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1.
Am Heart J ; 219: 47-57, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707324

RESUMO

BACKGROUND: Obesity is a risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). Whether obesity affects outcomes among those with T2D and atherosclerotic CVD (ASCVD) remains uncertain. Our objective was to investigate the relationship between body mass index (BMI) and ASCVD outcomes among TECOS participants with T2D and ASCVD. METHODS: BMI categories were defined as underweight/normal weight (BMI <25 kg/m2), overweight (25-29.9 kg/m2), obese class I (30-34.9 kg/m2), obese class II (35-39.9 kg/m2), and obese class III (≥ 40 kg/m2). Asian-specific BMI categories were applied to Asian participants. Kaplan-Meier survival analysis and Cox proportional hazards models were used to examine associations between baseline BMI and a composite CV outcome (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina). RESULTS: For 14,534 TECOS patients with available BMI, mean age was 65.5 years; 29.3% were female, 32.0% non-White, and 23.1% insulin-treated, with median 3 years' follow-up. At baseline, 11.6% (n = 1686) were underweight/normal weight, 38.1% (n = 5532) overweight, 32.2% (n = 4683) obese class I, 12.4% (n = 1806) obese class II, and 5.7% (n = 827) obese class III. The composite CV outcome occurred in 11.4% (n = 1663) of participants; the outcome risk was lower, compared with under/normal weight, in overweight (HR 0.83, 95% CI 0.71-0.98) and obese class I (HR 0.79, 95% CI 0.67-0.93) individuals. Obesity was not associated with worse glycemic control. CONCLUSIONS: The majority of TECOS participants with ASCVD and T2D were overweight or obese, yet overweight or obese class I individuals had lower CV risk than those who were under/normal weight. These results suggest the presence of an obesity paradox, but this paradox may reflect an epidemiological artifact rather than a true negative association between normal weight and clinical outcomes.

2.
Am Heart J ; 220: 137-144, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31812755

RESUMO

BACKGROUND: Although spontaneous reperfusion (SR) prior to primary percutaneous coronary intervention (pPCI) is associated with improved outcomes, its pathophysiology remains unclear. The objective of the study was to explore associations between SR in ST-segment elevation myocardial infarction (STEMI) using a multimarker cardiovascular proteins strategy METHODS: We evaluated STEMI patients from the Assessment of Pexelizumab in Acute Myocardial Infarction trial treated with pPCI within 6 hours from symptom onset. SR was core laboratory-defined as pre-PCI Thrombolysis in Myocardial Infarction flow 2 or 3. Ninety-one cardiovascular disease-related serum biomarkers drawn prior to PCI were analyzed using a high-throughput "targeted discovery" panel. Expression levels for individual biomarkers were compared between patients with/without SR. A hierarchical clustering method of biomarkers identified clusters of biomarkers that differentiated the 2 groups. Associations between individual biomarkers and clusters with SR were further evaluated by multivariable logistic regression. RESULTS: Of 683 patients studied, 290 had spontaneous reperfusion; those with compared to without SR were more likely noninferior STEMI and had lower clinical acuity and lower baseline levels of troponin and creatine kinase. SR was associated with a lower occurrence of 90-day composite of death, heart failure, or cardiogenic shock. Fifty-two of 91 individual biomarkers were significantly univariably associated with SR. Forty-five remained significant with adjustment for false discovery rate. Using cluster analysis, 26 biomarkers clusters were identified, explaining 72% of total covariance, and 13 biomarker clusters were significantly associated with SR after multivariable adjustment. SR was associated with higher mean expression levels of proteins in all 13 clusters. The cluster most strongly associated with SR consisted of novel proteins across various distinct, yet interlinked, pathobiological processes (kallikrein-6, matrix extracellular phosphoglycoprotein, matrix mettaloproteinaise-3, and elafin). CONCLUSIONS: Spontaneous reperfusion prior to pPCI in STEMI was associated with a lower risk of adverse clinical events. These exploratory data from a targeted discovery proteomics platform identifies novel proteins across diverse, yet complementary, pathobiological axes that show promise in providing mechanistic insights into spontaneous reperfusion in STEMI. CONDENSED ABSTRACT: Spontaneous reperfusion has been established with improved STEMI outcomes, yet its pathobiology is unclear and appears to involve diverse physiological processes. Using a 91-biomarker high-throughput proteomics platform, we studied 683 STEMI patients in the APEX AMI trial (290 had core laboratory-adjudicated pre-PCI TIMI 2/3 flow) and identified 52 proteins that univariably associate with spontaneous reperfusion. Cluster analysis identified 26 biomarker clusters (explaining 72% of total variance), 13 of which, after multivariable adjustment, were significantly associated with spontaneous reperfusion. Four proteins (kallikrein-6, matrix extracellular phosphoglycoprotein, matrix mettaloproteinaise-3, and elafin) across diverse, yet complementary, pathways appear to be associated most strongly with spontaneous reperfusion.

