Biolimus-eluting vs. other limus-eluting stents in NSTE-ACS: A pooled analysis of GLASSY and TWILIGHT.

BACKGROUND: Biodegradable polymer biolimus-eluting stents (BP-BES) may be associated with better outcomes in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) compared to other current-generation limus-eluting stents (LES). AIMS: To compare BP-BES with other current-generation LES in ACS patients undergoing PCI. METHODS: We pooled individual data of Non-ST-segment elevation (NSTE)-ACS patients from two large randomized controlled trials (GLASSY and TWILIGHT). The BP-BES groups consisted mostly of GLASSY patients, while the control group (other current-generation LES) included exclusively TWILIGHT patients. The primary outcome was major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, or stent thrombosis; the key secondary outcome was target-vessel failure (TVF). To account for trial design differences, outcomes were assessed at 3 months (short-term) and between 3 and 12 months (long-term) after PCI and subsequently pooled to estimate the 12-month hazards. RESULTS: Of 7107 and 6053 NSTE-ACS patients included in the short- and long-term analysis, 32.7% and 36.5% received a BP-BES, respectively. Risk of MACE associated with BP-BES versus other LES was similar at short-term (1.1% vs 1.3%, adjusted HR 0.86, 95%CI 0.53-1.38), lower at long-term (1.7% vs 3.1%, adjusted HR 0.49, 95%CI 0.34-0.72), and lower in the entire 12-month period (pooled adjusted HR 0.61, 95%CI 0.45-0.82). The cumulative 12-month risk of TVF was reduced with BP-BES (adjusted HR 0.52, 95%CI 0.38-0.70). CONCLUSION: BP-BES was associated with lower 12-month risks of MACE and TVF compared to other current generation LES among NSTE-ACS patients treated with abbreviated or standard ticagrelor-based DAPT. These non-randomized findings are hypothesis-generating. CONDENSED ABSTRACT: Differences in clinical outcomes may exist between biodegradable polymer biolimus-eluting stents (BP-BES) and other current-generation limus-eluting stent (LES) in patients with acute coronary syndrome (ACS). We pooled individual data of about 7000 Non-ST-segment elevation ACS patients undergoing PCI and treated with ticagrelor with or without aspirin from two large randomized controlled trials (GLASSY and TWILIGHT). BP-BES patients derived very largely from GLASSY and other LES patients from TWILIGHT. In this population, BP-BES compared to other current generation LES, were associated with a lower 12-month risk of major adverse cardiovascular events and target-vessel failure.

Ticagrelor Monotherapy Versus Dual-Antiplatelet Therapy After PCI: An Individual Patient-Level Meta-Analysis.

OBJECTIVES: The aim of this study was to compare ticagrelor monotherapy with dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents. BACKGROUND: The role of abbreviated DAPT followed by an oral P2Y12 inhibitor after PCI remains uncertain. METHODS: Two randomized trials, including 14,628 patients undergoing PCI, comparing ticagrelor monotherapy with standard DAPT on centrally adjudicated endpoints were identified, and individual patient data were analyzed using 1-step fixed-effect models. The protocol was registered in PROSPERO (CRD42019143120). The primary outcomes were the composite of Bleeding Academic Research Consortium type 3 or 5 bleeding tested for superiority and, if met, the composite of all-cause death, myocardial infarction, or stroke at 1 year, tested for noninferiority against a margin of 1.25 on a hazard ratio (HR) scale. RESULTS: Bleeding Academic Research Consortium type 3 or 5 bleeding occurred in fewer patients with ticagrelor than DAPT (0.9% vs. 1.7%, respectively; HR: 0.56; 95% confidence interval [CI]: 0.41 to 0.75; p < 0.001). The composite of all-cause death, myocardial infarction, or stroke occurred in 231 patients (3.2%) with ticagrelor and in 254 patients (3.5%) with DAPT (HR: 0.92; 95% CI: 0.76 to 1.10; p < 0.001 for noninferiority). Ticagrelor was associated with lower risk for all-cause (HR: 0.71; 95% CI: 0.52 to 0.96; p = 0.027) and cardiovascular (HR: 0.68; 95% CI: 0.47 to 0.99; p = 0.044) mortality. Rates of myocardial infarction (2.01% vs. 2.05%; p = 0.88), stent thrombosis (0.29% vs. 0.38%; p = 0.32), and stroke (0.47% vs. 0.36%; p = 0.30) were similar. CONCLUSIONS: Ticagrelor monotherapy was associated with a lower risk for major bleeding compared with standard DAPT, without a concomitant increase in ischemic events.

