Use Of Digitalis Research Articles

Hospitalizations With Adverse Events Caused by Digitalis Therapy Among Elderly Medicare Beneficiaries

Digitalis products are among the agents most frequently prescribed to the elderly, yet previous studies have not provided age-, race-, and sex-specific rates of utilization of digitalis by this population. Estimates of the rate of hospitalization with an adverse reaction from digitalis therapy have varied considerably between systems relying on passive reports and those using active surveillance. Medicare data from 1985 through 1991 and data from the 1987 National Medical Expenditure Survey were used to determine population-based estimates of the use of digitalis in elderly beneficiaries by age group, sex, and race. Hospitalization rates with an adverse event caused by digitalis therapy were calculated for those persons estimated to be using digitalis. Medicare data were used to identify the frequency of selected comorbidities among persons with an adverse event caused by digitalis therapy as well as the frequency of clinical manifestations associated with digitalis intoxication. Over 3 million Medicare beneficiaries were estimated to be using digitalis in 1987. A total of 202,011 hospitalizations with a coded adverse event caused by digitalis therapy were reported during the 7-year study period. Of persons estimated to be using digitalis, 8.53 per 1000 were hospitalized annually with an adverse event caused by digitalis therapy. Women, individuals with increasing age, and persons of black race, especially those with impaired renal function, were significantly (P < .05) more likely to experience hospitalization with an adverse event caused by digitalis therapy. This information may help identify categories of elderly patients who require more frequent monitoring to prevent adverse effects of digitalis therapy. Changes in the format of the hospital bill to include more diagnoses along with increased mandatory reporting of adverse drug events will improve the sensitivity of Medicare data for surveillance of adverse drug events.

Incidence of hospitalization for digitalis toxicity among elderly Americans

objective: To document the prevalence of digitalis use and the incidence of hospitalization caused by digitalis toxicity. design: Observational cohort followed for 6 years. setting: Urban community. participants: Persons were eligible if they were (1) enrolled in the Yale Health and Aging Project and (2) using digitalis when interviewed in 1982 or 1985. The Project comprises a sample of noninstitutionalized persons aged 65 years and over living in New Haven, Connecticut. methods: Between 1982 and 1988 when a Project participant was hospitalized in New Haven, a researcher reviewed the medical record and coded up to 16 International Classification of Diseases-Class 9 (ICD-9) diagnoses. To identify hospitalizations caused by digitalis, we reexamined records with ICD-9 codes suggesting toxicity. We confirmed the admission illness was an adverse drug reaction with a decision algorithm. results: The prevalence of digitalis use was 13% in 1982 and 12% in 1985. The incidence of hospitalization caused by definite or probable toxicity was 4.2% (95% confidence interval = 0.3% to 8.1%) over 6 years. Manifestations of toxicity were malaise or gastrointestinal symptoms (two patients) and heart block plus malaise or gastrointestinal symptoms (six patients). Use of quinidine was associated (P<.05) with toxicity. conclusion: Knowledge about the incidence of severe, morbid toxicity may help clinicians estimate and compare the risks and benefits of digitalis and alternate therapies.

Cardiac amyloidosis. General review

Cardiac amyloidosis, most often of AL type, is a non-exceptional disease as it represents 5 to 10% of non-ischemic cardiomyopathies. It realizes typically a restrictive cardiomyopathy. Nevertheless the wide diversity of possible presentation makes it a "big shammer" which must be evoked in front of every unexplained cardiopathy after the age of forty. If some associated manifestations can rapidly suggest the diagnosis, as a peripheric neuropathy especially a carpal tunnel syndrome or palpebral ecchymosis, cardiac involvement can also evolve in an apparently isolated way. The most suggestive paraclinic elements for the diagnosis are, in one hand, the increased myocardial echogenicity with a "granular sparkling" appearance seen throughout all walls of the left ventricle and, in the other hand, the association of a thickened left ventricle and a low voltage (electrocardiogram could also show pseudo-infarct Q waves). In front of such aspects, the proof of amyloidosis is brought by an extra-cardiac biopsy or by scintigraphy with labelled serum amyloid P component, so that the indications of endomyocardial biopsy are very limited today. The identification of the amyloid nature of a cardiopathy has an direct therapeutic implication: it contra-indicates the use of digitalis, calcium channel blockers and beta-blockers. The treatment of AL amyloidosis (chemotherapy with alkylant agents) remains very unsatisfactory especially in the cardiac involvement which is the most frequent cause of death (in AL amyloidosis). Last, cardiac amyloidosis is a bad indication for transplantation which results are burden by rapid progression of deposits especially in the gastro-intestinal tract and the nervous system.

