Post-COVID-19 Cardiopulmonary Symptoms: Predictors and Imaging Features in Patients after Hospital Discharge. / Sintomas Cardiopulmonares Pós-COVID-19: Preditores e Características de Imagem de Pacientes após a Alta Hospitalar.

BACKGROUND: Most of the evidence about the impact of the post-acute COVID-19 Syndrome (PACS) reports individual symptoms without correlations with related imaging. OBJECTIVES: To evaluate cardiopulmonary symptoms, their predictors and related images in COVID-19 patients discharged from hospital. METHODS: Consecutive patients who survived COVID-19 were contacted 90 days after discharge. The Clinic Outcome Team structured a questionnaire evaluating symptoms and clinical status (blinded for hospitalization data). A multivariate analysis was performed to address the course of COVID-19, comorbidities, anxiety, depression, and post-traumatic stress during hospitalization, and cardiac rehabilitation after discharge. The significance level was set at 5%. RESULTS: A total of 480 discharged patients with COVID-19 (age: 59±14 years, 67.5% males) were included; 22.3% required mechanical ventilation. The prevalence of patients with PACS-related cardiopulmonary symptoms (dyspnea, tiredness/fatigue, cough, and chest discomfort) was 16.3%. Several parameters of chest computed tomography and echocardiogram were similar in patients with and without cardiopulmonary symptoms. The multivariate analysis showed that PACS-related cardiopulmonary-symptoms were independently related to female sex (OR 3.023; 95% CI 1.319-6.929), in-hospital deep venous thrombosis (OR 13.689; 95% CI 1.069-175.304), elevated troponin I (OR 1.355; 95% CI 1.048-1.751) and C-reactive protein during hospitalization (OR 1.060; 95% CI 1.023-1.097) and depression (OR 6.110; 95% CI 2.254-16.558). CONCLUSION: PACS-related cardiopulmonary symptoms 90 days post-discharge are common and multifactorial. Beyond thrombotic and markers of inflammation/myocardial injury during hospitalization, female sex and depression were independently associated with cardiopulmonary-related PACS. These results highlighted the need for a multifaceted approach targeting susceptible patients.

FUNDAMENTO: A maioria da evidência sobre o impacto da síndrome COVID pós-aguda (PACS, do inglês, post-acute COVID-19 syndrome) descreve sintomas individuais sem correlacioná-los com exames de imagens. OBJETIVOS: Avaliar sintomas cardiopulmonares, seus preditores e imagens relacionadas em pacientes com COVID-19 após alta hospitalar. MÉTODOS: Pacientes consecutivos, que sobreviveram à COVID-19, foram contatados 90 dias após a alta hospitalar. A equipe de desfechos clínicos (cega quanto aos dados durante a internação) elaborou um questionário estruturado avaliando sintomas e estado clínico. Uma análise multivariada foi realizada abordando a evolução da COVID-19, comorbidades, ansiedade, depressão, e estresse pós-traumático durante a internação, e reabilitação cardíaca após a alta. O nível de significância usado nas análises foi de 5%. RESULTADOS: Foram incluídos 480 pacientes (idade 59±14 anos, 67,5% do sexo masculino) que receberam alta hospitalar por COVID-19; 22,3% necessitaram de ventilação mecânica. A prevalência de pacientes com sintomas cardiopulmonares relacionados à PACS (dispneia, cansaço/fadiga, tosse e desconforto no peito) foi de 16,3%. Vários parâmetros de tomografia computadorizada do tórax e de ecocardiograma foram similares entre os pacientes com e sem sintomas cardiopulmonares. A análise multivariada mostrou que sintomas cardiopulmonares foram relacionados de maneira independente com sexo feminino (OR 3,023; IC95% 1,319-6,929), trombose venosa profunda durante a internação (OR 13,689; IC95% 1,069-175,304), nível elevado de troponina (OR 1,355; IC95% 1,048-1,751) e de proteína C reativa durante a internação (OR 1,060; IC95% 1,023-1,097) e depressão (OR 6,110; IC95% 2,254-16,558). CONCLUSÃO: Os sintomas cardiopulmonares relacionados à PACS 90 dias após a alta hospitalar são comuns e multifatoriais. Além dos marcadores trombóticos, inflamatórios e de lesão miocárdica durante a internação, sexo feminino e depressão foram associados independentemente com sintomas cardiopulmonares relacionados à PACS. Esses resultados destacaram a necessidade de uma abordagem multifacetada direcionada a pacientes susceptíveis.

