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1.
Eur J Prev Cardiol ; : 2047487319882154, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615291

RESUMO

AIMS: Secondary prevention in patients with coronary artery disease and peripheral artery disease involves antithrombotic therapy and optimal control of cardiovascular risk factors. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) study, adding low-dose rivaroxaban on top of aspirin lowered cardiovascular events, but there is limited data about risk factor control in secondary prevention. We studied the association between risk factor status and outcomes, and the impact of risk factor status on the treatment effect of rivaroxaban, in a large contemporary population of patients with coronary artery disease or peripheral artery disease. METHODS AND RESULTS: We reported ischemic events (cardiovascular death, stroke, or myocardial infarction) in participants from the randomized, double-blind COMPASS study by individual risk factor (blood pressure, smoking status, cholesterol level, presence of diabetes, body mass index, and level of physical activity), and by number of risk factors. We compared rates and hazard ratios of patients treated with rivaroxaban plus aspirin vs aspirin alone within each risk factor category and tested for interaction between risk factor status and antithrombotic regimen. Complete baseline risk factor status was available in 27,117 (99%) patients. Status and number of risk factors were both associated with increased risk of ischemic events. Rates of ischemic events (hazard ratio 2.2; 95% confidence interval 1.8-2.6) and cardiovascular death (hazard ratio 2.0; 1.5-2.7) were more than twofold higher in patients with 4-6 compared with 0-1 risk factors (p < 0.0001 for both). Rivaroxaban reduced event rates independently of the number of risk factors (p interaction 0.93), with the largest absolute benefit in patients with the highest number of risk factors. CONCLUSION: More favorable risk factor status and low-dose rivaroxaban were independently associated with lower risk of cardiovascular events.

2.
Nutrients ; 11(10)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600930

RESUMO

A large body of evidence has linked unhealthy eating patterns with an alarming increase in obesity and chronic disease worldwide. However, existing methods of assessing dietary intake in nutritional epidemiology rely on food frequency questionnaires or dietary records that are prone to bias and selective reporting. Herein, metabolic phenotyping was performed on 42 healthy participants from the Diet and Gene Intervention (DIGEST) pilot study, a parallel two-arm randomized clinical trial that provided complete diets to all participants. Matching single-spot urine and fasting plasma specimens were collected at baseline, and then following two weeks of either a Prudent or Western diet with a weight-maintaining menu plan designed by a dietician. Targeted and nontargeted metabolite profiling was conducted using three complementary analytical platforms, where 80 plasma metabolites and 84 creatinine-normalized urinary metabolites were reliably measured (CV < 30%) in the majority of participants (>75%) after implementing a rigorous data workflow for metabolite authentication with stringent quality control. We classified a panel of metabolites with distinctive trajectories following two weeks of food provisions when using complementary univariate and multivariate statistical models. Unknown metabolites associated with contrasting dietary patterns were identified with high-resolution MS/MS, as well as co-elution after spiking with authentic standards if available. Overall, 3-methylhistidine and proline betaine concentrations increased in both plasma and urine samples after participants were assigned a Prudent diet (q < 0.05) with a corresponding decrease in the Western diet group. Similarly, creatinine-normalized urinary imidazole propionate, hydroxypipecolic acid, dihydroxybenzoic acid, and enterolactone glucuronide, as well as plasma ketoleucine and ketovaline increased with a Prudent diet (p < 0.05) after adjustments for age, sex, and BMI. In contrast, plasma myristic acid, linoelaidic acid, linoleic acid, α-linoleic acid, pentadecanoic acid, alanine, proline, carnitine, and deoxycarnitine, as well as urinary acesulfame K increased among participants following a Western diet. Most metabolites were also correlated (r > ± 0.30, p < 0.05) to changes in the average intake of specific nutrients from self-reported diet records reflecting good adherence to assigned food provisions. Our study revealed robust biomarkers sensitive to short-term changes in habitual diet, which is needed for accurate monitoring of healthy eating patterns in free-living populations, and evidence-based public health policies for chronic disease prevention.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31565735

