tertile, similar in the intermediate tertile, and higher in the upper SYNTAX score tertile. Percutaneous coronary intervention compared with CABG was associated with a similar long-term composite risk of death, myocardial infarction, or stroke (HR 1.06, 95% CI 0.82-1.37), with fewer events within 30 days after PCI offset by fewer events after 30 days with CABG (Pinteraction < .0001). Percutaneous coronary intervention was associated with greater rates of unplanned revascularization compared with CABG (HR 1.74, 95% CI 1.47-2.07). CONCLUSIONS: In patients undergoing revascularization for ULMCAD, PCI was associated with similar rates of mortality compared with CABG at a median follow-up of 39 months, but with an interaction effect suggesting relatively lower mortality with PCI in patients with low SYNTAX score and relatively lower mortality with CABG in patients with high SYNTAX score. Both procedures resulted in similar long-term composite rates of death, myocardial infarction, or stroke, with PCI offering an early safety advantage and CABG demonstrating greater durability.

Short- Versus Long-TermDual Antiplatelet Therapy AfterDrug-Eluting Stent Implantation

Randomized controlled trials comparing short- (#6 months) with long-term ($1 year) dual antiplatelettherapy (DAPT) after drug-eluting stent(s) (DES) placement have been insufficiently powered to detect significantdifferences in the risk of major adverse cardiac events (MACE).OBJECTIVES This study sought to compare clinical outcomes between short- (#6 months) and long-term (1 year)DAPT and among 3 months, 6 months, and 1 year of DAPT post-DES placement by performing an individual patient datapairwise and network meta-analysis.METHODS Randomized controlled trials comparing DAPT durations after DES placement were searched through theMEDLINE, EMBASE, and Cochrane databases and in international meeting proceedings. The primary study outcomewas 1-year risk of MACE (cardiac death, myocardial infarction, or definite/probable stent thrombosis).RESULTS Four trials including 8,180 randomized patients were identified. At 1-year follow-up, short-term DAPT wasassociated with similar rates of MACE (hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.86 to 1.43; p » 0.44), butsignificantly lower rates of bleeding (HR: 0.66; 95% CI: 0.46 to 0.94; p » 0.03) versus prolonged DAPT. Comparableresults were apparent in the landmark period between DAPT discontinuation and 1-year follow-up (for MACE: HR: 1.20;95% CI: 0.77 to 1.89; p » 0.42) (for bleeding: HR: 0.44; 95% CI: 0.21 to 0.91; p » 0.03). There were no significantdifferences in 1-year rates of MACE among 3-month versus 1-year DAPT, 6-month versus 1-year DAPT, or 3-month versus6-month DAPT.CONCLUSIONS Compared with prolonged DAPT, short-term DAPT is associated with similar rates of MACE but lowerrates of bleeding after DES placement.

Leukocyte count is a modulating factor for the mortality benefit of bivalirudin in ST-segment-elevation acute myocardial infarction: the HORIZONS-AMI trial.

BACKGROUND: Although the reduction in mortality with bivalirudin compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors in the Harmonizing Outcome with Revascularization and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial has been attributed to lower rates of major bleeding, alternative mechanisms have not been investigated in depth. We sought to investigate whether there might be an interaction between white blood cell (WBC) count and bivalirudin for the risk of mortality, and whether this interaction is independent of major bleeding. METHODS AND RESULTS: Among the 3602 patients enrolled in the HORIZONS-AMI trial, WBC count was available in 3433 (95.3%) patients. Patients were stratified according to WBC tertiles. At 1-year follow-up, bivalirudin was associated with significantly lower rates of mortality and cardiac mortality compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors in patients in the upper WBC tertile (all-cause death: 4.1% versus 9.3%, respectively; P=0.0004; cardiac death: 2.0% versus 6.9%; respectively; P<0.0001) but not in patients in the mid-WBC or lower WBC tertiles. The reduction of mortality with bivalirudin across WBC tertiles was independent of major bleeding, and a significant interaction was apparent for 1-year all-cause mortality and cardiac mortality between WBC and bivalirudin therapy. Similar findings were apparent at 3 years. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, a significant interaction between bivalirudin therapy and admission WBC count was apparent for 1-year mortality. The reduction in mortality was independent of major bleeding, suggesting that other mechanisms may be implicated in the survival benefit observed with bivalirudin. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Risk of stroke with percutaneous coronary intervention compared with on-pump and off-pump coronary artery bypass graft surgery: Evidence from a comprehensive network meta-analysis.

