Vorapaxar in atherosclerotic disease management.

OBJECTIVE: To review the pharmacology, efficacy, and safety of vorapaxar, a protease activator receptor-1 (PAR-1) antagonist, in the management of atherosclerotic diseases. DATA SOURCES: Peer-reviewed clinical trials and review articles were identified from MEDLINE and Current Content database (both 1966 to December 31, 2014) using the search terms vorapaxar and protease activator receptor antagonist. STUDY SELECTION AND DATA EXTRACTION: A total of 30 clinical studies were identified (16 clinical trials, including subanalyses, 14 related to pharmacology, pharmacokinetics, and pharmacodynamics and drug interactions). DATA SYNTHESIS: Two phase III clinical trials with vorapaxar have been published. In patients with non-ST segment elevation myocardial infarction (MI), vorapaxar failed to significantly reduce the primary efficacy end point (composite of cardiovascular death, MI, stroke, recurrent ischemia with hospitalization, and urgent coronary revascularization). Conversely, in a study of secondary prevention for patients with cardiovascular disease, the composite end point of cardiovascular death, MI, or stroke was significantly reduced. In both trials, the safety end points of major/minor bleeding were increased compared with placebo. In the secondary prevention trial, an increased incidence of intracranial hemorrhage led to the exclusion of patients with a prior history of stroke. CONCLUSION: Vorapaxar is approved for use with aspirin and/or clopidogrel in the secondary prevention of cardiovascular events in stable patients with peripheral arterial disease or a history of MI. However, the addition of vorapaxar to other antiplatelets can significantly increase the risk of bleeding. It is, therefore, essential to balance the need for further reduction of risk of thrombotic event with patient's individual bleeding risk.

Evaluation of Dosing Practices of Rivaroxaban and Dabigatran.

Background: Anticoagulation is standard practice for the prevention and treatment of thromboembolic events. Two of the newer agents, rivaroxaban (Xarelto) and dabigatran (Pradaxa) are being utilized frequently in the inpatient and outpatient settings. Prescribers may not appreciate the need for dose reduction in the setting of renal insufficiency. Objective: The objective of this study was to evaluate whether rivaroxaban and dabigatran were dosed according to recommendations in the package insert for patients with renal insufficiency. Methods: Eligible patients were those >18 years of age who received rivaroxaban or dabigatran as an inpatient or had a prescription filled from the outpatient pharmacy. The use of the Cockcroft-Gault equation was utilized to calculate creatinine clearance to evaluate whether patients had appropriate manufacturer recommended dose reductions based on their renal function. Results: There were very few patients (8 of 355, or 2.3%) who should have received a reduced dose when creatinine clearance was calculated utilizing actual body weight. In those patients with renal insufficiency, 3 of 6 (50.0%) patients receiving rivaroxaban and 1 of 2 (50%) patients receiving dabigatran were appropriately dosed. When ideal body weight was substituted for creatinine clearance calculation, there were 15 patients receiving rivaroxaban and 10 patients receiving dabigatran who fell below the creatinine clearance threshold for dose reduction. Conclusions: Based on this evaluation, very few patients required a dose reduction due to renal insufficiency. It is important for clinicians to always monitor renal function when utilizing these medications to optimize the benefits of the new oral anticoagulants while limiting potential deleterious effects. Furthermore, it is necessary to ensure that actual body weight is being utilized for creatinine clearance calculations with the new oral anticoagulants and not to base dosing on estimated glomerular filtration rate or other calculated creatinine clearance as this could lead to inappropriate dose reductions.

Cardiovascular Drug Shortages: Predominant Etiologies, Clinical Implications, and Management Strategies.