3.
Eur J Heart Fail ; 21(12): 1596-1604, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31820546

RESUMO

AIM: Describe the distinguishing features of heart failure (HF) patients with reduced ejection fraction (HFrEF) in the VICTORIA (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction) trial. METHODS AND RESULTS: Key background characteristics were evaluated in 5050 patients randomized in VICTORIA and categorized into three cohorts reflecting their index worsening HF event. Differences within the VICTORIA population were assessed and compared with PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and COMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure). VICTORIA patients had increased risk of mortality and rehospitalization: New York Heart Association class (40% class III), atrial fibrillation (45%), diabetes (47%), hypertension (79%) and mean estimated glomerular filtration rate of 61.5 mL/min/1.73 m2 . Baseline standard of HF care was very good: 60% received triple therapy. Their N-terminal pro-B-type natriuretic peptide was 3377 pg/mL [interquartile range (IQR) 1992-6380]. Natriuretic peptides were 30% higher level in the 67% patients with HF hospitalization <3 months, compared to those within 3-6 months of HF hospitalization and those randomized after recent outpatient intravenous diuretic therapy. Overall the median MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) risk score in VICTORIA was 23 (IQR 18-27) as compared to the MAGGIC risk score in PARADIGM-HF of 20 (IQR 16-24). CONCLUSIONS: VICTORIA comprises a broadly generalizable high-risk population of three unique clinical strata of worsening chronic HFrEF despite very good HF therapy. VICTORIA will establish the role of vericiguat, a soluble guanylate cyclase stimulator, in HFrEF.

4.
Am Heart J ; 218: 92-99, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31715435

RESUMO

BACKGROUND: The effects of ß-blocker therapy in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD) are unclear. We sought to evaluate associations between ß-blocker use in T2D with ASCVD and cardiovascular (CV) outcomes. METHODS: In patients with T2D and ASCVD enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), an inverse probability of treatment-weighted Cox proportional hazards model was used to examine the association between baseline ß-blocker therapy (at randomization) and the primary CV composite (defined as CV death, non-fatal myocardial infarction [MI], non-fatal stroke, or hospitalization for unstable angina), including in subgroups with prior MI and heart failure (HF); other outcomes evaluated included individual components of the primary composite, hospitalization for HF, and severe hypoglycemic events. RESULTS: Of the 14,671 patients randomized, 9322 (64%) were on a ß-blocker at baseline; these patients were more likely to have prior MI or HF. Over a median 3.0 (25th, 75th percentile: 2.2, 3.6) years, the risk of the primary CV composite was significantly higher with baseline ß-blocker use versus no ß-blocker use (4.5 vs. 3.4 events/100-patient years, adjusted hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05-1.29); no significant interaction was noted for patients with versus without prior MI or HF. Baseline ß-blocker use was not associated with risks for severe hypoglycemic events (HR 1.14, 95% CI 0.88-1.48). CONCLUSIONS: In this observational analysis of T2D and ASCVD, baseline ß-blocker use was not associated with risks for severe hypoglycemia yet also was not associated with CV risk reduction over 3 years of follow-up, supporting a randomized examination of chronic ß-blocker therapy in this patient population. (TECOS ClinicalTrials.gov number, NCT00790205).

5.
Circ Cardiovasc Interv ; 12(10): e008059, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31607152

RESUMO

BACKGROUND: Recent clinical trial data support a pharmacoinvasive strategy as an alternative to primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction. We evaluated whether this is true in a real-world prehospital ST-segment elevation myocardial infarction network using ECG assessment of reperfusion coupled with clinical outcomes within 1 year. METHODS: Of the 5583 ST-segment elevation myocardial infarction patients in the Alberta Vital Heart Response Program (Cohort 1 [2006-2011]: n=3593; Cohort 2 [2013-2016]: n=1990), we studied 3287 patients who received a pharmacoinvasive strategy with tenecteplase (April 2013: half-dose tenecteplase was employed in prehospital patients ≥75 years) or pPCI. ECGs were analyzed within a core laboratory; sum ST-segment deviation resolution ≥50% was defined as successful reperfusion. The primary composite was all-cause death, congestive heart failure, cardiogenic shock, and recurrent myocardial infarction within 1 year. RESULTS: The pharmacoinvasive approach was administered in 1805 patients (54.9%), (493 [27.3%] underwent rescue/urgent percutaneous coronary intervention and 1312 [72.7%] had scheduled angiography); pPCI was performed in 1482 patients (45.1%). There was greater ST-segment resolution post-catheterization/percutaneous coronary intervention with a pharmacoinvasive strategy versus pPCI (75.8% versus 64.3%, IP-weighted odds ratio, 1.59; 95% CI, 1.33-1.90; P<0.001). The primary composite was significantly lower with a pharmacoinvasive approach (16.3% versus 23.1%, IP-weighted hazard ratio, 0.84; 95% CI, 0.72-0.99; P=0.033). Major bleeding and intracranial hemorrhage were similar between a pharmacoinvasive strategy and pPCI (7.6% versus 7.5%, P=0.867; 0.6% versus 0.6%; P=0.841, respectively). In the 82 patients ≥75 years with a prehospital pharmacoinvasive strategy, similar ST-segment resolution and rescue rates were observed with full-dose versus half-dose tenecteplase (75.8% versus 88.9%, P=0.259; 31.0% versus 29.2%, P=0.867) with no difference in the primary composite (31.0% versus 25.0%, P=0.585). CONCLUSIONS: In this large Canadian ST-segment elevation myocardial infarction registry, a pharmacoinvasive strategy was associated with improved ST-segment resolution and enhanced outcomes within 1 year compared with pPCI. Our findings support the application of a selective pharmacoinvasive reperfusion strategy when delay to pPCI exists.