Long-term mortality after acute coronary syndromes among patients with normal, mildly reduced, or reduced ejection fraction.

AIMS: Left ventricular ejection fraction (LVEF) ≤ 40% is a well-established risk factor for mortality after acute coronary syndromes (ACS). However, the long-term prognostic impact of mildly reduced ejection fraction (EF) (LVEF 41-49%) after ACS remains less clear. METHODS AND RESULTS: This was a retrospective study enrolling patients admitted with ACS included in a single-centre databank. LVEF was assessed by echocardiography during index hospitalization. Patients were divided in the following categories according to LVEF: normal (LVEF ≥ 50%), mildly reduced (LVEF 41-49%), and reduced (LVEF ≤ 40%). The endpoint of interest was all-cause death after hospital discharge. A multivariable Cox model was used to adjust for confounders. A total of 3200 patients were included (1952 with normal EF, 375 with mildly reduced EF, and 873 with reduced EF). The estimated cumulative incidence rates of mortality at 10 years for patients with normal, mildly reduced, and reduced EF were 24.8%, 33.5%, and 41.3%, respectively. After adjustments, the presence of reduced EF was associated with higher mortality compared with normal EF [adjusted hazard ratio (HR) 1.64; 95% confidence interval (CI) 1.36-1.96; P < 0.001], as was mildly reduced EF compared with normal EF (adjusted HR 1.33; 95% CI 1.05-1.68; P = 0.019). The presence of reduced EF was not associated with a statistically significantly higher mortality compared with mildly reduced EF (adjusted HR 1.23; 95% CI 0.96-1.57; P = 0.095). CONCLUSIONS: In patients with ACS, mildly reduced EF measured in the acute phase was associated with higher long-term mortality compared with patients with normal EF. These data emphasize the importance of anti-remodelling therapies for ACS patients who have LVEF in the mildly reduced range.

Sintomas Cardiopulmonares Pós-COVID-19: Preditores e Características de Imagem de Pacientes após a Alta Hospitalar / Post-COVID-19 Cardiopulmonary Symptoms: Predictors and Imaging Features in Patients after Hospital Discharge

Resumo Fundamento A maioria da evidência sobre o impacto da síndrome COVID pós-aguda (PACS, do inglês, post-acute COVID-19 syndrome) descreve sintomas individuais sem correlacioná-los com exames de imagens. Objetivos Avaliar sintomas cardiopulmonares, seus preditores e imagens relacionadas em pacientes com COVID-19 após alta hospitalar. Métodos Pacientes consecutivos, que sobreviveram à COVID-19, foram contatados 90 dias após a alta hospitalar. A equipe de desfechos clínicos (cega quanto aos dados durante a internação) elaborou um questionário estruturado avaliando sintomas e estado clínico. Uma análise multivariada foi realizada abordando a evolução da COVID-19, comorbidades, ansiedade, depressão, e estresse pós-traumático durante a internação, e reabilitação cardíaca após a alta. O nível de significância usado nas análises foi de 5%. Resultados Foram incluídos 480 pacientes (idade 59±14 anos, 67,5% do sexo masculino) que receberam alta hospitalar por COVID-19; 22,3% necessitaram de ventilação mecânica. A prevalência de pacientes com sintomas cardiopulmonares relacionados à PACS (dispneia, cansaço/fadiga, tosse e desconforto no peito) foi de 16,3%. Vários parâmetros de tomografia computadorizada do tórax e de ecocardiograma foram similares entre os pacientes com e sem sintomas cardiopulmonares. A análise multivariada mostrou que sintomas cardiopulmonares foram relacionados de maneira independente com sexo feminino (OR 3,023; IC95% 1,319-6,929), trombose venosa profunda durante a internação (OR 13,689; IC95% 1,069-175,304), nível elevado de troponina (OR 1,355; IC95% 1,048-1,751) e de proteína C reativa durante a internação (OR 1,060; IC95% 1,023-1,097) e depressão (OR 6,110; IC95% 2,254-16,558). Conclusão Os sintomas cardiopulmonares relacionados à PACS 90 dias após a alta hospitalar são comuns e multifatoriais. Além dos marcadores trombóticos, inflamatórios e de lesão miocárdica durante a internação, sexo feminino e depressão foram associados independentemente com sintomas cardiopulmonares relacionados à PACS. Esses resultados destacaram a necessidade de uma abordagem multifacetada direcionada a pacientes susceptíveis.

