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2.
Circulation ; : CIR0000000000000759, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32008369

RESUMO

The mission of the American Heart Association is to be a relentless force for a world of longer, healthier lives. The American Heart Association has consistently prioritized the needs and perspective of the patient in taking positions on healthcare reform while recognizing the importance of biomedical research, providers, and healthcare delivery systems in advancing the care of patients and the prevention of disease. The American Heart Association's vision for healthcare reform describes the foundational changes needed for the health system to serve the best interests of patients and to achieve health care and coverage that are adequate, accessible, and affordable for everyone living in the United States. The American Heart Association is committed to advancing the dialogue around healthcare reform and has prepared this updated statement of our principles, placed in the context of the advances in coverage and care that have occurred after the passage of the Affordable Care Act, the rapidly changing landscape of healthcare delivery systems, and our evolving recognition that efforts to prevent cardiovascular disease can have synergistic benefit in preventing other diseases and improving overall well-being. These updated principles focus on expanding access to affordable health care and coverage; enhancing the availability of evidence-based preventive services; eliminating disparities that limit the availability and equitable delivery of health care; strengthening the public health infrastructure to respond to social determinants of health; prioritizing and accelerating investments in biomedical research; and growing a diverse, culturally competent health and healthcare workforce prepared to meet the challenges of delivering high-value health care.

3.
Circulation ; : CIR0000000000000753, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32078375

RESUMO

Understanding and addressing the unique health needs of people residing in rural America is critical to the American Heart Association's pursuit of a world with longer, healthier lives. Improving the health of rural populations is consistent with the American Heart Association's commitment to health equity and its focus on social determinants of health to reduce and ideally to eliminate health disparities. This presidential advisory serves as a call to action for the American Heart Association and other stakeholders to make rural populations a priority in programming, research, and policy. This advisory first summarizes existing data on rural populations, communities, and health outcomes; explores 3 major groups of factors underlying urban-rural disparities in health outcomes, including individual factors, social determinants of health, and health delivery system factors; and then proposes a set of solutions spanning health system innovation, policy, and research aimed at improving rural health.

4.
J Am Coll Cardiol ; 75(2): 133-144, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31948641

RESUMO

BACKGROUND: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). OBJECTIVES: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). METHODS: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. RESULTS: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). CONCLUSIONS: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).

8.
Circulation ; 140(13): 1115-1124, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31545683

RESUMO

Aspirin is the cornerstone of the antithrombotic management of patients with established atherosclerotic cardiovascular disease, but major guidelines provide conflicting recommendations for its use in primary prevention. Findings from recent randomized trials totaling >47 000 patients called into question the net clinical benefits of aspirin in primary prevention for 3 key populations: patients with diabetes mellitus, community-dwelling elderly individuals, and patients without diabetes mellitus who are at intermediate risk for atherosclerotic events. In the context of increasing emphasis on the use of other treatments for primary prevention in patients with moderate-high future risk of developing atherosclerotic cardiovascular disease, the efficacy and safety of aspirin for primary prevention has become uncertain. Key unresolved questions regarding the role of aspirin in primary prevention include the optimal drug formulation, dosing schedule, weight-based dose selection, and interplay between sex and treatment response. In the current era, most patients without established atherosclerotic cardiovascular disease should not be prescribed aspirin. Rather, aggressive management of comorbidities tailored to the expected cardiovascular risk needs to be emphasized. In this context, informed shared decision making between clinicians and patients regarding the use of aspirin for primary prevention of cardiovascular events is a suitable and laudable approach. In this article, we revisit the role of aspirin for the primary prevention of cardiovascular diseases by critically reviewing the key scientific literature, highlight key areas of uncertainties for future research, and propose a decisional framework for clinicians to support prescription of aspirin in primary prevention.

