RESUMEN

AIMS: Coronary artery disease (CAD) portends worse outcomes in heart failure (HF). We aimed to characterize patients with CAD and worsening HF with reduced ejection fraction (HFrEF) and evaluate post hoc whether vericiguat treatment effect varied according to CAD. METHODS AND RESULTS: Cox proportional hazards were generated for the primary endpoint of cardiovascular death or HF hospitalization (CVD/HFH). CAD was defined as previous myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting. Of 5048 patients in VICTORIA with available data on CAD status, 2704 had CAD and were older, were more frequently male, diabetic, and had a lower glomerular filtration rate than those without CAD (all p <0.0001). Use of implantable cardioverter defibrillators and cardiac resynchronization therapy (CRT) was higher in patients with versus without CAD (33.5% vs. 21.1%; p <0.0001 and 16.3% vs. 12.8%; p = 0.0006). The primary endpoint of CVD/HFH was higher in those with versus without CAD (40.6 vs. 30.1/100 patient-years; adjusted hazard ratio [HR] 1.23; p <0.001) as was all-cause mortality (17.9% vs. 12.7%; adjusted HR 1.32; p <0.001). The primary outcome of CVD/HFH associated with vericiguat in patients with or without CAD was 38.8 versus 27.6 per 100 patient-years and for placebo was 42.6 versus 32.7 per 100 patient-years (interaction p = 0.78). CONCLUSION: In this post hoc study, CAD was associated with more CVD and HFH in patients with HFrEF and worsening HF. Vericiguat was beneficial and safe regardless of concomitant CAD.

Asunto(s)

Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Compuestos Heterocíclicos con 2 Anillos , Disfunción Ventricular Izquierda , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Compuestos Heterocíclicos con 2 Anillos/uso terapéutico , Humanos , Masculino , Pirimidinas , Volumen Sistólico , Disfunción Ventricular Izquierda/tratamiento farmacológico

RESUMEN

AIMS Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated. METHODS AND RESULTS After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64­0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68­1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69­0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69­0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years. CONCLUSION The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect.

Asunto(s)

Humanos , Enfermedades Cardiovasculares/prevención & control , Infarto del Miocardio , Presión Sanguínea , Colesterol

RESUMEN

BACKGROUND AND PURPOSE: The HOPE-3 trial (Heart Outcomes Prevention Evaluation­3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups. METHODS: Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed. RESULTS: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59­1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55­1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34­1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41­2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52­0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37­0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59­2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57­2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36­0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23­0.72]). CONCLUSIONS: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated.

Asunto(s)

Femenino , Accidente Cerebrovascular/prevención & control , Antihipertensivos , Inhibidores de Hidroximetilglutaril-CoA Reductasas

RESUMEN

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)

Asunto(s)

Humanos , Masculino , Femenino , Persona de Mediana Edad , Enfermedades Cardiovasculares/prevención & control , Aspirina/administración & dosificación , Método Doble Ciego , Relación Dosis-Respuesta a Droga , Hemorragia Gastrointestinal/prevención & control , Anticoagulantes/administración & dosificación

RESUMEN

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)

Asunto(s)

Bacterias , Enfermedades Cardiovasculares , Aspirina

RESUMEN

OBJECTIVE: To assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk. METHODS: The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 × 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were ≥70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end. RESULTS: Cognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD ±3.5 years); 59% were women; 45% had hypertension; and 24% had ≥12 years of education. The mean difference in change in DSST scores was -0.91 (95% confidence interval [CI] -2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, -0.54 (95% CI -1.88 to 0.80) for rosuvastatin compared with placebo, and -1.43 (95% CI -3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures. CONCLUSIONS: Long-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people.(AU)

Asunto(s)

