Optimal Medical Therapy Prescribing Patterns and Disparities Identified in Patients with Acute Coronary Syndromes at an Academic Medical Center in an Area with High Coronary Heart Disease-Related Mortality.

BACKGROUND: Coronary heart disease (CHD)-related mortality is high in the southern United States. A five-drug pharmacotherapy regimen for acute coronary syndromes (ACS), defined as optimal medical therapy (OMT), can decrease CHD-related mortality. Studies have indicated that OMT is prescribed 50-60% of the time. Assessment of prescribing could provide insight into the potential etiology of disparate mortality. OBJECTIVE: The aim was to evaluate prescribing of OMT at discharge in patients presenting with an ACS event at an academic medical center and identify patients at risk of not receiving OMT. METHODS: A single-center, retrospective cohort of patients with ACS diagnosis between July 2013 and July 2015 was investigated, and a multivariable regression analysis conducted to identify populations at risk of not receiving OMT. RESULTS: A total of 864 patients were identified by International Classification of Diseases, Ninth Revision (ICD-9) codes, with 533 excluded and 331 analyzed. OMT was prescribed in 69.79%. Patients ≥ 75 years of age [p = 0.003; odds ratio (OR) 0.30; 95% confidence interval (CI) 0.136-0.673], unstable angina presentation (p = 0.042; OR 0.55; 95% CI 0.307-0.977), and surgical management (p = 0.001; OR 0.22; 95% CI 0.095-0.519) were less likely to receive OMT. CONCLUSIONS: The percentage of patients prescribed OMT exceeded the reported global percentage of prescribed OMT. However, disparities exist among specific populations.

ACCP Clinical Pharmacist Competencies.

The purpose of the American College of Clinical Pharmacy (ACCP) is to advance human health by extending the frontiers of clinical pharmacy. Consistent with this mission and its core values, ACCP is committed to ensuring that clinical pharmacists possess the knowledge, skills, attitudes, and behaviors necessary to deliver comprehensive medication management (CMM) in team-based, direct patient care environments. These components form the basis for the core competencies of a clinical pharmacist and reflect the competencies of other direct patient care providers. This paper is an update to a previous ACCP document and includes the expectation that clinical pharmacists be competent in six essential domains: direct patient care, pharmacotherapy knowledge, systems-based care and population health, communication, professionalism, and continuing professional development. Although these domains align with the competencies of physician providers, they are specifically designed to better reflect the clinical pharmacy expertise required to provide CMM in patient-centered, team-based settings. Clinical pharmacists must be prepared to complete the education and training needed to achieve these competencies and must commit to ongoing efforts to maintain competence through ongoing professional development. Collaboration among stakeholders will be needed to ensure that these competencies guide clinical pharmacists' professional development and evaluation by educational institutions, postgraduate training programs, professional societies, and employers.

Propofol-associated QTc prolongation.

OBJECTIVES: Propofol is a preferred agent for sedation in patients in the intensive care unit (ICU) due, in part, to its established safety profile. Despite this, recent case reports have suggested a potential for prolongation of the corrected QT interval (QTc) in ICU patients receiving propofol, though limited empirical work has been conducted to evaluate this association. As such, the purpose of this study was to assess the relationship between propofol infusion and QTc prolongation in a historical cohort of ICU patients. METHODS: A single-center, historical, observational, pre-post cohort analysis of medical records from admitted patients ⩾18 years old with cardiovascular disease was conducted, involving cases who received propofol infusion for ⩾3 hours with sequential electrocardiogram monitoring from 2006 to 2012. A multivariable, generalized linear model regression was employed to assess the primary outcome of on-propofol QTc interval (QTc2), controlling for various demographic and clinical factors. RESULTS: A total of 96 patients met inclusion criteria, averaging 56.1 ± 14.1 years of age and 86.1 ± 25.0 kg, with 37.5% being female. A mean prolongation in QTc interval of 30.4 ± 55.5 ms (p < 0.001) was observed during the propofol infusion, with 43.8% of cases exhibiting an on-infusion QTc2 of ⩾ 500 ms. Regression analyses suggested that prolongation in on-propofol QTc was independently associated with baseline QTc interval and amiodarone use, while weight as inversely associated with QTc2 (p < 0.05). CONCLUSION: This historical cohort analysis of adult ICU patients receiving propofol suggests that on-infusion QTc prolongation was associated with increasing baseline QTc interval and with amiodarone use. Further research is needed to evaluate the clinical significance and cause-and-effect relationship between potential QTc changes and propofol use in the ICU.

