Headache rate and cost of care following lumbar puncture at a single tertiary care hospital.

BACKGROUND: American Academy of Neurology guidelines recommend the use of noncutting needles because of lower rates of headache following lumbar puncture in randomized trials. We sought to determine the rate of headache using cutting needles and the potential cost savings of switching to noncutting needles. METHODS: We retrospectively reviewed the charts of all patients who had a lumbar puncture in the outpatient neurology clinic at a single institution between January 2004 and December 2005. Outcome data included occurrence of headache, back pain, or epidural hematomas within 2 weeks of the procedure. Costs associated with the use of the current system were compared with the projected costs of switching to a noncutting needle system. RESULTS: A total of 274 patients underwent lumbar puncture (62% women, mean age 53 ± 17 years, average weight 178 ± 43 pounds). Of these, 38 (14%) had a post-lumbar puncture headache. Eight patients (3%) reported back pain. No patients had an epidural hematoma. Twelve patients were admitted for a total of 18 hospital days, mainly for headache. Predictors of headache were younger age and no prior aspirin use. The rate of headache associated with the noncutting needle according to published literature is 4%. The estimated cost savings would have been approximately $20,000 per year (or approximately $73 per person). CONCLUSIONS: In this single-institution study, use of a noncutting needle would have potentially been associated with less adverse events and less cost. Further studies are warranted, including the possibility of premedication with aspirin.

Noninvasive assessment of acute cardiopulmonary effects of an oral single dose of sildenafil in patients with idiopathic pulmonary hypertension.

We aimed to assess the acute cardiopulmonary effects of a 100-mg oral single dose of sildenafil in patients with idiopathic pulmonary hypertension (IPAH) using a well-validated but less-used noninvasive echocardiographic method for the measurement of both systolic and diastolic pulmonary artery pressure (PAP), by tricuspid regurgitation (TR) velocity curve analysis. We studied 12 consecutive patients with IPAH (10 patients with New York Heart Association functional class III, and 2 patients with functional class II). A 100-mg oral single dose of sildenafil was added to previous medications of all patients and its immediate effects were evaluated 1, 5, and 12 h after treatment. Using paired analysis, administration of a 100-mg oral single dose of sildenafil led to a significant reduction in mean PAP and a remarkable increase in pulmonary acceleration time (PAT) 1 h after treatment (P = 0.000; 95% confidence interval [CI] 18.99-26.00 and P = 0.005; 95% CI -12.89 to -2.95, respectively). In addition, although the right heart dimensions (right atrium and right ventricle) showed a trend toward improvement, the differences were not statistically significant (P = 0.13 and P = 0.08, respectively). Our results demonstrated that Doppler examination of TR alone can be easily used for the estimate of systolic and diastolic PAP in patients with IPAH. This study also shows that sildenafil is the only drug given orally that can evaluate the vasodilatory capacity of the pulmonary vascular bed in patients with IPAH, with promising effects on mPAP and PAT in these patients.

Emerging drugs for pulmonary hypertension.

IMPORTANCE OF THE FIELD: Pulmonary arterial hypertension (PAH) is a clinical syndrome characterized by structural narrowing of the small pulmonary arteries that often culminates in fatal right heart failure. AREAS COVERED IN THIS REVIEW: PubMed was searched for PAH and treatment. Data from scientific meetings and pharmaceutical websites are also included. There are currently eight FDA approved drugs for PAH that fall into one of three classes: prostacyclins, endothelin-receptor antagonists and PDE-5 inhibitors. All have important limitations and morbidity and mortality remain high. Several new agents with similar mechanisms of action are in clinical development. Multiple novel therapeutic targets are being explored. New applications for PAH therapies, such as pulmonary hypertension due to left heart and lung disease, are also being investigated. WHAT THE READER WILL GAIN: An understanding of currently available drugs and those in clinical development for pulmonary hypertension. TAKE HOME MESSAGE: Drugs targeting the pulmonary vasculature have been an extremely active area of basic and clinical research for the past 20 years and will continue to be so for the foreseeable future. Considerable progress has been made, and yet there continues to be a great unmet medical need for developing more efficacious therapies.

Sildenafil citrate 100 mg starting dose in men with erectile dysfunction in an international, double-blind, placebo-controlled study: effect on the sexual experience and reducing feelings of anxiety about the next intercourse attempt.