Cognición , Hipertensión/complicaciones

RESUMEN

OBJECTIVE: To assess stroke/systemic embolism, major bleeding and other outcomes, and treatment effect of apixaban versus warfarin, in patients with atrial fibrillation (AF) and different types of valvular heart disease (VHD), using data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial. METHODS: There were 14 793 patients with known VHD status, categorised as having moderate or severe mitral regurgitation (MR) (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324); patients with moderate or severe mitral stenosis were excluded from the trial. Baseline characteristics, efficacy and safety outcomes were compared between each type and no significant VHD. Treatment effect was assessed using an adjusted model. Results Patients with MR or AR had similar rates of stroke/systemic embolism and bleeding compared with patients without MR or AR, respectively. Patients with AS had significantly higher event rates (presented as rate per 100 patient-years of follow-up) of stroke/ systemic embolism (3.47 vs 1.36; adjusted HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI 1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than patients without AS. The superiority of apixaban over warfarin on stroke/systemic embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to 1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96; interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to 1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the primary and secondary efficacy and safety outcomes, there was no evidence of a different effect of apixaban over warfarin in patients with any VHD subcategory. CONCLUSIONS: In anticoagulated patients with AF, AS is associated with a higher risk of stroke/systemic embolism, bleeding and death. The efficacy and safety benefits of apixaban compared with warfarin were consistent, regardless of presence of MR, AR or AS.

Asunto(s)

Válvula Aórtica , Fibrilación Atrial , Enfermedades de las Válvulas Cardíacas , Anticoagulantes

RESUMEN

METHOD AND RESULTS:Thrombo-embolic events were defined as stroke (ischaemic or unknown cause) or systemic embolism (SE). Clinical outcomes were estimated using the Kaplan­Meier method. All-cause mortality and International Society on Thrombosis and Haemostasis (ISTH) major bleeding after events were analysed using a Cox proportional hazards model with time-dependent covariates. Of 18 201 patients in ARISTOTLE, 365 experienced a thrombo-embolic event [337 strokes (ischaemic or unknown cause), 28 SE]; 46 (12.6%) of which were fatal. In the 30 days before and after a thrombo-embolic event, 11% and 37% of patients, respectively, were not taking an oral anticoagulant. During follow-up (median 1.8 years), 22 patients (7.1%/year) had a recurrent stroke, 97 (30.1%/year) died, and 10 (6.7%/year) had major bleeding. Compared with patients without a thrombo-embolic event, the short- and long-term adjusted hazards of death in patients with a thrombo-embolic event were high [30 days: HR 3.5, 95% CI 2.5­4.8; both P< 0.001]. The adjusted hazards of major bleeding were also high short-term (HR 10.37, 95% CI 3.87­27.78; P< 0.001) but not long-term (HR 1.7, 95% CI: 0.77­3.88; P= 0.18). CONCLUSIONS: Thrombo-embolic events were rare but associated with high short- and long-term morbidity and mortality. Substantial numbers of patients are not receiving oral anticoagulant therapy before and, despite this risk, after a first thrombo-embolic event.

Asunto(s)

Fibrilación Atrial , Trombosis , Modelos de Riesgos Proporcionales , Fibrinolíticos , Anticoagulantes

RESUMEN

SUMMARY BACKGROUND Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. METHODS This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle­brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57­0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35­0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69­1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45­1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12­2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17­2·40; p=0·0043). INTERPRETATION Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.

Asunto(s)

Enfermedad de la Arteria Coronaria , Inhibidores de Agregación Plaquetaria , Enfermedades de las Arterias Carótidas , Enfermedad Arterial Periférica , Rivaroxabán

RESUMEN

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...

Asunto(s)

Anticoagulantes , Aspirina , Cardiopatías

RESUMEN

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.

Asunto(s)

Accidente Cerebrovascular , Anticoagulantes , Fibrilación Atrial

RESUMEN

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.

