Erectile dysfunction: the need to be evaluated, the right to be treated.

Erectile dysfunction (ED) is commonly associated with cardiovascular disease, which has potentially fatal consequences if not managed appropriately. Physicians and patients for a number of reasons commonly ignore ED. Increased awareness of the health consequences of ED would encourage men and health care professionals to address this condition more freely, permitting appropriate screening and treatment of cardiovascular disease. Concerns about the risks of treating ED in the cardiac patient should not prevent ED from being discussed and we suggest that early acknowledgment of ED might prevent cardiovascular morbidity and even mortality. Specific guidelines for the management of ED in cardiac patients, produced by 2 expert panels, can also be applied to men without known cardiovascular disease.

Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference).

Recent studies have highlighted the relation between erectile dysfunction (ED) and cardiovascular disease. In particular, the role of endothelial dysfunction and nitric oxide in ED and atherosclerotic disease has been elucidated. Given the large number of men receiving medical treatment for ED, concerns regarding the risk for sexual activity triggering acute cardiovascular events and potential risks of adverse or unanticipated drug interactions need to be addressed. A risk stratification algorithm was developed by the First Princeton Consensus Panel to evaluate the degree of cardiovascular risk associated with sexual activity for men with varying degrees of cardiovascular disease. Patients were assigned to 3 categories: low, intermediate (including those requiring further evaluation), and high risk. This consensus study from the Second Princeton Consensus Conference corroborates and clarifies the algorithm and emphasizes the importance of risk factor evaluation and management for all patients with ED. The panel reviewed recent safety and drug interaction data for 3 phosphodiesterase (PDE)-5 inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease. Increasing evidence supports the role of lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease. Special management recommendations for patients taking PDE-5 inhibitors who present at the emergency department and other emergency medical situations are described. Finally, further research on the role of PDE-5 inhibition in treating patients with other medical or cardiovascular disorders is recommended.

Report of the National Heart, Lung, and Blood Institute working group on outcomes research in cardiovascular disease.

The National Heart, Lung, and Blood Institute convened a working group on outcomes research in cardiovascular disease (CVD). The working group sought to provide guidance on research priorities in outcomes research related to CVD. For the purposes of this document, "outcomes research" is defined as investigative endeavors that generate knowledge to improve clinical decision making and healthcare delivery to optimize patient outcomes. The working group identified the following priority areas: (1) national surveillance projects for high-prevalence CV conditions; (2) patient-centered care; (3) translation of the best science into clinical practice; and (4) studies that place the cost of interventions in the context of their real-world effectiveness. Within each of these topics, the working group described examples of initiatives that could serve the Institute and the public. In addition, the group identified the following areas that are important to the field: (1) promotion of the use of existing data; (2) facilitation of collaborations with other federal agencies; (3) investigations into the basic science of outcomes research, with an emphasis on methodological advances; (4) strengthening of appropriate study sections with individuals who have expertise in outcomes research; and (5) expansion of opportunities to train new outcomes research investigators. The working group concluded that a dedicated investment in CV outcomes research could directly improve the care delivered in the United States.

Erectile dysfunction therapy in special populations and applications: coronary artery disease.

Erectile dysfunction (ED) and coronary artery disease (CAD) interact in complex ways: ED is increasingly recognized as a harbinger or risk factor for CAD; a small proportion of cases (about 1%) of acute coronary syndromes (ACS), including acute myocardial infarction and sudden cardiac death, occur during or after sexual activity; the absolute risk associated with coitus, including that associated with the use of phosphodiesterase 5 (PDE5) inhibitors to treat ED, is extremely low; virtually all patients experiencing ACS have previously existing (but usually undiagnosed) CAD; and patients often have ED after ACS as a result of psychological factors or drugs, such as beta-blockers, used to treat CAD. The Princeton Guidelines provide a pragmatic approach to stratifying the risk of ACS in patients with established CAD or at high risk for future ACS. Only a minority of patients destined to experience ACS, including those events related to coitus, have established CAD. Yet, most have > or =2 coronary risk factors. The most pragmatic approach to decreasing the risk of ACS in such individuals is to maximize risk factor control and institute combination pharmacotherapy, including statins. The PDE5 inhibitors ameliorate not only ED but also endothelial cell dysfunction. Research to establish the role for PDE5 inhibitors in the prevention and control of ACS is in its early stages. The recognition that ED is a potential harbinger of underlying CAD and future ACS is an important milestone in the management of ED. Progress in integrating PDE5 inhibitors into clinical practice will depend on the success with which patients with ED are evaluated and aggressively treated for endothelial cell dysfunction.

Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference).

