Effects of dabigatran versus warfarin on 2-year cognitive outcomes in old patients with atrial fibrillation: results from the GIRAF randomized clinical trial.

BACKGROUND: Observational studies support a role for oral anticoagulation to reduce the risk of dementia in atrial fibrillation patients, but conclusive data are lacking. Since dabigatran offers a more stable anticoagulation, we hypothesized it would reduce cognitive decline when compared to warfarin in old patients with atrial fibrillation. METHODS: The GIRAF trial was a 24-month, randomized, parallel-group, controlled, open-label, hypothesis generating trial. The trial was done in six centers including a geriatric care unit, secondary and tertiary care cardiology hospitals in São Paulo, Brazil. We included patients aged ≥ 70 years and CHA2DS2-VASc score > 1. The primary endpoint was the absolute difference in cognitive performance at 2 years. Patients were assigned 1:1 to take dabigatran (110 or 150 mg twice daily) or warfarin, controlled by INR and followed for 24 months. Patients were evaluated at baseline and at 2 years with a comprehensive and thorough cognitive evaluation protocol of tests for different cognitive domains including the Montreal Cognitive Assessment (MoCA), Mini-Mental State Exam (MMSE), a composite neuropsychological test battery (NTB), and computer-generated tests (CGNT). RESULTS: Between 2014 and 2019, 5523 participants were screened and 200 were assigned to dabigatran (N = 99) or warfarin (N = 101) treatment. After adjustment for age, log of years of education, and raw baseline score, the difference between the mean change from baseline in the dabigatran group minus warfarin group was - 0.12 for MMSE (95% confidence interval [CI] - 0.88 to 0.63; P = 0.75), 0.05 (95% CI - 0.07 to 0.18; P = 0.40) for NTB, - 0.15 (95% CI - 0.30 to 0.01; P = 0.06) for CGNT, and - 0.96 (95% CI - 1.80 to 0.13; P = 0.02) for MoCA, with higher values suggesting less cognitive decline in the warfarin group. CONCLUSIONS: For elderly patients with atrial fibrillation, and without cognitive compromise at baseline that did not have stroke and were adequately treated with warfarin (TTR of 70%) or dabigatran for 2 years, there was no statistical difference at 5% significance level in any of the cognitive outcomes after adjusting for multiple comparisons. TRIAL REGISTRATION: Cognitive Impairment Related to Atrial Fibrillation Prevention Trial (GIRAF), NCT01994265 .

Aspirin responsiveness safely lowers perioperative cardiovascular risk.

INTRODUCTION: Vascular surgeries are related to high cardiac morbidity and mortality, and the maintenance of aspirin in the perioperative period has a protective effect. The purpose of this study was to evaluate the association between preoperative platelet aggregability and perioperative cardiovascular (CV) events. METHODS: A preoperative platelet aggregation test was performed on an impedance aggregometer in response to collagen and to arachidonic acid (AA) for 191 vascular surgery patients under chronic use of aspirin. We analyzed the following CV events: acute myocardial infarction, unstable angina, isolated troponin elevation, acute ischemic stroke, reoperation, and cardiac death. Hemorrhagic events were also evaluated and classified according to the Thrombolysis In Myocardial Infarction criteria. RESULTS: The incidence of CV events was 22% (n = 42). Higher platelet response to AA was associated with CV events, so that patients in the fourth quartile (higher than 11Ω) had almost twice the incidence of CV events when compared with the three lower quartiles: 35% vs 19%; P = .025. The independent predictors of CV events were hemodynamic instability during anesthesia (odds ratio [OR], 4.12; 95% confidence interval [CI], 1.87-9.06; P < .001), dyslipidemia (OR, 3.9; 95% CI, 1.32-11.51; P = .014), preoperative anemia (OR, 2.64; 95% CI, 1.19-5.85; P = .017), and AA platelet aggregability in the upper quartile (OR, 2.48; 95% CI, 1.07-5.76; P = .034). Platelet aggregability was not associated with hemorrhagic events, even when we compared the lowest quartile of AA platelet aggregability (0-1.00 Ω) with the three upper quartiles (>1.00 Ω; OR, 0.77; 95% CI, 0.43-1.37; P = .377). CONCLUSIONS: The degree of aspirin effect on platelet aggregability maybe important in the management of perioperative CV morbidity, without increment in the bleeding toll.

Impact of the period of the day on all-cause mortality and major cardiovascular complications after arterial vascular surgeries.

