RESUMO

BACKGROUND: Low dose rivaroxaban with aspirin reduced major cardiovascular events (MACE) compared to aspirin alone in patients with cardiovascular disease although effects on total events are unknown. METHODS: The COMPASS clinical trial randomized 27,395 participants with chronic coronary and/or peripheral artery disease to rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily, rivaroxaban 5 mg twice daily alone, or aspirin 100 mg daily. We analyzed total (first and recurrent) MACE outcomes of cardiovascular death, stroke, or myocardial infarction, and the primary safety outcome of major bleeding. Exploratory analyses included on-treatment and net clinical benefit. Total MACE and safety events were modeled for each treatment. RESULTS: MACE events were lowest in rivaroxaban with aspirin (379 first MACE, 432 total MACE) compared with rivaroxaban (448 first, 508 total) or aspirin alone (496 first, 574 total). Rivaroxaban and aspirin reduced total MACE events compared with aspirin alone [HR 0.75, 95% CI 0.66-0.85, P < .0001, number needed to treat for 2 years (NNT2y) of 63]. Total major bleeding was higher for rivaroxaban with aspirin compared to aspirin, but severe bleeding was not increased. The net clinical benefit of rivaroxaban plus aspirin was 20% higher compared with aspirin alone [HR 0.80 (95% CI 16.3%-31.6%)]. Rivaroxaban alone had no benefit on MACE outcomes compared with aspirin alone. MACE outcomes were similar for those on and off randomized treatment. CONCLUSIONS: Low dose rivaroxaban with aspirin significantly reduces first and total cardiovascular events compared with aspirin alone with a NNT2y of 63 and a 20% net clinical benefit.

Assuntos

RESUMO

Abstract 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 1.8­2.6) and cardiovascular death (hazard ratio 2.0; 1.5­2.7) were more than twofold higher in patients with 4­6 compared with 0­1 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. (AU)

Assuntos

RESUMO

BACKGROUND: Patients with chronic coronary artery disease or peripheral artery disease and history of heart failure (HF) are at high risk for major adverse cardiovascular events. We explored the effects of rivaroxaban with or without aspirin in these patients. METHODS: The COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) randomized 27 395 participants with chronic coronary artery disease or peripheral artery disease to rivaroxaban 2.5mg twice daily plus aspirin 100 mg daily, rivaroxaban 5 mg twice daily alone, or aspirin 100 mg alone. Patients with New York Heart Association functional class III or IV HF or left ventricular ejection fraction (EF) <30% were excluded. The primary major adverse cardiovascular events outcome comprised cardiovascular death, stroke, or myocardial infarction, and the primary safety outcome was major bleeding using modified International Society of Thrombosis and Haemostasis criteria. Investigators recorded a history of HF and EF at baseline, if available. We examined the effects of rivaroxaban on major adverse cardiovascular events and major bleeding in patients with or without a history of HF and an EF <40% or >/=40% at baseline. RESULTS: Of the 5902 participants (22%) with a history of HF, 4971 (84%) had EF recorded at baseline, and 12% had EF <40%. Rivaroxaban and aspirin had similar relative reduction in major adverse cardiovascular events compared with aspirin in participants with HF (5.5% versus 7.9%; hazard ratio [HR], 0.68; 95% CI, 0.53-0.86) and those without HF (3.8% versus 4.7%; HR, 0.79; 95% CI, 0.68-0.93; P for interaction 0.28) but larger absolute risk reduction in those with HF (HF absolute risk reduction 2.4%, number needed to treat=42; no HF absolute risk reduction 1.0%, number needed to treat=103). The primary major adverse cardiovascular events outcome was not statistically different between those with EF <40% (HR, 0.88; 95% CI, 0.55-1.42) and >/=40% (HR, 0.81; 95% CI, 0.67-0.98; P for interaction 0.36). The excesso hazard for major bleeding was not different in participants with HF (2.5% versus 1.8%; HR, 1.36; 95% CI, 0.88-2.09) than in those without HF (3.3% versus 1.9%; HR, 1.79; 95% CI, 1.45-2.21; P for interaction 0.26). There were no significant differences in the primary outcomes with rivaroxaban alone. CONCLUSIONS: In patients with chronic coronary artery disease or peripheral artery disease and a history of mild or moderate HF, combination rivaroxaban and aspirin compared with aspirin alone produces similar relative but larger absolute benefits than in those without HF.(AU)

Assuntos

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

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

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...

Assuntos

RESUMO

Increasing age is associated with a higher prevalence of atrial fibrillation (AF), and higher risks of stroke andbleeding. We report the effects of apixaban versus acetylsalicylic acid (ASA) in older patients (≥75 years and ≥85 years) compared with younger patients with AF unsuitable for vitamin K antagonists...

