Effect of oral milrinone on mortality in severe chronic heart failure

Article Abstract:

Positive inotropic drugs, such as milrinone, enhance the heart's contractile ability. These drugs work by altering various physiological mechanisms, but their long-term effectiveness and safety for people suffering from chronic heart failure has not been determined. To learn more about this issue, a study of mortality among patients with severe chronic heart failure was carried out at 119 medical centers in the US and Canada. The subjects were randomly assigned to receive either oral milrinone (561 patients) or a placebo drug (527 patients) in additional to their regular drug regimens. They were reevaluated every one to three months and dosage adjustments for all drugs were made as needed. The study began on January 24, 1989 and was stopped five months before its scheduled completion, on October 4, 1990. This decision was based on the adverse effect on survival among patients receiving milrinone. Thirty percent (168 patients) of the milrinone group died, compared with 24 percent (127 patients) of the placebo group. Milrinone was associated with a 34 percent increase in cardiovascular mortality and a 28 percent increase in death due to all causes. When patients were further subdivided according to such variables as the cause of heart failure, blood sodium levels, age, or presence of angina, milrinone was found to have adverse effects on all subgroups. No signs were seen of a beneficial effect of the drug on symptoms or functional capacity. The poor effects of the drug are at variance with laboratory results using laboratory animals, where milrinone improved both performance and survival. Milrinone works by enhancing cyclic AMP in the heart; in light of these and related results, it is likely that a decline in levels of myocardial cyclic AMP has adaptive value in chronic heart failure. (Consumer Summary produced by Reliance Medical Information, Inc.)

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A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure

Article Abstract:

Chronic heart failure is characterized by a disturbance in the heart's ability to pump a sufficient blood supply. Current long-term treatment with glycosides (digoxin), a drug affecting the contraction of heart muscle, is controversial. The amount of the drug needed to be effective is very close to toxic levels and this narrow margin of toxicity is difficult to manage. The effect cardiac glycosides have on certain patients having abnormal heart beats is unknown. Another drug, milrinone, increases the strength of muscle contraction, acts on heart muscles during relaxation, and dilates blood vessels. It has been shown to be a promising replacement for digoxin. The effect these two drugs alone and in combination have on exercise capability were evaluated in 230 patients with moderately severe heart failure. The length of time the patient was able to withstand the treadmill test increased while using both milrinone and digoxin or both. These drugs also reduced the need for further treatment to control heart failure in patients in sinus rhythms. Although milrinone reduced the incidence of progressive heart failure, it was not as effective as digoxin alone. The combination with digoxin offered no added benefits over digoxin alone. Digoxin offered better function of the left ventricle, the main pumping chamber, than milrinone. Ventricular arrhythmia, a type of abnormal heart beat, occurred more often when milrinone was given. The substitution or addition of milrinone for digoxin therefore, was not found to be beneficial in this particular study group.

Analysis, Testing, Prevention, Treadmill exercise tests, Arrhythmia, Heart function tests, Cardiotonic agents

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Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors

Article Abstract:

Patients with chronic heart failure who were treated with digoxin and angiotensin-converting-enzyme (ACE) inhibitors remained healthier than patients who continued the ACE inhibitors, but were no longer given digoxin. Digoxin is a drug used to maintain a steady heart rate and to increase the force of the heart's contractions. ACE inhibitors have many of the same benefits as digoxin but they are also known to increase the survival rate of patients. Patients with heart failure who were treated with a combination of digoxin, ACE inhibitors and diuretics were randomly assigned to one of two groups: 85 continued receiving digoxin and 93 received a placebo, an inactive substance. The patients were studied for 12 weeks, during which all other treatment was continued. Twenty-three (25%) of the patients receiving the placebo experienced worse heart failure. Only four in the digoxin group had similar complications. A decrease in exercise ability was noted in the placebo group. When patients rated their own progress, 31% of the placebo group indicated that they felt worse, compared to only 9% of the digoxin group.

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