OBJECTIVE: To review the literature surrounding the incidence, significance, and management of cardiovascular (CV) drug shortages. DATA SOURCES: A literature search was conducted using all available indexing databases from January 1996 to August 2013, coupled with assessments of the ASHP (American Society of Health System Pharmacists) and Food and Drug Administration Web sites designated to drug shortages. Data were also gathered through a review of listservs discussing this topic. DATA SYNTHESIS: CV drug shortages are among the top 5 national drug class shortages that are posing a threat to patient care and public health. When a drug shortage occurs, it requires modifications to prescribing and the method medications are processed by the pharmacy. These necessary yet cumbersome changes can potentially result in less-than-desirable prescribing options and increases in personnel time because of administrative and dispensing obstacles. Any one of these has the potential to increase costs and/or lead to worse outcomes. Several factors have been shown to contribute to these shortages, including manufacturing delays, increased demand, medication discontinuations, and lack of raw materials. In this article, we review 13 of the critical CV drug shortages, describe their role in therapy, discuss the reasons for the shortage, define their impact on patient care, and recommend alternative therapies. CONCLUSIONS: CV drug shortages are common and can potentially lead to deleterious patient outcomes. Institutions should develop plans for early identification, management, and resolution to minimize the clinical sequelae associated with drug shortages.

Assessment of prescribers' knowledge of the cost of medications.

BACKGROUND: In 2003, the World Health Organization reported that 50% of patients are adherent to long-term therapies. Frequently, the reason for a patient's nonadherence is the cost of medications. Even with prescription insurance coverage, patients may not be able to afford their medications. OBJECTIVE: To assess prescriber knowledge of the cost of commonly prescribed medications including atorvastatin, gabapentin, levofloxacin, losartan, pantoprazole, pioglitazone, and quetiapine. Secondary objectives were to evaluate how often prescribers consult a discounted drug list and a patient's prescription insurance coverage. METHODOLOGY: One hundred prescribers from the Medical University of South Carolina were surveyed from November 2010 to January 2011. Prescribers consisted of medical residents, attending physicians, fellows, nurse practitioners, and physician assistants. Wholesale prices of medications were determined using the Red Book, and prescription insurance prices were calculated from an average of the top 3 prescription insurance companies' copayments. RESULTS: Medical residents made up 72% of those surveyed, fellows 3%, attending physicians 12%, physician assistants 3%, and nurse practitioners 10%. The prescriber groups were unable to correctly determine the cost of medications of more than 50% of total possible responses. The majority of prescribers rarely asked about a patient's prescription insurance coverage or consulted a discounted drug list before writing a prescription. CONCLUSIONS: Prescribers are more likely to know the cost of medications for patients who have prescription insurance coverage versus those who do not.

Relationship between vancomycin trough concentrations and nephrotoxicity: a prospective multicenter trial.

Several single-center studies have suggested that higher doses of vancomycin, aimed at producing trough concentrations of >15 mg/liter, are associated with increased risk of nephrotoxicity. We prospectively assessed the relative incidence of nephrotoxicity in relation to trough concentration in patients with documented methicillin-resistant Staphylococcus aureus (MRSA) infections at seven hospitals throughout South Carolina. Adult patients receiving vancomycin for at least 72 h with at least one vancomycin trough concentration determined under steady-state conditions were prospectively studied. The relationship between vancomycin trough concentrations of >15 mg/ml and the occurrence of nephrotoxicity was assessed using univariate and multivariate analyses, controlling for age, gender, race, dose, length of therapy, use of other nephrotoxins (including contrast media), intensive care unit (ICU) residence, episodes of hypotension, and comorbidities. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or a ≥ 50% increase from the baseline for two consecutive measurements. MICs of vancomycin for the MRSA isolates were also determined. A total of 288 patients were studied between February 2008 and June 2010, with approximately one-half having initial trough concentrations of ≥ 15 mg/ml. Nephrotoxicity was observed for 42 patients (29.6%) with trough concentrations >15 mg/ml and for 13 (8.9%) with trough concentrations of ≤ 15 mg/ml. Multivariate analysis revealed vancomycin trough concentrations of >15 mg/ml and race (black) as risk factors for nephrotoxicity in this population. Vancomycin trough concentrations of >15 mg/ml appear to be associated with a 3-fold increased risk of nephrotoxicity.

