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British Journal of Clinical Pharmacology Sep 2011The pharmacotherapy for heart failure with normal ejection fraction (HFNEF) is not as well defined as that for the treatment for heart failure with reduced ejection... (Review)
Review
AIM
The pharmacotherapy for heart failure with normal ejection fraction (HFNEF) is not as well defined as that for the treatment for heart failure with reduced ejection fraction (HFREF). Studies of the various drugs given for HFNEF have revealed conflicting results. The aim of this systematic review was to determine whether there is any benefit with pharmacotherapy in HFNEF in terms of cardiac outcomes.
METHODS
Electronic and printed sources were searched until August 2010 for randomized controlled clinical trials (RCTs) comparing drug therapy with placebo in HFNEF. Weighted mean difference and pooled odds ratio (OR) with 95% confidence intervals were calculated.
RESULTS
A total of six RCTs including 8410 patients with a mean follow-up period of 21 months were included in the analysis. Although there were no significant differences in all cause mortality between the two groups (pooled OR 0.95, 95% CI 0.79, 1.13, P= 0.55), the subgroup analysis revealed a slight but non significant advantage with the β-adrenoceptor blocker group. There was no significant difference between the two groups in terms of cardiovascular mortality, hospitalization, worsening heart failure, ejection fraction, E : A ratio, deceleration time and E : E' ratio.
CONCLUSION
There was no significant benefit of pharmacotherapy in HFNEF. This might have been because of a lack of stringent inclusion criteria for patients in the trials and lower power of the studies. Hence trials with well defined inclusion criteria, better power, longer follow-up periods and with echocardiographic parameters as endpoints are required to shed further light on this topic.
Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Calcium Channel Blockers; Digoxin; Drug Therapy; Heart Failure; Humans; Randomized Controlled Trials as Topic; Stroke Volume
PubMed: 21518388
DOI: 10.1111/j.1365-2125.2011.03998.x -
The Cochrane Database of Systematic... Jan 2011Lendrum 1955 suggested that pulmonary edema secondary to congestive heart failure may contribute to neonatal respiratory distress syndrome (RDS). Based on this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lendrum 1955 suggested that pulmonary edema secondary to congestive heart failure may contribute to neonatal respiratory distress syndrome (RDS). Based on this hypothesis, investigators began to use digitalis glycosides to improve myocardial contractility and decrease congestive heart failure. The first use of digitalis glycosides in infants with RDS was reported by Stahlman 1959. Stahlman reported a reduction in mortality in an uncontrolled trial of digitalis in infants with RDS.
OBJECTIVES
To assess the effect of digoxin on mortality in premature infants at risk for or with RDS.
SEARCH STRATEGY
Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: digoxin; limits: age groups, newborn infants; publication type, clinical trial), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language.When updated in December 2008, the search was expanded to include Medline, CINHAL, and Embase (MeSH terms and text words: digoxin or digitalis; limits: age group, all infants; publication type: clinical trial).
SELECTION CRITERIA
Randomized and quazi-randomized controlled trials of digoxin in either the prevention or treatment of RDS are included in this overview.
DATA COLLECTION AND ANALYSIS
Data regarding clinical outcomes were excerpted from the trial reports by one review author (RS) and checked by the second review author (EO). Data were analyzed according to the standards of the Cochrane Neonatal Review Group.
MAIN RESULTS
Two randomized controlled trials have studied the effects of digoxin in the prevention and treatment of RDS. No improvement in respiratory status or mortality was noted. Meta-analysis of the effect of digoxin given to infants at risk of or with RDS on mortality does not suggest any benefit of digoxin treatment (typical relative risk 1.27 95% CI 0.78 to 2.07; typical risk difference 0.06, 95% CI -0.06 to 0.17).
AUTHORS' CONCLUSIONS
Although hemodynamic disturbances play a role in the overall pathogenesis of respiratory distress syndrome, the specific contribution of early congestive heart failure (unrelated to hemodynamically significant patent ductus arteriosus) does not appear to be a significant factor in RDS. Treatment with digoxin has no proven value in infants solely affected with RDS.
