Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction.

BACKGROUND: In patients with ST-elevation myocardial infarction (STEMI) who have multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions (complete revascularization) is superior to treatment of the culprit lesion alone. However, whether complete revascularization that is guided by fractional flow reserve (FFR) is superior to an angiography-guided procedure is unclear. METHODS: In this multicenter trial, we randomly assigned patients with STEMI and multivessel disease who had undergone successful PCI of the infarct-related artery to receive complete revascularization guided by either FFR or angiography. The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 1 year. RESULTS: The mean (±SD) number of stents that were placed per patient for nonculprit lesions was 1.01±0.99 in the FFR-guided group and 1.50±0.86 in the angiography-guided group. During follow-up, a primary outcome event occurred in 32 of 586 patients (5.5%) in the FFR-guided group and in 24 of 577 patients (4.2%) in the angiography-guided group (hazard ratio, 1.32; 95% confidence interval, 0.78 to 2.23; P = 0.31). Death occurred in 9 patients (1.5%) in the FFR-guided group and in 10 (1.7%) in the angiography-guided group; nonfatal myocardial infarction in 18 (3.1%) and 10 (1.7%), respectively; and unplanned hospitalization leading to urgent revascularization in 15 (2.6%) and 11 (1.9%), respectively. CONCLUSIONS: In patients with STEMI undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization at 1 year. However, given the wide confidence intervals for the estimate of effect, the findings do not allow for a conclusive interpretation. (Funded by the French Ministry of Health and Abbott; FLOWER-MI ClinicalTrials.gov number, NCT02943954.).

Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction.

BACKGROUND: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. METHODS: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. RESULTS: A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. CONCLUSIONS: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.).

Impact of established cardiovascular disease on outcomes in the randomized global leaders trial.

OBJECTIVE: To investigate the impact of different anti-platelet strategies on outcomes after percutaneous coronary intervention (PCI) in patients with established cardiovascular disease (CVD). METHODS: GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing one-month dual anti-platelet therapy (DAPT) with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. Established CVD was defined as ≥1 prior myocardial infarction, PCI, coronary artery bypass operation, stroke, or established peripheral vascular disease. The primary endpoint was a composite of all-cause death or new Q-wave MI at 2-years. The secondary safety endpoint was BARC 3 or 5 bleeding. Exploratory secondary endpoints were the patient-orientated composite endpoint and net adverse clinical events. RESULTS: Among the 15,761 patients in this cohort were 6,693 patients (42.5%) with established CVD. Compared to those without established CVD, these patients had significantly higher rates of the primary (5.1 vs. 3.3%, HR1.59[1.36-1.86], p < .001) and secondary composite endpoints with no significant differences in bleeding. There was a nonsignificant reduction in the primary endpoint in patients with established CVD receiving the experimental treatment (4.6 vs. 5.6%, HR0.82[0.66-1.02], p = .07). When comparing patients without CVD to those with one or three territories of CVD, the hazard ratio for the primary endpoint increased in unadjusted and adjusted models. CONCLUSIONS: The poorer outcomes in patients with established CVD are not mitigated by prolonged monotherapy with a potent P2Y12 inhibitor suggesting a greater need to focus on modifiable risk factors.

Rationale and design of Apo-I Event Reduction in Ischemic Syndromes I (AEGIS-I): A phase 2b, randomized, placebo-controlled, dose-ranging trial to investigate the safety and tolerability of CSL112, a reconstituted, infusible, human apoA-I, after acute myocardial infarction.