6.
J Cardiovasc Pharmacol ; 73(3): 149-154, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30540684

RESUMO

Little is known about the dosing and tolerability of sacubitril/valsartan (LCZ696; Entresto, Quebec, Canada) in a nonclinical trial population. This study was conducted to evaluate the use and tolerability of sacubitril/valsartan in patients followed at a multidisciplinary heart failure (HF) clinic. We performed a retrospective chart review of 126 patients with HF, initiated on sacubitril/valsartan, and seen at a specialty HF clinic between August 1, 2015, and August 1, 2017. We defined the target dose of sacubitril/valsartan as 200 mg twice a day. At baseline, median age was 67 years, 77% were men, median ejection fraction was 29%, and 86.5% of patients had symptoms of New York Heart Association class ≥II. Within 6 months of being transitioned onto sacubitril/valsartan therapy, 27.2% achieved the target dose of 200 mg twice a day, 40.8% achieved the target dose of 100 mg twice a day, and 32.0% achieved the target dose of 50 mg twice a day. The main reasons for not achieving target dose within 6 months included slower uptitration of therapy than in the trial (n = 41, 54.7%), a decrease in systolic blood pressure (n = 19, 25.3%), not completing blood work (n = 3, 4%), and patient noncompliance (n = 3, 4%). Overall, achievement of sacubitril/valsartan target doses was modest in a tertiary HF clinic, limited by various factors such as side effects and patients' medication noncompliance. Implementation of patient and clinician support pathways may improve uptake, uptitration, and maintenance of evidence-based doses in clinical practice.

8.
Int J Cardiol ; 264: 12-17, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29655952

RESUMO

BACKGROUND: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a known clinical conundrum with limited investigation. Using a large population-based cohort, we examined the incidence, demographic profile, use of evidence-based medicines (EBM) and clinical outcomes of MINOCA patients. METHODS: Patients hospitalized with a primary diagnosis of MI who underwent coronary angiography between 01/04/2002 and 31/03/2014 in Alberta, Canada, were included in the study. Comparisons were made between patients with MINOCA versus obstructive coronary disease (OCD). The primary composite endpoint was 1-year all-cause death or re-MI. RESULTS: Of 35,928 patients hospitalized with MI, 2092 (5.8%) had MINOCA. In-hospital mortality rate was 0.8% among MINOCA, and 2.7% among patients with OCD (p < 0.0001). At 6 months, cardiovascular EBM rates were significantly lower among MINOCA patients compared to OCD patients. One-year death/re-MI rate was 5.3% in MINOCA and 8.9% in patients with OCD (adjusted hazard ratio (AHR) 0.75, 95% confidence interval (CI) 0.62-0.92, p < 0.0001). Five-year mortality rates were 10.9% in MINOCA and 16.0% in patients with OCD. Upon further stratification, 770 (36.8%) of MINOCA patients had no angiographic evidence of CAD (i.e. normal angiograms). EBM rates were even lower among these patients. One-year death/re-MI rate among these patients was 3.9% as compared to 6.1% among MINOCA patients with stenosis <50% (AHR 0.68, 95% CI 0.44-1.07, p = 0.028). CONCLUSIONS: The population-level incidence of MINOCA is approximately 5%. Despite their apparently benign anatomic findings, efforts must be made to improve secondary prevention strategies to reduce the burden of long-term adverse outcomes in this population.


