digoxin and Substance-Withdrawal-Syndrome

The value of digoxin in the patient in normal sinus rhythm with chronic congestive heart failure continues to be controversial. Although many patients taking digoxin have no clinical deterioration after its discontinuance, there is a subgroup of patients (up to 30% of the total group) who demonstrate clinical deterioration on digoxin withdrawal. Patients with an S3 gallop and an enlarged left ventricle are especially likely to benefit from digoxin therapy. Furthermore, there is good evidence in patients with congestive heart failure that there is a persistent, chronic, positive inotropic effect with digoxin. Since digitalis is the only presently available, chronic, oral positive inotropic drug capable of increasing stroke volume at any given filling pressure, it should be used in patients with congestive heart failure.

Topics: Digitalis Glycosides; Digoxin; Diuretics; Heart Failure; Heart Rate; Humans; Myocardial Contraction; Physical Exertion; Substance Withdrawal Syndrome

Discontinuation of digoxin is associated with worsening heart failure (HF) symptoms. However, the long-term effects of discontinuation of digoxin therapy on mortality and morbidity in HF have not been well studied. Of the 7,788 participants in the Digoxin Investigation Group trial, 3,365 received digoxin before randomization. During the trial, digoxin was continued in 1,666 patients and discontinued in 1,699 patients. Using multivariable Cox regression analyses, we first determined the effect of discontinuation of digoxin on mortality and hospitalization during 39.7 months of median follow-up. Of the 1,666 patients continued on digoxin, 457 had low (0.5 to 0.9 ng/ml) and 340 had high (>or=1.0 ng/ml) serum digoxin concentrations (SDC) after 1 month of therapy and of the 1,699 patients whose digoxin was discontinued, 1,674 were alive at 1 month. We examined the effects of continuation of digoxin at low or high SDC. Compared with continuation of long-term digoxin therapy, discontinuation of digoxin was associated with a significant increase in all-cause hospitalization (adjusted hazard ratio [AHR] 1.18, 95% confidence interval [CI] 1.09 to 1.28, p <0.0001) and HF hospitalization (AHR 1.35, 95% CI 1.20 to 1.51, p <0.0001), but had no effect on all-cause mortality (AHR 1.06, 95% CI 0.95 to 1.19, p = 0.272). In contrast, continuation of digoxin at low SDC was associated with a reduction in all-cause mortality (AHR 0.75, 95% CI 0.63 to 0.90, p = 0.002), all-cause hospitalization (AHR 0.80, 95% CI 0.70 to 0.91, p = 0.001), and hospitalization for HF (AHR 0.60, 95% CI 0.50 to 0.73, p <0.0001). In conclusion, continuation of long-term digoxin therapy at low SDC was associated with reduction in mortality and hospitalization in ambulatory patients with chronic HF receiving background therapy with angiotensin-converting enzyme inhibitors and diuretics.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Diuretics; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Regression Analysis; Substance Withdrawal Syndrome

The purpose of this study was to determine whether digoxin is effective in patients with chronic, stable mild to moderate heart failure.. Digoxin has been a traditional therapy in heart failure, but methodologic limitations in earlier studies have prevented definitive conclusions regarding its efficacy.. Withdrawal of digoxin (placebo group, n = 46) or its continuation (digoxin group, n = 42) was performed in a prospective, randomized, double-blind, placebo-controlled multicenter trial of patients with chronic, stable mild to moderate heart failure secondary to left ventricular systolic dysfunction who had normal sinus rhythm and were receiving long-term treatment with diuretic drugs and digoxin.. Patients withdrawn from digoxin therapy showed worsened maximal exercise capacity (median change in exercise time -96 s) compared with that of patients who continued to receive digoxin (change in exercise time +4.5 s) (p = 0.003). Patients withdrawn from digoxin therapy showed an increased incidence of treatment failures (p = 0.039) (39%, digoxin withdrawal group vs. 19%, digoxin maintenance group) and a decreased time to treatment failure (p = 0.037). In addition, patients who continued to receive digoxin had a lower body weight (p = 0.044) and heart rate (p = 0.003) and a higher left ventricular ejection fraction (p = 0.016).. These data provide strong evidence of the clinical efficacy of digoxin in patients with normal sinus rhythm and mild to moderate chronic heart failure secondary to systolic dysfunction who are treated with diuretics.