Controversies Among the Hypertension Guidelines.

Hypertension affects 80 million people in the United States. It remains poorly controlled, with only 54% of diagnosed patients treated to blood pressure targets. Hypertension management is complex in part due to the volume of antihypertensive agents, variable patient needs and responses, and inconsistent design and outcomes from clinical trials. Therefore, trustworthy clinical practice guidelines have a key role in hypertension management. The United States experienced a 10-year gap in publication of hypertension guidelines, followed by multiple guideline publications in 2013. These guidelines led to more controversy than clarity, as there was discordance among them. This review summarizes the guidelines and clinical statements influencing the current debate in order to facilitate appropriate application.

Key articles and guidelines in the management of hypertension: 2015 update.

Hypertension is a major risk factor for cardiovascular disease. Evidence for optimal pharmacotherapy continues to accumulate at a very rapid pace; maintaining an up-to-date library of key articles for hypertension management can be challenging for busy clinicians. Further, there has been controversy surrounding the hypertension guidelines that were released in late 2013 and early 2014. The lack of congruence and simplicity in the current hypertension recommendations could result in delays with application of evidence to clinical practice. In order to facilitate clinicians' efficient access to high-impact clinical trials evaluating the management of hypertension, this compilation of annotated bibliographies was created to serve as a resource for any health care professional participating in the management of adult patients with hypertension.

Sorting it out: what JNC 8 is and what it is not.

The landscape for hypertension guideline development and dissemination has changed. The intense debate surrounding the recent JNC 8 publication obscures the value this guideline offers to providers managing hypertension. Recommendations published by the panel appointed to JNC 8, when interpreted and applied as intended, can indeed guide hypertension management. The purpose of this commentary is to pare down what the JNC 8 publication is and what is not, so as to transcend the controversy and foster application of these guidelines to clinical practice. 

ß-blockers: a review of their pharmacological and physiological diversity in hypertension.

OBJECTIVE: To review the pharmacology, pharmacokinetics, and pharmacodynamic properties of commonly used ß-blockers (atenolol, carvedilol, metoprolol succinate, metoprolol tartrate, and nebivolol). DATA SOURCES: A MEDLINE literature search (1966-May 2013) was performed using the following key terms: hypertension, ß-blockers, atenolol, carvedilol, metoprolol tartrate, metoprolol succinate, nebivolol, pharmacology, pharmacodynamics, pharmacokinetics, blood pressure, metabolic, lipid, central aortic pressure, diabetes, and insulin resistance. References from publications reviewed were included. STUDY SELECTION AND DATA EXTRACTION: English-language articles identified were reviewed. Animal studies and studies in patients for a primary diagnosis of coronary artery disease were excluded. DATA SYNTHESIS: ß-Blockers are no longer recommended first-line therapy for primary hypertension, based on data showing that ß-blockers are inferior to other antihypertensives and no better than placebo, in spite of provision of blood pressure reduction. Because atenolol is the ß-blocker used in 75% of these studies, uncertainty about widespread application to all ß-blockers exists. Different pharmacological and physiological properties, both within ß-blockers and compared with other antihypertensives, may explain divergent effects. Evidence shows that ß-blockers have a truncated effect on central aortic pressure, an independent predictor of cardiovascular events, compared with other antihypertensive classes; differences within the class may exist, but the evidence is inconclusive. Metabolic effects differ within the ß-blocker class, with evidence that carvedilol causes less metabolic dysregulation. CONCLUSION: Emerging evidence reveals physiological differences within the ß-blocker class and in comparison to other antihypertensives. These differences provide insight into the diverse clinical effects ß-blockers provide in cardiovascular disease.