BACKGROUND: Despite aggressive pharmacotherapy and stenting, there is a residual risk of major adverse cardiovascular events among patients with acute coronary syndrome. High-density lipoprotein (HDL) has been a major target for secondary acute coronary syndrome prevention; however, a better understanding of the physiologic function of HDL has demonstrated that a high cholesterol efflux capacity, rather than high HDL concentrations alone, may be critical to improving outcomes. CSL112, a reconstituted, infusible human apolipoprotein A-I, has been demonstrated to increase cholesterol efflux capacity and to have a protective effect in experimental models of atherosclerotic cardiovascular disease. DESIGN: The AEGIS-I trial (ClinicalTrials.govNCT02108262) is a phase 2b, multicenter, randomized, placebo-controlled, dose-ranging clinical trial to evaluate the hepatic and renal safety of multiple administrations of 2 doses of CSL112 among subjects with acute myocardial infarction (AMI). Approximately 1,200 subjects (400 per treatment group) with either normal renal function or mild renal impairment will be enrolled up to 7 days after an AMI and will be stratified by renal function and randomized in a 1:1:1 ratio to either 1 of 2 doses of CSL112 (either 2 g or 6 g) or placebo as a weekly 2-hour infusion over the course of 4 consecutive weeks. The coprimary safety endpoints will be the incidence of hepatic and renal toxicity, defined as either confirmed ALT >3 × ULN, total bilirubin >2 × ULN, serum creatinine ≥1.5×baseline value, or a new requirement for renal replacement therapy through the end of the active treatment period. SUMMARY: The AEGIS-I trial will characterize the safety profile of CSL112, a reconstituted formulation of apolipoprotein A-I, and will assess if administration to patients with a recent AMI is associated with a clinically significant alteration in either liver or kidney function when compared with placebo.

Safety and efficacy of drug-eluting stents in women: a patient-level pooled analysis of randomised trials.

BACKGROUND: The safety and efficacy of drug-eluting stents (DES) in the treatment of coronary artery disease have been assessed in several randomised trials. However, none of these trials were powered to assess the safety and efficacy of DES in women because only a small proportion of recruited participants were women. We therefore investigated the safety and efficacy of DES in female patients during long-term follow-up. METHODS: We pooled patient-level data for female participants from 26 randomised trials of DES and analysed outcomes according to stent type (bare-metal stents, early-generation DES, and newer-generation DES). The primary safety endpoint was a composite of death or myocardial infarction. The secondary safety endpoint was definite or probable stent thrombosis. The primary efficacy endpoint was target-lesion revascularisation. Analysis was by intention to treat. FINDINGS: Of 43,904 patients recruited in 26 trials of DES, 11,557 (26·3%) were women (mean age 67·1 years [SD 10·6]). 1108 (9·6%) women received bare-metal stents, 4171 (36·1%) early-generation DES, and 6278 (54·3%) newer-generation DES. At 3 years, estimated cumulative incidence of the composite of death or myocardial infarction occurred in 132 (12·8%) women in the bare-metal stent group, 421 (10·9%) in the early-generation DES group, and 496 (9·2%) in the newer-generation DES group (p=0·001). Definite or probable stent thrombosis occurred in 13 (1·3%), 79 (2·1%), and 66 (1·1%) women in the bare-metal stent, early-generation DES, and newer-generation DES groups, respectively (p=0·01). The use of DES was associated with a significant reduction in the 3 year rates of target-lesion revascularisation (197 [18·6%] women in the bare-metal stent group, 294 [7·8%] in the early-generation DES group, and 330 [6·3%] in the newer-generation DES group, p<0·0001). Results did not change after adjustment for baseline characteristics in the multivariable analysis. INTERPRETATION: The use of DES in women is more effective and safe than is use of bare-metal stents during long-term follow-up. Newer-generation DES are associated with an improved safety profile compared with early-generation DES, and should therefore be thought of as the standard of care for percutaneous coronary revascularisation in women. FUNDING: Women in Innovation Initiative of the Society of Cardiovascular Angiography and Interventions.

Geographic differences in patients with acute myocardial infarction in the PARADISE-MI trial.