Topics: Cardiotonic Agents; Digoxin; Humans; Infant, Newborn; Infant, Premature; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn
PubMed: 21249645
DOI: 10.1002/14651858.CD001080.pub2 -
BMJ Clinical Evidence Feb 2010Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort... (Review)
Review
INTRODUCTION
Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug treatments, and of drug and invasive treatments, for heart failure? What are the effects of angiotensin-converting enzyme inhibitors in people at high risk of heart failure? What are the effects of treatments for diastolic heart failure? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 85 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aldosterone receptor antagonists; amiodarone; angiotensin-converting enzyme inhibitors; angiotensin II receptor blockers; anticoagulation; antiplatelet agents; beta-blockers; calcium channel blockers; cardiac resynchronisation therapy; digoxin (in people already receiving diuretics and angiotensin-converting enzyme inhibitors); exercise; hydralazine plus isosorbide dinitrate; implantable cardiac defibrillators; multidisciplinary interventions; non-amiodarone antiarrhythmic drugs; and positive inotropes (other than digoxin).
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Treatment Outcome; Ventricular Dysfunction, Left
PubMed: 21718583
DOI: No ID Found -
Alimentary Pharmacology & Therapeutics Jun 2009Due to suppression of gastric acidity during antisecretory therapy, an impaired absorption of co-administered drugs may occur. (Review)
Review
BACKGROUND
Due to suppression of gastric acidity during antisecretory therapy, an impaired absorption of co-administered drugs may occur.
AIM
To review evidence of impaired drug absorption related to the use of co-administered PPIs or H2RAs.
METHODS
Systematic search of MEDLINE/EMBASE/SCOPUS databases (1980-September 2008) for English articles with keywords: drug malabsorption and absorption, stomach, anti-secretory/acid inhibitory drugs, histamine H2 antagonists, PPIs, gastric acid, pH, hypochlorhydria, gastric hypoacidity. From 2126 retrieved articles, 16 randomized crossover studies were identified investigating impaired absorption of nine different drugs in association with co-administration of PPIs or H2RAs. Information on investigated drug, study type, features of investigated subjects, study design, type of intervention, and study results were extracted.
RESULTS
The identified studies investigated the absorption kinetics of nine drugs. Acid suppression reduced absorption of ketoconazole, itraconazole, atazanavir, cefpodoxime, enoxacin and dipyridamole (median C(max) reduction by 66.5%). An increased absorption of nifedipine and digoxin (median AUC increase by 10%) and a 2-fold-increase in alendronate bioavailability were observed.
CONCLUSIONS
Gastric pH appears relevant for absorption of some cardiovascular or infectious disease agents. Antisecretory treatment may significantly modify the absorption of co-administered drugs.
Topics: Anti-Ulcer Agents; Drug Administration Schedule; Gastric Acid; Gastric Mucosa; Gastrointestinal Diseases; Histamine H2 Antagonists; Humans; Intestinal Absorption; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 19302263
DOI: 10.1111/j.1365-2036.2009.03993.x -
BMJ Clinical Evidence Apr 2008Atrial fibrillation is a supraventricular tachyarrhythmia, which is characterised by the presence of fast and uncoordinated atrial activation leading to reduced atrial... (Review)
Review
INTRODUCTION
Atrial fibrillation is a supraventricular tachyarrhythmia, which is characterised by the presence of fast and uncoordinated atrial activation leading to reduced atrial mechanical function. Risk factors for atrial fibrillation include increasing age, coexisting cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and coexisting infection.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral medical treatments to control heart rate in people with chronic (defined as longer than 1 week for this review) non-valvular atrial fibrillation? What is the effect of different treatment strategies (rate vs. rhythm) for people with persistent non-valvular atrial fibrillation? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta-blockers (with or without digoxin), calcium channel blockers (with or without digoxin), calcium channel blockers (rate limiting), digoxin, and rate versus rhythm control strategies.
Topics: Atrial Fibrillation; Atrial Function; Heart Rate; Humans; Risk Factors
PubMed: 19450316
DOI: No ID Found -
BMJ Clinical Evidence May 2008Risk factors for acute atrial fibrillation include increasing age, cardiovascular disease, alcohol, diabetes, and lung disease. Acute atrial fibrillation increases the... (Review)
Review
INTRODUCTION
Risk factors for acute atrial fibrillation include increasing age, cardiovascular disease, alcohol, diabetes, and lung disease. Acute atrial fibrillation increases the risk of stroke and heart failure. Acute atrial fibrillation resolves spontaneously within 24-48 hours in over 50% of people, however many people will require interventions to control heart rate or restore sinus rhythm.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions: to prevent embolism; for conversion to sinus rhythm; and to control heart rate in people with recent onset atrial fibrillation (within 7 days) who are haemodynamically stable? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 28 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: amiodarone, antithrombotic treatment before cardioversion, digoxin, diltiazem, direct current cardioversion, flecainide, propafenone, quinidine, sotalol, timolol, and verapamil.