INTRODUCTION: Sildenafil citrate 50 mg is the recommended starting dose for men with erectile dysfunction (ED); however, most men are later titrated to sildenafil 100 mg for improved efficacy. AIM: Assess the tolerability and efficacy of sildenafil initiated at the 100-mg dose in men with ED. METHODS: Men with ED (score < or =25 on the Erectile Function domain of the International Index of Erectile Function) who had received < or =6 total doses of a phosphodiesterase type 5 inhibitor and none within 4 weeks were randomized to 8 weeks of double-blind, placebo-controlled (DBPC), fixed-dose treatment (50 or 100 mg sildenafil or placebo) followed by 4 weeks of open-label flexible-dose sildenafil (50 or 100 mg). MAIN OUTCOME MEASURES: Efficacy, tolerability, treatment satisfaction, and other end points were measured at baseline and/or the end of the double-blind and open-label phases and compared between placebo and sildenafil initiated at doses of 50 and 100 mg. RESULTS: Improvements in DBPC patient-reported outcomes from baseline were statistically significant for both sildenafil 50 and 100 mg compared with placebo. At the end of DBPC treatment, 56% of men on the 100-mg dose felt no anxiety about the next intercourse attempt compared with 39% in the 50-mg group (odds ratio 2.03; P = 0.0197). Changes in functional scores from baseline were not statistically significant with the 100-mg dose compared with the 50-mg dose in the DBPC. Measures of treatment satisfaction and sexual experience significantly favored the 100-mg dose compared with the 50-mg dose in the DBPC. There was no increase in adverse events with the higher dose. CONCLUSIONS: Sildenafil at 50 mg or 100 mg significantly improved erection quality, treatment satisfaction, anxiety levels, and the sexual experience compared with placebo during DBPC. Sildenafil 100 mg improved the sexual experience and treatment satisfaction, and reduced feelings of anxiety compared with the 50-mg dose.

Sildenafil for the treatment of pulmonary hypertension in pediatric patients.

Sildenafil is a phosphodiesterase 5 inhibitor widely used for the treatment of pulmonary hypertension in children. Despite limited available safety and efficacy evidence, use of sildenafil continues to increase. To date, sildenafil use for pediatric pulmonary hypertension has been characterized for 193 children through 16 studies and 28 case series and reports. The primary efficacy data suggest that sildenafil is beneficial for facilitating the weaning of inhaled nitric oxide in children after cardiac surgery. Compiled safety data suggest that sildenafil is well tolerated among children with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease. This review summarizes the available data describing the use, safety, and efficacy of sildenafil for children with pulmonary hypertension.

Uroflowmetric assessment of acute effects of sildenafil on the voiding of men with erectile dysfunction and symptomatic benign prostatic hyperplasia.

PURPOSE: To evaluate the acute effects of sildenafil (50 mg) on the micturation of men with erectile dysfunction (ED) and concomitant benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS) using uroflowmetric parameters. MATERIALS AND METHODS: A total of 68 male patients randomized into two groups (36 treatment, 32 control groups) with International Prostate Symptom Score (IPSS) greater than 7 and International Index of Erectile Dysfunction-erectile function domain score lower than 26 were enrolled in the study. Patients in the treatment group received a single dose of 50 mg of oral sildenafil. Patients in the control group received no treatment. Prevoiding urine volumes determined ultrasonographically and voided urine volumes were also recorded. Statistical comparisons were made with the use of analysis of variance (ANOVA). RESULTS: Mean ages were similar between treatment and control groups (60.4 +/- 9.8 and 58.6 +/- 8.3 years, respectively, P = 0.430). In the treatment group the maximum and average flow rates increased significantly (Q (max) from 15.6 +/- 6.8 cc/s to 19.3 +/- 7.2 cc/s, P < 0.0001; Q (avg) from 7.3 +/- 3.0 cc/s to 9.1 +/- 3.0 cc/s, P < 0.0001) with sildenafil administration, while other parameters studied remained unchanged. CONCLUSION: Despite the limitations of variations of uroflowmetry, this study showed that sildenafil improves Q (max) and Q (avg) in patients suffering from ED with concomitant BPH-LUTS. Long-term studies are needed to evaluate the effects on IPSS, side effects, and drug interactions.

Comparative efficacy assessment of tamsulosin vs. tamsulosin plus tadalafil in the treatment of LUTS/BPH. Pilot study.

