RESUMEN
BACKGROUND: The cardiovascular safety of celecoxib, as compared with nonselective nonsteroidal antiinflammatory drugs (NSAIDs), remains uncertain. METHODS: Patients who required NSAIDs for osteoarthritis or rheumatoid arthritis and were at increased cardiovascular risk were randomly assigned to receive celecoxib, ibuprofen, or naproxen. The goal of the trial was to assess the noninferiority of celecoxib with regard to the primary composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke. Noninferiority required a hazard ratio of 1.12 or lower, as well as an upper 97.5% confidence limit of 1.33 or lower in the intention-to-treat population and of 1.40 or lower in the on-treatment population. Gastrointestinal and renal outcomes were also adjudicated. RESULTS: A total of 24,081 patients were randomly assigned to the celecoxib group (mean [±SD] daily dose, 209±37 mg), the naproxen group (852±103 mg), or the ibuprofen group (2045±246 mg) for a mean treatment duration of 20.3±16.0 months and a mean follow-up period of 34.1±13.4 months. During the trial, 68.8% of the patients stopped taking the study drug, and 27.4% of the patients discontinued follow-up. In the intention-to-treat analyses, a primary outcome event occurred in 188 patients in the celecoxib group (2.3%), 201 patients in the naproxen group (2.5%), and 218 patients in the ibuprofen group (2.7%) (hazard ratio for celecoxib vs. naproxen, 0.93; 95% confidence interval [CI], 0.76 to 1.13; hazard ratio for celecoxib vs. ibuprofen, 0.85; 95% CI, 0.70 to 1.04; P<0.001 for noninferiority in both comparisons). In the on-treatment analysis, a primary outcome event occurred in 134 patients in the celecoxib group (1.7%), 144 patients in the naproxen group (1.8%), and 155 patients in the ibuprofen group (1.9%) (hazard ratio for celecoxib vs. naproxen, 0.90; 95% CI, 0.71 to 1.15; hazard ratio for celecoxib vs. ibuprofen, 0.81; 95% CI, 0.65 to 1.02; P<0.001 for noninferiority in both comparisons). The risk of gastrointestinal events was significantly lower with celecoxib than with naproxen (P=0.01) or ibuprofen (P=0.002); the risk of renal events was significantly lower with celecoxib than with ibuprofen (P=0.004) but was not significantly lower with celecoxib than with naproxen (P=0.19). CONCLUSIONS: At moderate doses, celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety. (Funded by Pfizer; ClinicalTrials.gov number, NCT00346216 .).
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Artritis/tratamiento farmacológico , Enfermedades Cardiovasculares/inducido químicamente , Celecoxib/efectos adversos , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Ibuprofeno/efectos adversos , Naproxeno/efectos adversos , Anciano , Antiinflamatorios no Esteroideos/uso terapéutico , Enfermedades Cardiovasculares/mortalidad , Celecoxib/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Ibuprofeno/uso terapéutico , Análisis de Intención de Tratar , Enfermedades Renales/inducido químicamente , Masculino , Persona de Mediana Edad , Naproxeno/uso terapéutico , RiesgoRESUMEN
BACKGROUND AND AIM: Owing to wide-spread use, low-dose aspirin (LDA) produces a substantial amount of peptic ulcer disease. Current guidelines are ambivalent about the need for Helicobacter pylori eradication to protect against LDA ulcers. This study aimed to determine, through meta-analysis, if (and by how much) infection alters the baseline risk of peptic ulcers during LDA therapy. METHODS: Literature screening was performed in MEDLINE and EMBASE from inception to May 2018. Original studies reporting prevalence or incidence of uncomplicated ulcers in LDA users were included. Ulcer endpoints needed to be specified separately, according to H. pylori infection status. Meta-analysis was performed in MIX 2.0 Pro. RESULTS: Ten cross-sectional studies and seven randomized controlled trials were included (n = 5964). The pooled odds ratios with 95% confidence intervals (CI) for the risk of LDA ulcers in H. pylori-positive versus H. pylori-negative individuals were 1.68 (95%CI 1.40-2.02) and 1.65 (95%CI 1.29-2.08) under fixed-effects and random-effects models, respectively. Heterogeneity among studies was minimal (I2 = 26.9%). After adjusting for the protective effects of antisecretory drugs, the odds ratios increased to 1.94 (95%CI 1.54-2.46). CONCLUSION: This analysis suggests that H. pylori increases the risk of LDA ulcers by almost 70% in a population where some were taking proton pump inhibitors and/or other acid suppressants. Without antisecretory drugs, the risk almost doubles. Clinically, these findings may support the use of a test-and-treat approach to H. pylori in LDA users, particularly those already at higher risk of developing peptic ulcers.
