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Background: In patients with ST-segment elevation myocardial infarction (STEMI) who have multivessel disease, the FLOWER-MI trial found no significant clinical benefit to fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared to angiography-guided PCI., Aims: Our aim was to estimate the cost-effectiveness and cost-utility of FFR-guided PCI, the secondary endpoint of the FLOWER-MI trial., Methods: Costs, major adverse cardiovascular events (composite of all-cause death, non-fatal myocardial infarction [MI], and unplanned hospitalisation leading to urgent revascularisation), and quality-adjusted life years were calculated in both groups. The incremental cost-effectiveness and cost-utility ratios were estimated. Uncertainty was explored by probabilistic bootstrapping. The analysis was conducted from the perspective of the health care provider with a time horizon of one year., Results: At one year, the average cost per patient was 7,560€ (±2,218) in the FFR-guided group and 7,089€ (±1,991) in the angiography-guided group (p-value<0.01). The point estimates for the incremental cost-effectiveness and cost-utility ratios found that the angiography-guided strategy was cost saving and improved outcomes, with a probabilistic sensitivity analysis confirming dominance., Conclusions: The FFR-guided strategy at one year is unlikely to be cost effective compared to the angiography-guided strategy on both clinical and quality of life outcomes.

Aims: We aimed to update the logistic clinical SYNTAX score to predict 2 year all-cause mortality after contemporary percutaneous coronary intervention (PCI)., Methods and Results: We analyzed 15,883 patients in the GLOBAL LEADERS study who underwent PCI. The logistic clinical SYNTAX model was updated after imputing missing values by refitting the original model (refitted original model) and fitting an extended new model (new model, with, selection based on the Akaike Information Criterion). External validation was performed in 10,100 patients having PCI at Fu Wai hospital. Chronic obstructive pulmonary disease, prior stroke, current smoker, hemoglobin level, and white blood cell count were identified as additional independent predictors of 2 year all-cause mortality and included into the new model. The c-indexes of the original, refitted original and the new model in the derivation cohort were 0.74 (95% CI 0.72-0.76), 0.75 (95% CI 0.73-0.77), and 0.78 (95% CI 0.76-0.80), respectively. The c-index of the new model was lower in the validation cohort than in the derivation cohort, but still showed improved discriminative ability of the newly developed model (0.72; 95% CI 0.67-0.77) compared to the refitted original model (0.69; 95% CI 0.64-0.74). The models overestimated the observed 2 year all-cause mortality of 1.11% in the Chinese external validation cohort by 0.54 percentage points, indicating the need for calibration of the model to the Chinese patient population., Conclusions: The new model of the logistic clinical SYNTAX score better predicts 2 year all-cause mortality after PCI than the original model. The new model could guide clinical decision making by risk stratifying patients undergoing PCI., (© 2021 Wiley Periodicals LLC.)

Introduction: The GLOBAL LEADERS is an open-label, pragmatic and superiority randomised controlled trial designed to challenge the current treatment paradigm of dual antiplatelet therapy (DAPT) for 12 months followed by aspirin monotherapy among patients undergoing percutaneous coronary intervention. By design, all study endpoints are investigator reported (IR) and not subject to formal adjudication by an independent Clinical Event Committee (CEC), which may introduce detection, reporting or ascertainment bias., Methods and Analysis: We designed the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY) to prospectively implement, in a large sample of patients enrolled within the GLOBAL LEADERS trial (7585 of 15 991, 47.5%), an independent adjudication process of reported and unreported potential endpoints, using standardised CEC procedures, in order to assess whether 23-month ticagrelor monotherapy (90 mg twice daily) after 1-month DAPT is non-inferior to a standard regimen of DAPT for 12 months followed by aspirin monotherapy for the primary efficacy endpoint of death, non-fatal myocardial infarction, non-fatal stroke or urgent target vessel revascularisation and superior for the primary safety endpoint of type 3 or 5 bleeding according to the Bleeding Academic Research Consortium criteria.This study will comprehensively assess the comparative safety and efficacy of the two tested antithrombotic strategies on CEC-adjudicated ischaemic and bleeding endpoints and will provide insights into the role of a standardised CEC adjudication process on the interpretation of study findings by quantifying the level of concordance between IR-reported and CEC-adjudicated events., Ethics and Dissemination: GLASSY has been approved by local ethics committee of all study sites and/or by the central ethics committee for the country depending on country-specific regulations. In all cases, they deemed that it was not necessary to obtain further informed consent from individual subjects., Trial Registration Number: NCT01813435., Competing Interests: Competing interests: SL reports personal fees for advisory board participation from AstraZeneca, Chiesi and The Medicine Company. M Val reports grants from The Medicines Company, grants from Terumo, during the study; grants from AstraZeneca, and personal fees from Terumo, St Jude Vascular and Abbott Vascular, outside the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The aim of this study was to determine the prognostic significance of periprocedural bleeding based on various definitions on 30-day and one-year all-cause mortality in patients undergoing routine or urgent percutaneous coronary intervention (PCI)., Methods and Results: In this exploratory analysis of 25,107 patients enrolled in the three phase-3 CHAMPION trials, we assessed the prognostic impact of four bleeding scales (GUSTO, TIMI, ACUITY, and BARC) at 48 hrs. Follow-up all-cause mortality data were available at 30 days in all three trials, and at one year in CHAMPION PCI and CHAMPION PLATFORM. Bleeding rates within 48 hrs of PCI were variably identified by each clinical definition (range: <0.5% to >3.5%). Severe/major bleeding, measured by all bleeding scales, and blood transfusion requirement were independently associated with increased mortality at 30 days and one year after PCI (p<0.001 for all associations). Mild/minor bleeding was not independently predictive of one-year mortality (p>0.07 for all associations). Each bleeding definition demonstrated only modest ability to discriminate 30-day and one-year mortality (adjusted C-statistics range: 0.49 to 0.67)., Conclusions: Commonly employed clinical definitions variably identify rates of bleeding after PCI. Severe or major, but not mild or minor, bleeding is independently associated with increased 30-day and one-year mortality. These data may aid in selection of appropriate bleeding metrics in future clinical trials.

The prevalence of factors that are associated with an increased risk of stent thrombosis (ST), including smoking, diabetes mellitus, and small stent size, is different in women and men who underwent percutaneous coronary intervention. Thus, gender may potentially modify the relation between stent type and the incidence of ST during long-term follow-up. We explored the data of Patient Related Outcomes With Endeavor Versus Cypher stenting Trial (PROTECT) to evaluate this hypothesis. PROTECT randomized 2,061 women and 6,648 men who underwent percutaneous coronary intervention for various indications to Endeavor zotarolimus-eluting stenting (E-ZES) or Cypher sirolimus-eluting stenting (C-SES). Dual antiplatelet therapy was prescribed for at least 3 months. Data on study end points were collected until 5 years after randomization, including ST, death, and cardiovascular events. We analyzed end points and treatment effect (E-ZES vs C-SES) in relation to gender. Women were on average 4.7 years older (65.8 vs 61.1), had a higher prevalence of insulin-dependent diabetes mellitus, were less often smokers, and had a shorter total stent length than men. At discharge and throughout follow-up, a slightly lower fraction of women were using dual antiplatelet therapy. During 5-year follow-up, definite or probable ST was observed in 36 women (1.8%) and 152 men (2.4%; log-rank p = 0.15). E-ZES reduced the incidence of ST compared with C-SES in women (hazard ratio 0.58) and men (hazard ratio 0.61), with no evidence of heterogeneity (p = 0.89). In conclusion, in PROTECT, women and men had similar cumulative incidence of ST at 5 years after stent placement. The favorable effect of the study stent E-ZES over C-SES was not modified by gender., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: We evaluated the relationship of renal function and ischaemic and bleeding risk as well as the efficacy and safety of ticagrelor in stable patients with prior myocardial infarction (MI)., Methods and Results: Patients with a history of MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated glomerular filtration rate (eGFR), with <60 mL/min/1.73 m(2) pre-specified for analysis of the effect of ticagrelor on the primary efficacy composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events, MACE) and the primary safety endpoint of TIMI major bleeding. Of 20 898 patients, those with eGFR <60 (N = 4849, 23.2%) had a greater risk of MACE at 3 years relative to those without, which remained significant after multivariable adjustment (hazard ratio, HRadj 1.54, 95% confidence interval, CI 1.27-1.85, P < 0.001). The relative risk reduction in MACE with ticagrelor was similar in those with eGFR <60 (ticagrelor pooled vs. placebo: HR 0.81; 95% CI 0.68-0.96) vs. ≥60 (HR 0.88; 95% CI 0.77-1.00, Pinteraction = 0.44). However, due to the greater absolute risk in the former group, the absolute risk reduction with ticagrelor was higher: 2.7 vs. 0.63%. Bleeding tended to occur more frequently in patients with renal dysfunction. The absolute increase in TIMI major bleeding with ticagrelor was similar in those with and without eGFR <60 (1.19 vs. 1.43%), whereas the excess of minor bleeding tended to be more pronounced (1.93 vs. 0.69%)., Conclusion: In patients with a history of MI, patients with renal dysfunction are at increased risk of MACE and consequently experience a