Antithrombotic therapy in elderly patients with atrial fibrillation: effects and bleeding complications: a stratified analysis of the NASPEAF randomized trial.

AIMS: Atrial fibrillation patients with prior embolism have a high risk of vascular events in spite of anticoagulant therapy and elderly patients carry an additional risk. We analysed and compared vascular events-rate between older and younger than 75 years atrial fibrillation patients randomized to anticoagulant-alone or combined antiplatelet plus moderate-level anticoagulant therapy. METHODS AND RESULTS: A total of 967 patients stratified by age and the history of prior embolism were randomized to therapeutic doses of anticoagulant-alone or combined antithrombotic therapy. Primary events were fatal and non-fatal ischaemic or haemorrhagic stroke/transient ischaemic attack, systemic embolism and myocardial infarction, sudden death and death from bleeding. The elderly, compared with the younger patients, had higher event-rate [hazard ratio 2.31 (95% confidence interval 1.37-3.90), P < 0.003]. The elderly suffered higher severe bleeding event-rate during anticoagulant therapy. The combined, compared with the anticoagulant therapy, reduced the vascular events-rate in the elderly (P = 0.012) and caused less intracranial haemorrhages and less bleeding mortality, although more non-fatal gastric bleeding. CONCLUSION: The elderly with AF had a higher event-rate than the younger patients. A higher severe bleeding event-rate was also registered in elderly patients receiving anticoagulant therapy. Combined, compared with anticoagulant therapy, significantly reduced vascular events and bleeding mortality in elderly patients.

[Utility of NT-proBNP for diagnosing heart failure in a heterogeneous population of patients with dyspnea. Spanish multicenter study]. / Utilidad del NT-proBNP para el diagnóstico de insuficiencia cardiaca en una población heterogénea de pacientes con disnea. Estudio multicéntrico español.

INTRODUCTION AND OBJECTIVES: Recent studies have shown that brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are useful in the diagnosis of heart failure in patients presenting with dyspnea. However, the cutoff values used with these markers vary according to patient characteristics and dyspnea severity. The aim of this study was to investigate the diagnostic accuracy of using the plasma NT-proBNP level for identifying heart failure in a heterogeneous population of patients with dyspnea. METHODS: A multicentre study involving 247 consecutive patients with recent-onset dyspnea was carried out at 12 Spanish hospitals. Patients previously diagnosed with heart failure or any other condition known to cause dyspnea were excluded. RESULTS: Of the 247 patients, 161 (65%) had heart failure. The remaining 86 (35%) presented with dyspnea of non-cardiac origin. Plasma NT-proBNP levels were higher in patients with heart failure (5600 [7988] pg/mL vs 1182 [4406] pg/mL; P=.0001), and increased as functional status deteriorated (P=.036). The area under the receiver operating characteristic curve was 0.87 (0.02) (95% CI, 0.81-0.91) for the optimum cutoff value of 1335 pg/mL. The sensitivity of this cutoff value for diagnosing heart failure was 77% (95% CI, 70%-83%), the specificity was 92% (95% CI, 84%-97%), the positive predictive value was 94%, and the negative predictive value was 68%. CONCLUSIONS: The plasma NT-proBNP concentration provides an accurate means of diagnosing heart failure. However, the negative predictive value found in this study was somewhat lower than the values found in previous studies involving more homogeneous patient populations.

Effect of antithrombotic therapy in patients with mitral stenosis and atrial fibrillation: a sub-analysis of NASPEAF randomized trial.

AIMS: The randomized NASPEAF study included non-valvular with prior embolism and mitral stenosis patients in the same group. This is a sub-study to specially focus on the antithrombotic therapy in mitral stenosis. METHODS AND RESULTS: We analysed 311 patients with mitral stenosis, compared with 175 non-valvular atrial fibrillation patients with prior embolism, stratified by a history of previous embolism and assigned to anticoagulant therapy [target international normalized ratio (INR) = 2.0-3.0] or combined antiplatelet plus moderate intensity anticoagulant therapy. Median follow-up was 2.9 years. Outcomes were fatal and non-fatal embolism, stroke and myocardial infarction, sudden death, and death from bleeding. Combined therapy in mitral stenosis patients, compared with anticoagulant alone therapy, reduced the risk of vascular events by 58.3%. During equal therapy, the outcome annual rates were essentially the same in non-valvular and valvular patients [hazard ratio 0.90 (95% confidence interval 0.37-2.16), P = 0.81]. During anticoagulant alone therapy, the annual event rate in mitral stenosis patients without prior embolism was low (2.5%) and it was very high in patients with prior embolism (6.6%). CONCLUSION: Combined therapy was effective in mitral stenosis patients. Prior embolism patients are not efficiently protected with anticoagulant alone therapy for an INR of 2.0-3.0.

Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study.

OBJECTIVES: This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis. BACKGROUND: Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated. METHODS: We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism. RESULTS: Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy. CONCLUSIONS: The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients.