Hypotension after first-dose ACE inhibitor administration in heart failure--should doctors stop worrying?

Abstract

Heart failure therapy has dramatically changed in the last two decades. Whereas before, the focus was on symptomatic treatment of heart failure with diuretics and digitalis glycosides, the advent of ACE inhibitors, beta-blocking drugs and aldosterone receptor antagonists has drastically changed our insight in how to approach the heart failure patient. A number of large, controlled clinical trials have clearly indicated that these agents may impact on the natural history of the syndrome and not only improve symptoms, but, in addition, reduce morbidity and mortality. The first drug developed in this context, the ACE inhibitor, has been evaluated against placebo in patients with mild, moderate and severe heart failure, improving survival in each category; its reductions in mortality ranging from 16% in mild to moderate heart failure to 31% in patients with severe heart failure [1,2]. Furthermore, ACE inhibitors decrease hospitalisations for heart failure by approximately 15%. Importantly, in patients who have a reduced systolic left ventricular function, but are still asymptomatic, ACE inhibition prevents or retards the development of heart failure in 37% [3]. When then a beta-blocker is added to the ACE inhibitor, a further 30–35% reduction in mortality is achieved as well as an additional 30% reduction in hospitalisations in both mild, moderate as well as severe heart failure [4–7]. Similar figures are obtained when in advanced heart failure an aldosterone antagonist is added. In the only study investigating this, the RALES study, a 30% reduction in mortality and in cardiovascular hospitalisations was observed over and above those achieved by ACE inhibitors alone [8]. Thus, accumulating evidence from various controlled studies disprove the old notion of heart failure being a terminal disorder requiring symptomatic rather than preventive treatment. As a consequence the focus has shifted towards treatment in the early stages of the disease and to prevention. One might expect that, against this background of a sizeable improvement of survival and significant reductions in both heart failure and all-cause hospitalisations, patient management would have changed significantly over the past years. Indeed, patient management guidelines specify the need for early treatment with ACE inhibitors and beta-blockers, in the later stages followed by aldosterone antagonist being mandatory in the treatment of heart failure [9]. Nevertheless, despite the available evidence-based treatment strategies and clear and precise patient management guidelines, few patients actually receive optimal medical treatment. Somehow evidence-based medicine and strategies have not translated to clinical practice. Patients either do not receive the therapy they need or receive it in insufficient dosages. In the case of ACE inhibition this is particularly true. Nearly 15 years after the first large study demonstrating a beneficial effect of ACE inhibition on mortality in severe heart failure [1], later followed by other studies providing the same evidence in different degrees of heart failure [2,10], at present only 20–40% of patients with heart failure receive an ACE inhibitor, usually in dosages that do not conform to those used in the large studies, which, at least in that context, had shown their beneficial effect. Why is this? Quite a few possibilities may apply. Heart failure patients or patients at risk of heart failure are often not detected, as the required diagnostic tools are not or insufficiently available for the health care provider, who, in most instances, is the general practitioner. The patient or his relatives may to some extent be unknowingly at fault and be unaware of the disease, not perceiving its seriousness, and also be unaware of the therapeutic possibilities and not demand them. It is also likely that the health care provider may be at fault, again without realizing this. Health care providers of different backgrounds, e.g. general practitioners, internists or geriatricians, may not be aware of the results of the large, controlled studies showing the benefits of the ACE inhibitor. Doctors, including specialists, may not be convinced that the results of large, controlled studies on the effect of these medications