RESUMO
The first international guidance on antithrombotic therapy in the elderly came from the European Society of Cardiology Working Group on Thrombosis in 2015. This same group has updated its previous report on antiplatelet and anticoagulant drugs for older patients with acute or chronic coronary syndromes, atrial fibrillation, or undergoing surgery or procedures typical of the elderly (transcatheter aortic valve implantation and left atrial appendage closure). The aim is to provide a succinct but comprehensive tool for readers to understand the bases of antithrombotic therapy in older patients, despite the complexities of comorbidities, comedications and uncertain ischaemic- vs. bleeding-risk balance. Fourteen updated consensus statements integrate recent trial data and other evidence, with a focus on high bleeding risk. Guideline recommendations, when present, are highlighted, as well as gaps in evidence. Key consensus points include efforts to improve medical adherence through deprescribing and polypill use; adoption of universal risk definitions for bleeding, myocardial infarction, stroke and cause-specific death; multiple bleeding-avoidance strategies, ranging from gastroprotection with aspirin use to selection of antithrombotic-drug composition, dosing and duration tailored to multiple variables (setting, history, overall risk, age, weight, renal function, comedications, procedures) that need special consideration when managing older adults.
Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Substituição da Valva Aórtica Transcateter , Humanos , Idoso , Fibrinolíticos/efeitos adversos , Resultado do Tratamento , Aspirina/efeitos adversos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Anticoagulantes , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/tratamento farmacológico , Fibrilação Atrial/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversosAssuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Piridinas/efeitos adversos , Varfarina , Átrios do Coração , Tiazóis/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/efeitos adversos , Anticoagulantes , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do TratamentoAssuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Hirudinas , Heparina , Fragmentos de Peptídeos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Antitrombinas/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Resultado do TratamentoRESUMO
Several lines of evidence are consistent with the hypothesis that activated platelets contribute to colorectal tumorigenesis and metastatization through direct cell-cell interactions and the release of different lipid and protein mediators, and microvesicles. This review examines the clinical pharmacology of low-dose aspirin as a basis for discussing the mechanisms underlying the contribution of platelets to neoplastic transformation and progression of cancer via the development of metastases.
Assuntos
Aspirina/uso terapêutico , Neoplasias/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Animais , Humanos , Metástase Neoplásica , Neoplasias/metabolismo , Neoplasias/patologiaAssuntos
Fármacos Cardiovasculares , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Prevenção Secundária , Fármacos Cardiovasculares/uso terapêutico , Combinação de Medicamentos , Doenças Cardiovasculares/prevenção & controle , Anti-Hipertensivos , Adesão à MedicaçãoAssuntos
Fibrinolíticos/uso terapêutico , Trombose/tratamento farmacológico , Administração Oral , Fatores Etários , Anticoagulantes/uso terapêutico , Fatores de Coagulação Sanguínea/metabolismo , Fibrinolíticos/farmacocinética , Previsões , Hemorragia/prevenção & controle , Humanos , Infusões Parenterais , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Embolia Pulmonar/tratamento farmacológico , Antagonistas do Receptor Purinérgico P2Y/administração & dosagemRESUMO
Although the improved control of hyperglycaemia and other cardiovascular risk factors was associated with a parallel decline of atherosclerotic cardiovascular disease (ASCVD) and death in both type 1 (T1) and type 2 (T2) diabetes mellitus (DM), the burden of death and hospitalization for ASCVD remains significantly higher by about 2-fold versus the matched non-DM population. Life style interventions, such as physical activity and healthy diet, and drugs, such as statins and low-dose aspirin, may have beneficial effects by targeting one or multiple pathways responsible for accelerated atherosclerosis and its thrombotic complications. The debate on the benefit-risk balance of primary cardiovascular prevention with aspirin has been especially vivacious over the past two years, following the publication of three large randomized, placebo-controlled, primary prevention trials in different settings, spanning from healthy elderly to DM subjects. The aim of this review is to discuss the pathophysiological, pharmacological and clinical evidence supporting the appropriate use of low-dose aspirin in DM, within the context of the current multifactorial approach to primary cardiovascular prevention.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Prevenção Primária/métodos , Idoso , Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , MasculinoAssuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 1/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Angiopatias Diabéticas/prevenção & controle , Estado Pré-Diabético/prevenção & controle , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/diagnóstico , Dieta , Exercício Físico/fisiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Assistência Centrada no Paciente , Fumar/efeitos adversos , Prevenção do Hábito de Fumar , Adulto JovemRESUMO