Asunto(s)

Accidente Cerebrovascular , Fibrilación Atrial , Hemorragia

RESUMEN

BACKGROUND: A substantial portion of patients with atrial fibrillation (AF) also have coronary artery disease (CAD) and are at risk for coronary events. Warfarin is known to reduce these events, but increase the risk of bleeding. We assessed the effects of apixaban compared with warfarin in AF patients with and without prior CAD. METHODS AND RESULTS: In ARISTOTLE, 18,201 patients with AF were randomized to apixaban or warfarin. History of CAD was defined as documented CAD, prior myocardial infarction, and/or history of coronary revascularization. We analyzed baseline characteristics and clinical outcomes of patients with and without prior CAD and compared outcomes by randomized treatment using Cox models. A total of 6639 (36.5%) patients had prior CAD. These patients were more often male, more likely to have prior stroke, diabetes, and hypertension, and more often received aspirin at baseline (42.2% vs. 24.5%). The effects of apixaban were similar among patients with and without prior CAD on reducing stroke or systemic embolism and death from any cause (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.71-1.27, P for interaction=0.12; HR 0.96, 95% CI 0.81-1.13, P for interaction=0.28). Rates of myocardial infarction were numerically lower with apixaban than warfarin among patients with and without prior CAD. The effect of apixaban on reducing major bleeding and intracranial hemorrhage was consistent in patients with and without CAD. CONCLUSIONS: In patients with AF, apixaban more often prevented stroke or systemic embolism and death and caused less bleeding than warfarin, regardless of the presence of prior CAD. Given the common occurrence of AF and CAD and the higher rates of cardiovascular events and death, our results indicate that apixaban may be a better treatment option than warfarin for these high-risk patients.

Asunto(s)

Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/mortalidad , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/mortalidad , Pirazoles/administración & dosificación , Piridonas/administración & dosificación , Warfarina/administración & dosificación , Adulto , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Embolia/mortalidad , Embolia/prevención & control , Femenino , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Pirazoles/efectos adversos , Piridonas/efectos adversos , Factores de Riesgo , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/prevención & control , Resultado del Tratamiento , Warfarina/efectos adversos

RESUMEN

Background Small trials have suggested that radial access for percutaneous coronary intervention (PCI) reducesvascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronaryangiography with possible intervention.Methods The RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group,multicentre trial. Patients with ACS were randomly assigned (1:1) by a 24 h computerised central automated voiceresponse system to radial or femoral artery access. The primary outcome was a composite of death, myocardialinfarction, stroke, or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. Key secondary outcomes were death, myocardial infarction, or stroke; and non-CABG-related major bleeding at 30 days. A masked central committee adjudicated the primary outcome, components of the primary outcome, and stent thrombosis. All other outcomes were as reported by the investigators. Patients and investigators were not masked to treatment allocation. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01014273. Findings Between June 6, 2006, and Nov 3, 2010, 7021 patients were enrolled from 158 hospitals in 32 countries.3507 patients were randomly assigned to radial access and 3514 to femoral access. The primary outcome occurred in128 (3·7%) of 3507 patients in the radial access group compared with 139 (4·0%) of 3514 in the femoral access group (hazard ratio [HR] 0·92, 95% CI 0·72–1·17; p=0·50). Of the six prespecifi ed subgroups, there was a signifi cant interaction for the primary outcome with benefi t for radial access in highest tertile volume radial centres (HR 0·49, 95% CI 0·28–0·87; p=0·015)...

Asunto(s)

Angiografía Coronaria , Angioplastia , Arteria Femoral , Arteria Radial , Enfermedad Coronaria