Incidence of transmitted antiretroviral drug resistance in treatment-naive HIV-1-infected persons in a large South Central United States clinic.

BACKGROUND: Transmitted drug resistance (TDR) can limit effective treatment options to antiretroviral-naive HIV-infected persons and increase the risk of treatment failure. Limited estimates of TDR have been reported from the South Central United States. OBJECTIVE: To describe the incidence of TDR in Oklahoma and to examine whether TDR rates have increased with time. METHODS: This was a retrospective observational study of antiretroviral-naive patients at the Infectious Diseases Institute, a large infectious diseases clinic in Oklahoma City, Oklahoma, who had received baseline antiretroviral resistance testing. Mutations were screened using the 2011 International Antiviral Society-USA Drug Resistance Mutation (DRM) update, and categorized using the 2009 World Health Organization (WHO) Surveillance Drug Resistance Mutation (SDRM) list. RESULTS: Genotypic sequences from 428 patients revealed a 6.0% to 13.6% incidence of SDRMs between 2007 and 2011, though no progression in the frequency was apparent during the study period. Primary DRMs were detected in 12.6% of the sampled patients, most commonly involving nonnucleoside reverse transcriptase inhibitors (NNRTIs; 8.2%), followed by protease inhibitors (PIs; 3.5%) and nucleoside reverse transcriptase inhibitors (NRTIs; 3.3%). The K103N/S and E138A reverse transcriptase mutations were the most common DRMs identified, both present in 3.5% of patients. The L90M mutation was the most frequently observed PI SDRM (1.6%), while the T215C/D/I mutation was the most common NRTI SDRM identified (1.9%). This study was limited by the fact that the WHO SDRM list was last updated in 2009. CONCLUSIONS: The frequency of DRMs in central and western Oklahoma is similar to recently reported rates in the United States which lack data from this region. However, the frequency of second-generation NNRTI DRMs (4.4%) suggests the need to closely monitor epidemiologic trends for increasing resistance rates to individual classes of ARVs in order to predict the impact of TDR on therapeutic options.

Collaborative practice model between cardiologists and clinical pharmacists for management of patients with cardiovascular disease in an outpatient clinic.

The increasing prevalence of cardiovascular disease (CVD) has prompted leading cardiovascular organizations to advocate utilization of a team approach to patient care that includes nonphysician providers. In spite of that, the American College of Cardiology reported that nonphysician providers are underutilized in the management of patients with CVD. A survey of cardiologists revealed that the underutilization is a result of lack of understanding of how best to involve nonphysician providers in the health care team. Clinical pharmacists are one category of nonphysician providers that have recognized effectiveness in managing patients with CVD. No example of a comprehensive model of collaboration between cardiologists and clinical pharmacists is described in the literature that could serve to close this gap in understanding. The objective of this report is to describe a model of cardiologist-clinical pharmacist collaboration in the longitudinal management of patients with CVD that has been successfully implemented in 2 diverse settings. The implementation, evolution, scope of practice, required pharmacist training, logistical elements needed for success, and implementation barriers are reviewed. A summary of the patients referred to the clinic are examined as well.

Impact of a clinical pharmacist on a cardiovascular surrogate endpoint: a pilot study / Impacto de un farmacéutico clínico sobre un resultado intermedio cardiovascular: un estudio piloto