Assuntos
Síndrome Coronariana Aguda , Doença das Coronárias , Vasos Coronários/diagnóstico por imagem , Efeitos Adversos de Longa Duração , Infarto do Miocárdio , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/etiologia , Idoso , Alberta/epidemiologia , Causas de Morte , Angiografia Coronária/estatística & dados numéricos , Doença das Coronárias/complicações , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Vasos Coronários/patologia , Feminino , Humanos , Incidência , Efeitos Adversos de Longa Duração/etiologia , Efeitos Adversos de Longa Duração/mortalidade , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Fatores de Risco , Prevenção Secundária/métodos , Prevenção Secundária/organização & administração , Análise de Sobrevida
9.
Eur Heart J Acute Cardiovasc Care ; 7(6): 504-513, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28627230

RESUMO

AIMS: The STREAM study randomly assigned ST-elevation myocardial infarction (STEMI) patients to receive a pharmacoinvasive versus primary percutaneous coronary intervention reperfusion strategy. We assessed whether there was an association between outcomes based on randomisation at a community hospital versus a prehospital location. METHODS/RESULTS: Community hospital patients (358/1866 (19.2%)) were compared to prehospital patients and their outcomes categorised into pharmacoinvasive according to their treatment assignment. Compared to prehospital patients, community hospital patients had more diabetes (17.8% vs. 11.5%, P=0.001), higher Killip Class >1 (9.4% vs. 5.0%, P=0.002) and thrombolysis in myocardial infarction risk scores ⩾5 (18.2% vs. 12.4%, P=0.005). The 30-day primary endpoint (death, shock, congestive heart failure and re-infarction) for community hospital patients was 14.9% versus 13.2% for prehospital patients ( P=0.403). Community hospital pharmacoinvasive patients tended to receive less rescue (35.1% vs. 42.8%, P=0.062); when deployed their rescue was delayed 43 minutes. Community hospital patients undergoing primary percutaneous coronary intervention experienced a delay of 31 minutes versus prehospital patients. Pharmacoinvasive patients receiving scheduled angiography from a community hospital and prehospital patients had comparable times to angiography (17.7 vs. 18.7 hours) and low event rates (6.2% vs. 8.0%). Although the interaction between randomisation location and treatment received on the primary endpoint was not significant ( Pinteraction=0.065) those pharmacoinvasive patients requiring rescue from community hospitals had worse outcomes than prehospital rescue patients (odds ratio 2.28, 95% confidence interval 1.16-4.49). CONCLUSION: Within STREAM, STEMI patients randomly assigned at community hospitals had a higher baseline risk but similar outcomes compared to those studied prehospital patients irrespective of successful pharmacoinvasive therapy or primary percutaneous coronary intervention. However, worse outcomes in the pharmacoinvasive patients requiring rescue in community hospitals emphasises their need for immediate transfer to a percutaneous coronary intervention-capable hospital.


Assuntos
Serviços Médicos de Emergência , Fibrinolíticos/uso terapêutico , Hospitais Comunitários , Intervenção Coronária Percutânea/métodos , Medição de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Terapia Trombolítica/métodos , Alberta/epidemiologia , Angiografia Coronária , Eletrocardiografia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Taxa de Sobrevida/tendências , Resultado do Tratamento
10.
Circulation ; 135(23): 2299-2307, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28584030

RESUMO

Advances in cardiovascular medicine fueled by innovative clinical trials have dramatically improved the lives of patients worldwide. Commensurate with this progress has been a decline in morbid and mortal events. Accordingly, an increased propensity to collate patient outcomes in clinical trials has emerged that combines death and nonfatal complications into a single composite event. Despite the acknowledged benefits in trial efficiency from such an approach, this method assumes uniform directionality of each component, does not distinguish the relative clinical significance of each, and counts only the first occurrence of any event in the final tally within a conventional time to first event analysis. In this article, we evaluate the criticisms that have been leveled at this approach and provide an overview of recently published phase III cardiovascular trials using primary composite end points. We then explore what to anticipate from the large cohort of as-yet unpublished clinical trials in this arena. Last, we propose a variety of novel approaches that use composite end points and suggest a path forward to enhancing their use in future clinical trials.


Assuntos
Pesquisa Biomédica/métodos , Ensaios Clínicos como Assunto/métodos , Determinação de Ponto Final/métodos , Pesquisa Biomédica/normas , Ensaios Clínicos como Assunto/normas , Determinação de Ponto Final/normas , Humanos
11.
Am Heart J ; 188: 127-135, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28577668

RESUMO

BACKGROUND: Most patients with acute heart failure (AHF) admitted to critical care units (CCUs) are low acuity and do not require CCU-specific therapies, suggesting that they could be managed in a lower-cost ward environment. This study identified the predictors of clinical events and the need for CCU-specific therapies in patients with AHF. METHODS: Model derivation was performed using data from patients in the ASCEND-HF trial cohort (n=7,141), and the Acute Heart Failure Emergency Management community-based registry (n=666) was used to externally validate the model and to test the incremental prognostic utility of 4 variables (heart failure etiology, troponin, B-type natriuretic peptide [BNP], ejection fraction) using net reclassification index and integrated discrimination improvement. The primary outcome was an in-hospital composite of the requirement for CCU-specific therapies or clinical events. RESULTS: The primary composite outcome occurred in 545 (11.4%) derivation cohort participants (n=4,767) and 7 variables were predictors of the primary composite outcome: body mass index, chronic respiratory disease, respiratory rate, resting dyspnea, hemoglobin, sodium, and blood urea nitrogen (c index=0.633, Hosmer-Lemeshow P=.823). In the validation cohort (n=666), 87 (13.1%) events occurred (c index=0.629, Hosmer-Lemeshow P=.386) and adding ischemic heart failure, troponin, and B-type natriuretic peptide improved model performance (net reclassification index 0.79, 95% CI 0.046-0.512; integrated discrimination improvement 0.014, 95% CI 0.005-0.0238). The final 10-variable clinical prediction model demonstrated modest discrimination (c index=0.702) and good calibration (Hosmer-Lemeshow P=.547). CONCLUSIONS: We derived, validated, and improved upon a clinical prediction model in an international trial and a community-based cohort of AHF. The model has modest discrimination; however, these findings deserve further exploration because they may provide a more accurate means of triaging level of care for patients with AHF who need admission.