Topics: Body Weight; Chronic Disease; Digoxin; Diuretics; Double-Blind Method; Drug Monitoring; Drug Therapy, Combination; Exercise Test; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Stroke Volume; Substance Withdrawal Syndrome; Time Factors; Treatment Failure; Ventricular Function, Left

Topics: Clinical Trials as Topic; Coronary Disease; Digitalis Glycosides; Digoxin; Heart Failure; Heart Rate; Hemodynamics; Humans; Hypertension; Long-Term Care; Myocardial Contraction; Substance Withdrawal Syndrome

The evaluation of the long-term treatment of heart failure is complicated by many biological, clinical and technical problems. Chronic heart failure results from a variety of causes, each resulting in fundamentally different histopathological profiles. Once established chronic heart failure is unremitting, but the speed of progression of the haemodynamic derangement varies widely between different individuals. Moreover, the extent of the haemodynamic disorder correlates poorly with the severity of symptoms. The metabolism of drugs and the response of the damaged myocardium to these drugs is often quite different in the patient with heart failure than in the normal subject. Finally chronic heart failure is a terminal condition of relatively short duration so that clinical trials designed to test the efficacy of a drug treatment will fail if they are continued for more than a brief period, as all patients will die. It is against this complex biological background that the long-term clinical efficacy of diuretics and digitalis in the treatment of chronic heart failure must be evaluated.

Topics: Administration, Oral; Chronic Disease; Clinical Trials as Topic; Digoxin; Diuretics; Drug Interactions; Drug Therapy, Combination; Drug Tolerance; Heart Failure; Hemodynamics; Humans; Injections, Intravenous; Prognosis; Substance Withdrawal Syndrome

Discontinuation of digoxin in 56 patients with sinus rhythm who had been taking it for a long time did not produce clinical deterioration in 33 of 34 patients whose pre-withdrawal steady-state plasma-digoxin concentration was less than 0.8 ng/ml; fast atrial fibrillation developed in the other patient. 22 patients had plasma-digoxin levels between 0.8 and 2.0 ng/ml before withdrawal--of these, 7 deteriorated without digoxin (5 had atrial fibrillation, which was associated with congestive heart-failure, measurement of the pre-injection period/left-ventricular ejection time (P.E.P./L.V.E.T.) ratio suggested that digoxin did exert a sustained positive inotropic effect. Thus, successful discontinuation of digoxin was possible in 86% of the total group and was more likely when the plasma-digoxin concentration was below 0.8 ng/ml. Unexpected atrial fibrillation was the commonest development inthe 8 patients in whom digoxin withdrawal was unsuccessful.

Topics: Adult; Aged; Atrial Fibrillation; Clinical Trials as Topic; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Myocardial Infarction; Stimulation, Chemical; Substance Withdrawal Syndrome; Tachycardia

