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Biomedical subjects

Patricia A Howard

Publications and source records attributed to Patricia A Howard.

17 recordsLinked to original sources

Drug therapy recommendations from the 2005 ACC/AHA guidelines for treatment of chronic heart failure.

OBJECTIVE: To review and discuss key aspects of the drug therapy recommendations in the American College of Cardiology (ACC)/American Heart Association (AHA) 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure (HF) in the Adult. DATA SOURCES: Data were obtained from the ACC/AHA 2005 Guideline Update for Chronic HF. English-language clinical trials, observational studies, and pertinent review articles evaluating the pharmacotherapy of chronic HF were identified, based on MEDLINE searches through January 2006. STUDY SELECTION: Articles presenting information that impacts the evidence base for recommendations regarding the use of various drug therapies in patients with chronic HF were evaluated. DATA SYNTHESIS: The ACC/AHA 2005 Guideline Update for HF provides revised, evidence-based recommendations for the treatment of chronic HF. The new guidelines are based on a staging system that recognizes both the development and progression of HF. Recommendations are provided for 2 stages of patients (A and B) who do not yet have clinical HF but are clearly at risk and 2 stages (C and D) that include patients with symptomatic HF. The guidelines continue to emphasize the important role of neurohormonal blockade with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-adrenergic blockers, and aldosterone antagonists. Based on recent trials, updated recommendations address the roles of combination therapy and the selective addition of hydralazine and isosorbide dinitrate. Along with specific drug recommendations, information on the practical use of various drugs is provided. Although the guidelines primarily focus on HF due to systolic dysfunction, general recommendations are also provided for patients with preserved systolic function. CONCLUSIONS: The ACC/AHA 2005 Guideline Update provides evidence-based recommendations for healthcare professionals involved in the care of adults with chronic HF. Recent clinical trial findings have further clarified the evolving role of neurohormonal-blocking drugs in the prevention and treatment of HF.

American Heart Association↗

Risk-stratified evaluation of amiodarone to prevent atrial fibrillation after cardiac surgery.

BACKGROUND: Amiodarone prophylaxis (AMP) reduces the prevalence of postoperative atrial fibrillation (POAF) after cardiac surgery. We investigated the impact of AMP on the frequency and duration of POAF, the intensive care unit and hospital length of stay, and its cost-effectiveness in a risk-stratified cohort. METHODS: A retrospective, observational analysis of 509 patients who underwent cardiac surgery in 2003 was performed. Data sources included The Society of Thoracic Surgeons national database; medical and medication administration records; and the activity-based cost data from our institution. Risk stratification for POAF was determined using a validated risk index. Cost-effectiveness was determined from the hospital's perspective. RESULTS: The mean patient age was 63 years, 27% were female, 80% underwent coronary artery bypass grafting, and 29% underwent valve surgery. When a risk-stratified evaluation was made, 50% of patients were at an elevated risk for having POAF develop. When compared with nonprophylaxed patients, those receiving AMP (59%) experienced less POAF (31% vs 22%; p = 0.027) and shorter durations of POAF (4.7 vs 2.7 days; p = 0.025). In the elevated-risk group, AMP clinically (but not significantly) reduced length of stay in the intensive care unit (101 vs 68 hours; p > 0.05) and post-procedural hospital length of stay (9.7 vs. 7.9 days, p > 0.05). In the elevated-risk group, AMP was robustly cost-effective in reducing POAF. CONCLUSIONS: Amiodarone prophylaxis reduced the prevalence and duration of POAF. Baseline risk for POAF was a major determinant of the overall cost-effectiveness of AMP. The greatest cost savings with AMP was seen in patients at an elevated risk for POAF. These findings suggest the need for risk stratification when prescribing AMP.

Amiodarone↗

Development of a contemporary bleeding risk model for elderly warfarin recipients.