Assuntos
Gerenciamento Clínico , Insuficiência Cardíaca/diagnóstico , Hemodinâmica/fisiologia , Hospitalização/tendências , Unidades de Terapia Intensiva/estatística & dados numéricos , Sistema de Registros , Medição de Risco/métodos , Doença Aguda , Idoso , Alberta/epidemiologia , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/epidemiologia , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
12.
Int J Cardiol ; 241: 70-75, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28495247

RESUMO

BACKGROUND: We examined variation in hospital treatment and its relationship to clinical outcome in a large population-based cohort of ACS patients within a single payer-government funded health care system. METHODS: Patients hospitalized in 106 hospitals in Alberta, Canada with a primary diagnosis of ACS were included (July 1, 2010-March 31, 2013) with comparisons made across the three cardiac catheterization-capable hospitals (Sites A-C). Cox proportional-hazard regression models were used to examine the multivariable-adjusted association between site and 1-year death or repeat cardiovascular (CV) hospitalization (primary endpoint). RESULTS: Of 14,155 patients, 1938 (13.7%) were admitted to a community hospital without transfer to an invasive hospital (10.7% in-hospital death). The remaining were admitted (n=4514, 36.9%) or transferred (n=7703, 63.1%) to an invasive hospital (A:5480; B:3621; C:3116) where 11,247 (92.1%) underwent catheterization. Comorbidities and angiographic disease burden differed across sites. Variation in 30-day revascularization (PCI: 71.3%, 72.0%, 68.7%, p<0.001; CABG: 6.2%, 6.4%, 9.3%, p<0.001) and drug-eluting stent use for PCI (24.3%, 54.6%, 50.5%, p<0.001) were observed. After adjustment for patient demographics and comorbidities, variation in rates of 1-year death or CV hospitalization was observed among those with 30-day revascularization (p(interaction)<0.001; B versus A: HR 0.78, 95%CI 0.66-0.91; C versus A: HR 0.77, 95%CI 0.65-0.91; B versus C: HR 1.01, 95%CI 0.84-1.21). CONCLUSIONS: Despite a government funded health system, we have shown variation in hospital treatment exists. Following adjustment hospital site was associated with differences in clinical outcome within 1year. Hence, further efforts may be warranted to help address potential disparities in ACS care.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/terapia , Cateterismo Cardíaco/normas , Hospitais/normas , Síndrome Coronariana Aguda/diagnóstico , Idoso , Alberta/epidemiologia , Cateterismo Cardíaco/tendências , Estudos de Coortes , Feminino , Seguimentos , Hospitalização/tendências , Hospitais/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Resultado do Tratamento
14.
Diabetes Obes Metab ; 19(1): 78-86, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27607571

RESUMO

AIM: To examine fracture incidence among participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). RESEARCH DESIGN AND METHODS: We used data from 14 671 participants in the TECOS study who were randomized double-blind to sitagliptin (n = 7332) or placebo (n = 7339). Cumulative fracture incidence rates were calculated and their association with study treatment assignment was examined using multivariable Cox proportional hazards regression. RESULTS: The baseline mean (standard deviation) participant age was 65.5 (8.0) years, diabetes duration was 11.6 (8.1) years and glycated haemoglobin level was 7.2 (0.5)% [55.2 (5.5) mmol/mol], and 29.3% of participants were women and 32.1% were non-white. During 43 222 person-years' follow-up, 375 (2.6%; 8.7 per 1000 person-years) had a fracture; 146 were major osteoporotic fractures (hip, n = 34; upper extremity, n = 81; and clinical spine, n = 31). Adjusted analyses showed fracture risk increased independently with older age (P < .001), female sex (P < .001), white race (P < .001), lower diastolic blood pressure (P < .001) and diabetic neuropathy (P = .003). Sitagliptin, compared with placebo, was not associated with a higher fracture risk [189 vs 186 incident fractures: unadjusted hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.82 to 1.23, P = .944; adjusted HR 1.03, P = .745], major osteoporotic fractures (P = .673) or hip fractures (P = .761). Insulin therapy was associated with a higher fracture risk (HR 1.40, 95% CI 1.02-1.91; P = .035), and metformin with a lower risk (HR 0.76, 95% CI 0.59-0.98; P = .035). CONCLUSION: Fractures were common among people with diabetes in the TECOS study, but were not related to sitagliptin therapy. Insulin and metformin treatment were associated with higher and lower fracture risks, respectively.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Fraturas do Quadril/epidemiologia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , Fraturas por Osteoporose/epidemiologia , Fosfato de Sitagliptina/uso terapêutico , Fatores Etários , Idoso , Preservação de Sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/etiologia , Método Duplo-Cego , Quimioterapia Combinada , Grupo com Ancestrais do Continente Europeu , Feminino , Fraturas Ósseas/epidemiologia , Hemoglobina A Glicada/metabolismo , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais
15.
Heart ; 102(7): 527-33, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26783237