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Aspirina/efectos adversos , Gastritis/complicaciones , Gastritis/microbiología , Infecciones por Helicobacter , Úlcera Péptica/inducido químicamente , Úlcera Péptica/etiología , Aspirina/administración & dosificación , Bases de Datos Bibliográficas , Helicobacter pylori , Humanos , Incidencia , Úlcera Péptica/epidemiología , Úlcera Péptica/prevención & control , Prevalencia , RiesgoRESUMEN
Objective: Guidelines exist for the use of low-dose aspirin in the general population for primary cardiovascular (CV) prevention, but the risk-benefit considerations may differ in RA. While RA confers an increased CV risk, such patients more likely use NSAIDs and corticosteroids. Methods: We conducted a cohort study to assess potential risks and benefits of low-dose aspirin. We estimated incidence rates and hazard ratios (HRs) using Cox regression among subjects with RA but no known CV disease in the Prospective Randomized Evaluation of Celecoxib Integrated Safety Vs Ibuprofen Or Naproxen trial. The primary exposure of interest was low-dose aspirin, and all enrolled patients were provided open-label esomeprazole. The primary composite outcome was major NSAID toxicity, including major adverse CV event (MACE), clinically significant gastrointestinal events, renal events and all-cause mortality. Results: We found 1852 subjects with RA in Prospective Randomized Evaluation of Celecoxib Integrated Safety Vs Ibuprofen Or Naproxen without known CV disease; 540 reported using low-dose aspirin for CV prevention and 1312 did not. Any major NSAID toxicity was observed in 79 (6.0%) non-aspirin users and 37 (6.9%) aspirin users (P = 0.50). Aspirin users experienced all components of the primary outcome at a similar rate to non-users. In fully adjusted models, the risk for major NSAID toxicity was similar between aspirin exposure groups (HR = 1.08, 95% CI: 0.69, 1.69). The risk for MACE was also similar between exposure groups in age- and gender-adjusted models (HR = 1.23, 95% CI: 0.72, 2.10). Conclusion: RA patients using low-dose aspirin with chronic NSAIDs and esomeprazole had a similar risk of major NSAID toxicity and MACE as patients who did not.
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Artritis Reumatoide/tratamiento farmacológico , Aspirina/administración & dosificación , Enfermedades Cardiovasculares/prevención & control , Prevención Primaria/métodos , Administración Oral , Anciano , Antiinflamatorios no Esteroideos/administración & dosificación , Artritis Reumatoide/complicaciones , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVE: To determine whether the risk of upper gastrointestinal bleeding in patients taking low dose aspirin (≤ 325 mg/day) is increased in people with Helicobacter pylori infections. STUDY DESIGN: A systematic search for all publications since 1989 (when H. pylori was named) using search term equivalents for "upper gastrointestinal haemorrhage" and "aspirin". Articles were assessed individually for inclusion of data on H. pylori infection, as not all relevant papers were indexed with this term. Data that could be pooled were then subjected to meta-analysis, using a random effects model. DATA SOURCES: MEDLINE, Embase, Scopus, the Cochrane Library. DATA SYNTHESIS: Of 7599 retrieved publications, reports for seven case-control studies contained data suitable for meta-analysis; four were deemed high quality on the Newcastle-Ottawa scale. Upper gastrointestinal haemorrhage was more frequent in aspirin users infected with H. pylori than in those who were not (odds ratio [OR], 2.32; 95% CI, 1.25-4.33; P = 0.008). The heterogeneity of the studies was significant (Q = 19.3, P = 0.004; I2 = 68.9%, 95% CI, 31.5-85.9%), but the pooled odds ratio was similar after removing the two studies that contributed most to heterogeneity (OR, 2.34; 95% CI, 1.56-3.53; P < 0.001). The number needed to treat to prevent one bleeding event annually was estimated to be between 100 and more than 1000. CONCLUSIONS: The odds of upper gastrointestinal bleeding in patients taking low dose aspirin is about twice as great in those infected with H. pylori. Testing for and treating the infection should be considered in such patients, especially if their underlying risk of peptic ulcer bleeding is already high.