AIM: The globalization of clinical trials has highlighted geographic differences in patient characteristics, treatments, and outcomes. We examined these differences in PARADISE-MI. METHODS AND RESULTS: Overall, 23.0% were randomized in Eastern Europe/Russia, 17.5% in Western Europe, 12.2% in Southern Europe, 10.1% in Northern Europe, 12.0% in Latin America (LA), 9.3% in North America (NA), 10.0% in East/South-East Asia and 5.8% in South Asia (SA). Those from Asia, particularly SA, were different from patients enrolled in the other regions, being younger and thinner. They also differed in terms of comorbidities (high prevalence of diabetes and low prevalence of atrial fibrillation), type of myocardial infarction (more often ST-elevation myocardial infarction), and treatment (low rate of primary percutaneous coronary intervention). By contrast, patients from LA did not differ meaningfully from those randomized in Europe or NA. Use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (34.8%) and beta-blockers (65.5%) was low in SA, whereas mineralocorticoid receptor antagonist use was lowest in NA (22%) and highest in Eastern Europe/Russia (53%). Rates of the primary composite outcome of cardiovascular death or incident heart failure varied two-fold among regions, with the lowest rate in SA (4.6/100 person-years) and the highest in LA (9.2/100 person-years). Rates of incident heart failure varied almost six-fold among regions, with the lowest rate in SA (1.0/100 person-years) and the highest in Northern Europe (5.9/100 person-years). The effect of sacubitril/valsartan was not modified by region. CONCLUSION: In PARADISE-MI, there were substantial regional differences in patient characteristics, treatments and outcomes. Although the generalizability of these findings to a 'real-world' unselected population may be limited, these findings underscore the importance of considering both regional and within-region differences when designing global clinical trials.

Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors: JACC State-of-the-Art Review.

Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed.

P2Y12 inhibitor monotherapy in patients undergoing percutaneous coronary intervention.

For 20 years, dual antiplatelet therapy (DAPT), consisting of the combination of aspirin and a platelet P2Y12 receptor inhibitor, has been the gold standard of antithrombotic pharmacology after percutaneous coronary intervention (PCI). In the past 5 years, several investigations have challenged this paradigm by testing the efficacy and safety of P2Y12 inhibitor monotherapy (that is, without aspirin) following a short course of DAPT. Collectively, these studies suggested a reduction in the risk of major bleeding and no significant increase in thrombotic or ischaemic events compared with guideline-recommended DAPT. Current recommendations are evolving to inform clinical practice on the ideal candidates for P2Y12 inhibitor monotherapy after PCI. Generalizing the results of studies of P2Y12 inhibitor monotherapy requires a thorough understanding of their design, populations, interventions, comparators and results. In this Review, we provide an up-to-date overview on the use of P2Y12 inhibitor monotherapy after PCI, including supporting pharmacodynamic and clinical evidence, practical recommendations and future directions.

Excess risk attributable to traditional cardiovascular risk factors in clinical practice settings across Europe - The EURIKA Study.

BACKGROUND: Physicians involved in primary prevention are key players in CVD risk control strategies, but the expected reduction in CVD risk that would be obtained if all patients attending primary care had their risk factors controlled according to current guidelines is unknown. The objective of this study was to estimate the excess risk attributable, firstly, to the presence of CVD risk factors and, secondly, to the lack of control of these risk factors in primary prevention care across Europe. METHODS: Cross-sectional study using data from the European Study on Cardiovascular Risk Prevention and Management in Daily Practice (EURIKA), which involved primary care and outpatient clinics involved in primary prevention from 12 European countries between May 2009 and January 2010. We enrolled 7,434 patients over 50 years old with at least one cardiovascular risk factor but without CVD and calculated their 10-year risk of CVD death according to the SCORE equation, modified to take diabetes risk into account. RESULTS: The average 10-year risk of CVD death in study participants (N = 7,434) was 8.2%. Hypertension, hyperlipidemia, smoking, and diabetes were responsible for 32.7 (95% confidence interval 32.0-33.4), 15.1 (14.8-15.4), 10.4 (9.9-11.0), and 16.4% (15.6-17.2) of CVD risk, respectively. The four risk factors accounted for 57.7% (57.0-58.4) of CVD risk, representing a 10-year excess risk of CVD death of 5.66% (5.47-5.85). Lack of control of hypertension, hyperlipidemia, smoking, and diabetes were responsible for 8.8 (8.3-9.3), 10.6 (10.3-10.9), 10.4 (9.9-11.0), and 3.1% (2.8-3.4) of CVD risk, respectively. Lack of control of the four risk factors accounted for 29.2% (28.5-29.8) of CVD risk, representing a 10-year excess risk of CVD death of 3.12% (2.97-3.27). CONCLUSIONS: Lack of control of CVD risk factors was responsible for almost 30% of the risk of CVD death among patients participating in the EURIKA Study.

Profile and treatment of chronic coronary syndromes in European Society of Cardiology member countries: The ESC EORP CICD-LT registry.