Recent studies have highlighted the relation between erectile dysfunction (ED) and cardiovascular disease. In particular, the role of endothelial dysfunction and nitric oxide in ED and atherosclerotic disease has been elucidated. Given the large number of men receiving medical treatment for ED, concerns regarding the risk for sexual activity triggering acute cardiovascular events and potential risks of adverse or unanticipated drug interactions need to be addressed. A risk stratification algorithm was developed by the First Princeton Consensus Panel to evaluate the degree of cardiovascular risk associated with sexual activity for men with varying degrees of cardiovascular disease. Patients were assigned to 3 categories: low, intermediate (including those requiring further evaluation), and high risk. This consensus study from the Second Princeton Consensus Conference corroborates and clarifies the algorithm and emphasizes the importance of risk factor evaluation and management for all patients with ED. The panel reviewed recent safety and drug interaction data for 3 phosphodiesterase (PDE)-5 inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease. Increasing evidence supports the role of lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease. Special management recommendations for patients taking PDE-5 inhibitors who present at the emergency department and other emergency medical situations are described. Finally, further research on the role of PDE-5 inhibition in treating patients with other medical or cardiovascular disorders is recommended.

Nurse management for hypertension. A systems approach.

BACKGROUND: Standard office-based approaches to controlling hypertension show limited success. Such suboptimal hypertension control reflects in part the absence of both an infrastructure for patient education and frequent, regular blood pressure (BP) monitoring. We tested the efficacy of a physician-directed, nurse-managed, home-based system for hypertension management with standardized algorithms to modulate drug therapy, based on patients' reports of home BP. METHODS: We randomized outpatients requiring drug therapy for hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) criteria to receive usual medical care only (UC, n = 76) or usual care plus nurse care management intervention (INT, n = 74) over a 6-month period. RESULTS: Patients receiving INT achieved greater reductions in office BP values at 6 months than those receiving UC: 14.2 +/- 18.1 versus 5.7 +/- 18.7 mm Hg systolic (P < .01) and 6.5 +/- 10.0 versus 3.4 +/- 7.9 mm Hg diastolic, respectively (P < .05). At 6 months, we observed one or more changes in drug therapy in 97% of INT patients versus 43% of UC patients, and 70% of INT patients received two or more drugs versus 46% of UC. Average daily adherence to medication, measured by electronic drug event monitors, was superior among INT subjects (mean +/- SD, 80.5% +/- 23.0%) than among UC subjects (69.2 +/- 31.1%; t(113) = 2.199, P = .03). There were no significant adverse drug reactions in either group. CONCLUSIONS: Telephone-mediated nurse management can successfully address many of the systems-related and patient-related issues that limit pharmacotherapeutic effectiveness for hypertension.

Care management for low-risk patients with heart failure: a randomized, controlled trial.

BACKGROUND: Nurse care management programs for patients with chronic illness have been shown to be safe and effective. OBJECTIVE: To determine whether a telephone-mediated nurse care management program for heart failure reduced the rate of rehospitalization for heart failure and for all causes over a 1-year period. DESIGN: Randomized, controlled trial of usual care with nurse management versus usual care alone in patients hospitalized for heart failure from May 1998 through October 2001. SETTING: 5 northern California hospitals in a large health maintenance organization. PATIENTS: Of 2786 patients screened, 462 met clinical criteria for heart failure and were randomly assigned (228 to intervention and 234 to usual care). INTERVENTION: Nurse care management provided structured telephone surveillance and treatment for heart failure and coordination of patients' care with primary care physicians. MEASUREMENTS: Time to first rehospitalization for heart failure or for any cause and time to a combined end point of first rehospitalization, emergency department visit, or death. RESULTS: At 1 year, half of the patients had been rehospitalized at least once and 11% had died. Only one third of rehospitalizations were for heart failure. The rate of first rehospitalization for heart failure was similar in both groups (proportional hazard, 0.85 [95% CI, 0.46 to 1.57]). The rate of all-cause rehospitalization was similar (proportional hazard, 0.98 [CI, 0.76 to 1.27]). LIMITATIONS: The findings of this study, conducted in a single health care system, may not be generalizable to other health care systems. The overall effect of the intervention was minor. CONCLUSIONS: Among patients with heart failure at low risk on the basis of sociodemographic and medical attributes, nurse care management did not statistically significantly reduce rehospitalizations for heart failure or for any cause. Such programs may be less effective for patients at low risk than those at high risk.

Contemporary management of silent ischemia: the role of ambulatory monitoring.