Abstract Background Most of the evidence about the impact of the post-acute COVID-19 Syndrome (PACS) reports individual symptoms without correlations with related imaging. Objectives To evaluate cardiopulmonary symptoms, their predictors and related images in COVID-19 patients discharged from hospital. Methods Consecutive patients who survived COVID-19 were contacted 90 days after discharge. The Clinic Outcome Team structured a questionnaire evaluating symptoms and clinical status (blinded for hospitalization data). A multivariate analysis was performed to address the course of COVID-19, comorbidities, anxiety, depression, and post-traumatic stress during hospitalization, and cardiac rehabilitation after discharge. The significance level was set at 5%. Results A total of 480 discharged patients with COVID-19 (age: 59±14 years, 67.5% males) were included; 22.3% required mechanical ventilation. The prevalence of patients with PACS-related cardiopulmonary symptoms (dyspnea, tiredness/fatigue, cough, and chest discomfort) was 16.3%. Several parameters of chest computed tomography and echocardiogram were similar in patients with and without cardiopulmonary symptoms. The multivariate analysis showed that PACS-related cardiopulmonary-symptoms were independently related to female sex (OR 3.023; 95% CI 1.319-6.929), in-hospital deep venous thrombosis (OR 13.689; 95% CI 1.069-175.304), elevated troponin I (OR 1.355; 95% CI 1.048-1.751) and C-reactive protein during hospitalization (OR 1.060; 95% CI 1.023-1.097) and depression (OR 6.110; 95% CI 2.254-16.558). Conclusion PACS-related cardiopulmonary symptoms 90 days post-discharge are common and multifactorial. Beyond thrombotic and markers of inflammation/myocardial injury during hospitalization, female sex and depression were independently associated with cardiopulmonary-related PACS. These results highlighted the need for a multifaceted approach targeting susceptible patients.

Effects of DPP4 Inhibitor in Platelet Reactivity and Other Cardiac Risk Markers in Patients with Type 2 Diabetes and Acute Myocardial Infarction.

BACKGROUND: The management of acute myocardial infarction (AMI) presents several challenges in patients with diabetes, among them the higher rate of recurrent thrombotic events, hyperglycemia and risk of subsequent heart failure (HF). The objective of our study was to evaluate effects of DPP-4 inhibitors (DPP-4i) on platelet reactivity (main objective) and cardiac risk markers. METHODS: We performed a single-center double-blind randomized trial. A total of 70 patients with type 2 diabetes (T2DM) with AMI Killip ≤2 on dual-antiplatelet therapy (aspirin plus clopidogrel) were randomized to receive sitagliptin 100 mg or saxagliptin 5 mg daily or matching placebo. Platelet reactivity was assessed at baseline, 4 days (primary endpoint) and 30 days (secondary endpoint) after randomization, using VerifyNow Aspirin™ assay, expressed as aspirin reaction units (ARUs); B-type natriuretic peptide (BNP) in pg/mL was assessed at baseline and 30 days after (secondary endpoint). RESULTS: Mean age was 62.6 ± 8.8 years, 45 (64.3%) male, and 52 (74.3%) of patients presented with ST-segment elevation MI. For primary endpoint, there were no differences in mean platelet reactivity (p = 0.51) between the DPP-4i (8.00 {-65.00; 63.00}) and placebo (-14.00 {-77.00; 52.00}) groups, as well in mean BNP levels (p = 0.14) between DPP-4i (-36.00 {-110.00; 15.00}) and placebo (-13.00 {-50.00; 27.00}). There was no difference between groups in cardiac adverse events. CONCLUSIONS: DPP4 inhibitor did not reduce platelet aggregation among patients with type 2 diabetes hospitalized with AMI. Moreover, the use of DPP-4i did not show an increase in BNP levels or in the incidence of cardiac adverse events. These findings suggests that DPP-4i could be an option for management of T2DM patients with acute MI.

Effects of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients with Acute Myocardial Infarction.