BACKGROUND AND PURPOSE: Develop and validate a contemporary bleeding risk model to guide the clinical use of warfarin in the elderly atrial fibrillation (AF) population. METHODS: Chart-abstracted data from the National Registry of Atrial Fibrillation was combined with Medicare part A claims to identify major bleeding events requiring hospitalization. Using a split-sample technique, candidate variables that provided statistically stable relationships with major bleeding events were selected for model development. Three risk categories were created and validated. The new model was compared to existing bleeding risk models using c-statistics and Kaplan-Meier curves. RESULTS: Model development and validation was conducted on 26,345 AF patients who were > 65 years of age and had been discharged from the hospital while receiving warfarin therapy. The following eight variables were included in the final risk score model: age > or = 70 years; gender; remote bleeding; recent (ie, during index hospitalization) bleeding; alcohol/drug abuse; diabetes; anemia; and antiplatelet use. Bleeding rates were 0.9%, 2.0%, and 5.4%, respectively, for the groups with low, moderate, and high risk, compared to the bleeding rates for groups with moderate risk (1.5% and 1.0%) and high risk (1.8% and 2.5%) from other models. CONCLUSIONS: Using a nationally derived data set, we developed a model based on contemporary practice standards for determining major bleeding risk among AF patients receiving warfarin therapy. The larger sample size afforded the opportunity to incorporate additional risk factors. In addition, since the majority of our population was > 65 years of age, we had greater ability to stratify risk among the elderly.

Age Factors↗

Effectiveness of continuous infusions of loop diuretics for severe heart failure.

Heart failure is a growing worldwide epidemic resulting in frequent hospitalizations and increased resource utilization. A major cause of hospitalization is congestive symptoms and impaired functional capacity due to sodium and water retention. Diuretic resistance, which is common among patients with severe heart failure, may inhibit diuresis, thus prolonging hospitalizations. The current evidence suggests that continuous infusions are a potentially effective method for delivering high daily doses of diuretics and rapidly removing large amounts of excess sodium and water. In our experience, continuous intravenous infusions of furosemide are well tolerated and may shorten hospitalizations, which in turn reduces overall costs. Although the current evidence is largely limited to observational reports and small uncontrolled studies, the consistent findings of efficacy and safety warrant the further investigation of this treatment strategy in randomized controlled trials.

Diuretics↗

Eplerenone: a selective aldosterone receptor antagonist for patients with heart failure.

OBJECTIVE: To evaluate the pharmacology, pharmacokinetics, safety, and clinical use of eplerenone in heart failure (HF). DATA SOURCES: English-language MEDLINE searches were performed from 1966 to May 2004. Key words included eplerenone, aldosterone receptor antagonist, heart failure, myocardial infarction, left-ventricular dysfunction, and cost-effectiveness. Additional references were identified from bibliographies of selected articles. STUDY SELECTION AND DATA EXTRACTION: Human trials evaluating the efficacy, safety, and cost-effectiveness of aldosterone receptor antagonists in HF were evaluated. DATA SYNTHESIS: Eplerenone is the first selective aldosterone receptor antagonist. The drug is indicated to improve the survival of stable patients with left-ventricular systolic dysfunction (ejection fraction <40%) and clinical evidence of HF following acute myocardial infarction. Efficacy and safety in this population have been demonstrated in a large, randomized clinical trial. Eplerenone is associated with severe and sometimes life-threatening hyperkalemia. Patients with reduced renal function and diabetes, as well as those on other drugs that increase potassium levels, are at highest risk. Eplerenone is metabolized by the cytochrome P450 system and may interact with drugs that interfere with this system. A major advantage of eplerenone over the nonselective aldosterone receptor antagonist spironolactone is lack of binding to progesterone and androgen receptors, which is associated with drug-induced gynecomastia, breast pain, and impotence. CONCLUSIONS: The addition of eplerenone to traditional HF therapy has been shown to reduce morbidity and mortality in patients who develop left-ventricular dysfunction after acute myocardial infarction. Eplerenone's selectivity reduces sex hormone-related adverse effects. Despite these benefits, the overall cost-effectiveness has yet to be determined.

Animals↗

Combined anticoagulant-antiplatelet use and major bleeding events in elderly atrial fibrillation patients.

