Efficacy of antithrombotic therapy in chronic heart failure: The HELAS study

Abstract

Background: It is not clear if long-term antithrombotic treatment has a beneficial effect on the incidence of thromboembolism in chronic heart failure (CHF). The HELAS study (Heart failure Long-term Antithrombotic Study) is a multicentre, randomised, double-blind, placebocontrolled trial to evaluate antithrombotic treatment in patients with CHF. Methods: 197HF patients (EF < 35%) were enrolled. Patients with Ischaemic Heart Disease were randomised to receive either aspirin 325mg or warfarin. Patients with Dilated Cardiomyopathy (DCM) were randomised to receive either warfarin or placebo. Results: Analysis of the data from 312 patient years showed an incidence of 2.2 embolic events per 100 patient years, with no significant difference between groups. The incidence of myocardial infarction, hospitalisation, exacerbation of heart failure, death and haemorrhage were not different between the groups. No peripheral or pulmonary emboli were reported. Echocardiographic follow-up for 2 years showed an overall increase in left ventricular ejection fraction from 28.2 T 6 to 30.3 T 7 p < 0.05, which was most obvious in patients with DCM taking warfarin (EF 26.8 T 5.3 at baseline, 30.7 T 10 at 2 years, p < 0.05). Conclusions: (1) Overall embolic events are rare in heart failure regardless of treatment. (2) Treatment does not seem to affect outcome.

Thromboxane and prostacyclin biosynthesis in heart failure of ischemic origin: effects of disease severity and aspirin treatment

“…The homeostatic increase in vascular prostacyclin biosynthesis is impaired in this setting as compared with IHD without heart failure, thus creating an unbalance in PGI 2 vs. TXA 2 biosynthesis that may contribute to enhanced thrombotic risk. These findings provide a rationale for re-evaluating the efficacy and safety of aspirin in heart failure, at a daily dose regimen substantially lower than the COX-2 inhibiting regimen employed in earlier randomized trials [35,37]. …”

“…In the present study, 100 mg daily of aspirin only marginally reduced systemic prostacyclin biosynthesis. Thus, the higher than needed daily doses of aspirin used in heart failure trials [35][36][37] may have contributed to a pharmacodynamic interaction with ACE-inhibitors that is not apparent at lower doses [30]. Furthermore, it should be emphasized that inhibition of COX-2-dependent PGI 2 production may increase the risk of atherothrombotic events, particularly myocardial infarction [40], and this cardiotoxicity is readily detectable in aspirintreated patients with ongoing platelet activation [41].…”

“…WATCH (Warfarin and Antiplatelet Therapy in Chronic Heart failure) [36] and HELAS (Heart failure Long-term Antithrombotic Study) [37] trials. However, these trials employed 2-to 4-fold higher aspirin doses (162-325 mg daily) than currently recommended for the prevention of vascular events in IHD [38].…”

The evaluation of mean platelet volume levels in patients with idiopathic and ischemic cardiomyopathy: an observational study

“…Therefore, there is still conflicting data for the use of anti-platelet and anticoagulant agents in CMP. While some studies recommend the use of anti-platelet and anticoagulant agents in CMP, some studies do not recommend (30)(31)(32)(33)(34)(35). Moreover, use of antiplatelet agents has been associated with increased hospitalization rate due to their interactions with angiotensin-converting enzyme inhibitors (33,34).…”

Coexisting Cardiac and Hematologic Disorders

“…The addition of anticoagulant and/or antithrombotic therapy in those with coexisting atrial fibrillation or previous thromboembolic event is recommended; however, anticoagulant therapy for patients in sinus rhythm with reduced ejection fraction is less clear. Multiple randomized controlled trials have compared the use of warfarin, aspirin, and clopidigrel in this patient population with conflicting results [46][47][48] . Aspirin has been associated with increased risk for hospitalization and gastrointestinal bleeding; however, this may be due to an as yet undefined interaction with ACE inhibitors 49 .…”