INTRODUCTION: The high incidence of erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) in aging men and the same pathophysiology make probable to treat both disorders with the same treatment. Numerous authors evaluated the actions of PDE5i in improving the LUTS/(benign prostate hyperplasia) BPH. AIM: To assess the efficacy and safety of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus tadalafil 20 mg/day in patients with LUTS in a crossover design study. MAIN OUTCOMES MEASURES: International Prostate Symptoms Score (IPSS), IPSS Quality of Life (IPSS-QOL), maximum flow rate (Qmax), post-void residual volume (PVR), International Index of Erectile Function-Erectile Function Domain (IIEF-EF), Global Assessment Quality (GAQ). For the statistical analysis, a Tukey-Kramer multicomparison test was used. METHODS: A randomized, double-blind, crossover study was conducted from September 2007 to February 2008 in one center. Thirty men, older than 50 years old, with a history of LUTS/BPH of at least 6 months, were randomized into two groups to receive tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus tadalafil 20 mg/day for 45 days, and then switched to the other treatment mode for other 45 days. RESULTS: Twenty-seven patients completed the study. Improvements of IPSS score and IPSS-QOL were significant with both treatments but greater with the drug combination. Both regimens similarly improved the Qmax and decreased the PVR volume from baseline (P < 0.001) with no significant differences between tamsulosin alone vs. tamsulosin and tadalafil (P > 0.05). The IIEF improved with tamsulosin plus tadalafil (P < 0.001) but not with tamsulosin alone (P > 0.05). The GAQ showed that all patients preferred the combination scheme. Both treatments were well tolerated. CONCLUSION; Tamsulosin 0.4 mg/day plus tadalafil 20 mg/day was more effective than tamsulosin 0.4 mg/day alone to improve LUTS and erectile dysfunction and was also well tolerated. Large-scale, randomized, placebo-controlled studies are needed to further assess the long-term safety and effectiveness of these agents in treating LUTS/BPH with or without ED.

Assessment of the impact of sildenafil citrate on lower urinary tract symptoms in men with erectile dysfunction.

INTRODUCTION: Sildenafil citrate is an effective and well-tolerated oral erectogenic medication. Through phosphodiesterase type 5 (PDE5) inhibition, it induces relaxation in penile smooth muscle, resulting in erection. Due to its mild affinity for other PDE enzymes, it may cause smooth muscle relaxation in a number of other organs. Recent data suggest an association between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS). Anecdotally some patients cite improvement in LUTS while using sildenafil. AIM: This study was conducted to assess the impact of Viagra on LUTS, using the International Prostate Symptom Score (IPSS) questionnaire. MAIN OUTCOME MEASURE: International Index of Erectile Function (IIEF) and IPSS inventories. METHODS: Men presenting to a sexual dysfunction clinic who were candidates and opted for treatment with sildenafil completed the IIEF and IPSS. Men with the IPSS scores greater than 10 were enrolled and completed the IPSS and IIEF questionnaires at least 3 months after the commencement of sildenafil. Comparisons were made between pre- and posttreatment scores in the IPSS and erectile function (EF) domain of the IIEF. RESULTS: Forty-eight men were enrolled, with a mean age of 62 +/- 11 years. The mean improvement in the EF domain score was 7 points (P = 0.01). The mean improvement in the IPSS score was 4.6 points (P = 0.013) and in quality of life (QOL) score was 1.4 points (P = 0.025). In total, 60% of men improved their IPSS score, and 35% had at least a 4-point improvement in their score. The mean number of uses of sildenafil per week was 2.0 +/- 0.6. No significant correlation was seen between the degree of the IPSS improvement and baseline IPSS, baseline EF domain score, or magnitude of improvement in EF domain score. CONCLUSIONS: These data indicate a positive impact of Viagra on men with mild to moderate LUTS. It is presumed, although unproven, that the medication's effect is mediated through bladder neck/prostatic smooth muscle relaxation.

Erectile dysfunction following radical retropubic prostatectomy: epidemiology, pathophysiology and pharmacological management.