Noninvasive Predictors of Mortality for Patients with Chagas&amp;rsquo; Heart Disease: A Multivariate Stepwise Logistic Regression Study

This prospective investigation was conducted in an attempt to identify noninvasive predictors of mortality for patients with Chagas' heart disease through a multivariate stepwise logistic regression study. Fifty-six patients with a positive complement fixation test for Chagas' disease were followed up at the Cardiomyopathy Clinic of our institution from April 1990 to April 1992. Patient age was 59 +/- 17 years; 28 (50%) were male. Upon admission, 19 patients (33%) were in the New York Heart Association (NYHA) class III and 8 (14%) in the NYHA class IV. Systolic blood pressure was 125 +/- 23 mm Hg, diastolic blood pressure 76 +/- 11 mm Hg and resting heart rate 77 +/- 11 beats/min. Forty patients (71%) were given digitalis and 39 (69%) angiotensin-converting enzyme inhibitors. Plasma Na+ was 140 +/- 4 mEq/l, K+ was 4.34 +/- 0.73 mEq/l and creatinine level 1.34 +/- 0.31 mg/100 ml. Cardiomegaly was observed in the chest X-ray of 41 of 51 (79%) available patients. Atrial fibrillation was observed in the resting ECG of 24 of 54 (44%) available patients, premature ventricular contractions in 23 (41%), right bundle branch block in 26 (46%) and left anterior hemiblock in 26 (46%) patients. Echocardiography revealed a left ventricular ejection fraction of 0.45 +/- 0.16, left ventricular systolic dimension of 51.23 +/- 13.53 mm and left ventricular diastolic dimension of 62.94 +/- 19 mm. Sixteen (28%) patients died during the 2-year study, 11 of them suddenly.(ABSTRACT TRUNCATED AT 250 WORDS)

Digoxin is effective, but is it safe?

In the last 15 years several double-blind, placebo-controlled clinical trials have unequivocally shown that digitalis decreases symptoms of cardiac failure, results in a reduction in the need for hospitalization for treatment of congestive heart failure, and improves cardiac function. The major unresolved question concerning digitalis use is its safety. There are experimental data and clinical evidence that digitalis use may be associated with an increased mortality, particularly in the first year or two after an acute myocardial infarction. This increased mortality appears to be present even after adjustment for predictor covariants. This conclusion depends on the ability of statistical methods to account for differences in comorbidity. Since the question of digitalis safety remains after myocardial infarction, the physician should carefully examine the indications for administration of digitalis. More than the usual surveillance is required during chronic digitalis administration.

Medications and Chronic Diseases as Risk Factors for Falling Injuries in the Elderly

Diseases and medications associated with the occurrence of falls leading to medical treatment in elderly Finns (65 yrs or older) during a one-year period are presented. The design was that of a case-control study involving 380 fallers seeking medical treatment and 342 unmatched controls selected randomly from the population register. The occurrence of a fall was shown by logistic regression analysis to be related to advanced age, presence of benzodiazepine in the serum, hypertrophy of the prostate, poor mental capacity, presence of chronic lung disease and asthma, use of analgesics and use of digitalis in the men, and to advanced age, poor mental capacity, presence of benzodiazepine in the serum, use of analgesics and non-occurrence of lower limb arthrosis in the women. The corresponding log-linear models showed advanced age and the presence of benzodiazepine in the serum to be independent risk factors for falling both in the men and women. Furthermore, the use of analgesics was related to falling in the women with normal mental capacities. No disease was independently associated with falls. The results suggest caution in the use of benzodiazepines among the elderly.