Asunto(s)
Aspirina/efectos adversos , Infecciones por Helicobacter , Úlcera Péptica Hemorrágica , Adulto , Anciano , Anciano de 80 o más Años , Aspirina/administración & dosificación , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Helicobacter pylori , Humanos , Persona de Mediana Edad , Úlcera Péptica Hemorrágica/complicaciones , Úlcera Péptica Hemorrágica/epidemiología , Factores de RiesgoRESUMEN
AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs), both non-selective and selective cyclooxygenase-2 (COX-2) inhibitors, are among the most widely prescribed drugs worldwide, but associate with increased blood pressure (BP) and adverse cardiovascular (CV) events. PRECISION-ABPM, a substudy of PRECISION was conducted at 60 sites, to determine BP effects of the selective COX-2 inhibitor celecoxib vs. the non-selective NSAIDs naproxen and ibuprofen. METHODS AND RESULTS: In this double-blind, randomized, multicentre non-inferiority CV-safety trial, 444 patients (mean age 62 ± 10 years, 54% female) with osteoarthritis (92%) or rheumatoid arthritis (8%) and evidence of or at increased risk for coronary artery disease received celecoxib (100-200 mg bid), ibuprofen (600-800 mg tid), or naproxen (375-500 mg bid) with matching placebos in a 1: 1: 1 allocation, to assess the effect on 24-h ambulatory BP after 4 months. The change in mean 24-h systolic BP (SBP) in celecoxib, ibuprofen and naproxen-treated patients was -0.3 mmHg [95% confidence interval (CI), -2.25, 1.74], 3.7 (95% CI, 1.72, 5.58) and 1.6 mmHg (95% CI, -0.40, 3.57), respectively. These changes resulted in a difference of - 3.9 mmHg (P = 0.0009) between celecoxib and ibuprofen, of - 1.8 mmHg (P = 0.12) between celecoxib and naproxen, and of - 2.1 mmHg (P = 0.08) between naproxen and ibuprofen. The percentage of patients with normal baseline BP who developed hypertension (mean 24-h SBP ≥ 130 and/or diastolic BP ≥ 80 mmHg) was 23.2% for ibuprofen, 19.0% for naproxen, and 10.3% for celecoxib (odds ratio 0.39, P = 0.004 and odds ratio 0.49, P = 0.03 vs. ibuprofen and naproxen, respectively). CONCLUSIONS: In PRECISION-ABPM, allocation to the non-selective NSAID ibuprofen, compared with the COX-2 selective inhibitor celecoxib was associated with a significant increase of SBP, and a higher incidence of new-onset hypertension. CLINICALTRIALS: gov number NCT00346216.