BACKGROUND AND PURPOSE: Bleeding risks from combined antiplatelet-warfarin therapy have not been well-described in clinical practice. We examined antiplatelet therapy among warfarin users and the impact on major bleeding rates. METHODS: Retrospective cohort analysis of persons discharged on warfarin after an atrial fibrillation admission using data from Medicare's National Stroke Project. Data included Medicare claims, enrollment information, and medical record abstracted data. Logistic regression and Cox proportional hazards models were used to predict concurrent antiplatelet use and hospitalization with a major acute bleed within 90 days after discharge from the index AF admission. RESULTS: 10,093 warfarin patients met inclusion criteria with a mean age of 77 years; 19.4% received antiplatelet therapy. Antiplatelet use was less common among women, older persons, and persons with cancer, terminal diagnoses, dementia, and bleeding history. Persons with coronary disease were more likely to receive an antiplatelet agent. Antiplatelets increased major bleeding rates from 1.3% to 1.9% (P=0.052). In the multivariate analysis, factors associated with bleeding events included age (OR, 1.03; 95% CI, 1.002 to 1.05), anemia (OR, 2.52; 95% CI, 1.64 to 3.88), a history of bleeding (OR, 2.40; 95% CI, 1.71 to 3.38), and concurrent antiplatelet therapy (OR, 1.53; 95% CI, 1.05 to 2.22). CONCLUSIONS: Although concerns about increased bleeding risk with combined warfarin-antiplatelet therapy are not unfounded, the risk of bleeding is moderately increased. The decision to use concurrent antiplatelet therapy appears to be tempered by cardiac and bleeding risk factors.

Aged↗

Nonsteroidal anti-Inflammatory drugs and cardiovascular risk.

Nonsteroidal anti-inflammatory drugs (NSAID) inhibit cyclooxygenase (COX) enzymes, which exist in at least two isoforms, COX-1 and COX-2. Aspirin and older agents in this class are nonselective inhibitors of both COX-1 and COX-2. Newer agents termed "coxibs" are selective inhibitors of COX-2. Among the NSAID, only aspirin has been proven to significantly reduce cardiovascular risk, primarily through inhibition of COX-1-mediated platelet aggregation. It has been suggested that other nonselective agents, especially naproxen, may provide some lesser degree of cardioprotection, but conclusive evidence is lacking. Conversely, there are concerns that the COX-2 inhibitors may increase cardiovascular risk. However, mechanisms for this potentially adverse cardiovascular effect are unknown, and it is becoming increasingly clear that our understanding of the role of COX-2 in cardiovascular function is incomplete. Some studies have demonstrated a potentially beneficial effect of COX-2 on cardiovascular function that could be negated by COX-2 inhibition, while other studies have reported improved endothelial function with COX-2 inhibitors. Additionally, the impact of combined therapy with aspirin and other COX inhibitors is not yet clear. This article will review the studies that have examined these issues.

Animals↗

Role of C-reactive protein in cardiovascular disease.

OBJECTIVE: To discuss the role of C-reactive protein (CRP) in cardiovascular disease as a predictor of vascular events and identify key factors that increase or decrease this inflammatory marker. DATA SOURCES: Articles were identified through searches of MEDLINE (1966-July 2003), International Pharmaceutical Abstracts (1970-June 2003), and bibliographies of selected articles. Search terms included C-reactive protein, HMG-CoA reductase inhibitors, fenofibrate, niacin, aspirin, estrogen, thiazolidinediones, and raloxifene. data selection and data extraction: All studies relevant to CRP and cardiovascular disease or the effects of pharmacologic and nonpharmacologic interventions on CRP levels were evaluated. All information deemed relevant to this review was included. DATA SYNTHESIS: Numerous studies have shown a strong association between CRP levels and future vascular events (i.e., coronary, cerebrovascular, peripheral vascular disease), with minimal correlation to low-density-lipoprotein cholesterol. Clinical guidelines have recently been published indicating that CRP levels of <1, 1-3, and >3 mg/L correspond to low, moderate, and high risk, respectively, for future vascular events. Drugs including statins, fibrates, niacin, thiazolidinediones, and antiplatelet agents, as well as weight loss and exercise, have demonstrated efficacy in lowering CRP levels. CONCLUSIONS: CRP appears to be a valuable tool for predicting future vascular events in patients striving for primary or secondary prevention of cardiovascular disease. While several pharmacologic and nonpharmacologic interventions have been shown to lower CRP levels, the impact on clinical outcomes requires further study.

