[Long-term treatment of chronic heart failure by an inhibitor of angiotensin converting enzyme]. / Traitement au long cours de l'insuffisance cardiaque chronique par un inhibiteur de l'enzyme de conversion de l'angiotensine.

We studied the hemodynamic, echocardiographic, phonomechanographic and hormonal changes during acute (25 mg) and chronic (6 months--75 to 225 mg/day) treatment of 10 patients with congestive cardiac failure due to cardiomyopathy with dilatation with SQ 14 225 (Captopril). The following changes were observed after the single dose: an increase in cardiac output (p less than 0,001), in stroke volume (p less than 0,01), a reduction in heart rate (p less than 0,01), in peripheral resistance (p less than 0,001) and pulmonary capillary pressure (p less than 0,001). There were no significant changes in end systolic or end diastolic left ventricular internal diameter. Plasma renin activity increased (p less than 0,001); there was a concurrent fall in serum aldosterone (NS): the plasma concentration of converting enzyme decreased (p less than 0,001). There was a correlation between the increase in peripheral resistance under basal conditions and the basal plasma renin activity (R = 0,72, p less than 0,02). The decrease in peripheral resistance after captopril also correlated with basal plasma renin activity (R = 0,89, p less than 0,01). After six months continuous therapy, the hemodynamic effect was sustained and was accompanied by a significant symptomatic improvement. Left ventricular internal end systolic and end diastolic diameters decreased (p less than 0,01 and p less than 0,01 respectively). The pre-ejectional period decreased (p less than 0,05). Serum aldosterone fell significantly (p less than 0,001) as did plasma renin activity (p less than 0,01); the serum level of converting enzyme remained low with respect to its initial value. These results show that captopril may be useful in severe cardiac failure without tolerance during long-term administration. No renal or hematological toxicity was observed in this group of patients.

Long-term therapy of Parkinson's disease with amantadine, alone and combined with levodopa.

A dual study was conducted to assess (1) the long-term antiparkinsonian action of amantadine without levodopa and (2) the advantage of combined amantadine and levodopa over single-drug therapy, including changes in symptom severity when placebo replaces amantadine but levodopa is maintained.Good to excellent results were obtained in 25% of the total pool of 77 patients on amantadine. No decline in therapeutic effect took place during a mean follow-up of 21 months.Thirty-seven patients with considerable residual deficit after single-drug therapy derived improvement from the second drug (levodopa or amantadine). Gains in neurological signs and activities of daily living (ADL) ranged between 50 and 60% and for timed skills close to 25%. Depending on the individual indices, between 64 and 100% of patients improved with the second drug.Placebo instead of amantadine produced deterioration. There was 75% loss in ADL, 45% loss in timed skills and losses in neurological signs exceeded gains produced by two-drug therapy.