Utilizing a multidisciplinary approach to management of patients with certain chronic cardiovascular diseases (CVD) has been shown to improve treatment outcomes. The role of clinical pharmacists in comprehensive outpatient CVD management has not been evaluated. Objective: The objective of this pilot study was to evaluate the impact of a clinical pharmacist added to cardiologist care on blood pressure (BP), a key surrogate marker of CVD, in outpatients with CVD compared to cardiologist care alone. Methods: A retrospective, matched-control study was conducted in patients established in a cardiovascular clinic. The intervention was referral to a pharmacist clinic; control was usual care from the cardiologist. The surrogate marker evaluated was the change in BP. Results: Patients in the pharmacist-intervention (n=57) experienced significant reductions in diastolic BP (-2.6 mmHg, p=0.05) and nonsignificant reductions in systolic BP (-4.3 mmHg, p=0.16) compared to baseline, whereas patients in the control group experienced non-significant increases in both systolic and diastolic BP (+1.6/+0.7 mmHg, p=NS). Similarly, there were significant reductions in diastolic BP and nonsignificant reductions in systolic BP for the intervention group when compared to controls (difference 3.3 mmHg, p=0.04 and 5.9 mmHg, p=0.1, respectively). Lastly, the proportion of patients categorized as having Stage 2 BP was significantly reduced in the intervention group (p=0.02), but not in the controls (p=0.5). Conclusions: The multidisciplinary model of care that included a clinical pharmacist reduced BP more than usual care by a cardiologist alone. This benefit was demonstrated in complex patients with CVD who were already receiving specialized care. The impact of this model on clinical outcomes requires further evaluation and should be a high priority given the burden of CVD in the population (AU)

Utilizar un abordaje multidisciplinar para el manejo de pacientes con determinadas enfermedades cardiovasculares (CVD) ha demostrado mejorar los resultados del tratamiento. No ha sido evaluado el papel del farmacéutico clínico en manejo ambulatorio completo de las CVD. Objetivo: El objetivo de este estudio piloto fue evaluar el impacto del farmacéutico clínico añadido al cardiólogo en los cuidados de la presión arterial (BP), marcador intermedio clave de CVD, en pacientes ambulatorios con CVD comparando con el cardiólogo solo. Métodos: Se realizó un estudio retrospectivo de control emparejado en pacientes atendidos en una clínica cardiovascular. La intervención era la remisión a un farmacéutico clínico; el control fue la atención habitual del cardiólogo. El marcador intermedio evaluado fue el cambio en BP. Resultados: Los pacientes en el grupo intervención-farmacéutica (n=57) experimentaron reducciones significativas en la BP diastólica (-2.6 mmHg, p=0.05) y reducciones no significativas en la sistólica (-4.3 mmHg, p=0.16) comparadas con el inicio mientras que los pacientes en el grupo control experimentaron aumentos no significativos tanto en las BP sistólica como diastólica (+1.6/+0.7 mmHg, p=NS). Asimismo, hubo reducciones significativas en al BP diastólica y no significativas en la BP sistólica para el grupo intervención comparado con el control (diferencia 3.3 mmHg, p=0.04 y 5.9 mmHg, p=0.1, respectivamente). Por último, se redujo significativamente la proporción de pacientes en el grupo intervención clasificados como teniendo un estado 2 de BP (p=0,02) pero no en el grupo control (p=0,5). Conclusiones: El modelo multidisciplinario de cuidados que incluía un farmacéutico clínico redujo la BP más que el modelo habitual de cuidados con el cardiólogo solo. Este beneficio fue demostrado en pacientes con CVD compleja que ya estaban recibiendo cuidados especializados. El impacto de este modelo sobre los resultados clínicos requiere más evaluaciones y debería darse alta prioridad al daño de las CVD en esta población (AU)

Impact of a clinical pharmacist on a cardiovascular surrogate endpoint: a pilot study.

