Association between inflammation, lipid and hemostatic factors in patients with stable angina.

INTRODUCTION: Dyslipidemia and thrombotic processes are both clearly involved in atherogenesis and its secondary complications. Moreover, inflammation has also been shown to play an important role in the pathophysiology of atherosclerosis. Our objective was to determine the association between inflammation, lipids and thrombosis in a group of patients with stable angina. PATIENTS AND METHODS: 295 patients (217 males and 78 females) with a mean age of 65.69+/-11.24 years. Levels of C-reactive protein, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, lipoprotein(a), apolipoproteins A1 and B100, fibrinogen and D-dimer were determined for each. RESULTS: Arithmetic and geometric means of C-reactive protein in the sample were 10.7 and 1.4 mg/l, respectively. Distributing the sample by quartiles of C-reactive protein, we found a positive correlation between C-reactive protein, fibrinogen and D-dimer levels (p<0.000), and an inverse correlation for HDL cholesterol and apolipoprotein A1 (p<0.000). In multivariate analysis, fibrinogen (p<0.000) and D-dimer (p<0.01) levels were independently associated with high levels of C-reactive protein. Of the lipid factors, only apolipoprotein A1 (p<0.000) was independently and inversely associated with high levels of C-reactive protein. CONCLUSIONS: These data confirm the association between prothrombotic and inflammatory states and suggest the anti-inflammatory effect of apolipoprotein A1.

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.

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.

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.