particularly robust absolute risk reduction with long-term treatment with ticagrelor., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Introduction: Heart rate (HR) is a strong prognostic indicator in patients with coronary artery disease (CAD). However, there is only limited evidence on HR and the use of b-blockers in patients with CAD in contemporary clinical practice., Methods: CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis >50%, or chest pain associated with proven myocardial ischemia. A total of 33,283 patients from 45 countries were enrolled between November 2009 and July 2010; of these, 559 patients were enrolled in Greece (age 62.3 ± 10.6 years, 84.44% men)., Results: HR measured by pulse was 68.3 ± 10.2 bpm and by electrocardiogram 67.6 ± 10.9, with an excellent correlation (r=0.91, p<0.001). Overall, 42.8% had HR70 bpm. B-blockers were prescribed in 74.2% of patients. Resting HR by pulse on b-blocker was 67.8 bpm and without b-blocker 69.6 bpm (p=0.069). HR70 bpm was independently associated with a lack of physical activity, higher systolic blood pressure, and a higher prevalence of asthma or chronic obstructive pulmonary disease and carotid artery disease., Conclusion: Despite the use of HR lowering agents, the percentage of patients with HR70 bpm was high. It is likely that we can further improve HR control in Greek patients with stable CAD by both increasing the prescription of b-blockers and up-titrating their dose, as well as by using and up-titrating other available HR lowering agents.

Background: Atherothrombotic diseases are the leading health problems in the world, both in terms of morbidity and mortality. This study aimed to identify and quantify the predictors of medication, hospital and outpatient service use among patients with or at high risk of atherothrombotic disease., Methods: Two-year follow-up data were analyzed for 2873 Australian participants of the Reduction of Atherothrombosis for Continued Health (REACH) registry. The analysis was performed using generalized linear models with Poisson and Gamma distributions and log link function., Results: Participants with hypercholesterolemia, diabetes, hypertension, atrial fibrillation (AF), and history of coronary artery disease (CAD) used more medications (p<0.0001). The presence of diabetes predicted higher number of outpatient visits (RR=1.09, 95% CI: 1.07-1.11), as did AF (RR=1.10, 95% CI: 1.08-1.12). The presence of peripheral artery disease (PAD) regardless of ankle brachial index (ABI) status (abnormal or normal) increased the use of outpatient visits (RR=1.24, 95% CI: 1.20-1.29 and RR=1.12, 95% CI: 1.08-1.15), compared to those without PAD. Similarly, the presence of PAD regardless of ABI status increased the risk of vascular interventions, including coronary angioplasty, carotid surgery, amputation affecting lower-limb and peripheral bypass graft (RR=3.64, 95% CI: 2.01-6.60) (RR=2.8, 95% CI: 1.6-4.92) compared to patients without PAD., Conclusions: The presence of PAD regardless of ABI status predicts a higher number of outpatient visits, non-fatal cardiovascular endpoints and vascular-interventions, while diabetes predicts higher pharmaceutical use and outpatient visits. AF predicts the higher number of outpatient visits and non-fatal cardiovascular events., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Heart rate (HR) is an important risk factor in coronary artery disease (CAD). However, there is little contemporary data on HR and the use of HR-lowering medications, particularly beta-blockers, among patients with stable CAD in routine clinical practice., Aim: To describe HR in the Polish population of the CLARIFY registry, overall and in relation to beta-blocker use, and to assess the determinants of HR., Methods and Results: CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as either prior myocardial infarction or revascularisation procedure, or evidence of coronary stenosis of at least 50%, or chest pain associated with proven myocardial ischaemia. A total of 33,438 patients from 45 countries in Europe, the Americas, Africa, the Middle East, and Asia/Pacific were enrolled between November 2009 and July 2010. In Poland, 1,004 patients were enrolled between February and June 2010, which was the largest population among countries from Eastern Europe. Most patients were men (72.8%). Mean ± standard deviation age was 62.1 ± 9.1 years. HR determined by pulse was 69.3 ± 9.4 bpm and by electrocardiogram was 68.2 ± 10.6 bpm. Beta-blockers were used in 89.9% of patients. Resting HR ≥ 70 bpm was noted in 49.3% of all patients and in 48.6% of patients on beta-blockers. Resting HR ≥ 70 bpm was significantly more frequent among younger patients, and in those with diabetes, those being treated for arterial hypertension, and who lacked regular physical activity. Patients with HR ≥ 70 bpm at rest had more frequent symptoms of angina and more frequently needed hospitalisation due to heart failure., Conclusions: Despite a very high rate of beta-blocker use, almost 50% of patients with stable CAD had a resting HR ≥ 70 bpm, which was associated with more frequent angina and ischaemia. Further HR lowering is possible in many patients with CAD. Whether or not this will improve symptoms and outcomes is under investigation.

