Efficacy and cardiovascular safety of the new estrogen-free contraceptive pill containing 4 mg drospirenone alone in a 24/4 regime.

BACKGROUND: A new estrogen-free contraceptive has been approved by both the FDA and more than 15 European authorities. It is composed of drospirenone (DRSP) at a dosage of 4 mg in a regimen 24/4. The molecule is known to have anti-gonadotropic, anti-mineralocorticoid, anti-estrogenic, and antiandrogenic properties. The purpose of these clinical trials with a new estrogen-free contraceptive was to introduce a contraceptive method with high efficacy and showing a profile with low cardiovascular risks. METHODS: Three European and American multicenter clinical trials have been conducted in more than 2500 patients and more than 25,000 cycles, not only demonstrating an excellent efficacy (Pearl Index of 0.73) but also investigating possible cardiovascular risks. In the USA study, 422 participants (41.9%) had a risk factor for VTE, while in the European studies, 261 patients (16.6%) had at least one VTE risk factor. Amount of arterial and venous thromboembolic events, hemostasiological data, blood pressure development, and ECG data were evaluated. RESULTS: No single case of VTE was documented, no changes in hemastosiological parameters were observed, a small decrease in RR in patients with pretreatment values between 130 and 140 and/or 85 to 90 mm HG and no influence on ECG parameters were observed. CONCLUSIONS: The introduction of a new estrogen-free contraceptive with 4 mg of non-micronized drospirenone in a 24/4-day regimen expands contraception options for women as not only a high efficacy could be demonstrated during clinical trials but also a very high cardiovascular safety profile was observed even in women with cardiovascular risk factors. TRIAL REGISTRATION: EudraCT registration numbers: 2010-021787-15 & 2011-002396-42 . Clincaltrials.gov: NCT02269241 .

Potassium-lowering agents for the treatment of nonemergent hyperkalemia: pharmacology, dosing and comparative efficacy.

Hyperkalemia represents a common and potentially life-threating electrolyte abnormality, a complication frequently observed in patients with heart failure, kidney disease, diabetes or in those receiving drug therapies influencing the renin-angiotensin-aldosterone system. Elevated serum potassium levels are often the result of impaired urinary potassium elimination, inadequate or reduced cellular potassium uptake, severe heart failure, use of medications influencing potassium levels in the circulation, or, more commonly, a combination of these factors. Strategies for the treatment of nonemergent hyperkalemia include the use of cation-exchange resins, polymers or other novel mechanisms of potassium trapping, including sodium polystyrene sulfonate, patiromer and sodium zirconium cyclosilicate. These agents differ in their pharmacology and mechanism of action, clinical efficacy, including onset and extent of potassium-lowering effect, dosage and administration, and potential safety and adverse effect profiles. In this review, an evaluation of these characteristics, including clinical evidence and safety concerns, in the management of nonemergent hyperkalemia will be explored.

Heart Failure Due to Reduced Ejection Fraction: Medical Management.

Heart failure is an increasingly common condition resulting in high rates of morbidity and mortality. For patients who have heart failure and reduced ejection fraction, randomized clinical trials demonstrate consistent mortality benefit from angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, direct-acting vasodilators, beta blockers, and aldosterone antagonists. Additionally, some data show benefits from two new classes of drugs: angiotensin receptor blocker/neprilysin inhibitor and sinus node modulator. Diuretics and digoxin can be used as needed for symptom control. Statins are not recommended solely for treatment of heart failure. Implantable cardioverter-defibrillators and biventricular pacemakers improve mortality and function in selected patients. For patients who have been hospitalized for heart failure, disease management programs and telemonitoring can reduce hospitalizations and mortality.

Effect of the medical insurance on the quality of care for Chinese patients with chronic heart failure.