INTRODUCTION: Clopidogrel has been demonstrated to be effective in improving coronary microcirculation (CM) among patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolytics. Ticagrelor is a more potent adenosine diphosphate (ADP) receptor blocker proven to be superior to clopidogrel among patients with acute coronary syndromes. The present study aimed to compare the effects of ticagrelor and clopidogrel on CM in patients with STEMI treated with fibrinolytics. METHODS: The present study prospectively included 48 patients participating in the TREAT trial, which randomly assigned patients with STEMI undergoing fibrinolysis to ticagrelor versus clopidogrel. The primary endpoint of this study was the evaluation of the CM using the global myocardial perfusion score index (global MPSI) obtained by myocardial contrast echocardiography (MCE). Platelet aggregation to ADP was evaluated by Multiplate® and expressed as area under the curve (AUC). RESULTS: The global MPSI demonstrated no differences between the groups [mean 1.4 (1.2-1.5) in the ticagrelor group and 1.2 (1.2-1.5) in the clopidogrel group (p = 0.41)]. Platelet aggregability was lower in the ticagrelor group (18.1 ± 9.7 AUC), compared to the clopidogrel group (26.1 ± 12.5 AUC, p = 0.01). CONCLUSION: We found no improvement in coronary microcirculation with ticagrelor compared to clopidogrel among patients with STEMI treated with fibrinolytics, despite the fact that platelet aggregation to ADP was lower with ticagrelor. CLINICAL TRIALS REGISTRATION: NCT03104062.

Platelet Reactivity and Coagulation Markers in Patients with COVID-19.

INTRODUTION: COVID-19 is associated with an increased risk of thrombotic events. However, the contribution of platelet reactivity (PR) to the aetiology of the increased thrombotic risk associated with COVID-19 remains unclear. Our aim was to evaluate PR in stable patients diagnosed with COVID-19 and hospitalized with respiratory symptoms (mainly dyspnoea and dry cough), in comparison with a control group comprised of non-hospitalized healthy controls. METHODS: Observational, case control study that included patients with confirmed COVID-19 (COVID-19 group, n = 60) and healthy individuals matched by age and sex (control group, n = 60). Multiplate electrode aggregometry (MEA) tests were used to assess PR with adenosine diphosphate (MEA-ADP, low PR defined as < 53 AUC), arachidonic acid (MEA-ASPI, low PR < 86 AUC) and thrombin receptor-activating peptide 6 (MEA-TRAP, low PR < 97 AUC) in both groups. RESULTS: The rates of low PR with MEA-ADP were 27.5% in the COVID-19 group and 21.7% in the control group (OR = 1.60, p = 0.20); with MEA-ASPI, the rates were, respectively, 37.5% and 22.5% (OR = 3.67, p < 0.001); and with MEA-TRAP, the incidences were 48.5% and 18.8%, respectively (OR = 9.58, p < 0.001). Levels of D-dimer, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) were higher in the COVID-19 group in comparison with the control group (all p < 0.05). Thromboelastometry was utilized in a subgroup of patients and showed a hypercoagulable state in the COVID-19 group. CONCLUSION: Patients hospitalized with non-severe COVID-19 had lower PR compared to healthy controls, despite having higher levels of D-dimer, fibrinogen, and PAI-1, and hypercoagulability by thromboelastometry. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04447131.

Platelet Reactivity in Patients With Acute Coronary Syndromes Awaiting Surgical Revascularization.

BACKGROUND: Dual antiplatelet therapy is recommended for patients with acute coronary syndromes (ACS). Approximately 10% to 15% of these patients will undergo coronary artery bypass graft (CABG) surgery for index events, and current guidelines recommend stopping clopidogrel at least 5 days before CABG. This waiting time has clinical and economic implications. OBJECTIVES: This study aimed to evaluate if a platelet reactivity-based strategy is noninferior to standard of care for 24-h post-CABG bleeding. METHODS: In this randomized, open label noninferiority trial, 190 patients admitted with ACS with indications for CABG and on aspirin and P2Y12 receptor inhibitors, were assigned to either control group, P2Y12 receptor inhibitor withdrawn 5 to 7 days before CABG, or intervention group, daily measurements of platelet reactivity by Multiplate analyzer (Roche Diagnostics GmbH, Vienna, Austria) with CABG planned the next working day after platelet reactivity normalization (pre-defined as ≥46 aggregation units). RESULTS: Within the first 24 h of CABG, the median chest tube drainage was 350 ml (interquartile range [IQR]: 250 to 475 ml) and 350 ml (IQR: 255 to 500 ml) in the intervention and control groups, respectively (p for noninferiority <0.001). The median waiting period between the decision to undergo CABG and the procedure was 112 h (IQR: 66 to 142 h) and 136 h (IQR: 112 to 161 h) (p < 0.001), respectively. In the intention-to-treat analysis, a 6.4% decrease in the median in-hospital expenses was observed in the intervention group (p = 0.014), with 11.2% decrease in the analysis per protocol (p = 0.003). CONCLUSIONS: A strategy based on platelet reactivity-guided is noninferior to the standard of care in patients with ACS awaiting CABG regarding peri-operative bleeding, significantly shortens the waiting time to CABG, and decreases hospital expenses. (Evaluation of Platelet Aggregability in the Release of CABG in Patients With ACS With DAPT; NCT02516267).