Modulation of Na(+), K(+)-ATPase activity by acute and chronic opiates has been established for many years. However, the effects of digoxin, a putative inhibitor of Na(+), K(+)-ATPase, on naloxone-precipitated morphine withdrawal syndrome are unknown. In the present study, a digoxin dose-response curve was conducted to observe the effects on naloxone-precipitated withdrawal and locomotor activity in mice. Higher doses of digoxin (1.0 and 2.5 mg/kg) inhibited locomotor activity and naloxone-precipitated withdrawal jumping and weight loss, while lower doses of digoxin (0.1 and 0.25 mg/kg) inhibited withdrawal weight loss precipitated by naloxone without affecting locomotor activity and naloxone-precipitated withdrawal jumping. To explore the possible mechanisms underlying this behavior, another Na(+), K(+)-ATPase inhibitor ouabain, which does not cross the blood brain barrier, and another cardiotonic drug milrinone, a non-inhibitor of Na(+), K(+)-ATPase, were also included in the present study. Both milrinone and ouabain inhibited, in a dose-dependent manner, naloxone-precipitated weight loss while neither affected naloxone-precipitated withdrawal jumping nor locomotor activity in mice. These results indicate that both the cardiotonic effects and central inhibition of Na(+), K(+)-ATPase contribute to the inhibitory effects of digoxin on morphine withdrawal syndrome in mice.

Topics: Animals; Cardiotonic Agents; Digoxin; Female; Male; Mice; Milrinone; Morphine; Motor Activity; Naloxone; Ouabain; Sodium-Potassium-Exchanging ATPase; Substance Withdrawal Syndrome; Weight Loss

We investigated whether patients with mild heart failure due to left ventricular systolic dysfunction were at risk of worsening during digoxin withdrawal.. Deterioration during digoxin withdrawal is often believed to be restricted to patients with moderate to severe clinical evidence of heart failure. To test this hypothesis, we studied the outcome of patients categorized by treatment assignment and a clinical signs and symptoms heart failure score in two rigorously designed clinical heart failure trials: the Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin (PROVED) and the Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE) trial.. Potential differences in treatment failure, left ventricular ejection fraction and exercise capacity were evaluated in three groups of patients: those with mild heart failure (score < or = 2) who were withdrawn from digoxin (Dig WD Mild); those with moderate heart failure (score > 2) who were withdrawn from digoxin (Dig WD Moderate); and patients who continued receiving digoxin regardless of heart failure score (Dig Cont).. Heart failure score at randomization did not predict outcome during follow-up in Dig Cont-group patients. Dig WD Mild-group patients were at increased risk of treatment failure and had deterioration of exercise capacity and left ventricular ejection fraction compared with that in Dig Cont-group patients (all p < 0.01). Patients in the Dig WD Moderate group were significantly more likely to experience treatment failure than patients in either the Dig WD Mild or Dig Cont group (both p < 0.05).. Patients with systolic left ventricular dysfunction were at risk of clinical deterioration after digoxin withdrawal despite mild clinical evidence of congestive heart failure.

Topics: Aged; Digoxin; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Severity of Illness Index; Substance Withdrawal Syndrome; Systole; Ventricular Dysfunction, Left

Several studies have shown that the majority of patients receiving digoxin can be successfully withdrawn. A medical record review was conducted to determine whether, in practice, patients were being withdrawn from digoxin. Original indications for digoxin therapy in 163 outpatients were as follows: congestive heart failure (CHF), 50%; supraventricular tachycardia (SVT), 23%; CHF and SVT, 10%; and unknown/unclear, 17%. One third of these patients were withdrawn during the 3.5-year study, and 79% remained stable, off digoxin. The most significant predictor of withdrawal was chart indication of reassessment of the need for digoxin. The majority of the patients (68%) were reassessed, and of these, almost half were withdrawn. Physicians appear to be reassessing the need for digoxin therapy, resulting in higher withdrawal rates than previously reported. Results suggest that patients with unclear original indications, a onetime indication, or without clinical evidence of CHF or SVT can be successfully withdrawn.