RESUMO

OBJECTIVE: Uncertainty exists concerning the relative merits of pharmacological versus mechanical coronary reperfusion in patients presenting early with ST-elevation myocardial infarction (STEMI) with extensive myocardium at risk. Accordingly, we investigated whether the extent of baseline ST-segment shift was related to the response of either reperfusion modality in patients with STEMI presenting within 3 h of symptoms. METHODS: We analysed baseline ECGs from 1859 patients enrolled in the STrategic Reperfusion Early After Myocardial Infarction (STREAM) trial. The sum of ST-segment elevation (∑STE) and ST-segment deviation (∑STD) was categorised into quartiles and associations with the primary endpoint (30-day death/shock/congestive heart failure/re-myocardial infarction) for each reperfusion strategy (early fibrinolysis vs primary percutaneous coronary intervention) were explored. RESULTS: Overall, there was a progressive rise in the 30-day primary endpoint according to quartiles of baseline ∑STE (10.3% (0-5 mm), 12.4% (5.5-8.5 mm), 12.1% (9-13.5 mm), 17.6% (> 14.0 mm), p = 0.008) and ∑STD (9.0% (0-9 mm), 13.5% (9.5-14 mm), 14.7% (14.5-20 mm), 15.3% (> 20 mm), p = 0.019). Both ∑STE and ∑STD were associated with the primary endpoint (∑STE: p = 0.071; ∑STD: p = 0.024). However, there was no interaction between quartiles of baseline ∑STE or ∑STD and efficacy of either reperfusion strategy on the 30-day clinical outcomes (∑STE: p (interaction) = 0.696; ∑STD: p (interaction) = 0.542). CONCLUSIONS: These data demonstrate an association between ∑STE or ∑STD on the baseline ECG and clinical events at 30 days following reperfusion therapy in STEMI. More importantly, the response to different reperfusion strategies was not influenced by the extent of jeopardised myocardium. TRIAL REGISTRATION NUMBER: NCT00623623; Post-results.


Assuntos
Eletrocardiografia , Enoxaparina , Infarto do Miocárdio , Reperfusão Miocárdica , Intervenção Coronária Percutânea , Ticlopidina/análogos & derivados , Idoso , Clopidogrel , Pesquisa Comparativa da Efetividade , Eletrocardiografia/métodos , Eletrocardiografia/estatística & dados numéricos , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Reperfusão Miocárdica/efeitos adversos , Reperfusão Miocárdica/métodos , Avaliação de Resultados da Assistência ao Paciente , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Medição de Risco/métodos , Fatores de Risco , Análise de Sobrevida , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
16.
Catheter Cardiovasc Interv ; 88(2): 163-73, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26698636

RESUMO

OBJECTIVES: We evaluated outcomes associated with transradial vs. transfemoral approaches and vorapaxar in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) in the TRACER trial. BACKGROUND: Vorapaxar reduces ischemic events but increases the risk of major bleeding. METHODS: We compared 30-day and 2-year major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization) and noncoronary artery bypass graft (CABG)-related bleedings in 2,192 transradial and 4,880 transfemoral patients undergoing PCI after adjusting for confounding variables, including propensity for transradial access. RESULTS: Overall, 30-day GUSTO moderate/severe and non-CABG TIMI major/minor bleeding occurred less frequently in transradial (0.9% vs. 2.0%, P = 0.001) vs. transfemoral (1.1% vs. 2.5%, P = 0.005) patients. A similar reduction was seen at 2 years (3.3% vs. 4.7%, P = 0.008; 3.3% vs. 4.9%, P < 0.001, respectively). Transradial was associated with an increased risk of ischemic events at 30 days (OR 1.38, 95% CI 1.11-1.72; P = 0.004), driven primarily by increased periprocedural myocardial infarctions. At 2 years, rates of MACE were comparable (HR 1.14, 95% CI 0.98-1.33; P = 0.096). Although bleeding rates were higher with vorapaxar in transfemoral vs. transradial patients, there was no significant treatment interaction. Also, the access site did not modulate the association between vorapaxar and MACE. CONCLUSIONS: Transradial access was associated with lower bleeding rates and similar long-term ischemic outcomes, suggesting transradial access is safer than transfemoral access among ACS patients receiving potent antiplatelet therapies. Because of the nonrandomized allocation of arterial access, these results should be considered exploratory. © 2015 Wiley Periodicals, Inc.


