Conference Highlights Three Key Issues in Antihypertensive Therapy <continued trom last week)

Quality of Life and Antihypertensive Therapy This was the topic of the third session which was opened by Professor J.A. Schoenberger from Chicago,

who presented an overview of the current methodology used in this area. Severe hypertension carries significant risk for cardiovascular morbidity and mortality so treatment has clear benefits in the short and long term, but in mild hypertension patients often remain symptom-free for many years. Consequently, treatment, with its associated side effects, may in fact produce a deterioration in the patient's quality of life. Objective measurement of quality of life is not possible and indeed it may be seen differently by the patient, the physician and the patient's immediate family.

In a recent study of antihypertensive therapies, quality of life was assessed with a comprehensive questionnaire which covered the basic areas of well-being, physical symptoms, sexual function, work performance and satisfaction, emotional status, cognitive function, social participation and general life· satisfaction. This approach allowed a clear demonstration that, for the patient group studied, the quality of life was considered significantly better when treatment consisted of the ACE inhibitor, captopril, rather than either methyldopa or propranolol.

Effects on memory function and mood ••• Professor P.J. Richardson from London concentrated on the effects of antihypertensive drugs on cognitive

function, and memory in particular. It has been known for some years that some tj-blockers have central actions, including impairment of cognitive and memory function, and more recent investigations using propranolol demonstrated that the main effects are on verbal rather than visual memory. Little is known about the central effects of ACE inhibitors, although both captopril and enalapril have improved attention and visuo motor coordination in some studies. One investigation has compared the effects of enalapril and atenolol on memory function with respect to everyday procedures such as the learning and recall of telephone numbers and shopping lists, and it was found that there was a mild but consistent impairment of learning ability and both short and long term memory recall in the patients who received atenolol. In contrast, there was no impairment of memory or learning ability in the patients who were treated with enalapril.

The procedures involved in designing suitable tests for quality of life were described by Dr S. Jern of Gotenborg. Generic tests are non-specific and examine areas such as well-being and functional capacity, while disease-specific tests focus on the symptoms associated with a disease and the side-effects of any drugs used in treatment. The construction of a test questionnaire involves an initial selection of items to be studied, usually followed by preliminary selection of those which are most appropriate. These are then put 1n the form of questions with either a choice of alternative responses or a visuo-analogue response scale and the completed questionnaire then undergoes a pretest to eliminate unclear questions before be1ng put through a final evaluation of the reproducibility, validity and sensitivity of the test. Dr Jern then described a study which assessed mood in patients transferred from conventional antihypertensive therapy (13-blockers, diuretics and hydralazine) to placebo and then to treatment with enalapril. The switch to placebo (i.e. no treatment) produced a distinct increase in perceived well-being and there was a further slight increase after changing from placebo to enalapril.

... and safety of ACE inhibitors The final presentation was given by Dr N.J. Warner from MSD Rahway, who reviewed the safety profiles

of the ACE inhibitors enalapril, captopril and lisinopril. In double-blind comparisons with diuretics, vasodilators, P-blockers or calcium antagonists, the ACE inhibitors compared well both in terms of antihypertensive efficacy, and safety and tolerability. In general the ACE inhibitors seemed to provide a lower incidence of adverse effects and a lower rate of patient withdrawal. Early studies with captopril found relatively high incidences of rash, dysgeusia, neutropenia and proteinuria, but these were mostly the result of the use of high dosages and in more recent studies with lower dosages the occurrence of these side effects was considerably reduced. In studies with enalapril only rash, cough, orthostatic effects and hypotension occurred more frequently than with placebo, and early experience with lisinopril indicates a similar profile. Of the adverse effects seen with ACE inhibitors, hypotension, hyperkalaemia and renal impairment are directly related to the therapeutic effects of the drugs while angioedema and cough may result from inhibition of ACE, but by an as yet unknown mechanism.

ADIS Editors

10 INPHARMA" 17 October 1987 0156-2703/87/1017-0010/0$01.00/0 © ADIS Press