BACKGROUND: Gastroprotectant drugs are used for the prevention and treatment of peptic ulcer disease and might reduce its associated complications, but reliable estimates of the effects of gastroprotectants in different clinical settings are scarce. We aimed to examine the effects of proton-pump inhibitors (PPIs), prostaglandin analogues, and histamine-2 receptor antagonists (H2RAs) in different clinical circumstances by doing meta-analyses of tabular data from all relevant unconfounded randomised trials of gastroprotectant drugs. METHODS: We searched MEDLINE and Embase from Jan 1, 1950, to Dec 31, 2015, to identify unconfounded, randomised trials of a gastroprotectant drug (defined as a PPI, prostaglandin analogue, or H2RA) versus control, or versus another gastroprotectant. Two independent researchers reviewed the search results and extracted the prespecified outcomes and key characteristics for each trial. We did meta-analyses of the effects of gastroprotectant drugs on ulcer development, bleeding, and mortality overall, according to the class of gastroprotectant, and according to the individual drug within a gastroprotectant class. FINDINGS: We identified comparisons of gastroprotectant versus control in 849 trials (142â485 participants): 580 prevention trials (110â626 participants), 233 healing trials (24â033 participants), and 36 trials for the treatment of acute upper gastrointestinal bleeding (7826 participants). Comparisons of one gastroprotectant drug versus another were available in 345 trials (64â905 participants), comprising 160 prevention trials (32â959 participants), 167 healing trials (28â306 participants), and 18 trials for treatment of acute upper gastrointestinal bleeding (3640 participants). The median number of patients in each trial was 78 (IQR 44·0-210·5) and the median duration was 1·4 months (0·9-2·8). In prevention trials, gastroprotectant drugs reduced development of endoscopic ulcers (odds ratio [OR] 0·27, 95% CI 0·25-0·29; p<0·0001), symptomatic ulcers (0·25, 0·22-0·29; p<0·0001), and upper gastrointestinal bleeding (0·40, 0·32-0·50; p<0·0001), but did not significantly reduce mortality (0·85, 0·69-1·04; p=0·11). Larger proportional reductions in upper gastrointestinal bleeding were observed for PPIs than for other gastroprotectant drugs (PPIs 0·21, 99% CI 0·12-0·36; prostaglandin analogues 0·63, 0·35-1·12; H2RAs 0·49, 0·30-0·80; phet=0·0005). Gastroprotectant drugs were effective in preventing bleeding irrespective of the use of non-steroidal anti-inflammatory drugs (phet=0·56). In healing trials, gastroprotectants increased endoscopic ulcer healing (3·49, 95% CI 3·28-3·72; p<0·0001), with PPIs more effective (5·22, 99% CI 4·00-6·80) than prostaglandin analogues (2·27, 1·91-2·70) and H2RAs (3·80, 3·44-4·20; phet<0·0001). In trials among patients with acute bleeding, gastroprotectants reduced further bleeding (OR 0·68, 95% CI 0·60-0·78; p<0·0001), blood transfusion (0·75, 0·65-0·88; p=0·0003), further endoscopic intervention (0·56, 0·45-0·70; p<0·0001), and surgery (0·72, 0·61-0·84; p<0·0001), but did not significantly reduce mortality (OR 0·90, 0·72-1·11; p=0·31). PPIs had larger protective effects than did H2RAs for further bleeding (phet=0·0107) and blood transfusion (phet=0·0130). INTERPRETATION: Gastroprotectants, in particular PPIs, reduce the risk of peptic ulcer disease and its complications and promote healing of peptic ulcers in a wide range of clinical circumstances. However, this meta-analysis might have overestimated the benefits owing to small study bias. FUNDING: UK Medical Research Council and the British Heart Foundation.
Assuntos
Antiulcerosos/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Úlcera Péptica Hemorrágica/tratamento farmacológico , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/prevenção & controle , Prostaglandinas Sintéticas/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Humanos , Úlcera Péptica/complicações , Úlcera Péptica Hemorrágica/prevenção & controle , Prevenção SecundáriaRESUMO
The place of aspirin in primary prevention remains controversial, with North American and European organizations issuing contradictory treatment guidelines. More recently, the U.S. Preventive Services Task Force recommended "initiating low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years." This recommendation reflects increasing evidence for a chemopreventive effect of low-dose aspirin against colorectal (and other) cancer. The intent of this paper is to review the evidence supporting a chemopreventive effect of aspirin, discuss its potential mechanism(s) of action, and provide a conceptual framework for assessing current guidelines in the light of ongoing studies.
Assuntos
Aspirina/administração & dosagem , Neoplasias Colorretais/prevenção & controle , Prevenção Primária/métodos , Doenças Cardiovasculares/prevenção & controle , Relação Dose-Resposta a Droga , Humanos , Inibidores da Agregação Plaquetária/administração & dosagem , Guias de Prática Clínica como AssuntoRESUMO
Inactivation of platelet cyclooxygenase (COX)-1 by low-dose aspirin leads to long-lasting suppression of thromboxane (TX) A2 production and TXA2-mediated platelet activation and aggregation. This effect is necessary and sufficient to explain aspirin's unique (among other COX-1 inhibitors) effectiveness in preventing atherothrombosis, as well as its shared (with other antiplatelet agents) bleeding liability. However, different mechanisms of action have been suggested to explain other beneficial effects of aspirin, such as prevention of venous thromboembolism, chemoprevention of colorectal (and other) cancers, and reduced risk of dementia. These mechanisms include acetylation of other proteins in blood coagulation, inhibition of COX-2 activity, and other COX-independent mechanisms. The intent of this review is to develop the concept that the multifaceted therapeutic effects of low-dose aspirin may reflect pleiotropic consequences of platelet inhibition on pathophysiological tissue repair processes. Furthermore, the clinical implications of this concept will be discussed in terms of current clinical practice and future research.