Silent ischemia is highly prevalent among patients with ischemic heart disease and is associated with a poor prognosis in moderate/high risk outpatients who either exhibit exercise- or pharmacological-induced myocardial ischemia, or in those patients who demonstrate silent ischemia following an acute coronary syndrome. Pharmacotherapy, including beta-blockers, angiotensin-converting enzyme inhibitors, statins, calcium channel antagonists and antiplatelet agents, have all demonstrated a reduction in silent ischemia and an improvement in cardiac prognosis. The management of patients with ischemic heart disease is currently based on patients' report of anginal symptoms: documentation of silent ischemia, usually using ambulatory electrocardiography, is not incorporated into the routine management of coronary artery disease. Yet studies comparing ambulatory electrocardiography with exercise testing have shown these tests to be complementary. We review the evidence concerning the prognostic value of ambulatory electrocardiography for monitoring silent ischemia and the prognostic value of attenuating silent ischemia. Mitigation of silent ischemia improves cardiac prognosis and ambulatory electrocardiographic monitoring before and after treatment of silent ischemia can play a valuable role in the management of coronary artery disease.

Psychosocial treatment within sex by ethnicity subgroups in the Enhancing Recovery in Coronary Heart Disease clinical trial.

OBJECTIVE: Intervening in depression and/or low perceived social support within 28 days after myocardial infarction (MI) in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial did not increase event-free survival. The purpose of the present investigation was to conduct post hoc analyses on sex and ethnic minority subgroups to assess whether any treatment subgroup is at reduced or increased risk of greater morbidity/mortality. METHODS: The 2481 patients with MI (973 white men, 424 minority men, 674 white women, 410 minority women) who had major or minor depression and/or low perceived social support were randomly allocated to usual medical care or cognitive behavior therapy. Total mortality or recurrent nonfatal MI (ENRICHD primary endpoint) and cardiac mortality or recurrent nonfatal MI (secondary endpoint) were analyzed as composite endpoints by group for time to first event using Cox proportional hazards regression. RESULTS: There was a trend in the direction of treatment efficacy for white men for the primary endpoint (hazard ratio [HR], 0.80; 95% confidence interval, 0.61-1.05; p =.10) and a significant (p <.006, Bonferroni corrected) effect for the secondary endpoint (HR, 0.63; 95% CI, 0.46-0.87; p =.004). In contrast, the HRs for each of the other three subgroups were nonsignificant. The magnitude of differences in treatment effects between white men and the other subgroups remained significant for the secondary endpoint (p =.04) after adjustment for age, education, living alone, antidepressant use, comorbidity score, cardiac catheterization, ejection fraction, history of hypertension, and major depression. CONCLUSIONS: White men, but not other subgroups, may have benefited from the ENRICHD intervention, suggesting that future studies need to attend to issues of treatment design and delivery that may have prevented benefit among sex and ethnic subgroups other than white men.

Efficacy and safety of sildenafil citrate in men with erectile dysfunction and stable coronary artery disease.

This was a double-blind, placebo-controlled, flexible-dose study of the efficacy and safety of sildenafil in men with erectile dysfunction (ED) and clinically stable coronary artery disease (CAD). Patients were randomized to receive sildenafil or placebo for 12 weeks. Primary outcomes were questions 3 and 4 of the International Index of Erectile Function (IIEF). Secondary outcomes included the other IIEF questions and functional domains, the Life Satisfaction Checklist, the Erectile Dysfunction Inventory of Treatment Satisfaction, 2 global efficacy assessment questions, and intercourse success rate. By week 12, sildenafil-treated patients (n = 70) showed significant improvements on questions 3 and 4 compared with placebo-treated patients (n = 72; p <0.01). Larger percentages of sildenafil-treated patients reported improved erections (64%) and improved intercourse (65%) compared with placebo-treated patients (21% and 19%, respectively). Sildenafil-treated patients were highly satisfied with treatment and their sexual life compared with placebo-treated patients. Forty-seven percent of sildenafil- and 32% of placebo-treated patients experienced adverse events, including transient headache, hypertension, flushing, and dyspepsia. There were no serious drug-related cardiovascular effects. Thus, sildenafil is an effective and well-tolerated treatment for ED in men with CAD. Sildenafil was not associated with additional safety risks in this patient population.

Usefulness of ambulatory electrocardiographic monitoring for myocardial ischemia after coronary bypass.

Cardiac patients with asymptomatic myocardial ischemia have a poor prognosis. Ambulatory electrocardiographic monitoring can help to ensure that these patients, who are unaware of their high-risk status, are relieved of residual myocardial ischemia in response to cardioprotective medication, and rendered as low cardiac risk.

Pharmacotherapy for erectile dysfunction.