UNLABELLED: Utilizing a multidisciplinary approach to management of patients with certain chronic cardiovascular diseases (CVD) has been shown to improve treatment outcomes. The role of clinical pharmacists in comprehensive outpatient CVD management has not been evaluated. OBJECTIVE: The objective of this pilot study was to evaluate the impact of a clinical pharmacist added to cardiologist care on blood pressure (BP), a key surrogate marker of CVD, in outpatients with CVD compared to cardiologist care alone. METHODS: A retrospective, matched-control study was conducted in patients established in a cardiovascular clinic. The intervention was referral to a pharmacist clinic; control was usual care from the cardiologist. The surrogate marker evaluated was the change in BP. RESULTS: Patients in the pharmacist-intervention (n=57) experienced significant reductions in diastolic BP (-2.6 mmHg, p=0.05) and non-significant reductions in systolic BP (-4.3 mmHg, p=0.16) compared to baseline, whereas patients in the control group experienced non-significant increases in both systolic and diastolic BP (+1.6/+0.7 mmHg, p=NS). Similarly, there were significant reductions in diastolic BP and non-significant reductions in systolic BP for the intervention group when compared to controls (difference 3.3 mmHg, p=0.04 and 5.9 mmHg, p=0.1, respectively). Lastly, the proportion of patients categorized as having Stage 2 BP was significantly reduced in the intervention group (p=0.02), but not in the controls (p=0.5). CONCLUSIONS: The multidisciplinary model of care that included a clinical pharmacist reduced BP more than usual care by a cardiologist alone. This benefit was demonstrated in complex patients with CVD who were already receiving specialized care. The impact of this model on clinical outcomes requires further evaluation and should be a high priority given the burden of CVD in the population.

The beers criteria as an outpatient screening tool for potentially inappropriate medications.

OBJECTIVE: To determine the impact of using the Beers criteria (sometimes known as the Beers list) as an outpatient screening tool on the number or dosage of Beers criteria medications identified in patients' medication profiles immediately before an outpatient appointment. DESIGN: Nonrandomized, prospective pre-/post pilot study. SETTING: Six individual medicine and medicine-specialty clinics at a major academic medical center. PARTICIPANTS: All subjects were 65 years of age or older. INTERVENTIONS: Subjects 65 years of age or older had their medication profiles screened using the Beers criteria- medications potentially inappropriate for use in the elderly- prior to and directly after a scheduled appointment with their physician. Respective physicians were notified of any Beers criteria medications before the appointments. Physician options were to discontinue, continue, or change the dose of the medications identified with the option for justification of their decision. MAIN OUTCOME MEASURE: The difference from baseline (preappointment) to follow-up (postappointment) in the number or dosage of Beers criteria medications identified in patients' profiles. RESULTS: 120 eligible charts were reviewed. The average age of subjects was 74 years. Overall, 37.5% of subjects were on potentially inappropriate medications (PIMs) as defined by the Beers criteria. Sixty-three PIMs were flagged out of 120 profiles. For the primary outcome, 8/63 and 0/63 PIMs were discontinued or had a dosage change, respectively. This intervention resulted in a statistically significant reduction in the mean number of Beers criteria medications (P = 0.032). CONCLUSION: Use of the Beers criteria as a clinical intervention tool in an outpatient setting may be an effective method to reduce the number of PIMs prescribed in an elderly population.

Controversies in cardiac resynchronization therapy: do sex differences in response exist?

Cardiac resynchronization therapy (CRT) is well established in the treatment of patients with heart failure, but lacks data addressing sex differences in response. Women with heart failure outnumber men, but have additional comorbidities and typically are older. Women continue to be underrepresented in clinical trials, but examining their response to a therapy across multiple studies could provide significant insight into the treatment effect. The major clinical trials did have a significant percentage of female patients, but present minimal in subgroup analysis. A few small studies comparing the effect of CRT between men and women indicate a more positive effect in women. This early data suggests CRT is at least as effective in women as it is in men, and may have additional benefit in this population.

Effect of heart failure exacerbations on anticoagulation: a prospective, observational, pilot cohort study.