C-Reactive Protein↗

High-impact articles related to the pharmacotherapeutic management of systolic heart failure.

This compilation is part of a series of five articles identifying important literature in cardiovascular pharmacotherapy. This list focuses on pharmacotherapeutic management of acute decompensated and chronic heart failure. Most of the cited works present the results of landmark clinical studies that have shaped the management of patients with left ventricular systolic dysfunction. Limited primary literature is available for some topics; thus, pertinent review articles also are listed. In addition, consensus documents formed by expert panels in the United States and Europe are reviewed. This compilation may serve as a teaching tool, reference resource, or update of the literature for pharmacy clinicians, physicians, and students.

Heart Failure↗

Association of HMG-CoA reductase inhibitors with neuropathy.

OBJECTIVE: To review the possible association between statins and peripheral neuropathy. DATA SOURCES: Literature was obtained from MEDLINE (1984-September 2002) and International Pharmaceutical Abstracts (1970-June 2002). Key search terms included statin, neuropathy, and HMG-CoA reductase inhibitor. DATA SYNTHESIS: Epidemiologic studies and case reports suggest an increased risk of peripheral neuropathy with statin drugs. Most patients were receiving long-term therapy, although the onset was highly variable. The majority of cases were at least partially reversible with drug cessation. Specific risk factors or mechanisms have not been identified. CONCLUSIONS: Observational data suggest a link between chronic statin use and increased risk of peripheral neuropathy. However, the risk appears to be small relative to the significant cardioprotective benefits.

Adult↗

Aspirin resistance.

OBJECTIVE: To review the literature addressing the problem of aspirin resistance in patients with vascular disease. DATA SOURCES: A MEDLINE search (1966-February 2002) was performed. Key search terms included aspirin, resistance, resistant, failure, tolerance, and nonresponder. English-language studies were identified as well as pertinent references from these articles. DATA SYNTHESIS: Aspirin resistance has been reported in patients with cardiovascular, cerebrovascular, and peripheral vascular disease. Because of differences in the definition of resistance, variations in detection methods, and a lack of controlled trials, the true significance of the problem remains unknown. Multiple mechanisms for resistance have been proposed, including increased reactivity to platelet aggregating factors, genetic polymorphism, and alternate pathways for thromboxane synthesis. The studies to date have failed to demonstrate consistent relationships between aspirin's platelet-inhibiting effects, the impact of dosage escalation, and clinical outcomes. CONCLUSIONS: For many patients, aspirin is an effective antithrombotic agent. However, patients taking aspirin may demonstrate highly variable responses to in vitro tests for platelet aggregation and may experience breakthrough thromboembolic events. Although this phenomenon has been termed aspirin resistance, the lack of a uniform definition or agreement on diagnostic criteria precludes definitive recommendations at this time. In addition, strategies are needed to identify patients at risk for aspirin resistance who might benefit from alternative or combined antiplatelet therapy.

Aspirin↗

Severe heart failure in the elderly: potential benefits of high-dose and continuous infusion diuretics.

Heart failure (HF) is a growing problem among the elderly that results in significant morbidity and mortality. Congestive symptoms because of sodium and water retention are a major cause of impaired functional capacity and frequent hospitalisations. Patients with severe HF often develop resistance to traditional doses of diuretics. Subtherapeutic diuretic regimens may result in prolonged hospitalisation and thus increased costs. Numerous studies have shown that aggressive high-dose regimens of loop diuretics can be safely and effectively used in elderly patients with severe HF. Continuous intravenous infusions are a particularly effective method for delivering high daily doses of diuretics and rapidly removing large amounts of excess sodium and water. In our experience, continuous intravenous infusions are a well tolerated and effective treatment, which may shorten the duration of hospitalisation and in turn reduce the costs of treating elderly patients with HF.

Aged↗

The nature and frequency of potential warfarin drug interactions that increase the risk of bleeding in patients with atrial fibrillation.