BACKGROUND: International guidelines recommend pharmacotherapy combinations for chronic coronary syndromes (CCSs) but medical management remains suboptimal. DESIGN: The CICD-LT registry is investigating short- and long-term outcomes and management in patients in European Society of Cardiology (ESC) member countries, in a longitudinal ESC EURObservational Research Programme aimed at improving CCS management. METHODS: Between 1 May 2015 and 31 July 2018, 9174 patients with previous ST-elevation myocardial infarction (STEMI), non-STEMI or coronary revascularisation, or other CCS, were recruited during a routine ambulatory visit or elective revascularisation procedure. Baseline clinical data were recorded and prescribed medications analysed at initial contact and discharge, and according to patient gender and age (<75 vs. ≥75 years). RESULTS: Poorly controlled cardiovascular risk factors, including current smoking (18.5%), obesity (33.9%), diabetes (25.8%), raised low-density lipoprotein cholesterol (73.3%) and persistent hypertension (24.7%), were common across all cohorts. At ambulatory visit or admission, the guidelines-recommended combination of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, aspirin, statin and any antiplatelet agent was prescribed to 57.8% of patients with STEMI/NSTEMI. Differences in prescribing rates, including for combination therapies, were observed based on age and gender and persisted after adjustment for demographic factors. CONCLUSIONS: Cardiovascular risk factors were common in contemporary CCS patients and secondary prevention prescribing was suboptimal. Patients aged ≥75 years and, to some extent, female patients were less likely to receive guidelines-recommended drug combinations than younger and male patients. One- and two-year follow-up will study prescribing changes and associations between baseline characteristics/prescribing and subsequent clinical outcomes.

Antiplatelet strategies in acute coronary syndromes: design and methodology of an international collaborative network meta-analysis of randomized controlled trials.

INTRODUCTION: The optimal choice of oral P2Y12 receptor inhibitors has the potential to significantly influence outcomes. We seek to compare the safety and efficacy of the three most commonly used oral P2Y12 receptor inhibitors (clopidogrel, prasugrel, and ticagrelor) in acute coronary syndromes (ACS) via a comprehensive systematic review and network meta-analysis. EVIDENCE ACQUISITION: In line with the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, we performed a comprehensive search for RCTs which compared cardiovascular and hemorrhagic outcomes after use of at least two of the distinct oral P2Y12 receptor inhibitors (i.e. clopidogrel, prasugrel, and ticagrelor). A search strategy has been designed to systematically search multiple databases, including MEDLINE with PubMed interface, The Cochrane Central Register of Controlled Trials, and Embase. In addition, key inclusion criteria will be trial size of at least 100 patients and at least 1 month of follow-up time. Several prespecified subgroups will be explored, including Asian patients, patients presenting with ST-elevation myocardial infarction, patients of advanced age, and others. EVIDENCE SYNTHESIS: Exploratory frequentist pairwise meta-analyses will be based primarily on a random-effects method, relying on relative risks (RR) for short-term outcomes and incidence rate ratios (IRR) for long-term outcomes. Inferential frequentist network meta-analysis will be based primarily on a random-effects method, relying on RR and IRR as specified above. Results will be reported as point summary of effect, 95% CI, and P values for effect, and graphically represented using forest plots. CONCLUSIONS: An international collaborative network meta-analysis has begun to comprehensively analyze the safety and efficacy of prasugrel, ticagrelor and clopidogrel, each on a background of aspirin, for management of patients with ACS. It is our hope that the rigor and breadth of the undertaking described herein will provide novel insights that will inform optimal patient care for patients with ACS treated conservatively, or undergoing revascularization.

Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI): design and baseline characteristics.