Assuntos
Síndrome Coronariana Aguda/terapia , Cateterismo Periférico/métodos , Artéria Femoral , Lactonas/uso terapêutico , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/uso terapêutico , Piridinas/uso terapêutico , Artéria Radial , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/mortalidade , Idoso , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/mortalidade , Feminino , Hemorragia/induzido quimicamente , Humanos , Lactonas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/terapia , Readmissão do Paciente , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Punções , Piridinas/efeitos adversos , Recidiva , Retratamento , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/terapia , Fatores de Tempo , Resultado do Tratamento
17.
Eur Heart J Acute Cardiovasc Care ; 5(3): 231-42, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25897147

RESUMO

AIMS: Little is known regarding consequences of frailty in patients with acute coronary syndrome (ACS). We assessed the associations of frailty and outcomes in ACS patients who were participating in a clinical trial. METHODS AND RESULTS: The TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY ACS) trial randomized 9326 patients planned for medical management to prasugrel or clopidogrel. The primary endpoint was a composite of cardiovascular death, myocardial infarction (MI), or stroke over a period of 30 months. A frailty score based upon the Fried score was self-reported at baseline in patients aged ⩾65 years. Five frailty questions were recorded for 4996/5102 (97.9%) patients: 72.3% were classified as not-frail (0 items), 23.0% as pre-frail (1-2 items), and 4.7% as frail (⩾3 items). Increasing frailty score was associated with older age, diabetes, and higher Global Registry of Acute Coronary Events (GRACE) scores. Frailty was associated with a higher unadjusted incidence of the primary endpoint (pre-frail vs not-frail: 29.2% vs 23.1%; hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.19-1.61; p<0.001; frail vs not-frail: 39.7% vs 23.1%; HR: 1.76; 95% CI: 1.36-2.28; p<0.001), and all-cause mortality (pre-frail vs not-frail: 21.7% vs 15.0%; HR: 1.45; 95% CI: 1.22-1.73; p<0.001; frail vs not-frail: 30.2% vs 15.0%; HR: 1.98; 95% CI: 1.47-2.68; p<0.001). After adjustment for baseline characteristics and GRACE covariates, frailty remained independently associated with the primary endpoint: pre-frail vs not-frail, HR: 1.33; 95% CI: 1.15-1.54; p<0.001; frail vs not-frail, HR: 1.52; 95% CI: 1.18-1.98; p=0.002. There was no association of frailty with bleeding. CONCLUSION: Frailty is associated with the composite of cardiovascular death, MI, or stroke. Frailty assessment contributes to risk prediction and adds to the GRACE score.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Cloridrato de Prasugrel/administração & dosagem , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Clopidogrel , Método Duplo-Cego , Feminino , Idoso Fragilizado , Inquéritos Epidemiológicos , Humanos , Masculino , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Prognóstico , Ticlopidina/administração & dosagem , Ticlopidina/uso terapêutico , Resultado do Tratamento
18.
J Am Heart Assoc ; 4(12)2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26672080

RESUMO

BACKGROUND: Perioperative antiplatelet agents potentially increase bleeding after non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). The protease-activated receptor 1 antagonist vorapaxar reduced cardiovascular events and was associated with increased bleeding versus placebo in NSTE ACS, but its efficacy and safety in noncardiac surgery (NCS) remain unknown. We aimed to evaluate ischemic, bleeding, and long-term outcomes of vorapaxar in NCS after NSTE ACS. METHODS AND RESULTS: In the TRACER trial, 2202 (17.0%) patients underwent major or minor NCS after NSTE ACS over 1.5 years (median); continuing study treatment perioperatively was recommended. The primary ischemic end point for this analysis was cardiovascular death, myocardial infarction, stent thrombosis, or urgent revascularization within 30 days of NCS. Safety outcomes included 30-day NCS bleeding and GUSTO moderate/severe bleeding. Overall, 1171 vorapaxar and 1031 placebo patients underwent NCS. Preoperative aspirin and thienopyridine use was 96.8% versus 97.7% (P=0.235) and 89.1% versus 86.1% (P=0.036) for vorapaxar versus placebo, respectively. Within 30 days of NCS, no differences were observed in the primary ischemic end point between vorapaxar and placebo groups (3.4% versus 3.9%; adjusted odds ratio 0.81, 95% CI 0.50 to 1.33, P=0.41). Similarly, no differences in NCS bleeding (3.9% versus 3.4%; adjusted odds ratio 1.41, 95% CI 0.87 to 2.31, P=0.17) or GUSTO moderate/severe bleeding (4.2% versus 3.7%; adjusted odds ratio 1.15, 95% CI, 0.72 to 1.83, P=0.55) were observed. In a 30-day landmarked analysis, NCS patients had a higher long-term risk of the ischemic end point (adjusted hazard ratio 1.62, 95% CI 1.33 to 1.97, P<0.001) and GUSTO moderate/severe bleeding (adjusted hazard ratio 5.63, 95% CI 3.98 to 7.97, P<0.001) versus patients who did not undergo NCS, independent of study treatment. CONCLUSION: NCS after NSTE ACS is common and associated with more ischemic outcomes and bleeding. Vorapaxar after NSTE ACS was not associated with increased perioperative ischemic or bleeding events in patients undergoing NCS.