Assuntos

RESUMO

The pattern of atrial fibrillation (AF) occurrence—paroxysmal, persistent, or permanent—is associated with progressivestages of atrial dysfunction and structural changes and may therefore be associated with progressively higher stroke risk.However, previous studies have not consistently shown AF pattern to predict stroke but have been hampered bymethodological shortcomings of low power, variable event ascertainment, and variable anticoagulant use.Methodsand resultsWe analysed the rates of stroke and systemic embolism in 6563 aspirin-treated patients with AF from the ACTIVE-A/AVERROESdatabases. Therewas thorough searching for events and adjudication. Multivariable analyses were performedwith the adjustment for known risk factors for stroke. Mean age of patients with paroxysmal, persistent, and permanentAFwas 69.0+9.9, 68.6+10.2, and 71.9+9.8 years (P , 0.001). TheCHA2DS2-VASc scorewas similar in patients withparoxysmal and persistent AF (3.1+1.4), but was higher in patients with permanent AF (3.6+1.5, P , 0.001). Yearlyischaemic stroke rates were 2.1, 3.0, and 4.2% for paroxysmal, persistent, and permanent AF, respectively, with adjustedhazard ratio of 1.83 (P , 0.001) for permanent vs. paroxysmal and 1.44 (P » 0.02) for persistent vs. paroxysmal.Multivariable analysis identified age ≥ 75 year, sex, history of stroke or TIA, and AF pattern as independent predictorsof stroke, with AF pattern being the second strongest predictor after prior stroke or TIA.Conclusion In a large population of non-anticoagulated AF patients, pattern of AF was a strong independent predictor of stroke riskand may be helpful to assess the risk/benefit for anticoagulant therapy, especially in lower risk patients.

Assuntos

RESUMO

Background A major limitation of primary percutaneous coronary intervention (PPCI) for the treatment of ST-elevation

myocardial infarction (STEMI) is impaired microvascular perfusion due to embolization and obstruction of microcirculation with

thrombus. Manual thrombectomy has the potential to reduce distal embolization and improve microvascular perfusion. Clinical

trials have shown mixed results regarding thrombectomy.

Objective The objective of this study is to evaluate the efficacy of routine upfront manual aspiration thrombectomy during

PPCI compared with percutaneous coronary intervention alone in patients with STEMI.

Design This is a multicenter, prospective, open, international, randomized trial with blinded assessment of outcomes.

Patients with STEMI undergoing PPCI are randomized to upfront routine manual aspiration thrombectomy with the Export

catheter (Medtronic CardioVascular, Santa Rosa, CA) or to percutaneous coronary intervention alone. The primary outcome is

the composite of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or new or worsening New York

Heart Association class IV heart failure up to 180 days. The trial uses an event-driven design and will recruit 10,700 patients.

Summary The TOTAL trial will determine the effect of routine manual aspiration thrombectomy during PPCI on clinically

Assuntos

RESUMO

The pattern of atrial fibrillation (AF) occurrence—paroxysmal, persistent, or permanent—is associated with progressivestages of atrial dysfunction and structural changes and may therefore be associated with progressively higher stroke risk.However, previous studies have not consistently shown AF pattern to predict stroke but have been hampered by methodologicalshortcomings of low power, variable event ascertainment, and variable anticoagulant use.Methodsand resultsWe analysed the rates of stroke and systemic embolism in 6563 aspirin-treated patients with AF from the ACTIVE-A/AVERROESdatabases. Therewas thorough searching for events and adjudication. Multivariable analyses were performedwith the adjustment for known risk factors for stroke. Mean age of patients with paroxysmal, persistent, and permanentAFwas 69.0+9.9, 68.6+10.2, and 71.9+9.8 years (P , 0.001). TheCHA2DS2-VASc scorewas similar in patients withparoxysmal and persistent AF (3.1+1.4), but was higher in patients with permanent AF (3.6+1.5, P , 0.001). Yearlyischaemic stroke rates were 2.1, 3.0, and 4.2% for paroxysmal, persistent, and permanent AF, respectively, with adjustedhazard ratio of 1.83 (P , 0.001) for permanent vs. paroxysmal and 1.44 (P » 0.02) for persistent vs. paroxysmal. Multivariableanalysis identified age ≥ 75 year, sex, history of stroke or TIA, and AF pattern as independent predictors ofstroke, with AF pattern being the second strongest predictor after prior stroke or TIA.Conclusion In a large population of non-anticoagulated AF patients, pattern of AF was a strong independent predictor of stroke riskand may be helpful to assess the risk/benefit for anticoagulant therapy, especially in lower risk patients.

Assuntos