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For elderly AS patients fit for surgery, the patient's decision to refuse AVR is associated with a >12-fold increase in mortality risk. These findings have significant implications for informed decision-making when managing the fit, elderly patient with AS.

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Twenty-four patients with moderate to severe hypertension were treated for four weeks with captopril, an oral inhibitor of angiotensin-converting enzyme. The fall in blood pressure with captopril alone correlated with pretreatment plasma renin activity. The effect of adding either hydrochlorothiazide or propranolol to the captopril treatment was then studied. The addition of hydrochlorothiazide to captopril produced a dosedependent fall in blood pressure. At the higher dose of the diuretic this fall in blood pressure correlated with weight loss, suggesting that when the diuretic-induced compensatory rise in angiotensin II is prevented by captopril the fall in blood pressure becomes dependent on loss of sodium and water. In contrast, the addition of propranolol to captopril produced no further fall in blood pressure, suggesting that inhibition of angiotensinconverting enzyme prevents the blood pressure lowering effect of propranolol. This may have implications for the mechanism whereby beta-blockers alone lower blood pressure. These contrasting effects of hydrochlorothiazide and propranolol in the presence of captopril indicate that in patients whose hypertension is not controlled by captopril

Nineteen patients with chronic heart failure participated in a double blind crossover trial of captopril and prazosin -two drugs with differing neuroendocrine effects-to determine whether neuroendocrine changes could ex-

A non-sulfhydryl-containing inhibitor of angiotensinconverting enzyme (MK421) was given as a single dose in a randomised double-blind cross-over trial using 20 mg and 5 mg of MK421 or matched placebo to nine normotensive volunteers receiving a sodium intake of 150 mmol (mEq) daily. The two dosages of MK421 caused similar, significant falls in supine and standing blood pressure, which were maximum four to six hours after dosing (9 5-11 0% fall). With this fall in blood pressure there was a significant fall in activity of angiotensinconverting enzyme and in concentrations of plasma angiotensin II and aldosterone and a rise in plasma renin activity. Placebo caused no significant change in blood pressure or blood measurements.The study showed that MK421 inhibits angiotensinconverting enzyme activity and lowers blood pressure in normotensive subjects. It strongly suggested that the renin system plays an important part in maintaining blood pressure in normotensive subjects receiving normal sodium intake. The results also suggest that this nonsulfhydryl-containing converting-enzyme inhibitor will be an effective blood-pressure-lowering drug in patients with high blood pressure. A single dose of 5 mg was as effective at lowering blood pressure as a single dose of 20 mg.

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