AIMS: Patients surviving an acute myocardial infarction (AMI) are at risk of developing symptomatic heart failure (HF) or premature death. We hypothesized that sacubitril/valsartan, effective in the treatment of chronic HF, prevents development of HF and reduces cardiovascular death following high-risk AMI compared to a proven angiotensin-converting enzyme (ACE) inhibitor. This paper describes the study design and baseline characteristics of patients enrolled in the Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI) trial. METHODS AND RESULTS: PARADISE-MI, a multinational (41 countries), double-blind, active-controlled trial, randomized patients within 0.5-7 days of presentation with index AMI to sacubitril/valsartan or ramipril. Transient pulmonary congestion and/or left ventricular ejection fraction (LVEF) ≤40% and at least one additional factor augmenting risk of HF or death (age ≥70 years, estimated glomerular filtration rate <60 mL/min/1.73 m2 , diabetes, prior myocardial infarction, atrial fibrillation, LVEF <30%, Killip class ≥III, ST-elevation myocardial infarction without reperfusion) were required for inclusion. PARADISE-MI was event-driven targeting 708 primary endpoints (cardiovascular death, HF hospitalization or outpatient development of HF). Randomization of 5669 patients occurred 4.3 ± 1.8 days from presentation with index AMI. The mean age was 64 ± 12 years, 24% were women. The majority (76%) qualified with ST-segment elevation myocardial infarction; acute percutaneous coronary intervention was performed in 88% and thrombolysis in 6%. LVEF was 37 ± 9% and 58% were in Killip class ≥II. CONCLUSIONS: Baseline therapies in PARADISE-MI reflect advances in contemporary evidence-based care. With enrollment complete PARADISE-MI is poised to determine whether sacubitril/valsartan is more effective than a proven ACE inhibitor in preventing development of HF and cardiovascular death following AMI.

Clinical Application of High-Sensitivity Troponin Testing in the Atherosclerotic Cardiovascular Disease Framework of the Current Cholesterol Guidelines.

Importance: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol management guidelines identified 2 distinct groups of patients with atherosclerotic cardiovascular disease (ASCVD) prompting different treatment recommendations. Objective: To investigate whether the addition of high-sensitivity troponin (hsTn) testing to guideline-derived ASCVD risk can improve risk classification and downstream treatment recommendations. Design, Setting, and Participants: A prospective cohort biomarker substudy was performed that included 8635 patients enrolled in the Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial. Patients were assigned to risk groups of either very high-risk ASCVD or lower-risk ASCVD based on their cardiovascular history and comorbidities, in line with the 2018 AHA/ACC cholesterol management guidelines criteria. Patients were also classified on the basis of hsTnI level (ARCHITECT assay; Abbott) using cut points of 2 ng/L (limit of detection) and 6 ng/L (risk threshold), followed by joint classification on the basis of clinical features and hsTnI level. The setting was a nested prospective cohort study in a completed multinational trial. Participants were all patients who had a myocardial infarction 1 to 3 years before enrollment, were at least 50 years of age, and had at least 1 high-risk feature. The study dates were October 2010 to December 2014. The dates of analysis were June 2019 to January 2020. Main Outcomes and Measures: The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Results: Among 8635 patients enrolled in the PEGASUS-TIMI 54 trial, the median age was 65 years (interquartile range, 58-71 years), and 6614 (76.6%) were men; 8340 (96.6%) were White individuals and 176 (2.0%) were Black individuals. Patients meeting clinical criteria for the very high-risk ASCVD group had a primary end point 3-year event rate of 8.8% compared with 5.0% in the lower-risk ASCVD group (hazard ratio, 2.01; 95% CI, 1.58-2.57; P < .001). When patients in the very high-risk ASCVD group were further risk stratified by hsTnI level, 614 of 6789 patients (9.0%) with an undetectable hsTnI level had a 3-year event rate of 2.7% (<1% per year), which was less than the overall rate in the lower-risk ASCVD group. Analogously, in the lower-risk ASCVD group, 417 of 1846 patients (22.6%) with an hsTnI level exceeding 6 ng/L had an event rate of 9.1%, comparable to the overall rate in the very high-risk ASCVD group. The addition of hsTnI to guideline-derived ASCVD risk led to a net reclassification index at event rate of 0.15 (95% CI, 0.10-0.21). Overall, use of hsTnI reclassified 1031 of 8635 patients (11.9%) (1 in 11 with very high-risk ASCVD and 1 in 4 with lower-risk ASCVD). Conclusions and Relevance: The findings of this cohort substudy suggest that a strategy incorporating hsTn into a guideline-derived ASCVD risk algorithm provides enhanced risk stratification and reclassifies 11.9% of patients into a more appropriate risk group. This application of hsTn testing might be used to optimize the care of patients with ASCVD.

Management strategies and 5-year outcomes in Polish patients with stable coronary artery disease versus other European countries: data from the CLARIFY registry.