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Antiinflamatorios no Esteroideos/farmacología , Presión Sanguínea/efectos de los fármacos , Inhibidores de la Ciclooxigenasa 2/farmacología , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/fisiopatología , Celecoxib/administración & dosificación , Celecoxib/efectos adversos , Celecoxib/farmacología , Enfermedad de la Arteria Coronaria/etiología , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Método Doble Ciego , Femenino , Humanos , Hipertensión/inducido químicamente , Ibuprofeno/administración & dosificación , Ibuprofeno/efectos adversos , Ibuprofeno/farmacología , Masculino , Naproxeno/administración & dosificación , Naproxeno/efectos adversos , Naproxeno/farmacología , Osteoartritis/tratamiento farmacológico , Osteoartritis/fisiopatología , Estudios ProspectivosAsunto(s)
Rendimiento Académico/normas , Certificación/normas , Competencia Clínica/normas , Médicos Graduados Extranjeros/estadística & datos numéricos , Licencia Médica/normas , Facultades de Medicina/normas , Actitud del Personal de Salud , Australia , Evaluación Educacional , Regulación Gubernamental , Humanos , Examen Físico/normasRESUMEN
BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease in Western societies. Despite its significance, there are no well-proven pharmacological treatments. Two novel classes of potential pharmacotherapies are the glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4I), collectively known as incretin-based therapies. These have several metabolic and anti-inflammatory actions that may be of benefit in NAFLD. The aim of this meta-analysis was to evaluate their efficacy via a structured retrieval and pooled analysis of relevant studies. METHODS: Studies were sourced from electronic databases and meeting abstracts. Main inclusion criteria were original studies investigating treatment of adults with NAFLD using GLP-1 RA/DPP-4I. Key outcomes were a change in serum alanine transaminase (ALT), as a marker of liver inflammation, and improvement in disease status measured by imaging or histology. RESULTS: Initial searching retrieved 1357 peer-reviewed articles and abstracts. Four studies met all inclusion and exclusion criteria. There were a total of 136 participants with NAFLD and concomitant type 2 diabetes mellitus (T2DM). Meta-analysis (random-effects model) revealed a significant decrease in serum ALT following treatment (mean reduction 14.1 IU/L, 95% confidence intervals [CI] 8.3-19.8, P < 0.0001). In two studies with imaging and tissue data, treatment was found to significantly reduce steatosis, inflammation, and fibrosis. CONCLUSION: The significant decrease in a key biochemical marker of hepatic inflammation following treatment with incretin-based therapies, as well as improvements in imaging and histology, suggests these agents may be effective options for managing NAFLD with comorbid T2DM.
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Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Incretinas/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Alanina Transaminasa/sangre , Antiinflamatorios , Biomarcadores/sangre , Comorbilidad , Bases de Datos Bibliográficas , Diabetes Mellitus Tipo 2/epidemiología , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Quimioterapia Combinada , Receptor del Péptido 1 Similar al Glucagón/agonistas , Humanos , Incretinas/farmacología , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Resultado del TratamientoRESUMEN
In a recently published article in BMC Medicine, Scarpignato and colleagues present the results of a consensus conference that addressed several aspects of the management of pain in patients with osteoarthritis. The main areas covered include the relative safety in regard to gastrointestinal and cardiovascular adverse events of non-selective 'traditional' non-steroidal anti-inflammatory drugs (NSAIDs) versus cyclooxygenase-2 selective NSAIDs. The role of co-therapy with proton pump inhibitors in enhancing gastrointestinal safety is also reviewed. This commentary focuses on two areas that the consensus conference addressed, i) the whole length of gastrointestinal tract risk profile of the various NSAIDs (not just the ulcer risks in stomach and duodenum); ii) more recent information, but still some uncertainties, about the cardiovascular risks associated with the two classes of NSAID in general, and naproxen in particular. Please see related article: http://dx.doi.org/10.1186/s12916-015-0285-8.