Prevalence and Outcomes of Undiagnosed Peripheral Arterial Disease Among High Risk Patients in Australia: An Australian REACH Sub-Study.

BACKGROUND: Compared with other manifestations of cardiovascular disease, peripheral arterial disease (PAD) is under-diagnosed. This study aims to investigate the prevalence, risk profile and cardiovascular outcomes of undiagnosed PAD in Australian general practices. METHOD: A sub-study of the Australian Reduction of Atherothrombosis for Continued Health (REACH) Registry, a prospective cohort study of patients at high risk of atherothrombosis recruited from Australian general practices. Eligible patients for this study had no previous clinical diagnosis of PAD and had an ankle-brachial index (ABI) ≤1.4 at recruitment. RESULTS: Peripheral arterial disease was undiagnosed in 34% Australian REACH participants, 28% patients had low ABI (ABI<0.9) and 11% had intermittent claudication (IC) based on responses to the Edinburgh Claudication Questionnaire (ECQ). We found no significant differences in risk factor control between patient with or without PAD. Intermittent claudication patients had higher risks of non-fatal cardiovascular events and PAD interventions at one year, whereas all-cause mortality rate was higher among patients with ABI<0.9, especially in those who also reported IC. Finally, an ABI<0.9, together with poorly controlled risk factors were independent predictors of incident IC at one year. CONCLUSIONS: This study suggests a high rate of undiagnosed PAD among high risk patients in Australian primary health care. These patients are at high risk of events and therefore would potentially benefit from better secondary prevention measures.

Extent of coronary artery disease and outcomes after ticagrelor administration in patients with an acute coronary syndrome: Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial.

BACKGROUND: Extensive coronary artery disease (CAD) is associated with higher risk. In this substudy of the PLATO trial, we examined the effects of randomized treatment on outcome events and safety in relation to the extent of CAD. METHODS: Patients were classified according to presence of extensive CAD (defined as 3-vessel disease, left main disease, or prior coronary artery bypass graft surgery). The trial's primary and secondary end points were compared using Cox proportional hazards regression. RESULTS: Among 15,388 study patients for whom the extent of CAD was known, 4,646 (30%) had extensive CAD. Patients with extensive CAD had more high-risk characteristics and experienced more clinical events during follow-up. They were less likely to undergo percutaneous coronary intervention (58% vs 79%, P < .001) but more likely to undergo coronary artery bypass graft surgery (16% vs 2%, P < .001). Ticagrelor, compared with clopidogrel, reduced the composite of cardiovascular death, myocardial infarction, and stroke in patients with extensive CAD (14.9% vs 17.6%, hazard ratio [HR] 0.85 [0.73-0.98]) similar to its reduction in those without extensive CAD (6.8% vs 8.0%, HR 0.85 [0.74-0.98], Pinteraction = .99). Major bleeding was similar with ticagrelor vs clopidogrel among patients with (25.7% vs 25.5%, HR 1.02 [0.90-1.15]) and without (7.3% vs 6.4%, HR 1.14 [0.98-1.33], Pinteraction = .24) extensive CAD. CONCLUSIONS: Patients with extensive CAD have higher rates of recurrent cardiovascular events and bleeding. Ticagrelor reduced ischemic events to a similar extent both in patients with and without extensive CAD, with bleeding rates similar to clopidogrel.

Clinical characteristics and outcomes of acute coronary syndrome patients with left anterior hemiblock.

OBJECTIVE: We aimed to study the relationships between left anterior hemiblock (LAHB) and the patient characteristics, management, and clinical outcomes in the setting of acute coronary syndromes (ACS). METHODS: Admission ECGs of patients enrolled in the Global Registry of Acute Coronary Events (GRACE) ECG substudy, and the Canadian ACS Registry I, were analysed independently at a blinded core laboratory. Multivariable logistic regression analysis was performed to assess the independent associations between LAHB on the admission ECG and in-hospital and 6-month mortality. RESULTS: Of the 11 820 eligible ACS patients, 692 (5.9%) patients had LAHB. The presence of LAHB on admission was associated with older age, male sex, prior myocardial infarction, prior heart failure, worse Killip class, higher creatinine level, and higher GRACE risk score (all p<0.01). Patients with LAHB less frequently underwent cardiac catheterisation, coronary revascularisation or reperfusion therapy (all p<0.05). The LAHB group had higher in-hospital (6.9% vs 3.9%, p<0.001) and 6-month mortality (12.5% vs 7.7%, p<0.001). However, after adjusting for the known predictors of mortality in the GRACE risk models, LAHB was not independently associated with in-hospital death (OR 1.07, 95% CI 0.76 to 1.52, p=0.70), or death at 6 months (OR 1.00, 95% CI 0.75 to 1.34, p=0.99). CONCLUSIONS: Across the broad spectrum of ACS, LAHB was associated with significant comorbidities, high-risk clinical features on presentation, and worse unadjusted outcomes. However, LAHB was not an independent predictor of in-hospital and 6-month mortality and did not carry incremental prognostic value beyond the known prognosticators in the GRACE risk models.