INTRODUCTION An international registry of ambulatory patients with stable coronary artery disease (CLARIFY) allows a comparison of management and outcomes in real­life setting. OBJECTIVES We aimed to compare the management strategies and 5­year outcomes in patients from Poland and from other European countries. PATIENTS AND METHODS Stable coronary artery disease was defined as previous myocardial infarction (MI) or revascularization, coronary stenosis greater than 50%, or documented symptomatic myocardial ischemia. Patients were followed on an annual basis for 5 years. RESULTS Among the total of 32 703 patients, 1000 were enrolled in Poland, and 17 326 in other European countries. Polish patients were younger, with a higher proportion of women, smokers, and patients with previous MI, dyslipidemia, and hypertension. Patients in both cohorts received adequate medical treatment, with more Polish patients receiving ß­blockers. Blood pressure and lipid control to target was similar and remained low in both cohorts. Diabetes control and successful smoking cessation rates were lower in Poland than in other European countries. Polish patients more often underwent percutaneous coronary intervention. All­cause (8.5% vs 7.9%; P = 0.81) and cardiovascular death rates (5.3% vs 4.9%; P = 0.82) did not differ between the groups, but fatal or nonfatal MI occurred more often in the Polish cohort (5% vs 3.1%; P = 0.006). Angina control was better in Poland than in other European countries (Canadian Cardiovascular Society class II-IV, 11.5% vs 15.8% of patients; P <0.001). CONCLUSIONS Risk factor control was insufficient both in patients from Poland and in those from other European countries. The more frequent use of revascularization in Polish patients was not linked to improved outcomes, but, together with more extensive prescription of ß­blockers, might have contributed to better angina control.

EvaluatioN of ApiXaban in strOke and systemic embolism prevention in patients with non-valvular atrial fibrillation in clinical practice Setting in France, rationale and design of the NAXOS: SNIIRAM study.

Non-vitamin K antagonists oral anticoagulants (NOACs) have recently challenged vitamin-K antagonists (VKAs) for stroke and systemic embolism prophylaxis in patients with non-valvular atrial fibrillation (NVAF). Nevertheless, little information is available in routine clinical practice for France. The aim of this study is to describe the effectiveness and safety of apixaban, rivaroxaban, dabigatran or VKAs in routine clinical practice in adult NVAF patients for the prevention of stroke and systemic embolism in France. The NAXOS study is a nationwide observational retrospective cohort generated from the French national healthcare insurance database (SNIIRAM-a comprehensive in- and outpatient healthcare consumption database), consisting of eight distinct sub-cohorts of anticoagulant-naive or anticoagulant-experienced patients diagnosed with NVAF, newly initiated with either NOACs (dabigatran, rivaroxaban or apixaban) or VKAs. Patients will be included if initiating a new anticoagulant treatment for AF during the study period from 1 January 2014 to 31 December 2016. Primary effectiveness outcome will be the incidence of stroke or systemic thromboembolic events; primary safety outcome will be the incidence of major bleeding during the exposure period. The NAXOS study will provide routine clinical practice data on the effectiveness and safety profiles of apixaban vs other NOACs and VKAs in the prevention of stroke and systemic embolism in adult patients with NVAF in clinical practice conditions in France.

Interleukin-18 in patients with acute coronary syndromes.

BACKGROUND: We aimed to assess associations between circulating IL-18 concentrations and cardiovascular outcomes in patients with acute coronary syndromes (ACS). HYPOTHESIS AND METHODS: Plasma IL-18 concentrations were measured at admission, discharge, 1 month, and 6 months in patients with ACS in the PLATelet inhibition and patient Outcomes (PLATO) trial. Associations with outcomes were evaluated with Cox regression models on the composite of CV death, spontaneous myocardial infarction (sMI), or stroke; and on CV death or sMI separately, including adjustment for clinical risk factors and biomarkers (cTnT-hs, NT-proBNP, cystatin C, CRP-hs, and GDF-15). RESULTS: Median IL-18 concentrations at baseline, discharge, 1 month, and 6 months were 237, 283, 305, and 320 ng/L (n = 16 636). Male sex, obesity, diabetes, and plasma levels of cystatin C, GDF-15, and CRP-hs were independently associated with higher IL-18 levels. Higher baseline IL-18 levels were associated with the composite endpoint and with CV death (hazard ratio [HR] 1.05, 95% confidence interval [95% CI] 1.02-1.07 and HR 1.10, 95% CI 1.06-1.14, respectively, per 25% increase of IL-18 levels). Associations remained significant after adjustment for clinical variables but became non-significant after adjustment for all biomarkers (HR 1.01, 95% CI 0.98-1.04 and HR 1.04, 95% CI 1.00-1.08, respectively). There were no associations with sMI. CONCLUSIONS: In ACS patients, IL-18 concentrations increased after the acute event and remained increased for 6 months. Baseline IL-18 levels were significantly associated with CV mortality, independent of clinical characteristics and indicators of renal/cardiac dysfunction but this association was attenuated after adjustment for multiple biomarkers.