Topics: Aged; Digoxin; Drug Utilization; Female; Heart Failure; Humans; Male; Medical Records; Middle Aged; North Carolina; Outpatient Clinics, Hospital; Practice Patterns, Physicians'; Substance Withdrawal Syndrome; Tachycardia, Supraventricular

The frequency of therapy with digitalis glycosides was determined in 4.143 patients on their first visit at a medical outpatient clinic. 508 (12.3%) patients said to take digitalis. Of 480 (94.5%) patients, a digoxin serum concentration was obtained. It was in 229 (47.7%) patients below, in 31 (6.5%) above, and in 220 (45.8%) within the therapeutic range (0.8-2.0 ng/ml). From the 251 patients with a serum digoxin concentration greater than or equal to 0.8 ng/ml, 220 (87.7%) were not included in a withdrawal trial on the basis of predetermined criteria, mainly because of cardiac diseases (52%). Digitalis therapy was withdrawn in 31 patients. 5 patients started to take the drug again on their own; they were considered drop-outs. In the remaining 26 patients, no symptoms of heart failure appeared during a 3-month observation period; in 2 patients, however, atrial fibrillation requiring intervention occurred. Our results confirm the frequent use of digitalis therapy in Germany, but also the frequent presence of subtherapeutic serum digoxin concentrations. Withdrawal should be considered in patients with a questionable indication for this therapy; the occasional occurrence of supraventricular arrhythmias, and not so much of heart failure, should be anticipated.

Topics: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Female; Heart Diseases; Heart Failure; Humans; Male; Middle Aged; Substance Withdrawal Syndrome

Nursing home patients were studied to determine the usefulness of a maintenance dose of digoxin in elderly patients with normal sinus rhythm. Of 64 patients, 26 were identified to be on digoxin. Thorough history and physical examination were done on all the patients. Baseline electrocardiogram showed normal sinus rhythm in 19 patients, who were observed very closely for the period of four months after withdrawal of digoxin. Eighteen of 19 patients did well without digoxin, which suggests that most of the elderly nursing home patients with normal sinus rhythm do not need a maintenance dose of digoxin.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Male; Nursing Homes; Substance Withdrawal Syndrome

Topics: Aged; Digoxin; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Myocardial Infarction; Substance Withdrawal Syndrome

The need for maintenance treatment with digoxin was assessed in 10 elderly outpatients with sinus rhythm. Digoxin was withdrawn on the first day of the trial but any other treatment remained unchanged. The participants were seen once weekly on the same day for 5 consecutive weeks and assessed clinically, by the calculation of systolic time intervals and by M-mode echocardiography. In 2 patients the clinical condition deteriorated but in the rest digoxin was stopped without detrimental effects. Therefore, in the patient population selected, maintenance treatment with digoxin was deemed unnecessary in 90% of cases.

Topics: Aged; Digoxin; Echocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Substance Withdrawal Syndrome; Systole; Time Factors

Topics: Aged; Digoxin; Follow-Up Studies; Heart Failure; Humans; Substance Withdrawal Syndrome

Sudden withdrawal of oral therapy with hydralazine for reduction of afterload in a patient precipitated severe congestive heart failure. Signs of metabolic encephalopathy evolved due to low cardiac output. Reinstitution of therapy with hydralazine resulted in prompt improvement in cardiac and neurologic status. This case underscores the need for careful follow-up of such patients and argues against sudden withdrawal of vasodilator therapy.

Topics: Administration, Oral; Aged; Aortic Valve Insufficiency; Digoxin; Furosemide; Heart Failure; Hemodynamics; Humans; Hydralazine; Hypoxia, Brain; Injections, Intravenous; Male; Neurocognitive Disorders; Nitroprusside; Substance Withdrawal Syndrome; Vascular Resistance

The 83-year-old woman in this case report developed paranoid delusions and auditory hallucinations in association with toxic serum levels of digoxin, while remaining alert, unagitated, and coherent in thinking. No cardiovascular or metabolic abnormalities were discovered to account for her psychiatric symptoms. Her mental status rapidly returned to normal as serum digoxin declined to therapeutic levels.

Topics: Aged; Auditory Perception; Coronary Disease; Delusions; Digoxin; Female; Hallucinations; Humans; Paranoid Disorders; Substance Withdrawal Syndrome

Topics: Digoxin; Furosemide; Heart Failure; Humans; Long-Term Care; Substance Withdrawal Syndrome