Factors associated with actively working in the very long-term following acute coronary syndrome.

OBJECTIVES: Returning to work after an episode of acute coronary syndrome (ACS) is challenging for many patients, and has both personal and social impacts. There are limited data regarding the working status in the very long-term after ACS. METHODS: We retrospectively analyzed 1,632 patients who were working prior to hospitalization for ACS in a quaternary hospital and were followed-up for up to 17 years. Adjusted models were developed to analyze the variables independently associated with actively working at the last contact, and a prognostic predictive index for not working at follow-up was developed. RESULTS: The following variables were significantly and independently associated with actively working at the last contact: age>median (hazard-ratio [HR], 0.76, p<0.001); male sex (HR, 1.52, p<0.001); government health insurance (HR, 1.36, p<0.001); history of angina (HR, 0.69, p<0.001) or myocardial infarction (MI) (HR, 0.76, p=0.005); smoking (HR, 0.81, p=0.015); ST-elevation MI (HR, 0.81, p=0.021); anterior-wall MI (HR, 0.75, p=0.001); non-primary percutaneous coronary intervention (PCI) (HR, 0.77, p=0.002); fibrinolysis (HR, 0.61, p<0.001); cardiogenic shock (HR, 0.60, p=0.023); statin (HR, 3.01, p<0.001), beta-blocker (HR, 1.26, p=0.020), angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blocker (ARB) (HR, 1.37, p=0.001) at hospital discharge; and MI at follow-up (HR, 0.72, p=0.001). The probability of not working at the last contact ranged from 24.2% for patients with no variables, up to 80% for patients with six or more variables. CONCLUSIONS: In patients discharged after ACS, prior and in-hospital clinical variables, as well as the quality of care at discharge, have a great impact on the long-term probability of actively working.

Factors associated with actively working in the very long-term following acute coronary syndrome

OBJECTIVES: Returning to work after an episode of acute coronary syndrome (ACS) is challenging for many patients, and has both personal and social impacts. There are limited data regarding the working status in the very long-term after ACS. METHODS: We retrospectively analyzed 1,632 patients who were working prior to hospitalization for ACS in a quaternary hospital and were followed-up for up to 17 years. Adjusted models were developed to analyze the variables independently associated with actively working at the last contact, and a prognostic predictive index for not working at follow-up was developed. RESULTS: The following variables were significantly and independently associated with actively working at the last contact: age>median (hazard-ratio [HR], 0.76, p<0.001); male sex (HR, 1.52, p<0.001); government health insurance (HR, 1.36, p<0.001); history of angina (HR, 0.69, p<0.001) or myocardial infarction (MI) (HR, 0.76, p=0.005); smoking (HR, 0.81, p=0.015); ST-elevation MI (HR, 0.81, p=0.021); anterior-wall MI (HR, 0.75, p=0.001); non-primary percutaneous coronary intervention (PCI) (HR, 0.77, p=0.002); fibrinolysis (HR, 0.61, p<0.001); cardiogenic shock (HR, 0.60, p=0.023); statin (HR, 3.01, p<0.001), beta-blocker (HR, 1.26, p=0.020), angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blocker (ARB) (HR, 1.37, p=0.001) at hospital discharge; and MI at follow-up (HR, 0.72, p=0.001). The probability of not working at the last contact ranged from 24.2% for patients with no variables, up to 80% for patients with six or more variables. CONCLUSIONS: In patients discharged after ACS, prior and in-hospital clinical variables, as well as the quality of care at discharge, have a great impact on the long-term probability of actively working.

Relation of High Lipoprotein (a) Concentrations to Platelet Reactivity in Individuals with and Without Coronary Artery Disease.