Topics: Acute Disease; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Humans; Propafenone; Sotalol
PubMed: 19450312
DOI: No ID Found -
Journal of Medical Toxicology :... Dec 2006Cardioactive steroids (CASs) are found in plants, animals, and insects. Their affinity for Na+-K+ ATPase is attenuated by the type of lactone at carbon 17 (C17) of the... (Comparative Study)
Comparative Study Review
INTRODUCTION
Cardioactive steroids (CASs) are found in plants, animals, and insects. Their affinity for Na+-K+ ATPase is attenuated by the type of lactone at carbon 17 (C17) of the steroid backbone: those with 5-membered lactone rings, or cardenolides, are derived mostly from plants with 6-membered rings or from animals with bufadienolides. A systematic review of CAS poisoning was performed to compare the mortality rate of cardenolides and bufadienolides.
METHODS
MEDLINE was searched for articles using commonly reported names of CASs, and keywords were limited to human cases only. We searched cases from 1982 to 2003, so that supportive care was similar and digoxin-specific Fab was available. Identified reports of CAS poisoning were read to exclude cases involving licensed pharmaceuticals. Inclusion criteria included hyperkalemia, gastrointestinal symptoms, electrocardiographic evidence of CAS toxicity, digoxin serum concentration, or history of exposure to a substance containing a CAS. Clinical data was collected, including information about treatment with digoxin-specific Fab and treatment outcome.
RESULTS
Fifty-nine articles, describing 924 patients, were identified. Eight hundred ninety-seven patients (97%) ingested a CAS with a 5-membered lactone ring, and mortality was 6% (n = 54). Twenty-seven patients (2.9%) ingested a CAS with a 6-membered lactone ring, and mortality was 29.6% (n = 8). The difference in mortality rates was statistically significant (p < 0.001, [X2]). CASs with 6-member rings accounted for the highest percentage of nonsuicidal exposures.
CONCLUSION
Although cardenolides accounted for the majority of exposures, bufadienolides were five times more lethal than cardenolides.
Topics: Animals; Bufanolides; Cardenolides; Cardiotonic Agents; Molecular Structure; Mortality; Plant Preparations; Poisoning; Research Design
PubMed: 18072135
DOI: 10.1007/BF03161183 -
The Cochrane Database of Systematic... Oct 2006Cardenolides are naturally occurring plant toxins which act primarily on the heart. While poisoning with the digitalis cardenolides (digoxin and digitoxin) are reported... (Review)
Review
BACKGROUND
Cardenolides are naturally occurring plant toxins which act primarily on the heart. While poisoning with the digitalis cardenolides (digoxin and digitoxin) are reported worldwide, cardiotoxicity from other cardenolides such as the yellow oleander are also a major problem, with tens of thousands of cases of poisoning each year in South Asia. Because cardenolides from these plants are structurally similar, acute poisonings are managed using similar treatments. The benefit of these treatments is of interest, particularly in the context of cost since most poisonings occur in developing countries where resources are very limited.
OBJECTIVES
To determine the efficacy of antidotes for the treatment of acute cardenolide poisoning, in particular atropine, isoprenaline (isoproterenol), multiple-dose activated charcoal (MDAC), fructose-1,6-diphosphate, sodium bicarbonate, magnesium, phenytoin and anti-digoxin Fab antitoxin.
SEARCH STRATEGY
We searched MEDLINE, EMBASE, the Controlled Trials Register of the Cochrane Collaboration, Current Awareness in Clinical Toxicology, Info Trac, www.google.com.au, and Science Citation Index of studies identified by the previous searches. We manually searched the bibliographies of identified articles and personally contacted experts in the field.
SELECTION CRITERIA
Randomised controlled trials where antidotes were administered to patients with acute symptomatic cardenolide poisoning were identified.
DATA COLLECTION AND ANALYSIS
We independently extracted data on study design, including the method of randomisation, participant characteristics, type of intervention and outcomes from each study. We independently assessed methodological quality of the included studies. A pooled analysis was not appropriate.
MAIN RESULTS
Two randomised controlled trials were identified, both were conducted in patients with yellow oleander poisoning. One trial investigated the effect of MDAC on mortality, the relative risk (RR) was 0.31 (95% confidence interval (CI) 0.12 to 0.83) indicating a beneficial effect. The second study found a beneficial effect of anti-digoxin Fab antitoxin on the presence of cardiac dysrhythmias at two hours post-administration; the RR was 0.60 (95% CI 0.44 to 0.81). Other benefits were also noted in both studies and serious adverse effects were minimal. Studies assessing the effect of antidotes on other cardenolides were not identified. One ongoing study investigating the activated charcoal for acute yellow oleander self-poisoning was also identified.