Radical prostatectomy has been the time-honoured and standard treatment option for prostate cancer. Erectile dysfunction (ED) is one of the common quality-of-life issues following radical prostatectomy. The recovery of potency following radical prostatectomy varies from 16% to 86%. Although major modifications in surgical technique appear to be promising, the reported ED rates are still high. The time period required for the recovery of erectile function after surgery varies from 6 to 24 months. During this period of neuropraxia lack of natural erections produces cavernosal hypoxia. This cavernosal hypoxia has been implicated as one of the most important factors in the pathophysiology of ED. Cavernosal hypoxia predisposes to cavernosal fibrosis, ultimately producing venous leak and long-term ED. Interruption of this cascade of events has been the major challenge for physicians. Physicians have several options available for the treatment of ED. However, oral treatment options have quickly become established as first-line treatment options. Sildenafil has been most extensively studied in the radical prostatectomy population. In patients who do not respond to oral therapy alone, standard treatment options (intracavernosal injections, vacuum constriction devices and intraurethral alprostadil) are useful. Use of penile prostheses is one of the oldest treatment options available for the treatment of ED but is used only as a last resort. Initial attempts to promote the earlier recovery of erectile function appear to be promising. However, further confirmatory studies are essential. The roles of gene transfer and growth factors are still in experimental stages. In this review we discuss the epidemiology, pathophysiology and treatment options available for ED following radical prostatectomy.

Clinical and duplex US assessment of effects of sildenafil on cavernosal arteries of the penis: comparison with intracavernosal injection of vasoactive agents--initial experience.

PURPOSE: To prospectively evaluate the clinical response and hemodynamic changes in cavernosal arteries after oral administration of sildenafil without and with audiovisual sexual stimulation and to compare those responses with responses from intracavernosal injections of vasoactive agents. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Thirteen consecutive patients (age range, 22-77 years; mean, 60.4 years) with erectile dysfunction were evaluated with clinical assessment and cavernosal duplex ultrasonography (US). The patients were examined at two sessions 3 weeks apart. First, each patient received 100 mg of sildenafil citrate orally and was examined 60 minutes later without any sexual stimulation. Each patient then underwent repeat clinical and duplex US assessment after audiovisual sexual stimulation. Three weeks later, the patients underwent identical clinical evaluation and duplex US after intracavernosal injection of a commercially available combination of papaverine, prostaglandin E1, and phentolamine. Clinical and duplex US data (ie, peak systolic velocity [PSV]) were examined by using the Wilcoxon signed rank test for matched pairs. RESULTS: At rest, the overall mean cavernosal artery PSV was 1.08 cm/sec and remained unchanged after intake of sildenafil without any audiovisual stimulation, with no clinical evidence of erection. With the addition of audiovisual sexual stimulation, eight (62%) of 13 patients had penile congestion or erection, and six (46%) had a PSV greater than 25 cm/sec. With intracavernosal injection of the combination of three drugs, all 13 patients achieved congestion or erection, and 10 (77%) had a PSV greater than 25 cm/sec. Both clinical and duplex US responses to intracavernosal injection were significantly greater than they were to sildenafil with audiovisual sexual stimulation (P = .04 and .003, respectively). CONCLUSION: Oral sildenafil with audiovisual sexual stimulation led to a significant clinical response and increment in blood flow in the cavernosal arteries. However, more patients responded to intracavernosal injection of the combination of three drugs than to sildenafil, and the clinical response was significantly better.

Utilization and cost of sildenafil in a large managed care organization with a quantity limit on sildenafil.