RESUMO

AIMS: Cardiovascular risk factors are used for risk stratification in primary prevention. We sought to determine if simple cardiac risk scores are associated with magnetic resonance imaging (MRI)-detected subclinical cerebrovascular disease including carotid wall volume (CWV), carotid intraplaque haemorrhage (IPH), and silent brain infarction (SBI). METHODS AND RESULTS: A total of 7594 adults with no history of cardiovascular disease (CVD) underwent risk factor assessment and a non-contrast enhanced MRI of the carotid arteries and brain using a standardized protocol in a population-based cohort recruited between 2014 and 2018. The non-lab-based INTERHEART risk score (IHRS) was calculated in all participants; the Framingham Risk Score was calculated in a subset who provided blood samples (n = 3889). The association between these risk scores and MRI measures of CWV, carotid IPH, and SBI was determined. The mean age of the cohort was 58 (8.9) years, 55% were women. Each 5-point increase (∼1 SD) in the IHRS was associated with a 9 mm3 increase in CWV, adjusted for sex (P < 0.0001), a 23% increase in IPH [95% confidence interval (CI) 9-38%], and a 32% (95% CI 20-45%) increase in SBI. These associations were consistent for lacunar and non-lacunar brain infarction. The Framingham Risk Score was also significantly associated with CWV, IPH, and SBI. CWV was additive and independent to the risk scores in its association with IPH and SBI. CONCLUSION: Simple cardiovascular risk scores are significantly associated with the presence of MRI-detected subclinical cerebrovascular disease, including CWV, IPH, and SBI in an adult population without known clinical CVD.

4.
Circulation ; 140(18): 1451-1459, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31510769

RESUMO

BACKGROUND: Patients treated with antithrombotic drugs are at risk of bleeding. Bleeding may be the first manifestation of underlying cancer. METHODS: We examined new cancers diagnosed in relation to gastrointestinal or genitourinary bleeding among patients enrolled in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) and determined the hazard of new cancer diagnosis after bleeding at these sites. RESULTS: Of 27 395 patients enrolled (mean age, 68 years; women, 21%), 2678 (9.8%) experienced any (major or minor) bleeding, 713 (2.6%) experienced major bleeding, and 1084 (4.0%) were diagnosed with cancer during a mean follow-up of 23 months. Among 2678 who experienced bleeding, 257 (9.9%) were subsequently diagnosed with cancer. Gastrointestinal bleeding was associated with a 20-fold higher hazard of new gastrointestinal cancer diagnosis (7.4% versus 0.5%; hazard ratio [HR], 20.6 [95% CI, 15.2-27.8]) and 1.7-fold higher hazard of new nongastrointestinal cancer diagnosis (3.8% versus 3.1%; HR, 1.70 [95% CI, 1.20-2.40]). Genitourinary bleeding was associated with a 32-fold higher hazard of new genitourinary cancer diagnosis (15.8% versus 0.8%; HR, 32.5 [95% CI, 24.7-42.9]), and urinary bleeding was associated with a 98-fold higher hazard of new urinary cancer diagnosis (14.2% versus 0.2%; HR, 98.5; 95% CI, 68.0-142.7). Nongastrointestinal, nongenitourinary bleeding was associated with a 3-fold higher hazard of nongastrointestinal, nongenitourinary cancers (4.4% versus 1.9%; HR, 3.02 [95% CI, 2.32-3.91]). CONCLUSIONS: In patients with atherosclerosis treated with antithrombotic drugs, any gastrointestinal or genitourinary bleeding was associated with higher rates of new cancer diagnosis. Any gastrointestinal or genitourinary bleeding should prompt investigation for cancers at these sites. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.

5.
Curr Cardiol Rep ; 21(10): 115, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471666

RESUMO

PURPOSE OF REVIEW: Peripheral artery disease (PAD) affects an estimated 200 million people worldwide and is associated with significant cardiovascular morbidity and mortality. Cardiovascular risk is further increased among individuals with polyvascular disease, where either cerebrovascular or coronary artery disease is present in addition to PAD. In this review, we present common clinical scenarios encountered when managing patients with PAD and provide an evidence-based approach to prescribing optimal antithrombotics in this population. RECENT FINDINGS: The COMPASS trial recently demonstrated that rivaroxaban 2.5 mg BID + ASA daily significantly reduces major adverse cardiac and limb events in patients with PAD. Despite these advances, morbidity following MALE events remains high. With widespread approval by federal health regulators, the COMPASS regimen should be strongly considered in PAD patients who do not have a high bleeding risk. Implementing the COMPASS regimen in patients with PAD, along with other vascular risk reduction strategies, will have a substantial impact on reducing atherothromboembolic risk in patients with established vascular disease.