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Antiinflamatorios no Esteroideos/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Gastrointestinales/inducido químicamente , Osteoartritis/tratamiento farmacológico , HumanosRESUMEN
Patients receiving chronic nonsteroidal anti-inflammatory drugs (NSAIDs) and concomitant low-dose aspirin (LDA) are at increased risk of gastrointestinal (GI) toxicity. A fixed-dose combination of enteric-coated (EC) naproxen and immediate-release esomeprazole magnesium (NAP/ESO) has been designed to deliver a proton-pump inhibitor followed by an NSAID in a single tablet. To examine safety data from 5 Phase III studies of NAP/ESO in LDA users (≤ 325 mg daily, administered at any time during the study), and LDA non-users, data were analyzed from 6-month studies assessing NAP/ESO versus EC naproxen in patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis (n = 2), 3-month studies assessing NAP/ESO vs celecoxib or placebo in patients with knee osteoarthritis (n = 2), and a 12-month, open-label, safety study of NAP/ESO (n = 1). In an analysis of two studies, incidences of endoscopically confirmed gastric ulcers (GUs) and duodenal ulcers (DUs) were summarized by LDA subgroups. In the pooled analysis from all five studies, incidences of treatment-emergent adverse events (AEs) (including prespecified NSAID-associated upper GI AEs and cardiovascular AEs), serious AEs, and AE-related discontinuations were stratified by LDA subgroups. Overall, 2,317 patients received treatment; 1,157 patients received NAP/ESO and, of these, 298 received LDA. The cumulative incidence of GUs and DUs in the two studies with 6-month follow-up was lower for NAP/ESO vs EC naproxen in both LDA subgroups [GUs: 3.0 vs 27.9%, respectively, for LDA users, 6.4 vs 22.4%, respectively, for LDA non-users (both P < 0.001); DUs: 1.0 vs 5.8% for LDA users, 0.6 vs 5.3% for LDA non-users]. The incidence of erosive gastritis was lower in NAP/ESO- vs EC naproxen-treated patients for both LDA users [18.2 vs 36.5%, respectively (P = 0.004)] and LDA non-users [19.8 vs 38.5%, respectively (P < 0.001)]. Among LDA users, incidences of NSAID-associated upper GI AEs were: NAP/ESO, 16.1%; EC naproxen, 31.7%; celecoxib, 22.1%; placebo, 23.2%. Among LDA non-users, incidences of NSAID-associated upper GI AEs were: NAP/ESO, 20. %; EC naproxen, 36.6%; celecoxib, 18.5%; placebo, 18.9%. For LDA users, incidences of cardiovascular AEs were: NAP/ESO, 3.0%; EC naproxen, 1.0%; celecoxib, 0%; placebo, 0%. For LDA non-users, incidences of cardiovascular AEs were: NAP/ESO, 1.0%; EC naproxen, 0.6%; celecoxib, 0.3%; placebo, 0%. NAP/ESO appears to be well-tolerated in patients receiving concomitant LDA. For LDA users, AE incidence was less than that observed for EC naproxen. For most AE categories, incidences were similar among NAP/ESO, celecoxib and placebo groups. The safety of NAP/ESO appeared similar regardless of LDA use.
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Antiinflamatorios no Esteroideos/administración & dosificación , Antiulcerosos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Aspirina/administración & dosificación , Esomeprazol/administración & dosificación , Naproxeno/administración & dosificación , Osteoartritis/tratamiento farmacológico , Adolescente , Adulto , Antiulcerosos/efectos adversos , Aspirina/efectos adversos , Preparaciones de Acción Retardada , Método Doble Ciego , Esomeprazol/efectos adversos , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Naproxeno/efectos adversosAsunto(s)
Naproxeno , Pancreatitis , Antiinflamatorios no Esteroideos , Estudios de Casos y Controles , Celecoxib , Humanos , Ibuprofeno , Riesgo , TaiwánRESUMEN
Upper gastrointestinal bleeding (UGIB), especially peptic ulcer bleeding, remains one of the most important cause of hospitalisation and mortality world wide. In Asia, with a high prevalence of Helicobacter pylori infection, a potential difference in drug metabolism, and a difference in clinical management of UGIB due to variable socioeconomic environments, it is considered necessary to re-examine the International Consensus of Non-variceal Upper Gastrointestinal Bleeding with emphasis on data generated from the region. The working group, which comprised experts from 12 countries from Asia, recommended the use of the Blatchford score for selection of patients who require endoscopic intervention and which would allow early discharge of patients at low risk. Patients' comorbid conditions should be included in risk assessment. A pre-endoscopy proton pump inhibitor (PPI) is recommended as a stop-gap treatment when endoscopy within 24 h is not available. An adherent clot on a peptic ulcer should be treated with endoscopy combined with a PPI if the clot cannot be removed. Routine repeated endoscopy is not recommended. High-dose intravenous and oral PPIs are recommended but low-dose intravenous PPIs should be avoided. COX-2 selective non-steroidal anti-inflammatory drugs combined with a PPI are recommended for patients with very high risk of UGIB. Aspirin should be resumed soon after stabilisation and clopidogrel alone is no safer than aspirin plus a PPI. When dual antiplatelet agents are used, prophylactic use of a PPI reduces the risk of adverse gastrointestinal events.