INTRODUCTION: Advances in understanding of the biochemistry and physiology of penile erection have led to breakthroughs in pharmacotherapy of erectile dysfunction. AIM: To provide recommendations/guidelines concerning state-of-the-art knowledge for the putative molecular and cellular mechanisms of action of centrally and peripherally acting drugs currently utilized in pharmacotherapy of erectile dysfunction. METHODS: An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a two-year period. Concerning the Pharmacotherapy for Erectile Dysfunction Committee there were 25 experts from 10 countries. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. RESULTS: Selective and potent oral PDE5 inhibitors have significantly more affinity than cGMP and form broader molecular interactions with multiple amino acids, thereby blocking access to cGMP in the catalytic sites of the PDE5 enzyme. PDE5 inhibitors, which vary as to biochemical potency, selectivity and pharmacokinetics, lead to cGMP elevation and relaxation facilitation of penile corpus cavernosum smooth muscle cells following sexual stimulation. Various centrally acting drugs influence sexual behaviour. In particular, the dopaminergic substance apomorphine is a central enhancer that acts in the paraventricular nucleus of the hypothalamus as a dopamine (D2) receptor agonist, induces and increases penile erection responses via disinhibition, following sexual stimulation. CONCLUSIONS: There is a need for more research in the pharmacotherapeutic development of central and peripheral agents for safe and effective erectile dysfunction treatment.

Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial.

CONTEXT: Depression and low perceived social support (LPSS) after myocardial infarction (MI) are associated with higher morbidity and mortality, but little is known about whether this excess risk can be reduced through treatment. OBJECTIVE: To determine whether mortality and recurrent infarction are reduced by treatment of depression and LPSS with cognitive behavior therapy (CBT), supplemented with a selective serotonin reuptake inhibitor (SSRI) antidepressant when indicated, in patients enrolled within 28 days after MI. DESIGN, SETTING, AND PATIENTS: Randomized clinical trial conducted from October 1996 to April 2001 in 2481 MI patients (1084 women, 1397 men) enrolled from 8 clinical centers. Major or minor depression was diagnosed by modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and severity by the 17-item Hamilton Rating Scale for Depression (HRSD); LPSS was determined by the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Social Support Instrument (ESSI). Random allocation was to usual medical care or CBT-based psychosocial intervention. INTERVENTION: Cognitive behavior therapy was initiated at a median of 17 days after the index MI for a median of 11 individual sessions throughout 6 months, plus group therapy when feasible, with SSRIs for patients scoring higher than 24 on the HRSD or having a less than 50% reduction in Beck Depression Inventory scores after 5 weeks. MAIN OUTCOME MEASURES: Composite primary end point of death or recurrent MI; secondary outcomes included change in HRSD (for depression) or ESSI scores (for LPSS) at 6 months. RESULTS: Improvement in psychosocial outcomes at 6 months favored treatment: mean (SD) change in HRSD score, -10.1 (7.8) in the depression and psychosocial intervention group vs -8.4 (7.7) in the depression and usual care group (P<.001); mean (SD) change in ESSI score, 5.1 (5.9) in the LPSS and psychosocial intervention group vs 3.4 (6.0) in the LPSS and usual care group (P<.001). After an average follow-up of 29 months, there was no significant difference in event-free survival between usual care (75.9%) and psychosocial intervention (75.8%). There were also no differences in survival between the psychosocial intervention and usual care arms in any of the 3 psychosocial risk groups (depression, LPSS, and depression and LPSS patients). CONCLUSIONS: The intervention did not increase event-free survival. The intervention improved depression and social isolation, although the relative improvement in the psychosocial intervention group compared with the usual care group was less than expected due to substantial improvement in usual care patients.

Application of a nurse-managed inpatient smoking cessation program.

This study reports on the effectiveness of a nurse case-managed smoking cessation program for general hospitalized patients that was continued for 3 years after clinical trials were completed. Patients admitted to the hospital who smoked were offered a smoking cessation program during their hospitalization. The program included physician advice, bedside education and counseling with a nurse specially trained in smoking cessation techniques, take-home materials (videotape, workbook, and relaxation audiotape), nicotine replacement therapy if requested or indicated, and four nurse-initiated post-discharge telephone counseling calls. Of the 2091 patients identified as smokers, 52% enrolled in the program, 18% wanted to quit on their own, 20% did not want to quit, and 10% were ineligible. The 12-month self-reported cessation rate (7-day point prevalence) was 35% if patients lost to follow-up were considered smokers, 49% if not. Patients hospitalized for cancer, cardiovascular, or pulmonary reasons were most likely to participate and had the highest self-reported cessation rates (63%, 57%, and 46%, respectively). This nurse-managed smoking cessation intervention was effective when it was put into standard hospital practice outside of its originating randomized clinical trial structure. The program, relatively inexpensive to deliver, appears to be acceptable to the majority of smokers who are hospitalized, resulted in high 1-year cessation rates, and can be extended to hospital employees and their families, work-sites, and communities on a cost-recovery basis.