PURPOSE: To determine the frequency with which atrial fibrillation (AF) patients receiving warfarin are prescribed interacting drugs that could increase bleeding risks. METHODS: We retrospectively examined medical records for 704 Medicare beneficiaries > or = 65 years of age discharged from Kansas hospitals with AF. We identified all patients receiving warfarin and examined discharge prescriptions for drugs that could increase bleeding risk either by increasing the international normalized ratio (INR) or directly inhibiting hemostasis. RESULTS: Of 256 patients discharged on warfarin, 138 (54%) were prescribed another medication that could increase bleeding risk. Among these patients, 106 (41%) were discharged with a total of 150 prescriptions for drugs that could interact with warfarin to increase the INR. Antibiotics accounted for 67% of these prescriptions. Fifty-three patients (21%) received 56 prescriptions for drugs which could inhibit hemostasis. These were primarily antiplatelet drugs with 61% of the prescriptions for aspirin. Patients with coronary artery disease were more likely than others to be prescribed warfarin plus antiplatelet agents (OR = 2.80; p = 0.04). More than one interacting drug was prescribed for 20% of the patients. CONCLUSIONS: AF patients discharged on warfarin were frequently prescribed concomitant medications that increase bleeding risks. These patients should be closely monitored and counseled to watch for signs of bleeding.

Aged↗

Low molecular weight heparins in special populations.

Low molecular weight heparins (LMWH) are replacing unfractionated heparin (UH) as safe and effective agents for the prevention and treatment of thromboembolism. Although LMWH offer many advantages over UH, usage is less clearly defined in certain special populations, including renal dysfunction, obesity and pregnancy. This article will briefly review the pharmacology of LMWH and discuss usage in these special populations.

Anticoagulants↗

Patterns of ACE inhibitor use in elderly medicaid patients with heart failure.

The authors identified 321 elderly Kansas Medicaid patients with congestive heart failure and examined angiotensin-converting enzyme (ACE) inhibitor use. Using retrospective claims data, ACE inhibitor use was quantified and daily doses compared to a target enalapril-equivalent dose of 20 mg. The cohort patients averaged 80 years of age, 84% were female, and 70% resided primarily in a nursing home. Only 37.8% received an ACE inhibitor. Users were younger than nonusers (t=2.00; p=0.046), but there was no gender difference (odds ratio [OR], 1.4; 95% confidence interval [CI], 0.73, 2.6). ACE inhibitor users averaged eight prescriptions annually, providing approximately 257 medication days (70% of the study period). The average enalapril-equivalent daily dose was 10.6 mg, and only 22% received the target dose. Nursing home residents were less likely to receive an ACE inhibitor than ambulatory patients (OR, 0.55; 95% CI, 0.34, 0.89) but equally likely to receive target doses (OR, 1.3; 95% CI, 0.34, 4.9). ACE inhibitor use in the Kansas Medicaid congestive heart failure population is not consistent with practice guidelines, particularly among older and/or nursing home patients.

Adult↗

Heart failure drug utilization patterns for Medicaid patients before and after a heart failure-related hospitalization.

The authors examined heart failure (HF) drug utilization patterns in Medicaid patients before and after a HF-related hospitalization. This was a retrospective claims analysis of Kansas Medicaid beneficiaries hospitalized for HF between July 1, 2000, and March 31, 2001. HF drugs were tracked 6 months prior and 6 months following the admission. Angiotensin-converting enzyme (ACE) inhibitor doses were compared with target ranges. The cohort of 135 patients had a mean age of 53.6 years and was predominantly female (66.7%) and Caucasian (70.4%) with a high prevalence of cardiovascular comorbidities. Before hospitalization, less than one third of patients were receiving ACE inhibitors, angiotensin receptor blockers, beta blockers, digoxin, or vasodilators. Following hospitalization, increased utilization was observed for beta blockers, digoxin, and angiotensin receptor blockers, but overall usage remained low. ACE inhibitors and vasodilator use remained constant. ACE-inhibitor doses were below target ranges before and after hospitalization. In this Medicaid cohort, HF-related hospitalizations did not lead to improved HF therapy.

Adult↗