Comparison of bivalirudin versus heparin(s) during percutaneous coronary interventions in patients receiving prasugrel: a propensity-matched study.

BACKGROUND: Several percutaneous coronary intervention (PCI) trials have established that the use of bivalirudin (BIV) is associated with improved patient outcomes and substantial hospital cost savings, relative to heparin (HEP)-based regimens±glycoprotein IIb/IIIa inhibitors (GPIs). Whether these benefits persist with the use of prasugrel, a new third-generation oral thienopyridine, has not been previously evaluated. METHODS: Using the Premier hospital database, 6986 patients treated with prasugrel who underwent elective, urgent, or primary PCI between quarter 3, 2009 and quarter 4, 2010 from 166 US hospitals were identified. These patients received either BIV (n=3377) or HEP±GPI (n=3609) as procedural anticoagulation. Outcomes of interest included bleeding, transfusions, death, and hospital length of stay (LOS). To control for patient and hospital-level characteristics, propensity score-matching (PSM) analyses were performed. RESULTS: Mortality, clinically apparent bleeding, clinically apparent bleeding requiring transfusion, any transfusions, and LOS were all lower in patients treated with BIV as compared with patients treated with HEP±GPI. After PSM, the rate of transfusion was significantly lower with BIV (odds ratio: 0.57, 95% confidence interval: 0.34-0.96), and the hospital LOS was significantly shorter in patients treated with BIV compared with those treated with HEP±GPI (0.9±2.0 vs 1.2±2.3 days, P<0.0001). CONCLUSIONS: In patients undergoing PCI and treated with prasugrel, the use of BIV rather than HEP±GPI is associated with significantly lower transfusion rate and LOS. These results suggest that the previously documented safety and cost-effectiveness benefits of BIV remain applicable when prasugrel is used.

The economic implications of treating atherothrombotic disease in Australia, from the government perspective.

BACKGROUND: The management of atherothrombotic disease is responsible for a large proportion of direct medical costs in most countries, imposing a substantial financial burden on health care payers. There is limited knowledge about direct per-person medical costs using a "bottom-up" approach. OBJECTIVE: This study was designed to estimate the per-person direct medical costs incurred by communitybased subjects in Australia who have or are at high risk for atherothrombotic disease. The perspective was a governmental one, at the federal level for pharmaceuticals and at the state level for hospitalizations. METHODS: One-year follow-up data were obtained for Australian participants in the international REACH (Reduction of Atherothrombosis for Continued Health) Registry who were aged >or=45 years and had either established atherothrombotic disease (coronary artery disease, cerebrovascular disease, or peripheral artery disease [PAD]) or >or=3 risk factors for atherothrombotic disease. Information was extracted on the use of cardiovascular medications, hospitalizations, general practice visits, clinical pathology and imaging studies, and use of rehabilitation services. Bottom-up costing was undertaken by assigning unit costs to each health care item, based on Australian government reimbursement data for 2006-2007. Costs were estimated in Australian dollars. RESULTS: Data for 2873 Australian participants in the REACH Registry were included in the analysis. Mean (SD) annual pharmaceutical costs per person were A$1388 (A$645). Mean ambulatory care costs per person were A$704 (A$492), and mean hospitalization costs were A$10,711 (A$10,494). Compared with participants with >or=3 risk factors (adjusted for age and sex), participants with 2 to 3 affected vascular territories incurred A$160 more in mean pharmaceutical costs (95% CI, 78 to 256) and A$181 more in ambulatory care costs (95% CI, 107 to 252). Mean ambulatory care costs were A$132 greater among participants with PAD only relative to those with >or=3 risk factors (95% CI, 19 to 272). Hospital costs were not significantly increased with an increasing number of affected vascular territories. The greatest difference in direct hospital costs (A$943) was between participants with PAD relative to those with >or=3 risk factors (95% CI, -564 to 3545). CONCLUSIONS: From the government perspective, management of atherothrombotic disease in Australia was costly during the period studied, particularly among those with PAD only or disease affecting 2 to 3 vascular territories. Hospitalization accounted for the majority of health care expenditure associated with atherothrombotic disease, although the number of hospitalized participants was relatively small.