Assuntos
Síndrome Coronariana Aguda/complicações , Lactonas/uso terapêutico , Piridinas/uso terapêutico , Receptor PAR-1/antagonistas & inibidores , Procedimentos Cirúrgicos Operatórios/métodos , Idoso , Método Duplo-Cego , Feminino , Hemorragia/prevenção & controle , Humanos , Lactonas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Piridinas/efeitos adversos , Resultado do Tratamento
19.
Heart ; 101(19): 1554-61, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26175478

RESUMO

BACKGROUND: Randomised controlled trials have demonstrated improved outcomes with an early invasive strategy compared with routine care after fibrinolysis among patients with ST-elevation myocardial infarction. However, it remains uncertain whether specific patient subsets derive differential benefit from an early invasive strategy. METHODS: Using patient-level data from seven randomised trials, we studied the relationship between treatment assignment (early invasive vs standard care) and adverse cardiovascular events. The outcomes assessed were death/reinfarction at 30 days and at 1 year, as well as death/reinfarction/recurrent ischaemia, major bleeding and stroke at 30 days. The analyses were conducted in strata (age, sex, diabetes, prior infarction, Killip class, anterior infarction and time from symptom onset to fibrinolysis) to assess for an interaction between the stratifying variable and treatment assigned. RESULTS: There were 101 deaths and 115 recurrent infarctions at 30 days in 3010 patients. There were no strata where an invasive strategy conferred a differential treatment effect. With the exception of a marginally significant interaction between Killip class and treatment for death/reinfarction at 30 days and 1 year (p values for interaction 0.044 and 0.038, respectively), no interactions between the stratifying variables and treatment assignment were observed. CONCLUSIONS: Benefit from an early invasive strategy after fibrinolysis for ST-elevation myocardial infarction is similar across patient subgroups stratified by these clinical characteristics. Therefore, prediction of risk and benefit from an early invasive strategy after fibrinolysis for ST-elevation myocardial infarction is best achieved by global risk evaluation rather than specific patient characteristics.


Assuntos
Fibrinolíticos/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica/métodos , Tempo para o Tratamento , Idoso , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Razão de Chances , Seleção de Pacientes , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Fatores de Tempo , Resultado do Tratamento
20.
Am Heart J ; 169(6): 890-898.e1, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26027628

RESUMO

BACKGROUND: Elderly patients with ST-segment elevation myocardial infarction (STEMI) have worse outcomes and a greater risk of intracranial bleeding than nonelderly patients. Baseline characteristics, clinical outcomes, and the relationship of the tenecteplase (TNK) dose reduction to the efficacy, safety, and electrocardiographic indicators of reperfusion efficacy were evaluated in STEMI patients ≥75 years. METHODS: The STREAM trial evaluated early presenting STEMI patients who could not undergo primary percutaneous coronary intervention within 1 hour of first medical contact. Because of excess intracranial hemorrhage (ICH) in patients ≥75 years, the dose of TNK was reduced by 50%. RESULTS: Before dose amendment, there were 3 (7.1%) of 42 elderly patients with ICH; 2 of these were fatal, whereas no ICH occurred in the 93 elderly patients who received half-dose TNK postamendment. The median extent of ST-segment elevation resolution (≥50%) and proportion of patients with ≥2 mm in the electrocardiogram lead with greatest ST-segment elevation was comparable in elderly patients preamendment and postamendment (63.2% vs 56.0% and 43.6% vs 40.0%, respectively). Patients requiring rescue coronary intervention after TNK was also similar (42.9% vs 44.1%). The primary composite end point (30-day all-cause death, cardiogenic shock, congestive heart failure, and reinfarction) was 31.0% before versus 24.7% postamendment. CONCLUSIONS: Our data, from a modest-sized population of elderly STEMI patients, indicate that half-dose TNK reduces the likelihood of ICH without compromising reperfusion efficacy. These observations are hypothesis generating and warrant further confirmation in randomized clinical trials in the elderly.


Assuntos
Fibrinolíticos/administração & dosagem , Hemorragias Intracranianas/prevenção & controle , Infarto do Miocárdio/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Eletrocardiografia , Fibrinolíticos/efeitos adversos , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Radiografia , Tenecteplase , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
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