AUTHORS' CONCLUSIONS
There is some evidence to suggest that MDAC and anti-digoxin Fab antitoxin may be effective treatments for yellow oleander poisoning. However, the efficacy and indications of these interventions for the treatment of acute digitalis poisoning is uncertain due to the lack of good quality controlled clinical trials. Given pharmacokinetic differences between individual cardenolides, the effect of antidotes administered to patients with yellow oleander poisoning cannot be readily translated to those of other cardenolides. Unfortunately cost limits the use of antidotes such as anti-digoxin Fab antitoxin in developing countries where cardenolide poisonings are frequent. More research is required using relatively cheap antidotes which may also be effective.
Topics: Acute Disease; Antidotes; Cardenolides; Cardiac Glycosides; Charcoal; Humans; Phytotherapy; Poisoning; Randomized Controlled Trials as Topic; Thevetia
PubMed: 17054261
DOI: 10.1002/14651858.CD005490.pub2 -
British Journal of Clinical Pharmacology Oct 2002The aim of this work is to identify the medicines which interact with the herbal remedy St John's wort (SJW), and the mechanisms responsible. (Review)
Review
AIMS
The aim of this work is to identify the medicines which interact with the herbal remedy St John's wort (SJW), and the mechanisms responsible.
METHODS
A systematic review of all the available evidence, including worldwide published literature and spontaneous case reports provided by healthcare professionals and regulatory authorities within Europe has been undertaken.
RESULTS
A number of clinically significant interactions have been identified with prescribed medicines including warfarin, phenprocoumon, cyclosporin, HIV protease inhibitors, theophylline, digoxin and oral contraceptives resulting in a decrease in concentration or effect of the medicines. These interactions are probably due to the induction of cytochrome P450 isoenzymes CYP3A4, CYP2C9, CYP1A2 and the transport protein P-glycoprotein by constituent(s) in SJW. The degree of induction is unpredictable due to factors such as the variable quality and quantity of constituent(s) in SJW preparations. In addition, possible pharmacodynamic interactions with selective serotonin re-uptake inhibitors and serotonin (5-HT(1d)) receptor-agonists such as triptans used to treat migraine were identified. These interactions are associated with an increased risk of adverse reactions.
CONCLUSIONS
In Sweden and the UK the potential risks to patients were judged to be significant and therefore information about the interactions was provided to health care professionals and patients. The product information of the licensed medicines involved has been amended to reflect these newly identified interactions and SJW preparations have been voluntarily labelled with appropriate warnings.
Topics: Contraceptives, Oral; Cyclosporine; Digoxin; Drug Interactions; HIV Protease Inhibitors; Herb-Drug Interactions; Humans; Hypericum; Plant Extracts; Selective Serotonin Reuptake Inhibitors; Theophylline; Warfarin
PubMed: 12392581
DOI: 10.1046/j.1365-2125.2002.01683.x -
Revista Espanola de Cardiologia Jun 2001Recommendations for the treatment of heart failure were carried out by a systematic review of the available evidence of the different pharmacologic treatments. (Review)
Review
INTRODUCTION AND OBJECTIVES
Recommendations for the treatment of heart failure were carried out by a systematic review of the available evidence of the different pharmacologic treatments.
MATERIAL AND METHODS
The review focused on the treatment of chronic and systolic heart failure. All the studies published in english about the pharmacologic treatment of heart failure where identified. The evidence of every pharmacologic treatment was classified according to: a) efficacy variables (reduction of mortality and hospitalizations, improvement of functional class, ejection fraction and exercise tolerance), and b) the level of quality of the evidence according to an evaluation scale. The evidence was also reviewed for the comparisons and the combinations of the pharmacologic treatments, as well as for the toxicity and costs of treatments.
RESULTS
The recommendations were defined according to the NYHA functional class and were classified in the A, B and C categories according to the level of quality of the available evidence. The evidence on mortality was considered the most important. First line drugs, the alternatives and other possible treatments were take into account.
CONCLUSIONS
There is enough evidence based on information about some variables such as reduction of mortality or hospitalizations to carry out treatment recommendations in all stages of heart failure. This point out the interest ant the priority of used them in the evaluation and improvement of the results of heart failure.
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Calcium Channel Blockers; Cardiotonic Agents; Cost-Benefit Analysis; Digoxin; Diuretics; Evidence-Based Medicine; Heart Failure; Humans; Spironolactone; Vasodilator Agents
PubMed: 11412778
DOI: 10.1016/s0300-8932(01)76387-7