BACKGROUND: Conflicting results are reported about daytime variation on mortality and cardiac outcomes after non-cardiac surgeries. In this cohort study, we evaluate whether the period of the day in which surgeries are performed may influence all-cause mortality and cardiovascular outcomes in patients undergoing non-cardiac arterial vascular procedures. METHODS: 1,267 patients who underwent non-cardiac arterial vascular surgeries between 2012 and 2018 were prospectively included in our cohort and categorized into two groups: morning (7 a.m. to 12 a.m., 79%) and afternoon/night (12:01 p.m. to 6:59 a.m. in the next day, 21%) surgeries. Primary endpoint was all-cause mortality within 30 days and one year. Secondary endpoints were the incidence of perioperative myocardial injury/infarction (PMI), and the incidence of major adverse cardiac events (MACE, including acute myocardial infarction, acute heart failure, arrhythmias, cardiovascular death) at hospital discharge. RESULTS: After adjusting for confounders in the multivariable Cox proportional regression, all-cause mortality rates at 30 days and one year were higher among those who underwent surgery in the afternoon/night (aHR 1.6 [95%CI 1.1-2.3], P = 0.015 and aHR 1.7 [95%CI 1.3-2.2], P < 0.001, respectively). Afternoon/night patients had higher incidence of PMI (aHR 1.4 [95%CI 1.1-1.7], P < 0.001). There was no significant difference in the incidence of MACE (aHR 1.3 [95%CI 0.9-1.7], P = 0.074). CONCLUSIONS: In patients undergoing arterial vascular surgery, being operated in the afternoon/night was independently associated with increased all-cause mortality rates and incidence of perioperative myocardial injury/infarction.

[Hypolipidemic therapy under special conditions: acquired immune deficiency syndrome]. / Terapia hipolipemiante em situações especiais--síndrome de imunodeficiência adquirida.

Lipid alterations can be observed early among patients with AIDS disease. Commonly, these lipid abnormalities include low HDL-C and modest increase in triglyceride plasma levels. Highly Active Anti-Retroviral Therapy (HAART) in these patients may aggravate the dyslipidemia, with notable increases in triglycerides as well as in LDL-C. There are several mechanisms proposed to explain the mixed hyperlipidemia observed in these subjects, including different steps in lipid metabolism. The importance of the treatment of dyslipidemia became evident with the increased life expectancy and reports of cardiovascular complications in these individuals. There is an insulin resistance state in patients with AIDS disease under treatment with HAART, who present with lipodystrophy, hypertriglyceridemia, low levels of HDL-C. Antiretroviral drugs are metabolized by CYP P450 3A4 and interactions with some statins, especially with simvastatin are expected to occur. Treatment with lipid-lowering agents should be based on lipid profile and coronary risk. For hypertriglyceridemias, fibrates (mainly fenofibrate or bezafibrate) should be the drugs of choice, as well as statins (mainly pravastatin). Combined treatment using fibrates plus statins are recommended for severe mixed hyperlipidemias under very close monitoring for adverse effects.

Carotid stenosis management: a review for the internist.

Stroke is one of the most important causes of mortality and morbidity worldwide and, for a long time, was the leading cause of death in developed countries. Atherothrombotic carotid stenosis is one of the most important etiologies behind this event. If properly recognized and treated, lives can be saved, as well as long-term disabilities prevented. With population aging and improvements in surgical and clinical care, patients with several comorbidities will be referred for revascularization procedures more frequently, posing a challenge for physicians. The purpose of this review is to provide internists and clinicians with information based on several studies so they can offer to their patients, the best evidence-based care, indicating appropriate medical therapy, as well as referral to a vascular surgeon, or what contraindicates endarterectomy or angioplasty, depending on individual characteristics.

Acute myocardial infarction after noncardiac surgery.

Over 230 million surgeries are performed annually worldwide, cardiac complications being the most common causes of postoperative morbidity and mortality. As life expectancy has extended worldwide, a growing number of patients with multiple comorbidities have undergone noncardiac surgeries. Consequently, cardiovascular complications associated with those procedures are expected to increase, and perioperative acute myocardial infarction (AMI) might become a frequent problem. In Brazil, the number of noncardiac surgical procedures has also increased, and approximately three million surgeries are performed annually. Despite advances in surgical and anesthetic techniques, mortality and costs related to those procedures have also increased, thus, requiring the development of strategies to reduce mortality(4). The occurrence of perioperative AMI prolongs the need for intensive care and the hospital length of stay, increases the cost of hospitalization, and reduces long-term survival. This literature review approaches the pathophysiology, incidence, diagnosis and treatment of perioperative AMI based on current evidence.

Coronary plaque rupture in patients with myocardial infarction after noncardiac surgery: frequent and dangerous.

