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1.
Gastroenterology ; 157(3): 682-691, ago., 30 2019. ilus, tab
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1015771

RESUMO

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 x 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. (AU)


Assuntos
Bactérias , Doenças Cardiovasculares , Aspirina
2.
Gastroenterology ; 157(3): 682-691.e2, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31152740

RESUMO

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.


Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Rivaroxabana/administração & dosagem , Idoso , Aspirina/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Método Duplo-Cego , Esquema de Medicação , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/microbiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol/efeitos adversos , Doença Arterial Periférica/diagnóstico , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
3.
J Am Coll Cardiol ; 71(20): 2306-2315, 2018 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-29540326

RESUMO

BACKGROUND: Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There is limited information on the prognosis of patients who experience MALE. OBJECTIVES: Among participants with lower extremity PAD, this study investigated: 1) if hospitalizations, MACE, amputations, and deaths are higher after the first episode of MALE compared with patients with PAD who do not experience MALE; and 2) the impact of treatment with low-dose rivaroxaban and aspirin compared with aspirin alone on the incidence of MALE, peripheral vascular interventions, and all peripheral vascular outcomes over a median follow-up of 21 months. METHODS: We analyzed outcomes in 6,391 patients with lower extremity PAD who were enrolled in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial. COMPASS was a randomized, double-blind placebo-controlled study of low-dose rivaroxaban and aspirin combination or rivaroxaban alone compared with aspirin alone. MALE was defined as severe limb ischemia leading to an intervention or major vascular amputation. RESULTS: A total of 128 patients experienced an incident of MALE. After MALE, the 1-year cumulative risk of a subsequent hospitalization was 61.5%; for vascular amputations, it was 20.5%; for death, it was 8.3%; and for MACE, it was 3.7%. The MALE index event significantly increased the risk of experiencing subsequent hospitalizations (hazard ratio [HR]: 7.21; p < 0.0001), subsequent amputations (HR: 197.5; p < 0.0001), and death (HR: 3.23; p < 0.001). Compared with aspirin alone, the combination of rivaroxaban 2.5 mg twice daily and aspirin lowered the incidence of MALE by 43% (p = 0.01), total vascular amputations by 58% (p = 0.01), peripheral vascular interventions by 24% (p = 0.03), and all peripheral vascular outcomes by 24% (p = 0.02). CONCLUSIONS: Among individuals with lower extremity PAD, the development of MALE is associated with a poor prognosis, making prevention of this condition of utmost importance. The combination of rivaroxaban 2.5 mg twice daily and aspirin significantly lowered the incidence of MALE and the related complications, and this combination should be considered as an important therapy for patients with PAD. (Cardiovascular Outcomes for People Using Anticoagulation Strategies [COMPASS]; NCT01776424).

4.
Lancet ; 391(10117): 205-218, 2018 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-29132879

RESUMO

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012). INTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide. FUNDING: Bayer AG.


Assuntos
Aspirina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Doença da Artéria Coronariana/epidemiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Morbidade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle
5.
Lancet ; 391(10117): 205-218, 2018.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-36688

RESUMO

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants...(AU)


Assuntos
Rivaroxabana , Aspirina , Doença da Artéria Coronariana , Estudos de Casos e Controles
6.
N Engl J Med ; 377(14): 1319-1330, 2017 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-28844192

RESUMO

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).


Assuntos
Aspirina/uso terapêutico , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Aspirina/efeitos adversos , Aterosclerose/complicações , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Método Duplo-Cego , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Rivaroxabana/efeitos adversos , Prevenção Secundária/métodos
7.
Can J Cardiol ; 33(8): 1027-1035, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28754388

RESUMO

BACKGROUND: Long-term aspirin prevents vascular events but is only modestly effective. Rivaroxaban alone or in combination with aspirin might be more effective than aspirin alone for vascular prevention in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). Rivaroxaban as well as aspirin increase upper gastrointestinal (GI) bleeding and this might be prevented by proton pump inhibitor therapy. METHODS: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) is a double-blind superiority trial comparing rivaroxaban 2.5 mg twice daily combined with aspirin 100 mg once daily or rivaroxaban 5 mg twice daily vs aspirin 100 mg once daily for prevention of myocardial infarction, stroke, or cardiovascular death in patients with stable CAD or PAD. Patients not taking a proton pump inhibitor were also randomized, using a partial factorial design, to pantoprazole 40 mg once daily or placebo. The trial was designed to have at least 90% power to detect a 20% reduction in each of the rivaroxaban treatment arms compared with aspirin and to detect a 50% reduction in upper GI complications with pantoprazole compared with placebo. RESULTS: Between February 2013 and May 2016, we recruited 27,395 participants from 602 centres in 33 countries; 17,598 participants were included in the pantoprazole vs placebo comparison. At baseline, the mean age was 68.2 years, 22.0% were female, 90.6% had CAD, and 27.3% had PAD. CONCLUSIONS: COMPASS will provide information on the efficacy and safety of rivaroxaban, alone or in combination with aspirin, in the long-term management of patients with stable CAD or PAD, and on the efficacy and safety of pantoprazole in preventing upper GI complications in patients receiving antithrombotic therapy.


Assuntos
Anticoagulantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Terapia Trombolítica/normas , Humanos
8.
Can J Cardiol ; 33(8): 1027-1035, 2017.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-36563

RESUMO

BACKGROUND: Long-term aspirin prevents vascular events but is only modestly effective. Rivaroxaban alone or in combination with aspirin might be more effective than aspirin alone for vascular prevention in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). Rivaroxaban as well as aspirin increase upper gastrointestinal (GI) bleeding and this might be prevented by proton pump inhibitor therapy. METHODS: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) is a double-blind superiority trial comparing rivaroxaban 2.5 mg twice daily combined with aspirin 100 mg once daily or rivaroxaban 5 mg twice daily vs aspirin 100 mg once daily for prevention of myocardial infarction, stroke, or cardiovascular death in patients with stable CAD or PAD. Patients not taking a proton pump inhibitor were also randomized, using a partial factorial design, to pantoprazole 40 mg once daily or placebo. The trial was designed to have at least 90% power to detect a 20% reduction in each of the rivaroxaban treatment arms compared with aspirin and to detect a 50% reduction in upper GI complications with pantoprazole compared with placebo...(AU)


Assuntos
Cardiopatias , Anticoagulantes , Aspirina
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