6.
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
7.
Gastroenterology ; 157(2): 403-412, Aug., 2019. tabela, grafico
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1022748

RESUMO

BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials. (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/prevenção & controle , Aspirina/administração & dosagem , Método Duplo-Cego , Relação Dose-Resposta a Droga , Hemorragia Gastrointestinal/prevenção & controle , Anticoagulantes/administração & dosagem
8.
PLoS One ; 14(7): e0218816, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31276512

RESUMO

BACKGROUND: Childhood obesity is a world-wide concern due to its growing prevalence and association with cardiometabolic risk factors in childhood and subsequent adult cardiovascular disease. In young pre-school children, there is uncertainty regarding which of the commonly used anthropometric measures of childhood obesity is best associated with cardiometabolic risk factors. This study compared the utility of common measures used in identifying obesity in these young children. METHODS: The four commonly used metrics for identifying obesity in children: body fat percentage ≥ 90th percentile, waist circumference ≥ 90th percentile, BMI z score > 2 SD and waist-to-height ratio (WHtR) ≥ 0.5, were measured in a cohort of children born singleton, at full term and followed from birth (n = 761) to 5 years of age (n = 513). The utility of each in identifying cardiometabolic risk factors (fasting lipid profile, fasting blood glucose and blood pressure) was examined. RESULTS: At age 5 years, children with percent body fat ≥ 90th percentile or waist circumference ≥ 90th percentile, were associated with higher levels of triglycerides, glucose, and systolic and diastolic blood pressures than those < 90th percentile, respectively. Such differences were not obvious at age 3 years or at birth. A BMI z-score > 2 SD was associated with higher levels of triglycerides and systolic and diastolic blood pressure but not glucose at age 5 years. Differences in HDL cholesterol, fasting glucose and systolic blood pressure were observed in children with BMI z score > 2 SD at age 3 years but not with the other indices of obesity. As almost all children had WHtR ≥ 0.5 at birth, ages 1 and 3 years, this measure could not differentiate increased cardiometabolic risk. At age 5 years, the differences were much more obvious, with significant differences in triglycerides and systolic and diastolic blood pressures between those with WHtR ≥ 0.5 and those with < 0.5. CONCLUSION: Each of the four commonly used measures of childhood obesity shows moderate associations with cardiometabolic risk factors at 5 years, with no advantage of one measure over the other. These associations were less consistent at 3 years of age or younger. These observations have not been reported previously.

9.
J. Am. Coll. Cardiol ; 73(25): 3271-3280, Jul. 2019. gráfico, tabela
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1024371

RESUMO

BACKGROUND: The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial showed that the combination of low-dose rivaroxaban and aspirin reduced major vascular events in patients with stable vascular disease. OBJECTIVES: The purpose of this study was to identify subsets of patients at higher risk of recurrent vascular events, which may help focus the use of rivaroxaban and aspirin therapy. METHODS: COMPASS patients with vascular disease were risk stratified using 2 methods: the REACH (reduction of Atherothrombosis for Continued Health) atherothrombosis risk score and CART (Classification and Regression Tree) analysis. The absolute risk differences for rivaroxaban with aspirin were compared to aspirin alone over 30 months for the composite of cardiovascular death, myocardial infarction, stroke, acute limb ischemia, or vascular amputation; for severe bleeding; and for the net clinical benefit. RESULTS: High-risk patients using the REACH score were those with 2 or more vascular beds affected, history of heart failure (HF), or renal insufficiency, and by CART analysis were those with ≥2 vascular beds affected, history of HF, or diabetes. Rivaroxaban and aspirin combination reduced the serious vascular event incidence by 25% (4.48% vs. 5.95%, hazard ratio: 0.75; 95% confidence interval: 0.66 to 0.85), equivalent to 23 events prevented per 1,000 patients treated for 30 months, at the cost of a nonsignificant 34% increase in severe bleeding (1.34; 95% confidence interval: 0.95 to 1.88), or 2 events caused per 1,000 patients treated. Among patients with ≥1 high-risk feature identified from the CART analysis, rivaroxaban and aspirin prevented 33 serious vascular events, whereas in lower-risk patients, rivaroxaban and aspirin treatment led to the avoidance of 10 events per 1,000 patients treated for 30 months. CONCLUSIONS: In patients with vascular disease, further risk stratification can identify higher-risk patients (≥2 vascular beds affected, HF, renal insufficiency, or diabetes). The net clinical benefit remains favorable for most patients treated with rivaroxaban and aspirin compared with aspirin. (AU)