9.
JAMA Cardiol ; : 1-8, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31532454

RESUMO

Importance: Multiple states publicly report a hospital's risk-adjusted mortality rate for percutaneous coronary intervention (PCI) as a quality measure. However, whether reported annual PCI mortality is associated with a hospital's future performance is unclear. Objective: To evaluate the association between reported risk-adjusted hospital PCI-related mortality and a hospital's future PCI-related mortality. Design, Setting, and Participants: This study used data from the New York Percutaneous Intervention Reporting System from January 1, 1998, to December 31, 2016, to assess hospitals that perform PCI. Exposures: Public-reported, risk-adjusted, 30-day mortality after PCI. Main Outcomes and Measures: The primary analysis evaluated the association between a hospital's reported risk-adjusted PCI-related mortality and future PCI-related mortality. The correlation between a hospital's observed to expected (O/E) PCI-related mortality rates each year and future O/E mortality ratios was assessed. Multivariable linear regression was used to examine the association between index year O/E mortality and O/E mortality in subsequent years while adjusting for PCI volume and patient severity. Results: This study included 67 New York hospitals and 960 hospital-years. Hospitals with low PCI-related mortality (O/E mortality ratio, ≤1) and high mortality (O/E mortality ratio, >1) had inverse associations between their O/E mortality ratio in the index year and the subsequent change in the ratio (hospitals with low mortality, r = -0.45; hospitals with high mortality, r = -0.60). Little of the variation in risk-adjusted mortality was explained by prior performance. An increase in the O/E mortality ratio from 1.0 to 2.0 in the index year was associated with a higher O/E mortality ratio of only 0.15 (95% CI, 0.02-0.27) in the following year. Conclusions and Relevance: At hospitals with high or low PCI-related mortality rates, the rates largely regressed to the mean the following year. A hospital's risk-adjusted mortality rate was poorly associated with its future mortality. The annual hospital PCI-related mortality may not be a reliable factor associated with hospital quality to consider in a practice change or when helping patients select high-quality hospitals.

10.
NPJ Digit Med ; 2: 87, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531394

RESUMO

Monitoring and managing resident workload is a cornerstone of policy in graduate medical education, and the duty hours metric is the backbone of current regulations. While the duty hours metric measures hours worked, it does not capture differences in intensity of work completed during those hours, which may independently contribute to fatigue and burnout. Few such metrics exist. Digital data streams generated during the usual course of hospital operations can serve as a novel source of insight into workload intensity by providing high-resolution, minute-by-minute data at the individual level; however, study and use of these data streams for workload monitoring has been limited to date. Paging data is one such data stream. In this work, we analyze over 500,000 pages-two full years of pages in an academic internal medicine residency program-to characterize paging patterns among housestaff. We demonstrate technical feasibility, validity, and utility of paging burden as a metric to provide insight into resident workload beyond duty hours alone, and illustrate a general framework for evaluation and incorporation of novel digital data streams into resident workload monitoring.

11.
Circulation ; 140(19): 1578-1589, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31475572

RESUMO

BACKGROUND: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol ≥70 mg/dL or non-high-density lipoprotein cholesterol ≥100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. METHODS: In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were randomly assigned to alirocumab or placebo. The primary trial outcome (major adverse cardiovascular events, ie, coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) was examined according to American College of Cardiology/American Heart Association risk category. RESULTS: Of 18 924 participants followed for a median of 2.8 years, 11 935 (63.1%) were classified as VHR: 4450 (37.3%) had multiple prior ASCVD events and 7485 (62.7%) had 1 major ASCVD event and multiple high-risk conditions. Major adverse cardiovascular events occurred in 14.4% of placebo-treated patients at VHR versus 5.6% of those not at VHR. In the VHR category, major adverse cardiovascular events occurred in 20.4% with multiple prior ASCVD events versus 10.7% with 1 ASCVD event and multiple high-risk conditions. Alirocumab was associated with consistent relative risk reductions in both risk categories (hazard ratio=0.84 for VHR; hazard ratio=0.86 for not VHR; Pinteraction=0.820) and by stratification within the VHR group (hazard ratio=0.86 for multiple prior ASCVD events; hazard ratio=0.82 for 1 major ASCVD event and multiple high-risk conditions; Pinteraction=0.672). The absolute risk reduction for major adverse cardiovascular events with alirocumab was numerically greater (but not statistically different) in the VHR group versus those not at VHR (2.1% versus 0.8%; Pinteraction=0.095) and among patients at VHR with multiple prior ASCVD events versus a single prior ASCVD event (2.4% versus 1.8%; Pinteraction=0.661). CONCLUSIONS: The US guideline criteria identify patients with recent acute coronary syndrome and dyslipidemia who are at VHR for recurrent ischemic events and who may derive a larger absolute benefit from treatment with alirocumab. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402.

