Background Congestive heart failure is a common clinical syndrome, the incidence and prevalence of which appear to be increasing. Mortality and morbidity remain high despite major advances in the understanding of the pathophysiology and management of heart failure over recent years. Consequently there is a need for further therapies which can improve the outlook for patients with heart failure. The beta-blockers have traditionally been contraindicated in patients with heart failure. However, there is a strong rationale for using these agents in addition to the ACE inhibitors. The aims of this thesis were several fold. Firstly, to determine the magnitude of the problem which heart failure represents in New Zealand. Secondly, to determine the effects of beta-blockers, on LV size and function, symptoms, and exercise tolerance in patients with heart failure due to ischaemic heart disease. Finally, to conduct a systematic overview to determine the effects of beta-blockers on total mortality in patients with heart failure. Methods Data were obtained from the New Zealand Health Information Service regarding hospitalisations and deaths due to heart failure in New Zealand. A randomised, placebo-controlled trial of the effects of carvedilol, a vasodilator beta-blocker, was carried out in 20 hospitals in Australia and New Zealand. In this study patients with heart failure due to ischaemic heart disease were randomised to either carvedilol or placebo in addition to their usual treatment. An echocardiographic substudy was carried out in 10 of the 20 centres. The aims of this substudy were to determine the effects of carvedilol on left ventricular size and function, using quantitative 2D-echocardiography. Finally, the effects of beta-blockers on total mortality was examined in a systematic overview. Results The data regarding heart failure in New Zealand showed that each year there were an average of 8000 hospital admissions each year of 5000 patients with heart failure. In addition, there were at least 850 deaths each year directly related to heart failure. The cost associated with the hospital admissions was estimated at NZ$50 million per year, or 1% of the total health budget in New Zealand. The ANZ carvedilol study demonstrated firstly, that carvedilol is well tolerated in patients with heart failure due to ischaemic heart disease. Left ventricular ejection fraction improved compared with placebo treated patients and left ventricular size was reduced when assessed by M-mode echocardiography. Despite these improvements in left ventricular function, symptoms and exercise tolerance were unchanged. However, there was a reduction in a combined end-point of death or hospital readmission in the carvedilol group compared with placebo. The 2D-echocardigraphy substudy demonstrated that carvedilol reduced both end-diastolic and end-systolic volumes and prevented the progressive LV dilatation which occurred in the placebo group. These changes occurred with the improvement in LV ejection fraction which had previously been reported. In addition to these favourable effects on LV size and function, left ventricular regional wall motion was improved. The overview of 24 randomised trials involving 3141 patients showed that beta-blocker therapy reduced total mortality by 31% compared with control. Conclusions Firstly, the NZ data has confirmed that heart failure remains a major public health problem in New Zealand. The ANZ Carvedilol Trial has shown the carvedilol is safe and well tolerated in patients with heart failure due to ischaemic heart disease. Carvedilol improved left ventricular ejection fraction, reduced left ventricular volumes and improved left ventricular regional wall motion. In addition, carvedilol reduced death or hospital readmission but had little effect on symptoms or exercise tolerance. The results from the meta-analysis have shown that beta-blocker therapy reduced total mortality by approximately one-third. Such data support the use of beta-blockers in addition to ACE inhibitors in the treatment of patients with heart failure. However, further randomised, controlled trials are required to reliably determine the effects of beta-blockers in different patient subgroups, such as the elderly and those with more severe heart failure, as well as the effects on total mortality before such therapy can be recommended for widespread use in all patients with heart failure. / Whole document restricted, but available by request, use the feedback form to request access.
| Identifer | oai:union.ndltd.org:ADTP/247794 |
| Date | January 1997 |
| Creators | Doughty, Robert N. |
| Publisher | ResearchSpace@Auckland |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Whole document restricted but available by request. Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated., http://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm, Copyright: The author |
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