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Hemorragia Gastrointestinal/cirugía , Aspirina/uso terapéutico , Quimioterapia Combinada , Embolización Terapéutica , Endoscopía Gastrointestinal , Medicina Basada en la Evidencia/métodos , Hemorragia Gastrointestinal/tratamiento farmacológico , Humanos , Selección de Paciente , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pronóstico , Inhibidores de la Bomba de Protones/uso terapéutico , Factores de TiempoRESUMEN
Background: International medical graduates (IMGs) have made important contributions to Australian healthcare since colonization. Recent published data have documented source countries and characteristics of IMGs undertaking the examinations of the Australian Medical Council. However, information about those currently practicing in Australia is limited. Objective: To analyze a cross section of IMGs currently practicing in Australia to determine patterns of change in donor countries, other demographic characteristics, geographical locations, and their areas of specialization. Methods: A random sample of all practitioners on a national database was interrogated for their country of first medical qualification. Those who qualified outside Australia were then analyzed for demographic variables such as age, gender, country of origin, and years of graduation and immigration. Their practice locations were matched to the Australian Bureau of Statistics geographical framework, and their specialties compared with those of a random sample of graduates from Australian medical schools. Results: Over the approximately 60 years since those surveyed arrived in Australia, IMGs' countries/regions of origin have changed from mainly the UK and Ireland to Southern Asia, in line with demographic changes in Australia as a whole. Most arrived soon after graduation, and IMGs are twice IMGs as likely as local graduates to be working in a rural area of workforce shortage. Compared with local graduates, significantly more IMGs are working in general practice. Conclusions: IMGs currently practicing in Australia make up a substantial proportion of the workforce and are more likely than local graduates to provide health services in regional and remote areas.
RESUMEN
The search for the cause or causes of peptic ulcers has been a long one. It was recognised as early as the 19th Century that damage to the stomach or duodenal bulb was likely to result if the resistance of their mucosae to luminal acid was for some reason impaired. An early theory suggested microscopic vascular occlusion leading to local infarction could be the initiating event but evidence was lacking. Excessive acid secretion is seen in some patients but not in many so is implausible as the main factor in most ulcers. Cigarette smoking is a risk factor and chronic life difficulties has been shown to sometimes play a part, but we would now think that they play only minor roles to possibly tip the balance when a major etiologic factor is already present. The overwhelming evidence now is that the major etiologic factors in chronic peptic ulcer are ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) and infection with Helicobacter pylori. Understanding the mechanism of the first, and the discovery and demonstration of Koch's postulates for the second, have been instrumental in the award of two Nobel prizes.
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Úlcera Péptica/etiología , Antiinflamatorios no Esteroideos/efectos adversos , Duodeno/metabolismo , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Humanos , Mucosa Intestinal/metabolismo , Úlcera Péptica/metabolismo , Úlcera Péptica/psicología , Trastornos Psicofisiológicos/etiología , Medición de Riesgo , Factores de Riesgo , Fumar/efectos adversos , Estrés Psicológico/complicacionesRESUMEN
Salicylates have been used since antiquity to relieve pain and inflammation. However, it has been only in the last half century that evidence has emerged that aspirin causes reproducible acute and superficial injury to the gastric and duodenal mucosa, and is an important cause of complicated and uncomplicated peptic ulcer. Superficial damage to the mucosa occurs rapidly and reproducibly and acid and pepsin then produce a second wave of deeper injury. Most of the time this heals rapidly, but some focal deeper mucosal lesions (erosions) occur frequently and the point prevalence of frank ulcers in low dose aspirin users is around 10%. It is even more recently that aspirin's unique antiplatelet action has been recognized, with long-lasting inhibition of platelet aggregation due to irreversible inactivation of the cyclooxygenase-1 mediated production of thromboxane. It has now become the mainstay of pharmacological reduction of thrombotic risk in patients with cardiovascular diseases. In addition, evidence is accumulating about the cancer-reducing effects of blocking cyclooxygenase in a number of tissues. For example, recent data indicate that even at a 75-mg/day dose, it may reduce colorectal cancer risk after a lag of a year or so. Because of its widespread use for cardiovascular protection, aspirin is now one of the most frequently prescribed drugs-and gastroenterologists regularly need to deal with its ulcerative complications along the whole length of the gastrointestinal tract. Strategies that can be used to reduce these risks include using the lowest effective aspirin dose and co-prescribing acid suppressants.