Continuous versus intermittent infusion of furosemide in acute decompensated heart failure.

BACKGROUND: Despite advances in the treatment of chronic ambulatory heart failure, hospitalization rates for acute decompensated heart failure (ADHF) remain high. Although loop diuretics are used in nearly all patients with ADHF to relieve congestive symptoms, optimal dosing strategies remain poorly defined. METHODS AND RESULTS: This was a prospective, randomized, parallel-group study comparing the effectiveness of continuous intravenous (cIV) with intermittent intravenous (iIV) infusion of furosemide in 56 patients with ADHF. The dose and duration of furosemide as well as concomitant medications to treat ADHF were determined by physician preference. The primary end point of the study was net urine output (nUOP)/24 hours. Safety measures including electrolyte loss and hemodynamic instability were also assessed. Twenty-six patients received cIV and 30 patients received iIV dosing. The mean nUOP/24 hours was 2098+/-1132 mL in patients receiving cIV versus 1575+/-1100 mL in the iIV group (P=.086). The cIV group had significantly greater total urine output (tUOP) with 3726+/-1121 mL/24 hours versus 2955+/-1267 mL/24 hours in the iIV group (P=.019) and tUOP/mg furosemide with 38.0+/-31.0 mL/mg versus 22.2+/-12.5 mL/mg (P=.021). Mean weight loss was not significantly different between the groups. The cIV group experienced a shorter length of hospital stay (6.9+/-3.7 versus 10.9+/-8.3 days, P=.006). There were no differences in safety measures between the groups. CONCLUSIONS: The cIV of furosemide was well tolerated and significantly more effective than iIV for tUOP. In addition, continuous infusion appears to provide more efficient diuresis.

Barriers to clopidogrel adherence following placement of drug-eluting stents.

BACKGROUND: Nonadherence to clopidogrel after drug-eluting stent (DES) placement is associated with in-stent thrombosis and adverse cardiac events. OBJECTIVE: To identify the incidence of and barriers associated with nonadherence to clopidogrel in patients receiving DES. METHODS: Patients who received a DES between March 1, 2004, and August 31, 2005, from a single academic medical center were eligible. Telephone interviews were conducted 6 or more months following discharge. Nonadherence was defined as premature discontinuation of or less than 80% adherence to clopidogrel. Patients were asked to identify barriers to adherence. Differences between adherent and nonadherent patients were analyzed using chi(2) and t-test analysis. RESULTS: Of the 674 patients identified, 257 (38%) participated. The nonadherence rate was 20%. The majority (58%) of nonadherent patients discontinued therapy prematurely. Patients identified the main reason for discontinuation as medical barriers (18.56%), including perceived adverse effects (9.28%). The incidence of rash was higher in patients who were nonadherent (12% vs 4%; p = 0.049). Overall, 49% of patients recalled receiving discharge counseling regarding adverse effects. A financial barrier was identified by 22 (42%) patients in the nonadherent and 73 (36%) in the adherent group, of whom 64% and 52%, respectively, reported having insurance coverage for medications. Adherent patients reported higher copays ($29.69 vs $18.14; p = 0.01). CONCLUSIONS: Prospective studies should be conducted to aid in identifying patients at risk for nonadherence and possible in-stent thrombosis in order to identify interventions to improve adherence.

Evaluation of aldosterone antagonist utilization in heart failure with reduced and preserved ejection fraction at an academic medical center.