RESUMEN

Background Vitamin K antagonists have been shown to prevent stroke in patients with atrial fibrillation. However, many patients are not suitable candidates for or are unwilling to receive vitamin K antagonist therapy, and these patients have a high risk of stroke. Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients.Methods In a double-blind study, we randomly assigned 5599 patients with atrial fibrillation who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable to receive apixaban (at a dose of 5 mg twice daily) or aspirin (81 to 324 mgper day), to determine whether apixaban was superior. The mean follow up period was 1.1 years. The primary outcome was the occurrence of stroke or systemic embolism.Results Before enrollment, 40% of the patients had used a vitamin K antagonist. The data and safety monitoring board recommended early termination of the study because of a clear benefit in favor of apixaban. There were 51 primary outcome events (1.6% per year) among patients assigned to apixaban and 113 (3.7% per year) among those assigned to aspirin (hazard ratio with apixaban, 0.45; 95% confidence interval [CI],0.32 to 0.62; P<0.001). The rates of death were 3.5% per year in the apixaban group and 4.4% per year in the aspirin group (hazard ratio, 0.79; 95% CI, 0.62 to 1.02; P = 0.07).There were 44 cases of major bleeding (1.4% per year) in the apixaban group and 39 (1.2% per year) in the aspirin group (hazard ratio with apixaban, 1.13; 95% CI, 0.74 to 1.75; P = 0.57); there were 11 cases of intracranial bleeding with apixaban and 13 with aspirin. The risk of a first hospitalization for cardiovascular causes was reduced with apixaban as compared with aspirin (12.6% per year vs. 15.9% per year, P<0.001). The treatment effects were consistent among important subgroups...

Asunto(s)

Fibrilación Atrial , Pacientes , Preparaciones Farmacéuticas , Vitamina K

RESUMEN

Background Major bleeding in acute coronary syndromes (ACS) is associated with an increased risk of subsequentmortality and recurrent ischemic events. Observational data and small randomized trials suggest that radial instead of femoralaccess for coronary angiography/intervention results in fewer bleeding complications, with preserved and possibly improvedefficacy. Radial access versus femoral access has yet to be formally evaluated in a randomized trial adequately powered forthe comparison of clinically important outcomes.Objectives The aim of this study is to evaluate the efficacy and safety of radial versus femoral access for coronaryangiography/intervention in patients with ACS managed with an invasive strategy.Design This was a multicenter international randomized trial with blinded assessment of outcomes. 7021 patients withACS (with or without ST elevation) have been randomized to either radial or femoral access for coronary angiography/intervention. The primary outcome is the composite of death, myocardial infarction, stroke, or non–coronary artery bypassgraft-related major bleeding up to day 30. The key secondary outcomes are (1) death, myocardial infarction, or stroke up today 30 and (2) non–coronary artery bypass graft-related major bleeding up to day 30. Percutaneous coronary intervention(PCI) success rates will also be compared between the two access sites.Conclusions The RIVAL trial will help define the optimal access site for coronary angiography/intervention in patientswith ACS.

Asunto(s)

Angiografía Coronaria , Arteria Femoral , Enfermedad Coronaria

RESUMEN

Background: Even though sirolimus-eluting stents (SES) have been shown to significantly improve binaryrestenosis and target lesion revascularisation rates (TLR) compared to bare metal stents in diabeticpatients, the revascularisation rate is still higher than those of non-diabetics. Whether a double dose (DD)of sirolimus on a stent would provide a greater reduction in neointimal hyperplasia compared to single dose(SD) SES in de novo coronary lesion of diabetic patients is unknown.Methods and results: A total of 56 patients (58 lesions) were prospectively randomised in a double blindfashion in a 1:1 ratio to SD (30 lesions) versus DD (28 lesions). Procedure success was achieved in allpatients. QCA results at 6 months were comparable between groups, including the primary endpoint of instentlate lumen loss (0.19±0.29 mm in SD versus 0.18±0.33 mm in DD, p=0.96). Furthermore, restenosiswas not found inside the stent in either group. By IVUS, there was no late/acquired incomplete stentapposition at follow-up, and% neointimal volume was 2.2±1.8% in SD versus 1.7±2.0% in DD, p=0.44. At1-year clinical follow-up, there was no significant difference between groups for major events, includingTLR which occurred in 1 patient in SD versus 3 patients in DD, p=0.61. Overall, there was only 1 subacutestent thrombosis (DD arm), and no late thromboses.Conclusions: Double dose SES did not improve the prevention of neointimal proliferation in diabetic patientswith de novo coronary lesion compare to single dose SES.

Asunto(s)

Diabetes Mellitus , Reestenosis Coronaria , Sirolimus , Stents