BACKGROUND: Some studies have suggested that heart failure (HF) is associated with excessive anticoagulation, but definitive data or data showing causation do not exist. Knowledge of risk factors for excessive anticoagulation is critical to manage warfarin therapy safely. OBJECTIVE: This study characterized the relation between HF-associated hypervolemia and excessive anticoagulation in patients with HF taking chronic warfarin therapy. METHODS: This was a prospective, observational pilot study conducted in a university-based HF clinic. Patients aged 18 to 85 years with HF and taking warfarin were enrolled and were observed for episodes of hypervolemia. Hypervolemia was determined based on multiple clinical factors, including patient-reported symptoms and physical examination. Anticoagulation was assessed longitudinally per standard of care by measurement of the international normalized ratio (INR). A chi(2) analysis was used to determine whether hypervolemia was associated with an increased risk of excessive anticoagulation. Paired and unpaired t tests were used for ad hoc analyses. RESULTS: Forty patients with 41 HF episodes who were taking warfarin were enrolled between December 2003 and July 2007. Mean (SD) age was 67.2 (11.1) years and mean weight was 218.5 (62.8) pounds; 29 patients (72.5%) were men and 34 (85.0%) were white. Most had systolic dysfunction (n = 26; 65.0%) and were taking warfarin for atrial fibrillation (n = 33; 82.5%); the mean weekly warfarin dose was 30.8 (17.5) mg. There were 41 evaluable hypervolemia episodes over a mean follow-up of 14.5 (9.0) months. The mean INR change during hypervolemia was -0.02 (0.82) INR unit (P = NS vs baseline). No association was found between hypervolemia episodes and INR increases of > or =50% (P = NS); the results remained nonsignificant for both diastolic and systolic HF when analyzed separately. There was no significant change from baseline INR between patients classified with mild, moderate, or severe hypervolemia or between patients classified according to New York Heart Association (NYHA) functional class (all, P = NS). Patients with NYHA class III had a lower weekly warfarin dose than those with NYHA class II (25.73 vs 31.75 mg; P < 0.01). CONCLUSION: Mild hypervolemia did not appear to be related to excessive anticoagulation in these patients with HF taking chronic warfarin therapy.

Integration of team-based learning strategies into a cardiovascular module.

OBJECTIVES: To integrate components of team-based learning (TBL) into a cardiovascular module to increase students' responsibility for their own learning and actively engage students across 2 campuses in patient cases. DESIGN: An existing cardiovascular course module was modified by replacing 8 hours of lectures with self-directed learning (SDL) assignments and transforming case discussion sessions using TBL methodologies. Case discussions were delivered using TBL methods to increase engagement of all students across both campuses while maintaining a low faculty-to-student ratio in the classrooms. Readiness assurance quizzes were performed with each SDL assignment and TBL case session. ASSESSMENT: Student and faculty satisfaction improved with the addition of SDL assignments and TBL cases without adverse effects on grades in the wake of the 14% decrease in lecture time. Total faculty time required increased primarily in the first year because of development of course materials. CONCLUSION: A modified TBL format was successfully integrated into a lecture-based cardiovascular module, resulting in improved student and faculty satisfaction with the course and no adverse effect on student performance.

Anticoagulation in patients with heart failure and normal sinus rhythm.

PURPOSE: The evidence evaluating the risk of thrombosis and the efficacy and risk of anticoagulation in patients with systolic heart failure (HF) and normal sinus rhythm is reviewed. SUMMARY: Although a subject of investigation for over 50 years, use of anticoagulation in patients with HF remains an area of controversy and clinical debate. While early studies reported variable thromboembolism rates in HF (1.9-42.4 events per 100 patient years), the annual rate from larger and more recent trials ranged from 1% to 3%. The trials evaluating the role of oral anticoagulants to reduce thromboembolism and mortality outcomes in patients with a reduced ejection fraction (EF) have provided ambiguous results. Early studies and post hoc analyses of large clinical trials have demonstrated a reduction in thromboembolic events, risk of stroke, and mortality. In contrast, recent underpowered prospective controlled studies found no benefit in the use of warfarin in patients with systolic HF and normal sinus rhythm. The low-to-moderate risk of thromboembolism in patients with HF and the questionable benefit of anticoagulation need to be weighed against the potential for hemorrhagic complications caused by this therapy. The available data collectively suggest that the risk of using warfarin in patients with reduced EF may outweigh any possible benefit, if one exists at all. CONCLUSION: Anticoagulation therapy in patients with HF and normal sinus rhythm is not supported by the limited evidence. The benefits of anticoagulation in such patients may not compensate for the relatively high risk of major bleeding caused by the treatment.

Key articles and guidelines in the management of hypertension: 2008 update.