BACKGROUND: Aldosterone antagonists (AA) have historically been underutilized despite evidence that they reduce morbidity, mortality, and readmission rates to the hospital when used appropriately. OBJECTIVE: We sought to determine if AAs were being prescribed in accordance with the 2013 ACCF/AHA guidelines and if there was any benefit surrounding 30-day readmissions or 30-day mortality for patients taking AAs with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a retrospective chart review of adult patients who were discharged between October 1, 2015 and February 1, 2016 with any ICD-10 code for heart failure to assess compliance with guideline directed medical therapy. At baseline, patients were stratified by HFpEF and HFrEF. Patients were excluded if they died during the admission, discharged with hospice care, received a heart transplant or ventricular assist device, if they were miscoded or left against medical advice. Descriptive statistics, and Chi Square were used to evaluate the data. RESULTS: We reviewed 601 patient charts for eligibility in our study, and determined 438 met the criteria for inclusion. Ninety-seven patients (22%) received an AA. Within the HFrEF group, only 37% of patients who were eligible per 2013 ACCF/AHA guidelines, received an AA at time of discharge. Fourteen percent of HFpEF patients were discharged on an AA. We found a trend towards decreased rates of our 30-day outcomes in patients who took AAs in both the HFpEF and HFrEF groups. CONCLUSIONS: AAs were underutilized during the timeframe we evaluated, despite the evidence for their use.

Key Articles and Guidelines in the Management of Heart Failure: 2018 Update.

Heart failure is one of the leading causes of hospitalizations in the United States, with >1 million admissions yearly and a 25% risk of readmissions within 1 month. In order to assist clinicians, we provide an update of the heart failure bibliography that was published in Pharmacotherapy in 2008, which followed the original bibliography published in 2004. A significant number of clinical trials and observational studies have been conducted since the early 1980s to guide management of heart failure patients. Major advances have occurred in the past 10 years, and our understanding of the diagnosis, prevention, and management of heart failure has evolved substantially during this time period. Specific areas of this review include heart failure risk factors, management of comorbid conditions, acute heart failure management, chronic heart failure management, advanced heart failure, device therapy, lifestyle modification, and medication and therapy management, including medication adherence. Key consensus guidelines and statements are also included. This bibliography of key heart failure papers aims to provide clinicians and their trainees with a valuable clinical reference resource and teaching tool that may be used to optimize the care of patients with heart failure.

Type 2 diabetes mellitus and heart failure.

Diabetes mellitus and heart failure are common comorbidities, and their prevalence has increased significantly over the past decade. We examined the relationships between diabetes and heart failure, the effect of commonly prescribed antidiabetic drugs on the development of heart failure, and the benefits and risks of recommended heart failure therapies in patients with diabetes. Compared with patients with heart failure who do not have diabetes, patients with both diabetes and heart failure have a poorer prognosis, including a 1.5-2-fold higher risk of mortality. Based on the results of randomized controlled trials, insulin and sulfonylureas do not appear to protect against or contribute to the development of new-onset heart failure, whereas metformin may modestly reduce the risk. The use of metformin in patients with established heart failure is controversial; retrospective analyses have shown that metformin may have a beneficial effect on outcomes, but there are no prospective, randomized clinical trials to support its use in this population. The thiazolidinediones, however, contribute to the development of heart failure and increase the risk of heart failure exacerbations particularly when used in combination with insulin. Recommendations for the treatment of symptomatic heart failure in patients with diabetes have been largely derived from post hoc analyses or preplanned subgroup analyses in landmark clinical trials. The data clearly support the use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for both the prevention and treatment of symptomatic heart failure in patients with diabetes. Despite concerns regarding the potential risks of beta-blockers in patients with diabetes, these drugs have a clear mortality benefit in patients with stages B and C heart failure. Therefore, patients with diabetes should not be denied beta-blocker therapy unless there is a clear contraindication. Likewise, aldosterone receptor antagonists should be added to standard therapies in patients with stages C and D heart failure. Future heart failure studies should include a sufficiently large diabetes cohort to conduct meaningful preplanned subgroup analyses that examine the effect of proposed treatments on both heart failure-related and diabetes-related outcomes.

Prevalence of anemia in clinic patients with heart failure and cost analysis of epoetin treatment.