Digoxin in Heart Failure

Although two centuries of anecdotal clinical evidence support the use of cardiac glycosides for the treatment of heart failure, controversy has surrounded their efficacy and appropriate indications. Early in this century, two of the founders of the clinical discipline of cardiology, Sir James Mackenzie in London and Henry Christian in Boston, had sharply differing views that have tended to persist in the United Kingdom and the United States, respectively. Mackenzie advocated the use of digitalis only in patients with supraventricular tachyarrhythmias, such as atrial fibrillation, whereas Christian believed that “digitalis . . . has a striking effect on those changes . . .

Aortic valve stenosis

Aortic valve stenosis may be congenital or acquired. Medical management includes advice to avoid heavy physical effort, prevention of infective endocarditis, use of digitalis and diuretics for cardiac failure, and preservation of atrial systole. When operation is necessary, open aortic valve commissurotomy is preferred in children and replacement of the valve is preferred in adults. Women of childbearing age should use conventional barrier contraceptives, and those with severe stenosis should have valve replacement before becoming pregnant. Aortic valvuloplasty, particularly in adults, is only of temporary benefit.

How should physicians view heart failure? The philosophical and physiological evolution of three conceptual models of the disease

During the last 50 years, physicians have developed three distinct conceptual models of heart failure that have provided a rational basis for the treatment of the disease. In the 1940s through the 1960s, physicians regarded heart failure principally as an edematous disorder and formulated a cardioorenal model of the disease in an attempt to explain the sodium retention of these patients. This model led to the widespread use of digitalis and diuretics. In the 1970s and 1980s, physicians viewed heart failure principally as a hemodynamic disorder and formulated a cardiocirulatory model of the disease in an attempt to explain patients' symptoms and disability. This model ted to the widespread use of peripheral vasodilators and the development of novel positive inotropic agents. Now, in the 1990s, physicians are beginning to think about heart failure as a neurohormonal disorder in an attempt to explain the progression of the disease and its poor long-term survival. This new conceptual framework has ted to the widespread use of converting-enzyme inhibitors and the development of β bockers for the treatment of heart failure. Which conceptual model most accurately describes the syndrome of heart failure and leads physicians to utilize the most effective treatment? This paper critically reviews the available evidence supporting and refuting the validity of all three models of heart failure. We conclude that, to varying degrees, all three approaches provide useful, but incomplete, insights into this physiologically complex and therapeutically challenging disease.

Digitalis and heart failure: Does digitalis really produce beneficial effects through a positive inotropic action?

Although digitalis was introduced to medicine long ago, the drug is still extensively used in clinical practice today. Opinions on its mechanism of action have undergone much change in the course of time, and the way in which cardiovascular effects are produced is still not completely clear. Limitations and contraindications for the use of digitalis substances are reported, especially in the treatment of ischemic heart disease. Preliminary data regarding the effects of digitalis on the diastolic phase are unfavorable, although the relationship between digitalis and diastolic function ought to be studied in greater depth in various clinical conditions. In spite of many recent trials, the old question of the usefulness of digitalis in the chronic treatment of patients in sinus rhythm and heart failure is still debated. An important clinical benefit in the chronic use of digitalis appears restricted to a relatively small proportion of patients with severe congestive heart failure, while in the majority of chronically treated subjects the effects of the drug are scanty or insignificant. The beneficial effect of digitalis used chronically is essentially believed to be due to its positive inotropic action. Since the vagomimetic and the antiadrenergic effects of digitalis have been demonstrated to be independent from its inotropic action, they could be considered determinants of the clinical benefits of digitalis. These indirect effects may be useful in the control of the negative neuroendocrine response developing during congestive heart failure. Thus the statement that digitalis is essentially an inotropic agent seems restrictive; its definition should reflect the favorable effects obtained in some cases of congestive heart failure rather than its various and contrasting underlying mechanisms of action.