Context: β-Blockers remain the standard of care after a myocardial infarction (MI). However, the benefit of β-blocker use in patients with coronary artery disease (CAD) but no history of MI, those with a remote history of MI, and those with only risk factors for CAD is unclear., Objective: To assess the association of β-blocker use with cardiovascular events in stable patients with a prior history of MI, in those with CAD but no history of MI, and in those with only risk factors for CAD., Design, Setting, and Patients: Longitudinal, observational study of patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry who were divided into 3 cohorts: known prior MI (n = 14,043), known CAD without MI (n = 12,012), or those with CAD risk factors only (n = 18,653). Propensity score matching was used for the primary analyses. The last follow-up data collection was April 2009., Main Outcome Measures: The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure., Results: Among the 44,708 patients, 21,860 were included in the propensity score-matched analysis. With a median follow-up of 44 months (interquartile range, 35-45 months), event rates were not significantly different in patients with β-blocker use compared with those without β-blocker use for any of the outcomes tested, even in the prior MI cohort (489 [16.93%] vs 532 [18.60%], respectively; hazard ratio [HR], 0.90 [95% CI, 0.79-1.03]; P = .14). In the CAD without MI cohort, the associated event rates were not significantly different in those with β-blocker use for the primary outcome (391 [12.94%]) vs without β-blocker use (405 [13.55%]) (HR, 0.92 [95% CI, 0.79-1.08]; P = .31), with higher rates for the secondary outcome (1101 [30.59%] vs 1002 [27.84%]; odds ratio [OR], 1.14 [95% CI, 1.03-1.27]; P = .01) and for the tertiary outcome of hospitalization (870 [24.17%] vs 773 [21.48%]; OR, 1.17 [95% CI, 1.04-1.30]; P = .01). In the cohort with CAD risk factors only, the event rates were higher for the primary outcome with β-blocker use (467 [14.22%]) vs without β-blocker use (403 [12.11%]) (HR, 1.18 [95% CI, 1.02-1.36]; P = .02), for the secondary outcome (870 [22.01%] vs 797 [20.17%]; OR, 1.12 [95% CI, 1.00-1.24]; P = .04) but not for the tertiary outcomes of MI (89 [2.82%] vs 68 [2.00%]; HR, 1.36 [95% CI, 0.97-1.90]; P = .08) and stroke (210 [6.55%] vs 168 [5.12%]; HR, 1.22 [95% CI, 0.99-1.52]; P = .06). However, in those with recent MI (≤1 year), β-blocker use was associated with a lower incidence of the secondary outcome (OR, 0.77 [95% CI, 0.64-0.92])., Conclusion: In this observational study of patients with either CAD risk factors only, known prior MI, or known CAD without MI, the use of β-blockers was not associated with a lower risk of composite cardiovascular events.