OBJECTIVE: Erectile dysfunction (ED) affects approximately 30 million men in the United States. The objectives of this study were to (1) assess the cost and utilization of sildenafil citrate (Viagra), an oral therapeutic agent for ED, in a large managed care organization (MCO) with a quantity limit of 6 units per 30-day supply and (2) describe the incidence of comorbid conditions and the severity of cardiovascular disease in adult male users of sildenafil. METHODS: Pharmacy claims for sildenafil were identified from an administrative database of claims with dates of service in calendar year 2001 for male members aged 18 years or older. Medical claims for MCO members who had sildenafil claims were used to identify comorbid diseases and categorize patients by degree of cardiovascular risk. High risk was defined as having at least 1 medical claim with a diagnosis of diabetes mellitus, ischemic heart disease, abdominal aortic aneurysm, or peripheral arterial disease, and medium risk was defined as not having any diagnosis in the high-risk category but at least 1 cardiovascular risk factor that included smoking, hypertension, hypercholesterolemia, family history of premature coronary heart disease, or being aged 45 years or older. RESULTS: There were 67,914 pharmacy claims for sildenafil during 2001 for 20,281 MCO members, an average of 3.3 pharmacy claims per patient. The prevalence of sildenafil use was 54.1 per 1,000 male MCO members aged 18 years or older. The total allowed charges for sildenafil pharmacy claims in 2001 were 3.56 million US dollars, of which patients paid 26.6% in average cost-share, and the net MCO cost per member per month (PMPM) was 0.18 US dollars. A total of 1,681 patients (8.3%) exceeded their quantity restrictions for sildenafil tablets in 2001, of which 1,362 (81.0%) paid cash and 319 (19.0%, or 1.6% of all sildenafil users) appealed and received approval from the MCO for additional sildenafil tablets beyond the restriction of 6 tablets per month. Medical claims were available for 15,644 sildenafil patients (77.1%), and 12,720 sildenafil users (81.3% of those with medical claims) were judged to be at high or medium cardiovascular risk. CONCLUSIONS: A quantity limit of 6 tablets of sildenafil per 30-day period was associated with a drug cost to users and the MCO of 0.25 US dollars PMPM. Sildenafil users paid an average cost-share of 26.6%, resulting in a net drug cost of 0.18 US dollars PMPM to the MCO.

Private prescription costs for sildenafil within the NHS: a telephone survey.

Because of the restrictions on prescribing for impotence within the NHS, doctors routinely write private prescriptions for sildenafil. The aim of this study was to determine the variation in cost of a private prescription of four 100 mg tablets of sildenafil. A selection of different pharmacy types within five areas in England was surveyed. We telephoned a total of 86 pharmacies and we were quoted prices ranging from pounds 28.20 to pounds 42.33. There was a significant difference in price between area and between pharmacy type. Best prices are not necessarily found at the major pharmacy chains or hospital pharmacies, as might be expected. NHS doctors and patients need to be aware of this significant difference in cost.

Cilostazol: a review of its use in intermittent claudication.

UNLABELLED: Cilostazol (Pletal) is a selective inhibitor of phosphodiesterase-III with antiplatelet, antithrombotic and vasodilating properties. It also exhibits antiproliferative effects on smooth muscle cells and has beneficial effects on high density lipoprotein-cholesterol and triglyceride levels.Randomized, double-blind, placebo-controlled 12- to 24-week trials in >2000 patients with moderate to severe intermittent claudication demonstrated that cilostazol generally significantly increased walking distances and improved quality of life compared with placebo. Additionally, a large comparative 24-week trial showed that cilostazol 100 mg twice daily was significantly more effective than pentoxifylline 400mg three times daily (pentoxifylline was not significantly different from placebo). Cilostazol was generally well tolerated. Adverse events reported significantly more often with cilostazol than with placebo included headache, diarrhea, abnormal stools, infection, rhinitis and peripheral edema and in comparison with pentoxifylline were headache, diarrhea, abnormal stools and palpitations. Adverse events were generally mild to moderate in intensity, transient or resolved after symptomatic treatment and rarely required treatment withdrawal. Significant drug interactions are observed when cilostazol is coadministered with other agents that inhibit cytochrome P450 (CYP) 3A4 (e.g. erythromycin or diltiazem) or CYP2C19 (e.g. omeprazole). As a result, in Europe cilostazol is contraindicated in patients receiving CYP3A4 or CYP2C19 inhibitors and in the US it is recommended that dosage reduction for cilostazol be considered during coadministration of cilostazol and CYP3A4 or CYP2C19 inhibitors. Conversely, cilostazol itself does not appear to inhibit CYP3A4. Coadministration of cilostazol with aspirin or warfarin did not result in any clinically significant changes to coagulation parameters, bleeding time or platelet aggregation. CONCLUSION: In six of eight well designed clinical trials, cilostazol was significantly more effective than placebo in increasing walking distances and improving the quality of life of patients with moderate to severe intermittent claudication. In addition, limited comparative data have shown that cilostazol has superior efficacy compared with pentoxifylline. Cilostazol is also generally well tolerated. Additional comparative trials are required to confirm these results, to determine the place of cilostazol in relation to other agents or exercise therapy and risk factor reduction alone, and to establish the effects of long-term treatment with cilostazol in patients with intermittent claudication. Cilostazol is contraindicated in several subpopulations of patients, particularly those with congestive heart failure and severe hepatic or renal impairment. Nonetheless, current data support the choice of cilostazol as a promising therapy amongst the limited options available for patients with intermittent claudication.