Need for a large randomized trial to evaluate the effects of digitalis on morbidity and mortality in congestive heart failure

Despite major advances in the prevention and treatment of cardiovascular diseases, the incidence and prevalence of congestive heart failure (CHF) have been increasing in recent years. As the average age of the population increases, the prevalence of CHF is expected to continue to increase. The number of deaths in which CHF was considered the underlying or contributing cause increased from 51,000 in 1955 to 274,000 by 1988 in the United States. Even accounting for population growth and an increase in the number of elderly, this represents a 2-fold increase. Additionally, CHF was responsible for about 643,000 hospitalizations in 1988. Digitalis is one of the drugs most commonly prescribed for CHF and has been used for > 200 years. In 1990, digoxin was one of the most commonly prescribed drugs in the United States, accounting for > 21 million prescriptions. There has been little decline in the drug's use over the last 5 years, indicating that newer treatments for CHF have not replaced the widespread use of digitalis. Despite these findings, considerable controversy surrounds the appropriateness of its role and value in treating CHF patients who are in sinus rhythm. A number of recent, uncontrolled studies have arrived at apparently contradictory conclusions concerning the effects of digitalis on mortality in postmyocardial infarction and heart failure patients. A large, double-blind, randomized, controlled clinical trial to evaluate the effects of digitalis on mortality, morbidity and quality of life is being sponsored by the National Heart, Lung, and Blood Institute in conjunction with the Department of Veterans Affairs Cooperative Studies Program. Patients with CHF and an ejection fraction ≤0.45 will be randomized to receive digoxin or placebo along with other standard therapy. Patients with an ejection fraction > 0.45 also will be enrolled in a parallel but separate ancillary study. Patient recruitment started in early March 1991, and about 7,500 to 8,000 patients are expected to be enrolled over 3 years and followed for a minimum of 2 further years or until the end of the study. Results are expected to become available in 1995 or 1996.

Survival prognosis in geriatric patients admitted to permanent institutional care.

The influence of clinical and laboratory findings on the two-year survival prognosis was investigated in 558 geriatric patients admitted to permanent institutional care. The patients surviving for two years (52%) were somewhat younger (79 vs 82 years, p less than 0.01), and on admission had significantly higher diastolic blood pressure (p less than 0.001), serum thyroxin (p less than 0.05), serum albumin (p less than 0.01) and blood haemoglobin (p less than 0.05), but lower treatment score (p less than 0.001), serum creatinine (p less than 0.001), and fasting plasma glucose (p less than 0.05). Decreased survival prognosis was also found in patients with abnormal serum sodium, chloride, and potassium (p less than 0.05 or less). However, an excess mortality of patients with abnormal laboratory data occurred within the first month after admission. Stepwise logistic regression analysis disclosed that the three-month survival prognosis was significantly impaired by low blood pressure (less than 110/70 mmHg), high treatment score (greater than 22), elevated serum creatinine (greater than 150 mumol/L), use of digitalis and atrial fibrillation. Poor two-year survival was further associated with the use of diuretics, and diabetes mellitus. The risk for death was lowest in patients with elevated blood pressure (greater than 160/95 mmHg). These data verify the significance of the clinically common diseases and indicators of homeostasis in the assessment of geriatric hospital patients, and demonstrate the nature of "terminal decline" in geriatric practice.

Events in the cardiac arrhythmia suppression trial: Baseline predictors of mortality in placebo-treated patients

Patients randomized to placebo in the encainide and flecainide arms of the Cardiac Arrhythmia Suppression Trial (CAST) have been found to have a relatively low 1-year mortality rate of 3.9% in comparison with previous studies of patients in the postmyocardial infarction period. To determine the comparability of CAST with previous studies, baseline variables were examined in the 743 patients randomized to placebo in the flecainide and encainide arms of CAST. Twenty-three baseline characteristics were correlated with major outcome events: arrhythmic death (16 events), total mortality (26 events) and congestive heart failure (51 events).On multivariate analysis the risk of new or worsening congestive heart failure was significantly associated with diuretic use, diabetes, high New York Heart Association functional class, age, prolonged QRS duration and low ejection fraction. The risk of arrhythmic death or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, history of heart failure, use of digitalis, diabetes and prolonged QRS duration. Total mortality or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, diabetes, ST segment depression, high functional class, prolonged QRS duration and low ejection fraction.The variables at baseline associated with mortality from all causes or arrhythmic death or resuscitated cardiac arrest and heart failure in the CAST placebo-treated patients are similar to those identified in previous postmyocardial infarction studies. Thus, the observation of increased mortality in CAST associated with the administration of encainide and flecainide for suppression of ventricular premature depolarizations is probably applicable to any comparably defined group of patients in the postmyocardial infarction period.