Hypertension remains a major risk factor for cardiovascular disease. The optimal choice of pharmacologic and nonpharmacologic treatment regimens is based on a plethora of published literature. This compilation is the initial update to the Key Articles and Guidelines in the Management of Hypertension authored by members of the Cardiology Practice and Research Network of the American College of Clinical Pharmacy, which appeared in Pharmacotherapy in 2004. We present synopses of clinical trials, meta-analyses, clinical practice guidelines, and other pertinent literature published between May 2003 and June 2007.

Side effects of using nitrates to treat heart failure and the acute coronary syndromes, unstable angina and acute myocardial infarction.

Nitrates are potent venous dilators and anti-ischemic agents. They are widely used for the relief of chest pain and pulmonary congestion in patients with acute coronary syndromes and heart failure. Nitrates, however, do not reduce mortality in patients with acute coronary syndromes. Combination of nitrates and hydralazine when given in addition to beta-blockers and angiotensin-converting enzyme (ACE) inhibitors reduce mortality and heart failure hospitalizations in patients with heart failure due to left ventricular systolic dysfunction who are of African-American origin. Side effects during nitrate therapy are common but are less well described in the literature compared with the reported side effects in patients with stable angina pectoris. The reported incidence of side effects varies highly among different studies and among various disease states. Headache is the most commonly reported side effect with an incidence of 12% in acute heart failure, 41-73% in chronic heart failure, 3-19% in unstable angina and 2-26% in acute myocardial infarction. The reported incidence of hypotension also differs: 5-10% in acute heart failure, 20% in chronic heart failure, 9% in unstable angina and < 1-48% in acute myocardial infarction, with the incidence being much higher with concomitant nitrate therapy plus angiotensin-converting enzyme inhibitors. Reported incidence of dizziness is as low as 1% in patients with acute myocardial infarction to as high as 29% in patients with heart failure. Severe headaches and/or symptomatic hypotension may necessitate discontinuation of nitrate therapy. Severe life threatening hypotension or even death may occur when nitrates are used in patients with acute inferior myocardial infarction associated with right ventricular dysfunction or infarction, or with concomitant use of phosphodiesterase-5 inhibitors or N-acetylcysteine. Despite the disturbing observational reports in the literature that continuous and prolonged use of nitrates may lead to increased mortality and recurrent myocardial infarction in patients with stable coronary artery disease, no such adverse effects of nitrates have been reported in the large randomized trials in patients with acute myocardial infarction or chronic heart failure.

Aldosterone antagonists in the treatment of heart failure.

PURPOSE: The clinical benefits, adverse effects, pharmacokinetics, and recommendations for the appropriate use of the aldosterone antagonists spironolactone and eplerenone in patients with heart failure are reviewed. SUMMARY: Heart failure is a clinical syndrome characterized by the functional inability of the ventricle to meet the metabolic demands of the body. Renal hypoperfusion occurs as a result of reduced cardiac output, resulting in the activation of the renin-angiotensin-aldosterone system, which compensates for the hypoperfusion. However, this contributes to the pathology of the disease by, among other actions, increasing the release of aldosterone. Aldosterone has been shown to cause coronary inflammation, cardiac hypertrophy, myocardial fibrosis, ventricular arrhythmias, and ischemic and necrotic lesions. There are currently two aldosterone antagonists commercially available in the United States, spironolactone and eplerenone. Spironolactone is a nonselective aldosterone antagonist, and eplerenone is selective to the aldosterone receptor. Although numerous clinical trials have evaluated the efficacy of each drug, no studies have directly compared spironolactone and eplerenone. Both have been shown to improve morbidity and mortality in patients with advanced heart failure. Adverse effects of both spironolactone and eplerenone include potentially life-threatening hyperkalemia, which can be induced by renal insufficiency, diabetes mellitus, advanced heart failure, advanced age, and concurrent drug therapy. CONCLUSION: Spironolactone and eplerenone are life-saving agents in patients with advanced heart failure and may benefit patients with mild heart failure. Potassium and renal function must be routinely assessed to minimize the risk of life-threatening hyperkalemia.