INTRODUCTION: Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease (CAD). To the best of our knowledge, this is the first study addressing the relationship between Lp(a) and platelet reactivity in primary and secondary prevention. METHODS: Lp(a) was evaluated in 396 individuals with (82.3%) and without (17.7%) obstructive CAD. The population was divided into two groups according to Lp(a) concentrations with a cutoff value of 50 mg/dL. The primary objective was to evaluate the association between Lp(a) and adenosine diphosphate (ADP)-induced platelet reactivity using the VerifyNow™ P2Y12 assay. Platelet reactivity was also induced by arachidonic acid and collagen-epinephrine (C-EPI) and assessed by Multiplate™, platelet function analyzer™ 100 (PFA-100), and light transmission aggregometry (LTA) assays. Secondary objectives included the assessment of the primary endpoint in individuals with or without CAD. RESULTS: Overall, 294 (74.2%) individuals had Lp(a) < 50 mg/dL [median (IQR) 13.2 (5.8-27.9) mg/dL] and 102 (25.8%) had Lp(a) ≥ 50 mg/dL [82.5 (67.6-114.5) mg/dL], P < 0.001. Univariate analysis in the entire population revealed no differences in ADP-induced platelet reactivity between individuals with Lp(a) ≥ 50 mg/dL (249.4 ± 43.8 PRU) versus Lp(a) < 50 mg/dL (243.1 ± 52.2 PRU), P = 0.277. Similar findings were present in individuals with (P = 0.228) and without (P = 0.669) CAD, and regardless of the agonist used or method of analysis (all P > 0.05). Finally, multivariable analysis did not show a significant association between ADP-induced platelet reactivity and Lp(a) ≥ 50 mg/dL [adjusted OR = 1.00 [(95% CI 0.99-1.01), P = 0.590]. CONCLUSION: In individuals with or without CAD, Lp(a) ≥ 50 mg/dL was not associated with higher platelet reactivity.

Influence of Direct Thrombin Inhibitor and Low Molecular Weight Heparin on Platelet Function in Patients with Coronary Artery Disease: A Prospective Interventional Trial.

INTRODUCTION: The interaction between anticoagulants and platelet function is complex. Previous publications showed mixed results regarding the role of heparins in platelet aggregation. On the other hand, the direct thrombin inhibitor (DTI) dabigatran might enhance the risk of myocardial infarction in patients with atrial fibrillation, which could be related to increased platelet aggregability. METHODS: This was a prospective, interventional study of patients with chronic coronary artery disease (CAD) taking low-dose aspirin. The objective of the current study was to compare the effects of dabigatran versus enoxaparin on platelet aggregability. Subjects initially were on orally administered dabigatran for 5 days followed by subcutaneously administered enoxaparin after a 30-day washout period. Platelet function was assessed at baseline and after each intervention by multiple electrode aggregometry (MEA-ASPI) (primary endpoint), serum thromboxane B2 (TXB2), VerifyNow Aspirin™, and coagulation tests (secondary endpoints). RESULTS: Compared to baseline MEA-ASPI values, dabigatran increased platelet aggregation while enoxaparin decreased platelet aggregation (+ 5 U ± 24.1 vs - 6 U ± 22.2, respectively, p = 0.012). The TXB2 assay showed the same pattern (+ 2 pg/ml for dabigatran vs - 13 pg/ml for enoxaparin, p = 0.011). None of the additional tests showed significant differences between the groups. Individually, compared to baseline TXB2 results, enoxaparin significantly decreased platelet activation [33 (16.5-95) pg/mL vs 20 (10-52) pg/mL, respectively, p = 0.026], but no significant differences were observed with dabigatran. CONCLUSIONS: DTI and anti-Xa drugs exert opposite effects on platelet function. A significant decrease in platelet activation through COX1 (also known as prostaglandin G/H synthase 1) was observed with enoxaparin, but no significant differences in platelet function were observed with dabigatran. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02389582.

Increased bodyweight and inadequate response to aspirin in individuals with coronary artery disease.