STUDY OBJECTIVES: To determine the prevalence of anemia in an outpatient heart failure clinic, describe the type of anemia in patients treated there, and evaluate the potential costs associated with epoetin therapy in this cohort. DESIGN: Single-center, retrospective cohort analysis (part 1) and a literature-based economic decision analysis (part 2). DATA SOURCE: Medical records from a multidisciplinary, outpatient, heart failure clinic, and published hospitalization and drug-use data. PATIENTS: We evaluated 170 adults with chronic heart failure who were enrolled in the clinic and for whom at least one complete blood count was recorded between January 1, 2003, and April 15, 2006. MEASUREMENTS AND MAIN RESULTS: In part 1, demographic and clinical data were extracted from electronic medical records. The overall prevalence of anemia was 47.6% or 47.1%, as based on World Health Organization or National Kidney Foundation definitions, respectively. Normocytic anemia was characterized in 75.0% of patients. In part 2, heart failure hospitalization rates and costs, drug acquisition, and drug administration were estimated by using the published literature. In a hypothetical cohort of 100 patients with heart failure and comorbid anemia, the costs associated with outpatient epoetin and intravenous iron therapy exceeded savings in hospitalization costs by $83,070. Results of 1-way sensitivity analyses generally confirmed robustness of the model. CONCLUSION: Anemia is a common comorbidity in patients with chronic heart failure treated in the outpatient clinic. Although the current evidence is insufficient to support the use of epoetin in this population, initial findings indicate that epoetin and intravenous iron therapy may be associated with positive clinical outcomes. From a pharmacoeconomic standpoint, however, a reduction in the cost of heart failure-related hospitalization does not offset the cost of epoetin and intravenous iron therapy.

Evaluation of treatment with direct thrombin inhibitors in patients with heparin-induced thrombocytopenia.

STUDY OBJECTIVE: To evaluate the efficacy, safety, and associated costs of anticoagulation with argatroban, bivalirudin, and lepirudin for managing patients with heparin-induced thrombocytopenia (HIT) or presumed HIT. DESIGN: Retrospective medical record review. SETTING: University-affiliated teaching hospital. PATIENTS: Forty-two patients who were hospitalized between January 1 and December 31, 2004, and who were treated with bivalirudin, argatroban, or lepirudin for at least 24 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the time to reach the desired goal for activated partial thromboplastin time (aPTT). Secondary outcomes were the number of aPTT measurements within the therapeutic range, costs, treatment duration, clinical outcomes, and adverse events. Of the 42 patients who met the inclusion criteria, 24 received bivalirudin, 13 received argatroban, and 5 received lepirudin. Patients receiving bivalirudin who reached therapeutic aPTTs attained them sooner than those receiving either argatroban or lepirudin (8.5 vs 14 and 24 hrs, respectively, p=0.124). Average percentage of therapeutic aPTTs/patient was greatest in the argatroban group (62%), followed by the bivalirudin (57%) and lepirudin (29%) groups (p=0.062). Average drug cost/day/patient was greater in the lepirudin group than the other groups, whereas average laboratory costs were similar among groups. Treatment duration was longer with argatroban than with bivalirudin or lepirudin. Bleeding rates were similar in the argatroban and bivalirudin groups, but higher than in the lepirudin group. A composite of clinical outcomes (deep vein thrombosis, nonfatal myocardial infarction, nonfatal stroke, limb amputation, and all-cause mortality) were similar among the three groups. CONCLUSION: All three drugs were effective as anticoagulants for patients with HIT or presumed HIT. Based on average use and average wholesale price, bivalirudin cost less per day than the other two agents. Although not yet approved by the United States Food and Drug Administration for management of HIT, bivalirudin appears to be a viable treatment alternative for anticoagulation therapy.

Making the Transition from Student to Resident: A Method to Individualize a PGY1 Program.

A Postgraduate Year One (PGY1) resident's concerns, limitations, and strengths may be self-identified early in the residency year but are reliant on self-awareness and insight. Program directors commonly find difficulty in identifying a resident's specific knowledge deficits at the beginning of the program. A standardized resident examination can identify limitations early in training and these results can be incorporated into a tailored resident development plan. A total of sixty-two PGY1 residents completed the examination pre- and post-training over a five-year timespan. Scores increased in most core disciplines in each of the five years, indicating an overall improvement in resident knowledge throughout their PGY1 year. The approach of utilizing the scores for the resident's individualized plan allows for customization to ensure that the resident addresses knowledge gaps where necessary.