Background: Despite robust efficacy in the reduction of ischemic events in patients who require percutaneous coronary intervention (PCI), current P2Y(12) inhibitors have limitations. In particular, they require hours to be effective, and they can only be administered orally. Cangrelor is an intravenous, potent, and reversible P2Y(12) inhibitor with fast onset and offset of action. We designed CHAMPION PHOENIX to evaluate the efficacy and safety of cangrelor in patients with atherosclerosis undergoing PCI., Trial Design: The CHAMPION PHOENIX is a randomized, double-blind, double-dummy, superiority trial comparing cangrelor with clopidogrel standard of care in approximately 10,900 patients who have not previously received a P2Y(12) inhibitor and who require PCI, including patients with stable angina and with acute coronary syndromes (with or without ST-segment elevation). The primary objective of the study is to demonstrate that cangrelor will reduce the incidence of the composite of death, myocardial infarction (MI), ischemia-driven revascularization, or stent thrombosis in the 48 hours after randomization compared with clopidogrel without excessive periprocedural bleeding. The key secondary objective is to demonstrate that cangrelor will reduce the incidence of stent thrombosis. Myocardial infarction will be defined according to the universal MI definition, adapting the definition of PCI-related (type 4a) MI. Bleeding will be assessed according to the thrombolysis in myocardial infarction, GUSTO, and Bleeding Academic Research Consortium (BARC) scales., Conclusion: The CHAMPION PHOENIX may establish the role of cangrelor in the care of patients who require PCI across the spectrum of stable and unstable coronary diseases in the setting of current treatment strategies., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: Approximately 10% of patients with myocardial infarction (MI) have no obstructive coronary artery disease. The prognosis and role of intensified antiplatelet therapy in those patients were evaluated.Methods: We analysed data from the Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events-Seventh Organisation to Assess Strategies in Ischaemic Symptoms trial randomising patients with ACS referred for early intervention to receive either double-dose (600 mg, day 1; 150 mg, days 2-7; then 75 mg/day) or standard-dose (300 mg, day 1; then 75 mg/day) clopidogrel. Outcomes in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) versus those with obstructive coronary artery disease (CAD) and their relation to standard-dose versus double-dose clopidogrel were evaluated. The primary outcome was cardiovascular (CV) death, MI or stroke at 30 days.Results: We included 23 783 patients with MI and 1599 (6.7%) with MINOCA. Patients with MINOCA were younger, presented more frequently with non-ST-segment elevation MI and had fewer comorbidities. All-cause mortality (0.6% vs 2.3%, p=0.005), CV mortality (0.6% vs 2.2%, p=0.006), repeat MI (0.5% vs 2.3%, p=0.001) and major bleeding (0.6% vs 2.4%, p<0.0001) were lower among patients with MINOCA than among those with obstructive CAD. Among patients with MINOCA, 2.1% of patients in the double-dose clopidogrel group and 0.6% in the standard-dose group experienced a primary outcome (HR 3.57, 95% CI 1.31 to 9.76), whereas in those with obstructive CAD, rates were 4.3% and 4.7%, respectively (HR 0.91, 95% CI 0.80 to 1.03; p value for interaction=0.011).Conclusions: Patients with MINOCA are at lower risk of recurrent CV events compared with patients with MI with obstructive CAD. Compared with a standard clopidogrel-based dual antiplatelet therapy (DAPT) regimen, an intensified dosing strategy appears to offer no additional benefit with a signal of possible harm. Further randomised trials evaluating the effects of potent DAPT in patients with MINOCA are warranted.Trial Registration Number: NCT00335452. [ABSTRACT FROM AUTHOR]

Objective: To evaluate cardiovascular (CV) outcomes in outpatients with coronary artery disease (CAD) living alone compared with those living with others.Methods: The prospeCtive observational LongitudinAl RegIstry oF patients with stable coronarY artery disease (CLARIFY) included outpatients with stable CAD. CLARIFY enrolled participants in 45 countries from November 2009 to July 2010, with 5 years of follow-up. Living arrangement was documented at baseline. The primary outcome was a composite of major adverse cardiovascular events (MACEs) defined as CV death, myocardial infarction (MI) and stroke.Results: Among 32 367 patients, 3648 patients were living alone (11.3%). After multivariate adjustment, there were no residual differences in MACE among patients living alone compared with those living with others (HR 1.04, 95% CI 0.92 to 1.18, p=0.52); however, there was significant heterogeneity in the exposure effect by sex (Pinteraction<0.01). Specifically, men living alone were at higher risk for MACE (HR 1.17, 95% CI 1.002 to 1.36, p=0.047) as opposed to women living alone (HR 0.82, 95% CI 0.65 to 1.04, p=0.1), predominantly driven by a heterogeneous effect by sex on MI (Pinteraction=0.006). There was no effect modification for MACE by age group (Pinteraction=0.3), although potential varying effects by age for MI (Pinteraction=0.046) and stroke (Pinteraction=0.05).Conclusions: Living alone was not associated with an independent increase in MACE, although significant sex-based differences were apparent. Men living alone may have a worse prognosis from CV disease than women; further analyses are needed to elucidate the mechanisms underlying this difference.Trial Registration Number: ISRCTN43070564. [ABSTRACT FROM AUTHOR]