Effects of caffeine on bone and the calcium economy.

Caffeine-containing beverage consumption has been reported to be associated with reduced bone mass and increased fracture risk in some, but not most, observational studies. Human physiological studies and controlled balance studies show a clear but only a very small depressant effect of caffeine itself on intestinal calcium absorption, and no effect on total 24-h urinary calcium excretion. The epidemiologic studies showing a negative effect may be explained in part by an inverse relationship between consumption of milk and caffeine-containing beverages. Low calcium intake is clearly linked to skeletal fragility, and it is likely that a high caffeine intake is often a marker for a low calcium intake. The negative effect of caffeine on calcium absorption is small enough to be fully offset by as little as 1-2 tablespoons of milk. All of the observations implicating caffeine-containing beverages as a risk factor for osteoporosis have been made in populations consuming substantially less than optimal calcium intakes. There is no evidence that caffeine has any harmful effect on bone status or on the calcium economy in individuals who ingest the currently recommended daily allowances of calcium.

Relationship between patient self-assessment of erectile dysfunction and the sexual health inventory for men.

BACKGROUND: The Sexual Health Inventory for Men (SHIM) has been shown to possess favorable statistical properties in diagnosing the presence and severity of erectile dysfunction (ED). However, the SHIM has not been compared with patient self-assessment of ED. OBJECTIVE: This article describes an independent-validation study examining the correlation and agreement between the SHIM and patient self-assessment of ED with respect to the severity of ED at baseline and after treatment, and in terms of change from baseline. METHODS: The study population consisted of 247 male outpatients with ED participating in a multicenter, double-blind, placebo-controlled, flexible-dose (25-100 mg/d) Phase IIIb clinical trial in which they were randomized equally to sildenafil citrate or placebo. Patients assessed their degree of ED as severe, moderate, minimal/mild, or no problem at baseline and after 12 weeks of treatment. They also responded to the 5 questions on the SHIM, after which their degree of ED was calculated based on the SHIM total score. RESULTS: In general, the SHIM and the single-item self-assessment question produced similar descriptive profiles of the severity of ED. Kendall tau-b correlations were 0.66 (95% CI, 0.58-0.74) at baseline, 0.86 (95% CI, 0.82-0.90) after treatment, and 0.72 (95% CI, 0.67-0.77) for change from baseline. Agreement between instruments, measured by the weighted kappa statistic, mirrored the correlations at baseline and after treatment. As expected, both measures correlated moderately with improvement in erections and treatment satisfaction of both patient and partner. CONCLUSION: The moderate-to-high correlation and agreement between the SHIM and patient self-assessment of ED validate the SHIM for use in the diagnostic classification of ED severity.

Rationale and design of the OPTIME CHF trial: outcomes of a prospective trial of intravenous milrinone for exacerbations of chronic heart failure.

BACKGROUND: The optimal management of an acute exacerbation of chronic heart failure (CHF) is uncertain. There is little randomized evidence available to support the various treatment strategies for patients hospitalized with an exacerbation of CHF. Inotropic agents may produce beneficial hemodynamic effects, and although they are currently used in these patients, their effect on clinical response and impact on clinical outcome is unclear. We present a unique and simple study designed to determine whether a treatment strategy for CHF exacerbations that includes an intravenous agent with inotropic properties can reduce hospital length of stay and lead to improved patient outcome. METHODS: The OPTIME CHF (Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure) trial is an ongoing multicenter, randomized, placebo-controlled trial of a treatment strategy for patients with acute exacerbations of CHF. The design of this study provides a novel approach to the evaluation of treatment strategies in the care of this population. The OPTIME CHF design uses early initiation of intravenous milrinone as both an adjunct to the best the medical therapy and to facilitate optimal dosing of standard oral therapy for heart failure. Patients with known systolic heart failure requiring hospital admission for a CHF exacerbation are randomly assigned within 48 hours of admission to receive a 48-hour infusion of either intravenous milrinone or placebo. The primary end point of this design is a reduction in the total hospital days for cardiovascular events within 60 days after therapy. Enrollment of 1000 patients began July 7, 1997, at 80 US centers and is projected to conclude in late 1999.