Impact of Norepinephrine Shortage on Outcomes in Patients with Septic Shock.

PURPOSE: With the previous norepinephrine shortage, alternative agents were required to treat patients with septic shock. This retrospective study evaluated whether the shortage of norepinephrine had an adverse effect on patients admitted to the intensive care unit with a diagnosis of severe sepsis or septic shock. METHODS: This was a retrospective chart review, which compared patients who received norepinephrine versus those who did not. Eligible patients were those ≥ 18 years old who were admitted to an intensive care unit with a diagnosis of sepsis and were initiated on a vasopressor to maintain hemodynamic stability. The specific primary endpoint was whether using norepinephrine versus other vasopressors had an effect on ICU length of stay. Secondary outcomes included mortality, blood pressure, mean arterial pressure, development of renal insufficiency, and vasopressor requirements. RESULTS: There were 288 patients screened and 214 patients who met the inclusion criteria (norepinephrine group=106 and nonnorepinephrine group=108). After accounting for potential differences in disease severity (APACHE II score), age, weight and gender, there was no difference in ICU length of stay (p=0.4); however, the odds of survival were 5.9 (95% CI: 3.1 to 11.1) times higher for those in the non-norepinephrine group (p<0.0001). CONCLUSION: Based on this retrospective analysis, patients that did not receive norepinephrine had a similar ICU LOS but had a higher rate of survival. The norepinephrine shortage did not have an adverse effect on patient outcomes.

Pharmacy residency training measured through a standardized knowledge test.

PURPOSE: The use of a standardized knowledge test to assess postgraduate year 1 (PGY1) pharmacy residency training was evaluated. METHODS: This was a retrospective review of a prospectively administered exam. A bank of questions was developed by preceptors from each of the core rotation disciplines: general medicine (including ambulatory care and oncology), pediatrics, critical care (including transplantation), drug information, operations, practice management, and psychiatry. Board-certified pharmacy specialists at our institution were asked to submit 5-10 questions with answers that would likely be encountered by residents during rotation in their specific specialty area. The exam was administered at the beginning and the end of the resident's PGY1 year. RESULTS: A total of 49 PGY1 residents completed the examination during the first and last months of their residency training. Residents' overall scores improved 5-10% annually from baseline to completion of their residency. The mean overall exam score significantly improved from baseline after completion of a PGY1 residency at our institution for all four class years. All four residency classes demonstrated an increase from baseline scores in most core disciplines with the exception of practice management, which decreased every year of the examination. CONCLUSION: Scores on a standardized exam developed to assess the baseline knowledge of incoming PGY1 residents and the effect of one year of residency training improved in the majority of practice areas at the end of the year compared to scores at the beginning of the year.

The cardiovascular effects of eplerenone, a selective aldosterone-receptor antagonist.

BACKGROUND: The role of the renin-angiotensin-aldosterone system in the pathophysiology and treatment of hypertension and heart failure has been extensively studied. Angiotensin-converting enzyme inhibitors and angiotensin II-receptor blockers have been shown to effectively reduce blood pressure, protect the kidney, and reduce morbidity and mortality in patients with heart failure. Therefore, there is increased interest in the effects of aldosterone and the use of aldosterone-receptor antagonists in the treatment of cardiovascular disease. Eplerenone is the first selective aldosterone-receptor antagonist approved for the treatment of hypertension and left ventricular (LV) dysfunction after acute myocardial infarction (AMI). OBJECTIVE: The goal of this article was to review the pharmacologic properties, clinical efficacy, and tolerability of eplerenone in the treatment of hypertension, LV dysfunction, and proteinuria. METHODS: Relevant English-language articles were identified through searches of MEDLINE (1966-May 2003), Current Contents, and International Pharmaceutical Abstracts (1970-May 2003) using the terms hypertension, heart failure, eplerenone, aldosterone, and aldosterone antagonist. Other pertinent publications were identified from the reference lists of the identified articles. Information was also obtained from abstracts presented at national meetings and data on file with the manufacturer. RESULTS: In clinical trials, eplerenone alone and in combination with renin-angiotensin blockade significantly reduced both systolic and diastolic blood pressure compared with placebo (P < 0.05 to P < 0.001). In EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study), the addition eplerenone to optimal medical therapy reduced morbidity and mortality in patients with AMI and LV dysfunction, although the incidence of serious hyperkalemia was also significantly greater. In comparisons with spironolactone, eplerenone was associated with a lower incidence of gynecomastia and other sex hormone-related adverse effects. CONCLUSIONS: Either alone or in combination with other antihypertensive agents, eplerenone appears to be effective for the treatment of hypertension. Morbidity and mortality were reduced when eplerenone was added to standard therapy for LV dysfunction complicating AMI. The use of eplerenone for hypertension or heart failure may be limited in patients at risk for hyperkalemia.