Recent reports have suggested that aspirin effect might be influenced by bodyweight, with decreased efficacy in heavier individuals. We investigated the influence of bodyweight on aspirin pharmacodynamics in two independent datasets of patients taking non-enteric coated aspirin 100 mg QD for coronary artery disease (CAD). In the first dataset, 368 patients had their platelet aggregation assessed using VerifyNow Aspirin and measured in Aspirin Reaction Units (ARU). In the second dataset, 70 patients had serum thromboxane B2 (TXB2) dosage assessed by an ELISA assay and measured in pg/mL. Platelet aggregation was independently associated with bodyweight, with 8.41 (95% CI 1.86-14.97; adjusted p-value = 0.012) increase in ARU for every 10 kg. Furthermore, the rate of non-response to aspirin (defined as ARU ≥ 550) was significantly associated with increased bodyweight (adjusted p-value = 0.007), with OR = 1.23 (95% CI 1.06-1.42) for every 10 kg. Similar results were found considering body mass index (in kg/m2), with 15.5 (95% CI 5.0 to 25.9; adjusted p-value = 0.004) increase in ARU for every 10 kg and non-response OR = 1.43 (95% CI 1.13 to 1.81, adjusted p-value = 0.003) for every 5 kg/m2. Moreover, serum TXB2 was higher in patients weighting more than 70 kg (222.6 ± 62.9 versus 194.9 ± 61.9 pg/mL; adjusted p-value = 0.018). In two different datasets of patients with CAD on non-enteric coated aspirin 100 mg QD, increased bodyweight was independently associated with impaired response to aspirin.

The Use of Oral Beta-Blockers and Clinical Outcomes in Patients with Non-ST-Segment Elevation Acute Coronary Syndromes: a Long-Term Follow-Up Study.

BACKGROUND: The role of beta-blockers in patients with acute coronary syndromes is mainly derived from studies including patients with ST-segment elevation myocardial infarction. Little is known about the use of beta-blockers and associated long-term clinical outcomes in patients with non-ST-elevation acute coronary syndromes (NSTEACS). METHODS: We analyzed short- and long-term clinical outcomes of 2921 patients with NSTEACS using or not oral beta-blockers in the first 24 h of the acute coronary syndromes (ACS) presentation. The association between beta-blocker use and mortality was assessed using a propensity score adjusted analysis (N = 1378). RESULTS: Patients starting oral beta-blockers in the first 24 h of hospitalization, compared with patients who did not, had lower rates of in-hospital mortality (OR = 0.52, 95% CI 0.33 to 0.74, P = 0.002) and higher mean survival times in the long-term follow-up (11.86±0.4 years vs. 9.92±0.39 years, P < 0.001). CONCLUSION: The use of beta-blockers in the first 24 h of patients presenting with NSTEACS was associated with better in-hospital and long-term mortality outcomes.

Ticagrelor for the prevention of ischemic events in patients with prior myocardial infarction and peripheral artery disease.

INTRODUCTION: Cardiovascular disease (CVD) is the main cause of death in the world. Coronary artery disease (CAD) is the most common form of CVD presentation, but the prevalence of peripheral artery disease (PAD) is increasing. Patients with polyvascular disease comprise a very high-risk population that has been infrequently studied. Areas covered: The authors review the current evidence of the efficacy and safety of ticagrelor in the setting of acute coronary syndrome and stable patients post-MI with and without PAD and summarize its pharmacokinetics, pharmacodynamics, and regulatory issues. Expert opinion: Randomized studies showed that ticagrelor is superior to clopidogrel in patients with acute coronary syndromes, and is superior to placebo in the chronic phase (>1 year) post-myocardial infarction. Sub-analyses of these studies suggest that patients with myocardial infarction and PAD, compared to patients without these characteristics, may have greater benefit with ticagrelor. Nonetheless, the global evidence about the role of ticagrelor in patients with myocardial infarction and PAD remains relatively sparse, and a prospective randomized trial testing this hypothesis would be necessary to provide more definite data regarding the efficacy and safety of ticagrelor in this very high-risk population.

The role of invasive therapies in elderly patients with acute myocardial infarction.

INTRODUCTION: In elderly patients with acute myocardial infarction, very little is known about the role of surgical myocardial revascularization and percutaneous coronary intervention (invasive therapies--IT), especially in the context of long-term outcomes after hospital discharge. METHODS: We analyzed 1588 patients with MI who had been included prospectively in a databank and followed for up to 7.5 years. In this population, 548 patients were >70 years old (elderly group--EG), and 1040 were <70 years of age (younger group--YG); 1088 underwent IT during hospitalization, and the remaining 500 were treated medically (conservative therapy--CT). Patients were monitored either by visit or by phone at least once a year. A standard questionnaire was administered to all patients. The impact of IT was analyzed with both non-adjusted and adjusted models. RESULTS: By the end of the follow-up period, the survival rates for the IT and CT groups were, respectively, 71.9% versus 47.2% in the global population (hazard ratio=0.55, P<0.001), 81.5% versus 66.6% in the YG (hazard ratio=0.68, P=0.018) and 48.8% versus 20.3% in the EG (hazard ratio=0.58, P<0.001). In the adjusted models, the hazard ratios were 0.62 (P<0.001) in the global population, 0.74 in the YG (P=0.073) and 0.64 (P=0.001) in the EG. CONCLUSION: Long-term follow-up of patients with myocardial infarction revealed that IT during the in-hospital phase was at least as effective in elderly patients as in younger patients.