Assuntos
Doenças Vasculares/tratamento farmacológico , Aspirina , Anticoagulantes
11.
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
12.
J Am Coll Cardiol ; 73(25): 3271-3280, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31248548

RESUMO

BACKGROUND: The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial showed that the combination of low-dose rivaroxaban and aspirin reduced major vascular events in patients with stable vascular disease. OBJECTIVES: The purpose of this study was to identify subsets of patients at higher risk of recurrent vascular events, which may help focus the use of rivaroxaban and aspirin therapy. METHODS: COMPASS patients with vascular disease were risk stratified using 2 methods: the REACH (REduction of Atherothrombosis for Continued Health) atherothrombosis risk score and CART (Classification and Regression Tree) analysis. The absolute risk differences for rivaroxaban with aspirin were compared to aspirin alone over 30 months for the composite of cardiovascular death, myocardial infarction, stroke, acute limb ischemia, or vascular amputation; for severe bleeding; and for the net clinical benefit. RESULTS: High-risk patients using the REACH score were those with 2 or more vascular beds affected, history of heart failure (HF), or renal insufficiency, and by CART analysis were those with ≥2 vascular beds affected, history of HF, or diabetes. Rivaroxaban and aspirin combination reduced the serious vascular event incidence by 25% (4.48% vs. 5.95%, hazard ratio: 0.75; 95% confidence interval: 0.66 to 0.85), equivalent to 23 events prevented per 1,000 patients treated for 30 months, at the cost of a nonsignificant 34% increase in severe bleeding (1.34; 95% confidence interval: 0.95 to 1.88), or 2 events caused per 1,000 patients treated. Among patients with ≥1 high-risk feature identified from the CART analysis, rivaroxaban and aspirin prevented 33 serious vascular events, whereas in lower-risk patients, rivaroxaban and aspirin treatment led to the avoidance of 10 events per 1,000 patients treated for 30 months. CONCLUSIONS: In patients with vascular disease, further risk stratification can identify higher-risk patients (≥2 vascular beds affected, HF, renal insufficiency, or diabetes). The net clinical benefit remains favorable for most patients treated with rivaroxaban and aspirin compared with aspirin.

14.
Gastroenterology ; 157(2): 403-412.e5, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31054846

RESUMO

BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528). CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.


Assuntos
Anticoagulantes/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Úlcera Péptica/prevenção & controle , Inibidores da Bomba de Prótons/administração & dosagem , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/epidemiologia , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Resultado do Tratamento
15.
Vasc Med ; 24(2): 132-140, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30799766

RESUMO

Patients with peripheral artery disease (PAD) are at high risk for ischemic cardiovascular complications. While single antiplatelet therapy (SAPT), predominantly aspirin, has long been the standard antithrombotic treatment in stable PAD, there have now been greater than 40,000 PAD patients randomized to varying antiplatelet and/or anticoagulant regimens. In this review, we provide a summary of the current evidence for antithrombotics in stable PAD, focusing on the rates of major adverse cardiovascular events (MACE), major adverse limb events (MALE), and major bleeding. SAPT has a limited role in the treatment of asymptomatic PAD, particularly in the absence of concomitant coronary artery disease. In symptomatic PAD, SAPT is effective in preventing MACE, though treatment with a thienopyridine appears marginally superior to aspirin. Dual antiplatelet therapy (DAPT) suggests benefit over SAPT in reducing MACE and MALE, though studies to date are not conclusive and/or are associated with excess major bleeding. Combining moderate to high intensity vitamin K antagonists with antiplatelet therapy does not reduce MACE or MALE and increases life-threatening bleeding. Rivaroxaban 2.5 mg BID in addition to aspirin reduces the incidence of both MACE and MALE as compared to aspirin alone, without increasing life-threatening bleeding. This regimen is associated with a reduced severity of MALE when it does occur. Comparisons across antithrombotic trials in PAD are challenging given the heterogeneity of patient populations and the differing assessment of outcomes. The vascular medicine practitioner can reduce ischemic cardiac and limb events, as well as minimize life-threatening bleeding, by choosing the optimal antithrombotic regimen in their PAD patients.