The efficacy and safety of cangrelor in single vessel vs multivessel percutaneous coronary intervention: Insights from CHAMPION PHOENIX.

BACKGROUND: The intravenous, rapidly acting P2Y12 inhibitor cangrelor reduces the rate of ischemic events during PCI with no significant increase in severe bleeding. However, the efficacy and safety of cangrelor compared with clopidogrel in patients treated with single vessel (SV)-percutaneous coronary intervention (PCI) or multivessel (MV)-PCI remains unexplored. METHODS: We studied the modified intention-to-treat population of patients from the CHAMPION PHOENIX trial who were randomized to either cangrelor or clopidogrel. We used logistic regression and propensity score matching to evaluate the effect of cangrelor compared with clopidogrel on the primary efficacy outcome (composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis) at 48 hours. The safety outcome was moderate or severe Global Utilization of Streptokinase and tPA for Occluded Arteries bleeding at 48 hours. HYPOTHESIS: Cangrelor is as efficacious and safe as clopidogrel in both SV and MV PCI. RESULTS: Among 10 854 patients, 9204 (85%) underwent SV- and 1650 (15%) MV-PCI. After adjustment, cangrelor was associated with similar reductions vs clopidogrel in the primary efficacy outcome in patients undergoing SV-PCI (4.5% vs 5.2%; odds ratio [OR] 0.81 [0.66-0.98]) or MV-PCI (6.1% vs 9.8%, OR 0.59 [0.41-0.85]; Pint 0.14). Similar results were observed after propensity score matching (SV-PCI: 5.5% vs 5.9%, OR 0.93 [0.74-1.18]; MV-PCI: 6.2% vs 8.9%, OR 0.67 [0.44-1.01]; Pint 0.17). There was no evidence of heterogeneity in the treatment effect of cangrelor compared with clopidogrel for the safety outcome. CONCLUSIONS: In patients undergoing SV- or MV-PCI, cangrelor was associated with similar relative risk reductions in ischemic complications and no increased risk of significant bleeding compared with clopidogrel, which highlights the expanding repertoire of options for use in complex PCI.

Effect of Increasing Stent Length on 3-Year Clinical Outcomes in Women Undergoing Percutaneous Coronary Intervention With New-Generation Drug-Eluting Stents: Patient-Level Pooled Analysis of Randomized Trials From the WIN-DES Initiative.

OBJECTIVES: The aim of this study was to examine whether stent length per patient and stent length per lesion are negative markers for 3-year outcomes in women following percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DES). BACKGROUND: In the era of advanced stent technologies, whether stent length remains a correlate of adverse outcomes is unclear. METHODS: Women treated with new-generation DES in 14 randomized trials from the WIN-DES (Women in Innovation and Drug-Eluting Stents) pooled database were evaluated. Total stent length per patient, which was available in 5,403 women (quartile 1, 8 to 18 mm; quartile 2, 18 to 24 mm; quartile 3, 24 to 36 mm; quartile 4, ≥36 mm), and stent length per lesion, which was available in 5,232 women (quartile 1, 8 to 18 mm; quartile 2, 18 to 20 mm; quartile 3, 20 to 27 mm; quartile 4, ≥27 mm) were analyzed in quartiles. The primary endpoint was 3-year major adverse cardiovascular events (MACE), defined as a composite of all-cause death, myocardial infarction, or target lesion revascularization. RESULTS: In the per-patient analysis, a stepwise increase was observed with increasing stent length in the adjusted risk for 3-year MACE (p for trend <0.0001), myocardial infarction (p for trend <0.001), cardiac death (p for trend = 0.038), and target lesion revascularization (p for trend = 0.011) but not definite or probable stent thrombosis (p for trend = 0.673). In the per-lesion analysis, an increase was observed in the adjusted risk for 3-year MACE (p for trend = 0.002) and myocardial infarction (p for trend <0.0001) but not other individual endpoints. On landmark analysis for late event rates between 1 and 3 years, stent length per patient demonstrated weak associations with target lesion revascularization (p = 0.0131) and MACE (p = 0.0499), whereas stent length per lesion was not associated with higher risk for any late events, suggesting that risk was established early within the first year after PCI. CONCLUSIONS: In this pooled analysis of women undergoing PCI with new-generation DES, increasing stent length per patient and per lesion were independent predictors of 3-year MACE but were not associated with definite or probable stent thrombosis.