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Antiinflamatorios no Esteroideos/uso terapéutico , Anticarcinógenos/uso terapéutico , Aspirina/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Anticarcinógenos/efectos adversos , Aspirina/efectos adversos , Inhibidores de la Ciclooxigenasa/uso terapéutico , Relación Dosis-Respuesta a Droga , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Humanos , Intestinos/efectos de los fármacos , Intestinos/patología , Úlcera Péptica/inducido químicamente , Úlcera Péptica/patología , Úlcera Péptica/prevención & control , Inhibidores de Agregación Plaquetaria/efectos adversos , Guías de Práctica Clínica como Asunto , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: Pain management in patients with osteoarthritis or rheumatoid arthritis often requires long-term use of nonsteroidal antiinflammatory drugs (NSAIDs). However, the relative cardiovascular safety of these therapies remains uncertain. METHODS: The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION) trial will evaluate the cardiovascular safety of celecoxib, ibuprofen, and naproxen. Approximately 20,000 patients with symptomatic osteoarthritis or rheumatoid arthritis at high risk for, or with, established cardiovascular disease will be randomized in this double-blind, triple dummy, multinational, multicenter study. The primary end point is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The trial will continue until 762 primary events occur with at least 18 months follow-up. Noninferiority of any of the regimens will require a 97.5% upper CI of the hazard ratio (HR) < or =1.33 and point estimate < or =1.12 for both intent-to-treat (ITT) and modified ITT populations. CONCLUSION: PRECISION, the first study of patients with high cardiovascular risk chronically treated with a cyclooxygenase-2 selective inhibitor or nonselective NSAID, will define the relative cardiovascular safety profile of celecoxib, ibuprofen, and naproxen and provide data to help guide NSAID use for pain management for this population.
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Artritis/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Ibuprofeno/uso terapéutico , Naproxeno/uso terapéutico , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Celecoxib , Inhibidores de la Ciclooxigenasa/administración & dosificación , Inhibidores de la Ciclooxigenasa/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Estudios de Seguimiento , Humanos , Ibuprofeno/administración & dosificación , Persona de Mediana Edad , Naproxeno/administración & dosificación , Estudios Prospectivos , Pirazoles/administración & dosificación , Sulfonamidas/administración & dosificación , Resultado del TratamientoRESUMEN
There have been numerous and dramatic advances in our understanding of the mechanisms, causes and treatments of upper gastrointestinal diseases in the past 50 years. This review focuses on a few, not dealt with elsewhere in this special issue of the Journal. The early history of the recognition that nonsteroidal anti-inflammatory drugs are a major cause of peptic ulcer is described, with particular attention to the work of the pioneering Australian investigators. The story of the development of the histamine H(2)-receptor antagonists and the proton pump inhibitors is also outlined.