Assuntos
Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Anticoagulantes/efeitos adversos , Tomada de Decisão Clínica , Quimioterapia Combinada , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Seleção de Pacientes , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Fatores de Risco , Resultado do Tratamento
16.
Thromb Haemost ; 119(4): 576-585, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30703812

RESUMO

The most common causes of ischaemic stroke are represented by carotid artery atherosclerotic disease (CAAD) and atrial fibrillation. While oral anticoagulants substantially reduce the incidence of thromboembolic stroke (< 1%/year), the rate of ischaemic stroke and other cardiovascular disease events in patients with CAAD remains high, ranging from 8.4 to 18.1 events per 100 patient-years. Similar to any other atherosclerotic disease, anti-thrombotic therapies are proposed for CAAD to reduce stroke and other cardiovascular events. The 2017 European Society of Cardiology (ESC)/European Society for Vascular Surgery (ESVS) guidelines recommend for patients with asymptomatic CAAD ≥60% the use of aspirin 75 to 100 mg once daily or clopidogrel 75 mg once daily at the exception of patient at very high bleeding risk. For patients with symptomatic CAAD ≥50%, the use of aspirin 75 to 100 mg once daily or clopidogrel 75 mg once daily is recommended. New perspectives for anti-thrombotic therapy for the treatment of patients with CAAD come from the novel dual pathway strategy combining a low-dose anticoagulant (i.e. rivaroxaban) and aspirin that may help reduce long-term ischaemic complications in patients with CAAD. This review summarizes current evidence and recommendations for the anti-thrombotic management of patients with symptomatic or asymptomatic CAAD or those undergoing carotid revascularization.


Assuntos
Aterosclerose/tratamento farmacológico , Doenças das Artérias Carótidas/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Aspirina/administração & dosagem , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Cardiologia/métodos , Doenças Cardiovasculares/complicações , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/epidemiologia , Clopidogrel/uso terapêutico , Feminino , Hemorragia , Humanos , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica , Risco , Rivaroxabana/administração & dosagem
17.
Circulation ; 139(12): 1472-1482, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30667276

RESUMO

BACKGROUND: Lipoprotein(a) [Lp(a)] levels predict the risk of myocardial infarction (MI) in populations of European ancestry; however, few data are available for other ethnic groups. Furthermore, differences in isoform size distribution and the associated Lp(a) concentrations have not fully been characterized between ethnic groups. METHODS: We studied 6086 cases of first MI and 6857 controls from the INTERHEART study that were stratified by ethnicity and adjusted for age and sex. A total of 775 Africans, 4443 Chinese, 1352 Arabs, 1856 Europeans, 1469 Latin Americans, 1829 South Asians, and 1221 Southeast Asians were included in the study. Lp(a) concentration was measured in each participant using an assay that was insensitive to isoform size, with isoform size being assessed by Western blot in a subset of 4219 participants. RESULTS: Variations in Lp(a) concentrations and isoform size distributions were observed between populations, with Africans having the highest Lp(a) concentration (median=27.2 mg/dL) and smallest isoform size (median=24 kringle IV repeats). Chinese samples had the lowest concentration (median=7.8 mg/dL) and largest isoform sizes (median=28). Overall, high Lp(a) concentrations (>50 mg/dL) were associated with an increased risk of MI (odds ratio, 1.48; 95% CI, 1.32-1.67; P<0.001). The association was independent of established MI risk factors, including diabetes mellitus, smoking, high blood pressure, and apolipoprotein B and A ratio. An inverse association was observed between isoform size and Lp(a) concentration, which was consistent across ethnic groups. Larger isoforms tended to be associated with a lower risk of MI, but this relationship was not present after adjustment for concentration. Consistent with variations in Lp(a) concentration across populations, the population-attributable risk of high Lp(a) for MI varied from 0% in Africans to 9.5% in South Asians. CONCLUSIONS: Lp(a) concentration and isoform size varied markedly between ethnic groups. Higher Lp(a) concentrations were associated with an increased risk of MI and carried an especially high population burden in South Asians and Latin Americans. Isoform size was inversely associated with Lp(a) concentration, but did not significantly contribute to risk.