BACKGROUND: Although some trials have reported that on-pump coronary artery bypass graft (CABG) surgery may be associated with higher rates of stroke than percutaneous coronary intervention (PCI), whether stroke is more common after off-pump CABG compared with PCI is unknown. We therefore sought to determine whether off-pump CABG is associated with an increased risk of stroke compared with PCI by means of network meta-analysis. METHODS: Randomized controlled trials (RCTs) comparing CABG vs PCI were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. RESULTS: Eighty-three RCTs with 22,729 patients randomized to on-pump CABG (n = 10,957), off-pump CABG (n = 7,119), or PCI (n = 4,653) were analyzed. Thirty-day rates of stroke were significantly lower in patients treated with PCI compared with either off-pump CABG (odds ratio [OR]; 0.39, 95% CI, 0.19-0.83) or on-pump CABG (OR, 0.26; 95% CI, 0.12-0.47). Compared with on-pump CABG, off-pump CABG was associated with significantly lower 30-day risk of stroke (OR, 0.67; 95% CI, 0.41-0.95). However, in sensitivity analyses restricted to high-quality studies, studies with more than either 100 or 1,000 patients, or studies with protocol definition or adjudication of stroke by a clinical events committee, the precision of the point estimate for the 30-day risk of stroke between off-pump vs on-pump CABG was markedly reduced. CONCLUSIONS: Percutaneous coronary intervention is associated with lower 30-day rates of stroke than both off-pump and on-pump CABG. Further studies are required to determine whether the risk of stroke is reduced with off-pump CABG compared with on-pump CABG.

Association among leukocyte count, mortality, and bleeding in patients with non-ST-segment elevation acute coronary syndromes (from the Acute Catheterization and Urgent Intervention Triage StrategY [ACUITY] trial).

Although inflammation is involved in the pathogenesis of acute coronary syndromes, the extent of inflammation is not routinely assessed, and its prognostic implications in patients with non-ST-segment elevation acute coronary syndrome have not been investigated in depth. We analyzed the prognostic implications of an elevated white blood cell count (WBCc) in patients with moderate and high-risk non-ST-segment elevation acute coronary syndrome undergoing an early invasive strategy in the large-scale Acute Catheterization and Urgent Intervention Triage StrategY trial. The WBCc at admission was available for 13,678 of 13,819 patients (98.9%). The patients in the upper tertile of the WBCc had an increased risk of 30-day major bleeding, 1-year mortality, and definite/probable stent thrombosis compared to those in the mid or lower tertiles. On multivariate analysis, the WBCc was an independent predictor of 30-day major bleeding and 1-year cardiac, noncardiac, and all-cause mortality. The association between the WBCc and cardiac mortality was present in multiple prespecified subgroups, with no significant interaction between the WBCc and age, gender, diabetes, smoking, renal dysfunction, elevated baseline biomarkers, antithrombotic therapy, revascularization, and Thrombolysis In Myocardial Infarction risk score. The WBCc remained an independent predictor of mortality after adjusting for bleeding, C-reactive protein level, and angiographic variables, including left ventricular ejection fraction, Thrombolysis In Myocardial Infarction flow, and number of diseased vessels. The WBCc significantly improved the prognostic accuracy of the Thrombolysis In Myocardial Infarction risk score, with a net reclassification improvement of 11% (p <0.0001). In conclusion, in patients with moderate- and high-risk non-ST-segment elevation acute coronary syndrome, an elevated admission WBCc was an independent predictor of 30-day major bleeding, and 1-year cardiac, noncardiac, and all-cause mortality.