Effects of Body Mass Index on Clinical Outcomes in Female Patients Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents: Results From a Patient-Level Pooled Analysis of Randomized Controlled Trials.

OBJECTIVES: This study sought to investigate the effect of different body mass index (BMI) categories on clinical outcomes in female patients treated with percutaneous coronary intervention (PCI) and drug-eluting stents. BACKGROUND: Patients with higher BMI might, paradoxically, have better long-term clinical outcomes after acute coronary syndrome treated with PCI. METHODS: We pooled patient-level data for female participants from 26 randomized trials on PCI with drug-eluting stents. Patients were stratified into underweight (BMI, <18.5), normoweight (BMI, 18.5 to 24.9), overweight (BMI, 25 to 29.9), obese (BMI, 30 to 34.9), or morbidly obese (BMI, ≥35). The primary endpoint was major adverse cardiac events, a composite of death, myocardial infarction, or target lesion revascularization at 3 years. RESULTS: Among 11,557 female patients included in the pooled database, 9,420 were treated with a drug-eluting stent and had BMI data available. Patients with higher BMI were significantly younger and with more cardiovascular risk factors. Only 139 patients were underweight and had significantly higher adjusted rates of cardiac mortality and all-cause mortality than the rest of the population (hazard ratio: 2.20 [1.31 to 3.71] compared with normoweight). There was a significantly lower frequency of unadjusted 3-year all-cause mortality in overweight, obese, and severely obese patients compared with normoweight. However, following multivariable analysis, a trend toward increased risk of death in severely obese patients was observed, describing an inverse "J"-shaped relation between BMI and 3-year mortality. Conversely, the relationship between BMI and other outcomes, such as major adverse cardiac events, was flat for normoweight and higher BMI. CONCLUSIONS: The risk of 3-year adjusted cardiac events did not differ across BMI groups, whereas the risk of all-cause mortality compared with normoweight was significantly higher in underweight patients and lower in overweight patients with a trend toward increased risk in the severely obese population.

Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.

BACKGROUND: B-type natriuretic peptide is released from the cardiac ventricles in response to increased wall tension. METHODS: We conducted a prospective study of 1586 patients who came to the emergency department with acute dyspnea and whose B-type natriuretic peptide was measured with a bedside assay. The clinical diagnosis of congestive heart failure was adjudicated by two independent cardiologists, who were blinded to the results of the B-type natriuretic peptide assay. RESULTS: The final diagnosis was dyspnea due to congestive heart failure in 744 patients (47 percent), dyspnea due to noncardiac causes in 72 patients with a history of left ventricular dysfunction (5 percent), and no finding of congestive heart failure in 770 patients (49 percent). B-type natriuretic peptide levels by themselves were more accurate than any historical or physical findings or laboratory values in identifying congestive heart failure as the cause of dyspnea. The diagnostic accuracy of B-type natriuretic peptide at a cutoff of 100 pg per milliliter was 83.4 percent. The negative predictive value of B-type natriuretic peptide at levels of less than 50 pg per milliliter was 96 percent. In multiple logistic-regression analysis, measurements of B-type natriuretic peptide added significant independent predictive power to other clinical variables in models predicting which patients had congestive heart failure. CONCLUSIONS: Used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide is useful in establishing or excluding the diagnosis of congestive heart failure in patients with acute dyspnea.