The role of invasive therapies in elderly patients with acute myocardial infarction

INTRODUCTION: In elderly patients with acute myocardial infarction, very little is known about the role of surgical myocardial revascularization and percutaneous coronary intervention (invasive therapies - IT), especially in the context of long-term outcomes after hospital discharge. METHODS: We analyzed 1588 patients with MI who had been included prospectively in a databank and followed for up to 7.5 years. In this population, 548 patients were ¡Ý70 years old (elderly group - EG), and 1040 were <70 years of age (younger group - YG); 1088 underwent IT during hospitalization, and the remaining 500 were treated medically (conservative therapy - CT). Patients were monitored either by visit or by phone at least once a year. A standard questionnaire was administered to all patients. The impact of IT was analyzed with both non-adjusted and adjusted models. RESULTS: By the end of the follow-up period, the survival rates for the IT and CT groups were, respectively, 71.9% versus 47.2% in the global population (hazard ratio=0.55, P<0.001), 81.5% versus 66.6% in the YG (hazard ratio=0.68, P=0.018) and 48.8% versus 20.3% in the EG (hazard ratio=0.58, P<0.001). In the adjusted models, the hazard ratios were 0.62 (P<0.001) in the global population, 0.74 in the YG (P=0.073) and 0.64 (P=0.001) in the EG. CONCLUSION: Long-term follow-up of patients with myocardial infarction revealed that IT during the in-hospital phase was at least as effective in elderly patients as in younger patients.

Role of oral blockade of platelet glycoprotein IIb/IIIa on neutrophil activation in patients with acute coronary syndromes.

Orbofiban is a unique antiplatelet agent that inhibits the binding of fibrinogen to gycoprotein (GP) IIb/IIIa integrin receptors and thus prevents platelet aggregation induced by various agents. However, recent studies indicate that treatment with orbofiban does not reduce the incidence of recurrent ischemic events. The mechanisms underlying the lack of benefit of orbofiban in patients with acute coronary syndromes are not completely clear. The purpose of this study was to characterize the effects of orbofiban on cellular activation (neutrophil superoxide generation) and surface expression of adhesion molecules of circulating neutrophils (CD18, CD11b, and L-selectin) and platelets (P-selectin and GP IIb/IIIa) in patients with acute coronary syndromes. After 5-7 days, orbifiban (50 mg BID) did not reduce PMN adhesion molecule expression and ex vivo-stimulated PMN superoxide generation--as was observed in the placebo group, without orbofiban. In contrast, orbofiban induced marked reductions in GP IIb/IIIa and P-selectin expressions after 5-7 days of treatment. The sustained neutrophil activation observed with orbofiban may have a role on the recurrent thrombotic events observed with orbofiban treatment in the OPUS-TIMI 16 trial.

Primary coronary angioplasty in a nonagenarian.

A woman aged 98 years entered the tertiary hospital service with a picture of acute myocardial infarction of the extensive anterior wall, which began 4 hours earlier. Due to the large myocardial risk area suggested by the electrocardiogram, the patient was taken to the hemodynamics laboratory for the performance of emergency coronary arteriography, which revealed occlusion in the proximal third of the anterior descending artery. Primary angioplasty followed by stent grafting was successfully performed. The patient had a satisfactory evolution (Killip I) and was discharged from the hospital on the seventh postinfarction day. We discuss here aspects of thrombolysis and coronary percutaneous interventions in the aged.

Angioplastia coronariana primária em nonagenária / Primary coronary angioplasty in a nonagenarian

A woman aged 98 years entered the tertiary hospital service with a picture of acute myocardial infarction of the extensive anterior wall, which began 4 hours earlier. Due to the large myocardial risk area suggested by the electrocardiogram, the patient was taken to the hemodynamics laboratory for the performance of emergency coronary arteriography, which revealed occlusion in the proximal third of the anterior descending artery. Primary angioplasty followed by stent grafting was successfully performed. The patient had a satisfactory evolution (Killip I) and was discharged from the hospital on the seventh postinfarction day. We discuss here aspects of thrombolysis and coronary percutaneous interventions in the aged