Events in the cardiac arrhythmia suppression trial (CAST): Mortality in patients surviving open label titration but not randomized to double-blind therapy

The patient characteristics and outcomes were studied in the 318 patients who survived open label drug titration in the Cardiac Arrhythmia Suppression Trial (CAST) and who were not randomized to double-blind therapy and in 942 patients, who were randomized to double-blind placebo therapy. The patients randomized to placebo therapy had a lower total mortality or resuscitated cardiac arrest rate (4% vs. 8.5%). However, at baseline, nonrandomized patients were dissimilar from patients randomized to placebo in the following ways: older; lower left ventricular ejection fraction; greater use of digitalis, diuretic drugs and antihypertensive agents; lesser use of beta-adrenoceptor blocking agents and more frequent prior cardiac problems, including runs of ventricular tachycardia and left bundle branch block. A matched comparison that took these inequities into account showed no significant differences in mortality or rate of resuscitation from cardiac arrest between nonrandomized patients and clinically equivalent patients randomized to placebo. Cox regression analysis indicated that two factors significantly increased the hazard ratio for arrhythmic death or resuscitated cardiac arrest in the nonrandomized patients: female gender (4.7, p less than 0.05) and electrocardiographic events (ventricular tachycardia, proarrhythmia, widened QRS complex, heart block, bradycardia) during open label titration (7.0, p less than 0.005). However, some potentially important differences between men and women were not included in the Cox regression model. Of the nonrandomized patients, approximately 70% were not randomized because of lack of suppression of ventricular premature depolarizations or adverse events, or both, and the remaining 30% because of patient or private physician request with no indication of another reason.(ABSTRACT TRUNCATED AT 250 WORDS)

Digitoxin-associated mortality in acute myocardial infarction

The use of digitalis in patients who have sustained an acute myocardial infarction has been controversial. A number of reports have suggested that the use of the glucoside actually can increase mortality. In all previous reports, digoxin has been the glucoside in use. In 620 patients admitted to Hamar Hospital from January 1, 1982 to December 31, 1984 with an acute myocardial infarction, 159 were using digitoxin at entry. Their survival until January 1, 1985 was compared with the rest of the population, not using digitoxin. The patients on digitoxin had a significantly higher mortality than those who were not, with a relative risk ratio of 2.33. However, major differences in baseline risk factors existed, and a multivariate Cox regression analysis was employed to adjust for the inequalities in baseline covariates. Only variables available at the entry of the index infarction were used for adjustment. Serum sodium, serum creatinine, age and no smoking were identified in a backward selection procedure as independently influencing mortality. By adjusting for these variables the relative risk ratio was reduced to 1.41, but digitoxin still exerted a significant influence on mortality. It is concluded that the results obtained with the use of digitoxin during a myocardial infarction is similar to previous reports with digoxin. Most of the excess mortality in the digitoxin group can be accounted for by inequalities in baseline characteristics. However, the possibility that a small excess in mortality is due to the digitalis glucoside cannot be excluded.

Antiarrhythmic Treatment of Atrial Arrhythmias

Atrial premature beats seldom require an antiarrhythmic treatment; reassurance and suppression of coffee, alcohol, and tobacco generally suffice. Acute atrial fibrillation is best treated by electrical cardioversion if it induces acute cardiovascular decompensation. If it is not poorly tolerated, the arrhythmia may be treated with digitalis at doses sufficient to keep the ventricular response rate at 70-90/min. This therapy may restore sinus rhythm, but conversion to sinus rhythm often requires the combined use of digitalis with a beta-blocker or class I antiarrhythmic drug (quinidine, disopyramide, procainamide, propafenone, or flecainide). Digitalis must be avoided in the presence of a preexcitation, and class IA agents, which facilitate atrioventricular (AV) nodal transport, must never be used without digitalis. Chemical cardioversion may also be achieved by i.v. amiodarone. Long-term prevention of recurrences after cardioversion or in the presence of recurrent paroxysmal atrial fibrillation requires digitalis combined with a class I agent, or a beta-blocker, preferably sotalol. Amiodarone is also very efficacious. Special mention should be made of atrial fibrillations of vagal or sympathetic origin, which are best treated by amiodarone, or beta-blockade (nadolol), respectively. In the presence of chronic established atrial fibrillation, digitalis in combination with a beta-blocking agent or a calcium antagonist, such as verapamil or diltiazem, may be useful to slow the ventricular response rate. If successful control cannot be obtained, catheter ablation of the AV node with implantation of a rate-responsive pacemaker must be contemplated. The therapeutic approach in patients with chronic atrial fibrillation, whether or not associated, is similar to atrial flutter.(ABSTRACT TRUNCATED AT 250 WORDS)