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Gastroenterología/historia , Fármacos Gastrointestinales/historia , Enfermedades Gastrointestinales/historia , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/historia , Australia , Gastroenterología/tendencias , Reflujo Gastroesofágico/tratamiento farmacológico , Reflujo Gastroesofágico/historia , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/tratamiento farmacológico , Antagonistas de los Receptores H2 de la Histamina/historia , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Úlcera Péptica/inducido químicamente , Úlcera Péptica/historia , Inhibidores de la Bomba de Protones/historia , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: Calcineurin-inhibitor immunosuppressants (tacrolimus and ciclosporin) have been associated with an exposure-related increase in tumour recurrence following liver transplantation for hepatocellular carcinoma (HCC). Conversely, mechanistic target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) have been suggested to reduce recurrence rates and improve survival in this patient group. AIM: To clarify the potential benefit of mTOR-inhibitors in HCC transplant patients by comparing recurrence and survival outcomes with calcineurin-inhibitor-based immunosuppression. METHODS: A systematic review and meta-analysis was performed. The inclusion criteria were observational or interventional studies reporting the effect of early-initiated (<6 months post-transplant) mTOR-inhibitor-based immunosuppression on survival or tumour recurrence in patients transplanted with HCC, compared to a control of calcineurin-inhibitor-based therapy. RESULTS: Meta-analysis demonstrated that compared with calcineurin-inhibitor controls, recurrence-free-survival was significantly increased with mTOR-inhibitor-based therapy at 1-year (Risk-Ratio (RR): 1.09, 95% CI: 1.01-1.18) and 3-years (RR: 1.1, 95% CI: 1.01-1.21) post-transplant, with a nonsignificant increase at 5-years (RR: 1.15, 95% CI: 0.99-1.35). Overall survival was improved at 1-year (RR: 1.07, 95% CI: 1.02-1.12), 3-years (RR: 1.1, 95% CI: 1.02-1.19), and 5-years (RR: 1.18, 95% CI: 1.08-1.29). Recurrence-rate was lower in the mTOR-inhibitor arm (RR: 0.67, 95% CI: 0.56-0.82), with no significant increase in acute rejection (RR: 1.1, 95% CI: 0.94-1.28). CONCLUSIONS: mTOR-inhibitor-based immunosuppression may be a preferable option in patients transplanted with HCC. It improves recurrence-free-survival over at least three years and reduces the recurrence rate compared with standard calcineurin-inhibitor-based therapy, with no significant increase in the rate of acute rejection. Future research should clarify the effect in higher vs lower risk cohorts.
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Inhibidores de la Calcineurina/uso terapéutico , Carcinoma Hepatocelular/terapia , Inmunosupresores/uso terapéutico , Neoplasias Hepáticas/terapia , Trasplante de Hígado , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Ciclosporina/uso terapéutico , Everolimus/uso terapéutico , Humanos , Terapia de Inmunosupresión , Recurrencia Local de Neoplasia/etiología , Sirolimus/uso terapéutico , Tacrolimus/uso terapéuticoRESUMEN
BACKGROUND: Infliximab is an effective salvage therapy in acute severe ulcerative colitis; however, the optimal dosing strategy is unknown. We performed a systematic review and meta-analysis to examine the impact of infliximab dosage and intensification on colectomy-free survival in acute severe ulcerative colitis. METHODS: Studies reporting outcomes of hospitalized steroid-refractory acute severe ulcerative colitis treated with infliximab salvage were identified. Infliximab use was categorized by dose, dose number, and schedule. The primary outcome was colectomy-free survival at 3 months. Pooled proportions and odds ratios with 95% confidence intervals were reported. RESULTS: Forty-one cohorts (n = 2158 cases) were included. Overall colectomy-free survival with infliximab salvage was 79.7% (95% confidence interval [CI], 75.48% to 83.6%) at 3 months and 69.8% (95% CI, 65.7% to 73.7%) at 12 months. Colectomy-free survival at 3 months was superior with 5-mg/kg multiple (≥2) doses compared with single-dose induction (odds ratio [OR], 4.24; 95% CI, 2.44 to 7.36; P < 0.001). However, dose intensification with either high-dose or accelerated strategies was not significantly different to 5-mg/kg standard induction at 3 months (OR, 0.70; 95% CI, 0.39 to 1.27; P = 0.24) despite being utilized in patients with a significantly higher mean C-reactive protein and lower albumin levels. CONCLUSIONS: In acute severe ulcerative colitis, multiple 5-mg/kg infliximab doses are superior to single-dose salvage. Dose-intensified induction outcomes were not significantly different compared to standard induction and were more often used in patients with increased disease severity, which may have confounded the results. This meta-analysis highlights the marked variability in the management of infliximab salvage therapy and the need for further studies to determine the optimal dose strategy.