18.
Curr Opin Cardiol ; 34(2): 178-184, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30543542

RESUMO

PURPOSE OF REVIEW: To suggest a practical approach for the application of data from the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial in patients with peripheral artery disease (PAD). RECENT FINDINGS: The COMPASS trial showed that low-dose rivaroxaban 2.5 mg twice daily plus daily aspirin was superior to aspirin alone in reducing major adverse cardiovascular and cerebrovascular events, and major adverse limb events among patients with stable atherosclerotic vascular disease, including those with PAD. The risk for major bleeding, however, was higher with rivaroxaban plus aspirin. Critical limb ischemia at baseline (rest pain, ulcer, or gangrene), previous limb or foot amputation, or a history of peripheral revascularization surgery or stenting were independently associated with increased major adverse limb events within the trial. SUMMARY: Intensification of antithrombotic therapy with low-dose rivaroxaban plus aspirin should be considered in low bleeding risk PAD patients who are at increased risk for ischemic and/or limb events. A practical approach for clinicians is presented to help incorporate COMPASS data into practice.

19.
Future Cardiol ; 14(6): 443-453, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30417662

RESUMO

The cardiovascular outcomes for people using anticoagulation strategies (NCT01776424) trial randomized 27,395 patients with stable coronary artery disease or peripheral artery disease (PAD) to receive rivaroxaban 5 mg twice-daily alone, the combination of rivaroxaban 2.5 mg twice-daily and aspirin 100 mg daily, or aspirin 100 mg daily alone. The combination arm resulted in a 24% reduction in the primary end point of cardiovascular death, stroke or myocardial infarction, and an 18% reduction in mortality. Rivaroxaban alone did not produce any additional benefit compared with aspirin. The combination therapy also reduced major adverse limb events, including amputation, in patients with PAD. Based on these results, the addition of rivaroxaban to aspirin is expected to substantially reduce morbidity and mortality in patients with stable coronary or PAD.

20.
Lancet ; 392(10161): 2288-2297, 2018 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-30217460

RESUMO

BACKGROUND: Dietary guidelines recommend minimising consumption of whole-fat dairy products, as they are a source of saturated fats and presumed to adversely affect blood lipids and increase cardiovascular disease and mortality. Evidence for this contention is sparse and few data for the effects of dairy consumption on health are available from low-income and middle-income countries. Therefore, we aimed to assess the associations between total dairy and specific types of dairy products with mortality and major cardiovascular disease. METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large multinational cohort study of individuals aged 35-70 years enrolled from 21 countries in five continents. Dietary intakes of dairy products for 136 384 individuals were recorded using country-specific validated food frequency questionnaires. Dairy products comprised milk, yoghurt, and cheese. We further grouped these foods into whole-fat and low-fat dairy. The primary outcome was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios (HRs) were calculated using multivariable Cox frailty models with random intercepts to account for clustering of participants by centre. FINDINGS: Between Jan 1, 2003, and July 14, 2018, we recorded 10 567 composite events (deaths [n=6796] or major cardiovascular events [n=5855]) during the 9·1 years of follow-up. Higher intake of total dairy (>2 servings per day compared with no intake) was associated with a lower risk of the composite outcome (HR 0·84, 95% CI 0·75-0·94; ptrend=0·0004), total mortality (0·83, 0·72-0·96; ptrend=0·0052), non-cardiovascular mortality (0·86, 0·72-1·02; ptrend=0·046), cardiovascular mortality (0·77, 0·58-1·01; ptrend=0·029), major cardiovascular disease (0·78, 0·67-0·90; ptrend=0·0001), and stroke (0·66, 0·53-0·82; ptrend=0·0003). No significant association with myocardial infarction was observed (HR 0·89, 95% CI 0·71-1·11; ptrend=0·163). Higher intake (>1 serving vs no intake) of milk (HR 0·90, 95% CI 0·82-0·99; ptrend=0·0529) and yogurt (0·86, 0·75-0·99; ptrend=0·0051) was associated with lower risk of the composite outcome, whereas cheese intake was not significantly associated with the composite outcome (0·88, 0·76-1·02; ptrend=0·1399). Butter intake was low and was not significantly associated with clinical outcomes (HR 1·09, 95% CI 0·90-1·33; ptrend=0·4113). INTERPRETATION: Dairy consumption was associated with lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

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