PURPOSE: The pathophysiology of acute coronary syndromes (ACS) after noncardiac surgery is not established yet. Thrombosis over a vulnerable plaque or decreased oxygen supply secondary to anemia or hypotension may be involved. The purpose of this study was to investigate the pathophysiology of ACS complicating noncardiac surgery. METHODS: Clinical and angiographic data were prospectively recorded into a database for 120 consecutive patients that had an ACS after noncardiac surgery (PACS), for 120 patients with spontaneous ACS (SACS), and 240 patients with stable coronary artery disease (CAD). Coronary lesions with obstructions greater than 50% were classified based on two criteria: Ambrose's classification and complex morphology. The presence of Ambrose's type II or complex lesions were compared between the three groups. RESULTS: We analyzed 1470 lesions in 480 patients. In PACS group, 45% of patients had Ambrose's type II lesions vs. 56.7% in SACS group and 16.4% in stable CAD group (P<0.001). Both PACS and SACS patients had more complex lesions than patients in stable CAD group (56.7% vs. 79.2% vs. 31.8%, respectively; P<0.001). Overall, the independent predictors of plaque rupture were being in the group PACS (P<0.001, OR 2.86; CI, 1.82-4.52 for complex lesions and P<0.001, OR 3.43; CI, 2.1-5.6 for Ambrose's type II lesions) or SACS (P<0.001, OR 8.71; CI, 5.15-14.73 for complex lesions and P<0.001, OR 5.99; CI, 3.66-9.81 for Ambrose's type II lesions). CONCLUSIONS: Nearly 50% of patients with perioperative ACS have evidence of coronary plaque rupture, characterizing a type 1 myocardial infarction.

Non-cardiac surgery in developing countries: epidemiological aspects and economical opportunities--the case of Brazil.

BACKGROUND: Worldwide distribution of surgical interventions is unequal. Developed countries account for the majority of surgeries and information about non-cardiac operations in developing countries is scarce. The purpose of our study was to describe the epidemiological data of non-cardiac surgeries performed in Brazil in the last years. METHODS AND FINDINGS: This is a retrospective cohort study that investigated the time window from 1995 to 2007. We collected information from DATASUS, a national public health system database. The following variables were studied: number of surgeries, in-hospital expenses, blood transfusion related costs, length of stay and case fatality rates. The results were presented as sum, average and percentage. The trend analysis was performed by linear regression model. There were 32,659,513 non-cardiac surgeries performed in Brazil in thirteen years. An increment of 20.42% was observed in the number of surgeries in this period and nowadays nearly 3 million operations are performed annually. The cost of these procedures has increased tremendously in the last years. The increment of surgical cost was almost 200%. The total expenses related to surgical hospitalizations were more than $10 billion in all these years. The yearly cost of surgical procedures to public health system was more than $1.27 billion for all surgical hospitalizations, and in average, U$445.24 per surgical procedure. The total cost of blood transfusion was near $98 million in all years and annually approximately $10 million were spent in perioperative transfusion. The surgical mortality had an increment of 31.11% in the period. Actually, in 2007, the surgical mortality in Brazil was 1.77%. All the variables had a significant increment along the studied period: r square (r(2)) = 0.447 for the number of surgeries (P = 0.012), r(2) = 0.439 for in-hospital expenses (P = 0.014) and r(2) = 0.907 for surgical mortality (P = 0.0055). CONCLUSION: The volume of surgical procedures has increased substantially in Brazil through the past years. The expenditure related to these procedures and its mortality has also increased as the number of operations. Better planning of public health resource and strategies of investment are needed to supply the crescent demand of surgery in Brazil.

Transient global amnesia as a manifestation of acute myocardial infarction: a case of missed sudden cardiac death?

Acute myocardial infarction may lead to several clinical manifestations and many times this diagnosis is missed. Transient global amnesia (TGA) is a well-defined clinical syndrome of unknown etiology. Several mechanisms have been proposed but only trigger events have been clearly associated with the attack. We describe a case of acute myocardial infarction manifestated by TGA.

Spondylodiscitis and infectious endocarditis: a round-trip to be considered.

The association between spondylodiscitis and endocarditis was first reported in 1965 by de Sèze et al. The most common clinical picture of this association is musculoskeletal symptoms preceding endocarditis diagnosis, but we report here a case of spondylodiscitis complicating endocarditis in its late course. A 70-year-old man, with an established diagnosis of mitral valve endocarditis caused by Streptococcus intermedius, early submitted to surgical treatment because of heart failure, who had an uneventful recovery up to the 12th day of antibiotic therapy when he presented intensive backache, with tenderness in the two lower lumbar vertebras. Spondylodiscitis was confirmed by a magnetic resonance imaging and the treatment was non-esteroidal anti-inflammatory and analgetics drug, with good results, and prolongation of antibiotic treatment up to 3 months. Appropriate diagnosis of this association has important consequences, as the need of a longer antibiotic therapy course, which can range from 6 weeks to 3 months.