Heart Failure and First Dose Hypotension After Angiotensin Converting Enzyme Inhibitors

Abstract

The first-dose induced decrease in blood pressure in some patients following the administration of ACE inhibitors is a fact causing some concern among clinicians prescribing these drugs. However, an overview of clinical trials and the authors' own experience clearly point to the possibility of reducing the incidence and/or severity of first-dose hypotension. Apart from appropriate clinical measures to be taken, the choice of the ACE inhibitor seems to be of crucial importance as some (fosinopril, perindopril) produce less hypotension than others. Thus, with due circumspection, ACE inhibitors can safely retain their position as the cornerstone of the treatment of chronic heart failure.First-dose hypotension has been recognized as a potential limiting factor in the use of ACE inhibitors in the treatment of chronic heart failure (CHF) and after acute myocardial infarction (AMI). Concerns regarding firstdose hypotension may increase the risk of renal, myocardial, or cerebral hypoperfusion that may result. The incidence of first-dose hypotension after ACE inhibitors reported in large clinical trials is small, varying from 0.7 % in the SAVE trial to 13.3 % in the OPTIMAAL trial 1,2 . This variation reflects differences in study design, in patient selection, in the definition of first-dose hypotension, and in drug selection. The major reason for the low number of these events reported is a very infrequent use of ambulatory blood pressure monitoring, and thus the incidence of less than 10 % reflects only symptomatic or casually measured hypotension. A number of smaller trials have reported a much higher incidence of first-dose hypotension, affecting as many as one third of the patients. SYMPTOMS OF FIRST-DOSE HYPOTENSIONThe most frequently reported symptoms of drug-induced hypotension are those related to cerebral hypoperfusion. These include light headiness, dizziness, headache, general weakness and visual disturbances 3 . In elderly patients, drug-induced hypotension has also been associated with falling. Several studies conducted in the community and in long-term residential care facilities have found drug-induced hypotension to be the primary cause of falling in both fit and frail elderly patients [4][5][6] . The clinical consequences of first-dose hypotension assume particular relevance in this patient population because the compensatory circulatory response to hypotensive stimuli, pre-existing vascular disease or both declines with age 7,34 . With more severe first-dose hypotension, the subsequent drop in cerebral blood flow can lead to a sudden brief loss of consciousness (syncope), often accompanied by bradycardia 8 . This may be especially dangerous in patients with heart failure. The incidence of syncope following initiation of an ACE inhibitor appears to have decreased dramatically over the last decade to between 0.5 and 2.2 %, although this may reflect changes in reporting practices 9,10 . Many clinicians continue to monitor closely the response to the first dose of an ACE inhibitor in patients with grade 3 ...

Potential side effects of renin inhibitors – mechanisms based on comparison with other renin–angiotensin blockers

“…It has been recommended that ACE inhibitor/ARB therapy be discontinued at least 10 h before anaesthesia, in order to reduce the risk of immediate postinduction hypotension [50]. It is possible to minimise the incidence or severity of first-dose hypotension by the careful selection of specific RAS inhibitors [44].…”

“…The incidence of reported hypotension is relatively low with both classes of agent and varies depending on the patient selection and the binding kinetics of the individual drug [41]. However, first-dose hypotension is still a concern in dehydrated, de-compensated patients with heart failure and bilateral renal artery stenosis [42], and in the elderly [43,44]. Worry about drug-induced hypotension, along with the renal dysfunction may be one reason for their underuse in patients with heart failure, as reflected in a recent survey of general practitioners of six European countries [45].…”