OBJECTIVE: To assess the effect of medical insurance on the quality of care for patients with chronic heart failure (CHF). DESIGN: Seven quality indicators were used to assess the association between medical insurance and quality of care. Statistical analyses were conducted using multilevel logistic models for the total population and the subpopulation stratified by sex and age. PARTICIPANTS: In total, 1862 CHF patients who were admitted in 20 tertiary hospitals between 1 January 2009 and 31 October 2010. RESULTS: Of 1862 patients, 53.8% patients had basic medical insurance and 26.9% patients paid the hospital costs by themselves. After adjusting for confounding factors, patients with New Rural Cooperative Medical Scheme (NRCMS) were more likely to receive warfarin (odds ratios [OR], 3.89; 95% confidence interval [CI], 1.08-13.99; P = 0.038), but less likely to receive aldosterone receptor antagonist (OR, 0.21; 95% CI, 0.08-0.56; P = 0.002) than patients without any medical insurance. Urban Employee Basic Medical Insurance (UEBMI) and NRCMS were associated with more use of discharge instructions ([OR, 3.54; 95% CI, 2.44-5.13; P < 0.001] and [OR, 2.09; 95% CI, 1.21-3.62; P = 0.009], respectively). After stratified by sex, male patients with UEBMI were more likely to receive the evaluation of left ventricular function than male patients without any medical insurance (OR, 1.78; 95% CI, 1.06-2.98; P = 0.029). CONCLUSIONS: UEBMI and NRCMS could increase the adherence to quality indicators of CHF to some extent. Improving the medical insurance system is expected to achieve equality in medical security and improve the quality of care for CHF patients.

Angiotensin II receptor blocker combined with eplerenone or hydrochlorothiazide for hypertensive patients with diabetes mellitus.

Experimental models recently suggested an interaction between aldosterone and adipose tissue, but clinical investigation has been limited. We studied the effects of eplerenone compared to hydrochlorothiazide (HCTZ) on blood pressure (BP), glucose, and lipid levels in 50 patients with essential hypertension (EHT) and type 2 diabetes mellitus whose BP failed to reach target levels with 8 mg of candesartan alone. BP improved similarly in both groups over the 12-month study period, but BMI, waist circumference, and LDL-cholesterol were decreased in the eplerenone group, while glycohemoglobin was elevated in the HCTZ group.

[Update on therapy of chronic heart failure. Innovations and studies from last year]. / Update zur Therapie der chronischen Herzinsuffizienz. Neue Erkenntnisse und Studien des letzten Jahres.

Chronic heart failure is one of the most common chronic diseases worldwide with increasing prevalence and incidence. Due to the high morbidity and mortality a standardized and evidence-based therapy is crucial. The present review article gives an overview about the innovations in 2014 based on the current guidelines of the European Society of Cardiology. First, improvements in established medication regimens regarding beta blockers and mineralocorticoid receptor antagonists as well as treatment options for heart rate reduction will be explained. Second, new pharmacological developments, such as angiotensin receptor neprilysin inhibition will be discussed. Finally, new insights into common comorbidities of patients with chronic heart failure, such as atrial fibrillation and hyperkalemia will be presented.

[Chronic heart failure : current guideline recommendations and innovations]. / Chronische Herzinsuffizienz : Aktuelle Leitlinienempfehlungen und neue Erkenntnisse.

Chronic heart failure is one of the most common chronic diseases worldwide with increasing prevalence and incidence. Due to the high morbidity and mortality a standardized and evidence-based therapy is essential. The present article gives an overview of the innovations from 2014 based on the current guidelines of the European Society of Cardiology. First, improvements of established medication regimens regarding beta blockers, mineralocorticoid receptor antagonists and treatment options for heart rate reduction and disease management programs will be explained. Second, new pharmacological developments, such as the new substance class of angiotensin receptor blockers and neprilysin inhibitors (ARNI), will be presented. Finally, new insights into common comorbidities of chronic heart failure patients, such as atrial fibrillation and hyperkalemia will be discussed.

Acne vulgaris in the context of complex medical co-morbities: the management of severe acne vulgaris in a female with retinitis pigmentosa - utilizing pulse dye laser in conjunction with medical therapy.

