VASODILATORS IN CONGESTIVE HEART FAILURE

Minoxidil improves cardiac function and may be useful if fluid retention can be controlled Minoxidil is a potent, orally effective vasodilator, which has been used as an antihypertensive agent. 11 patients with severe chronic congestive heart failure were given a single dose of minoxidil IOmg, followed after at least 6 hours by 15mg, then 20mg, 25mg (9 patients each time) and 30mg (7 patients). All patients were taking maintenance digoxin and diuretics. The maximum increase in cardiac output occurred 4-6 hours after each dose. At these times, there were no significant changes in the mean heart rate or arterial BP from the control values, although the changes in individual patients were variable, and a few patients experienced tachycardia, while 2 patients had hypotension and the dose could not be raised above lOmg. The cardiac index increased by 42% after the lOmg dose, 47% after 15mg and 63% after 20mg (compared with control) with no further increase at higher doses. A significant corresponding fall in systemic vascular resistance occurred after minoxidil (42% with 20mg dose). There was a significant increase in stroke work index and stroke volume index (52% with 20mg), and pulmonary capillary wedge pressure either decreased or remained unchanged in all patients, indicating an improvement in left ventricular function after minoxidil. Eight patients continued maintenance minoxidil therapy. 6f the 3 patients who dropped out after initial evaluation, had hypotension, 1 supraventricular tachycardia after minoxidil 15mg, and 1 had only modest haemodynamic improvement after the 30mg dose. All patients on maintenance therapy retained fluid and gained weight, and the dose offrusemide (furosemide) was increase to counteract this. Minoxidil was discontinued in 3 patients because of excessive weight gain and worsening congestive symptoms, and 1 patient died suddenly after discharge from hospital. In the other 4 patients there was clinical improvement after 12 weeks, and weight gain was controlled by increased frusemide doses. There was also sustained improvement in haemodynamic parameters and left ventricular function. The optimal dose was 20mg bid in most cases. McKay, C.R. et al.: American Heart Journal 104: 575 (Sep 1982)

And a preliminary study suggests beneficial results from IV diazoxide Diazoxide, a potent, long acting arteriolar dilator, has been used for many years in the treatment of hypertension. Nine men with refractory congestive heart failure (most had been treated unsuccessfully with other vasodilators) were given successive diazoxide 300mg IV infusions, each over lO min (mean total dose 670mg), until cardiac output responded satisfactorily, arterial pressure reduced more than lOOmm Hg, or heart rate increased more than lO beats/min. The initial 300mg dose gave a significant increase in cardiac index (from 2.0 to 2.8 L/min/m2), stroke volume index (from 24 to 32 ml/m2), stroke work index (from 28 to 36 g/m m2), and a significant decrease in systemic vascular resistance (from 1700 to 1190 dyne·sec•cm·5). These effects were more pronounced after the total dose had been administered, and haemodynamic measurements did not return to control levels for an average 9.7 hours. Diazoxide increased the heart rate from 87 to a maximum of 98 beats/min after 2 hours, while mean arterial pressure did not change significantly, although it decreased moderately in 2 patients. One hour after diazoxide administration, systemic vascular resistance fell by a maximum of 44%, and cardiac, stroke volume and stroke work indices rose by 64, 49 and 36% respectively, remaining significantly improved from the control values for 8 hours. Pulmonary capillary wedge pressure fell more slowly, reaching a minimum of 25mm Hg (compared with 33mm Hg control) at 4 hours. Despite numerous side effects, particularly hyperglycaemia, which may accompany diazoxide therapy ' ... the striking hemodynamic improvement produced by intravenous diazoxide suggests that this medication may have a role in the management of severe heart failure and that it may be worthwhile to evaluate the effects of oral diazoxide in selected CHF patients.' Massie, B.M. et al.: American Heart Journal !04: 581 (Sep 1982)

But hydralazine seems no better than placebo The arteriolar dilator hydralazine has been reported in previous, uncontrolled trials to increase cardiac output, improve symptoms and enhance exercise tolerance in patients with chronic heart failure. In a multicentre, double-blind trial, patients with chronic congestive heart failure were given either hydralazine, titrated to a maximum of 50mg qid (mean 188 mgjday: 16 subjects), or placebo (16 subjects), for 26 weeks. Digitalis and diuretics were also taken. Five patients from the hydralazine group, and 6 from the placebo group did not complete the trial. There were no significant changes from the control values of bodyweight, heart rate, mean arterial pressure, symptoms, or radiographic and echocardiographic measurements, during the administration of hydralazine or placebo, and there were no significant differences between the 2 groups. The left ventricular ejection fraction, which was below normal at the start of the trial, was not significantly altered after 5 weeks in either group. Treadmill exercise duration increased significantly from control within 4 weeks, in both the hydralazine group (from 259 to 347 sec) and the placebo group (from 271 to 340 sec), and remained elevated, with no significant difference between regimens. The number of complicating events was not significantly different in the hydralazine (8) or placebo (13) groups. Hydralazine therefore was found to be no better than placebo in the long term treatment of chronic heart failure, when used as the sole vasodilator. Franciosa, J.A. eta!.: American Heart Journal 104: 587 (Sep 1982)

8 INPHARMA 6 Nov 1982 0156-2703/82/11 06-0008{0$01 .00{0 © A DIS Press