The biology of thrombin in acute coronary syndromes.

Thrombin, a serine protease, is the keystone of the twin processes of hemostasis and thrombosis. Through procoagulant, anticoagulant, and antifibrinolytic mechanisms, thrombin helps maintain vascular integrity in the face of hemorrhage. These same mechanisms, however, allow for the pathologic formation of thrombi in response to endothelial damage, which accompanies the erosion or rupture of atherosclerotic plaques. Alone or incorporated into plaques, thrombi can cause vessel occlusion resulting in acute coronary syndromes (ACS). Inhibiting thrombin can improve clinical outcomes in ACS, as well as in procedures such as percutaneous coronary interventions, which are designed to open the occluded vessels that cause ACS. Such improvements in outcomes with thrombin inhibition reflect the central and multivariate role of thrombin in thrombus formation.

Combination antiplatelet therapy: implications for pharmacists.

OBJECTIVES: To present two case reports of patients who received suboptimal oral antiplatelet therapy and to review recent changes in national guidelines for management of acute coronary syndromes. DATA SOURCES: Personal observation by the authors, and clinical practice guidelines and related clinical trials of the American Heart Association and the American College of Cardiology. SUMMARY: The American College of Cardiology and the American Heart Association revised the guidelines for administration of antiplatelet and anticoagulant therapy in patients with unstable angina and non-ST-segment elevation myocardial infarction in March 2002. Two cases observed by the authors illustrate the consequences of suboptimal antiplatelet therapy when a combination of two antiplatelet drugs should have been administered. CONCLUSION: Evidence from recent randomized controlled trials led to changes in the national guidelines for administration of oral antiplatelet therapy in patients with acute coronary syndromes. Pharmacists should be aware of these changes and counsel patients about appropriate administration of antiplatelet drugs.

Anemia in patients with coronary artery disease.

The pathophysiology of impaired hemodynamic and nonhemodynamic responses to anemia in patients with coronary artery disease is discussed. In animals, experimentally induced coronary artery disease significantly inhibits the hemodynamic response to surgical blood loss; anecdotal evidence in humans corroborates these findings. Erythropoietic response to surgical blood loss may also be blunted in patients with coronary artery disease. Regardless of whether anemia is the result of a preexisting condition or surgical blood loss, its presence worsens outcomes in patients with coronary artery disease who undergo cardiac surgery. The combination of coronary artery disease and anemia has resulted in acute myocardial infarction as well. Finally, anemia after noncardiac surgery is associated with an increased risk of myocardial ischemia, potentially creating a cycle in which blood loss and myocardial ischemia exacerbate each other. Oral iron replacement therapy after elective cardiac surgery increases adverse events without significantly improving hematocrit and hemoglobin levels or iron stores. Allogeneic blood transfusions are less than ideal, and autologous blood transfusion with erythropoietin administration is only possible before elective procedures. New procedures and medications have reduced the blood loss associated with percutaneous coronary intervention, and minimization of blood loss during percutaneous coronary intervention has potentially major clinical and economic implications.