12.
Circulation ; 140(10): e545-e546, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31479316
13.
Lancet ; 394(10204): 1169-1180, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31484629

RESUMO

BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8-3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74-0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, pinteraction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78-1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75-1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48-2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36-3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74-1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75-0·95, p=0·005, in contrast to patients without PCI where it did not, pinteraction=0·012. Benefit was present irrespective of time from most recent PCI. INTERPRETATION: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk. FUNDING: AstraZeneca.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Aspirina/uso terapêutico , Doenças Cardiovasculares/mortalidade , Angiografia Coronária , Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , Estenose Coronária/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea , Prevenção Secundária , Acidente Vascular Cerebral/epidemiologia
14.
N Engl J Med ; 381(14): 1309-1320, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31475798

RESUMO

BACKGROUND: Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear. METHODS: In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria. RESULTS: A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P = 0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P = 0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P = 0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02). CONCLUSIONS: In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.).


Assuntos
Aspirina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Aspirina/efeitos adversos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hemorragia/mortalidade , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação de Plaquetas/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/efeitos adversos , Resultado do Tratamento
16.
Circ Cardiovasc Interv ; 12(8): e007604, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31416357

RESUMO

BACKGROUND: Patients with atrial fibrillation (AF) treated with percutaneous coronary intervention (PCI) require multiple antithrombotic therapies. The optimal strategy is debated suggesting increased treatment variation. This study sought to characterize site-level variation in antithrombotic therapies in AF patients after PCI and determine the association with outcomes. METHODS: Using the retrospective TREAT-AF study (The Retrospective Evaluation and Assessment of Therapies in AF) from the Veterans Health Administration, patients with newly diagnosed, nonvalvular AF between 2004 and 2015 followed by a PCI with a P2Y12-antagonist prescription were identified. Patients were grouped according to the therapy dispensed 7 days before until 30 days after the PCI: oral anticoagulation plus platelet inhibition (OAC+PI) or platelet inhibition only. A combined outcome of death, myocardial infarction, stroke, or major bleeding was assessed 1 year after PCI and Cox regression was performed to estimate hazard ratios. RESULTS: Of 230 762 patients with newly diagnosed AF, 4042 (1.8%) underwent PCI and received a P2Y12-antagonist during the observation period (age, 67±9 years; CHA2DS2-VASc, 2.7±1.7; HAS-BLED, 2.6±1.2). Among these, 47% were prescribed OAC+PI, and 53% platelet inhibition only 7 days before until 30 days after the PCI. Across 63 sites, the use of OAC+PI ranged from 19% to 66%. Prescription of OAC+PI was independently associated with a reduction in the combined outcome of death, myocardial infarction, stroke, or major bleeding compared with platelet inhibition only (adjusted hazard ratio, 0.85; 95% CI, 0.73-0.99; P=0.033). CONCLUSIONS: In patients with established AF undergoing PCI, the use of OAC+PI varied substantially across sites in the 30 days post-PCI. Anticoagulation appeared to be underutilized but was associated with improved outcomes. Strategies to promote OAC+PI and minimize site variation may be useful, particularly in light of recent randomized trials.

17.
J Am Coll Cardiol ; 74(9): 1177-1186, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31466614

RESUMO

BACKGROUND: Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death. OBJECTIVES: This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). METHODS: Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. The primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003). RESULTS: In each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [-2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [-0.1% to 1.0%], 0.5% [-1.9% to 2.9%], and 3.6% [0.0% to 7.2%]). CONCLUSIONS: Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).

18.
Circ Cardiovasc Interv ; 12(7): e007342, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31296081

RESUMO

BACKGROUND: In the CHAMPION PHOENIX trial, cangrelor reduced the primary composite end point of death, myocardial infarction (MI), ischemia-driven revascularization, or stent thrombosis at 48 hours. This study aimed to explore the impact of event adjudication and the prognostic importance of MI reported by a clinical events committee (CEC) or site investigators (SIs). METHODS AND RESULTS: Data from the CHAMPION PHOENIX trial of patients undergoing elective or nonelective percutaneous coronary intervention were analyzed. A CEC systematically identified and adjudicated MI using predefined criteria, a computer algorithm to identify suspected events, and semilogarithmic plots to review biomarker changes. Thirty-day death was modeled using baseline characteristics. Of 10 942 patients, 462 (4.2%) patients had at least 1 MI by 48 hours identified by the CEC (207 [3.8%] cangrelor; 255 [4.7%] clopidogrel; odds ratio [OR] 0.80; 95% CI, 0.67-0.97; P=0.022), and 143 patients had at least 1 MI by 48 hours reported by the SI (60 [1.1%] cangrelor; 83 [1.5%] clopidogrel; OR, 0.72; 95% CI, 0.52-1.01; P=0.053). Of the 462 MIs identified by the CEC, 92 (20%) were reported by SI, and 370 (80%) were not. Of the 143 MI reported by the SI, 51 (36%) were not confirmed by CEC. All categories were associated with an increased adjusted risk for 30-day death (CEC: OR, 5.35; 95% CI, 2.56-11.2; P<0.001; SI: 9.08 [4.01-20.5]; P<0.001; CEC and SI: 10.9 [3.23-36.6]; P<0.001; CEC but not SI: 4.69 [1.94-11.3]; P<0.001; SI but not CEC: 15.4 [5.26-44.9]; P<0.001). CONCLUSIONS: In patients undergoing percutaneous coronary intervention, CEC procedures identified 3 times as many MIs as the SI reported. Compared with clopidogrel, cangrelor significantly reduced MIs identified by the CEC with a qualitatively similar relative risk reduction in MIs reported by the SI. MIs identified by CEC or reported by SI were independently associated with worse 30-day death. Central adjudication identified additional, prognostically important events. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01156571.