Withdrawal of maintenance digoxin from institutionalized elderly

Chronic use of digitalis is common amongst the institutionalized elderly. Associated with digitalis use is the potential for toxicity and/or adverse reactions. In this study maintenance digoxin was withdrawn from 14 elderly nursing home residents in sinus rhythm. Subjects were followed over 18 months for evidence of dysrhythmia or heart failure. One resident had an episode of supraventricular tachycardia which required digoxin to be restarted. One resident developed left heart failure, treated with oral diuretic. For 12 of the 14 residents, withdrawal of maintenance digoxin was achieved without deleterious effect. This study suggests that maintenance digoxin may be withdrawn safely in elderly nursing home residents in sinus rhythm and without history of atrial dysrhythmia.

Mortality and morbidity during one year of follow‐up in suspected acute myocardial infarction in relation to early diagnosis: experiences from the MIAMI trial

From a large randomized multicentre trial of metoprolol in suspected acute myocardial infarction (n = 5778) we report on the outcome during 1 year of follow-up, in relation to early diagnosis. Patients who developed a confirmed infarction had a 1-year mortality rate of 12.8%. This was significantly higher than the mortality rate of 6.3% (P less than 0.001) in patients with possible infarction and it was also higher than that in patients with no infarction, which was 5.0% (P less than 0.001). A multivariate analysis showed that independent risk predictors in the clinical history of patients without confirmed infarction were a history of angina pectoris, chronic use of digitalis and advanced age. After 1 year, angina pectoris was most common in patients with an initial possible infarction. These patients were also in most urgent need of bypass surgery. We thus conclude that the mortality during 1 year of follow-up among patients with an initially strongly suspected acute myocardial infarction was clearly related to whether or not the patient developed a myocardial infarction.

Risk factors for male breast cancer: A Franco‐Swiss case‐control study

In order to evaluate risk factors in male breast cancer, a case-control study of 91 histologically diagnosed cases and 255 cancer controls, matched for age and year of diagnosis, was conducted in Villejuif (France) and Geneva (Switzerland). Factors studied included marital history, occupational exposure, associated diseases, family history of breast cancer, history of radiation exposure and drugs which increase or are suspected of increasing prolactin or estrogen levels. Cases were significantly more likely to be bachelors or to work as butchers than were the controls. Other statistically significant risk factors identified were family history of breast cancer and therapeutic use of digitalis. Elevated risks, although not significant, were observed for individuals with a past history of tuberculosis, hyperthyroidism, liver cirrhosis or gallstone, who had been treated with isoniazid, or who had worked in high environmental temperatures. Further studies are needed to confirm our results particularly as regards hormonal imbalance and genetic factors.

Two‐year survival after myocardial infarction

We have studied 773 consecutive cases (706 individuals) with definite myocardial infarction treated in the Coronary Care Unit at Danderyd Hospital in Stockholm during the period 1984-85. Hospital mortality was 12.9% in all patients and 8.9% in patients under 70 years of age. Six hundred and six patients were discharged from the hospital and followed up for 2 years. The 2-year mortality in ischaemic heart disease was 14.4% in all patients and 9.5% in patients under 70 years of age and, including all causes of death, 20.3% and 14.6%, respectively. Our policy for medical treatment included frequent use of beta-adrenergic blocking agents, even in heart failure, and restricted use of antiarrhythmic drugs and digitalis. A short delay of admission may have been beneficial for the result of different kinds of anti-ischaemic intervention. Furthermore, a routinely performed exercise ECG before discharge and after 6 weeks, as part of a structured follow-up, has improved our ability to detect complications at an early stage and to optimize medical treatment.