19.
Am Heart J ; 215: 106-113, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31310855

RESUMO

Patients with a recent acute coronary syndrome (ACS) receiving oral antiplatelets and anticoagulants are at risk for bleeding and subsequent adverse non-bleeding-related events. METHODS: In this post hoc analysis, we evaluated 7,392 high-risk patients (median follow-up 241 days) with a recent ACS randomized to apixaban or placebo in APPRAISE-2. Clinical events during a 30-day period after Thrombolysis in Myocardial Infarction (TIMI) major/minor bleeding were analyzed using unadjusted and adjusted Cox proportional-hazards models. RESULTS: In total, 153 (2.1%) patients experienced TIMI major/minor bleeding during follow-up. Bleeding risk for patients on triple therapy (apixaban, thienopyridine, and aspirin) was increased compared with those on dual therapy (apixaban plus aspirin: hazard ratio [HR] 2.02, 95% CI 1.08-3.79; thienopyridine plus aspirin: HR 1.99, 95% CI 1.41-2.83). Those receiving apixaban/aspirin had similar bleeding risk compared with those receiving thienopyridine/aspirin (HR 1.01, 95% CI 0.53-1.95). Patients who experienced TIMI major/minor bleeding had an increased risk of 30-day all-cause mortality (HR 24.7, 95% CI 15.34-39.66) and ischemic events (HR 6.7, 95% CI 3.14-14.14). CONCLUSIONS: In a contemporary cohort of high-risk patients after ACS, bleeding was associated with a significantly increased risk of subsequent ischemic events and mortality regardless of antithrombotic or anticoagulant strategy. Patients receiving apixaban plus aspirin had a similar bleeding risk compared with those receiving thienopyridine plus aspirin. Interventions to improve outcomes in patients after ACS should include strategies to optimize the reduction in ischemic events while minimizing the risk of bleeding.

20.
Lancet Diabetes Endocrinol ; 7(8): 618-628, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31272931

RESUMO

BACKGROUND: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4-1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. METHODS: ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1-12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65-1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. FINDINGS: At study baseline, 5444 patients (28·8%) had diabetes, 8246 (43·6%) had prediabetes, and 5234 (27·7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2·20-2·28 mmol/L), after 4 months' treatment with alirocumab (0·80 mmol/L), or after 4 months' treatment with placebo (2·25-2·28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2·8 years was greater in patients with diabetes (16·4%) than in those with prediabetes (9·2%) or normoglycaemia (8·5%); hazard ratio (HR) for diabetes versus normoglycaemia 2·09 (95% CI 1·78-2·46, p<0·0001) and for diabetes versus prediabetes 1·90 (1·65-2·17, p<0·0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2·3%, 95% CI 0·4 to 4·2) than in those with prediabetes (1·2%, 0·0 to 2·4) or normoglycaemia (1·2%, -0·3 to 2·7; absolute risk reduction pinteraction=0·0019). Among patients without diabetes at baseline, 676 (10·1%) developed diabetes in the placebo group, compared with 648 (9·6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1·00, 95% CI 0·89-1·11). HRs were 0·97 (95% CI 0·87-1·09) for patients with prediabetes and 1·30 (95% CI 0·93-1·81) for those with normoglycaemia (pinteraction=0·11). INTERPRETATION: After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0·65-1·30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes. FUNDING: Sanofi and Regeneron Pharmaceuticals.

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