Acne vulgaris is a pervasive inflammatory disorder of the skin, with multiple etiologies and treatment options. Although first-line therapies exist, it is often the case that a patient will present with an underlying disorder that prohibits the use of most currently accepted treatment modalities. We present a patient with severe acne vulgaris and a history of retinitis pigmentosa who was treated with 595 nanometer pulsed dye laser therapy, in conjunction with therapeutic alternatives to first-line acne medications. Our patient exhibited a significant and sustained improvement with the combined use of 595 nanometer pulsed dye laser, Yaz (drospirenone-ethinyl estradiol), dapsone, topical metronidazole, sodium-sulfacetamide wash, and topical azelaic acid. The positive results in this case, suggest that this combined treatment modality may serve as an example of a safe and effective treatment alternative in the management of acne vulgaris complicated by medical co-morbidities that contraindicate the use of most first-line treatment options.

Combined versus sequential diuretic treatment of ascites in non-azotaemic patients with cirrhosis: results of an open randomised clinical trial.

OBJECTIVE: The aim of the study was to compare sequential versus combined diuretic therapy in patients with cirrhosis, moderate ascites and without renal failure. DESIGN: One hundred patients were randomly assigned to the two diuretic treatments. The sequential treatment provided potassium canrenoate at the initial dose of 200 mg/day, then increased to 400 mg/day. Non-responders were treated with 400 mg/day of potassium canrenoate and furosemide at an initial dose of 50 mg/day, then increased to 150 mg/day. The combined treatment provided the initial dose of 200 mg/day of potassium canrenoate and 50 mg/day of furosemide, then increased to 400 mg/day and 150 mg/day, respectively. RESULTS: Most patients who received sequential treatment responded to potassium canrenoate alone (19% to 200 mg/day and 52.63% to 400 mg/day, respectively). Most patients who received the combined treatment responded to the first two steps (40% to the first step and 50% to the second, ie, 400 mg/day of potassium canrenoate plus 100 mg/day of furosemide). Adverse effects (38% vs 20%, p<0.05), in particular, hyperkalaemia (18% vs 4%, p<0.05), were more frequent in patients who received sequential therapy. As a consequence, the per cent of patients who resolved ascites without changing the effective diuretic step was higher in those who received the combined treatment (56% vs 76%, p<0.05). CONCLUSIONS: The combined diuretic treatment is preferable to the sequential one in the treatment of moderate ascites in patients with cirrhosis and without renal failure. NCT00741663. This work is an open randomised clinical trial.

Effect of eplerenone versus spironolactone on cortisol and hemoglobin A1(c) levels in patients with chronic heart failure.

BACKGROUND: It has been reported that mineralocorticoid receptor antagonist improves the prognosis of chronic heart failure (CHF). Recently, hemoglobin A1(c) (HbA1(c)) levels have been reported to be an independent risk factor for mortality in CHF, suggesting the important role of insulin resistance in CHF. We compared the metabolic effect of a selective mineralocorticoid receptor blocker eplerenone with spironolactone in CHF patients. METHODS: One hundred seven stable outpatients with mild CHF, who were already receiving standard therapy for CHF, were randomized (1:2) to spironolactone (25 mg/d) or eplerenone (50 mg/d). Plasma levels of B-type natriuretic peptide, adiponectin, HbA1(c) and cortisol were measured before and after 4 months treatment with spironolactone or eplerenone. RESULTS: There were no differences in baseline characteristics including hemodynamic parameters and plasma levels of biomarkers between 2 groups. In both groups, plasma B-type natriuretic peptide levels were significantly decreased and plasma aldosterone levels were significantly increased after 4 months. In patients receiving spironolactone (n = 34), plasma adiponectin levels were significantly decreased (12.6 ± 1.4-11.2 ± 1.3 µg/mL, P < .0001) and HbA1(c) and cortisol levels were significantly increased (5.61 ± 0.1-5.8 ± 0.1%, P < .0001, 11.3 ± 0.8-14.7 ± 1.3 µg/dL, P = .003, respectively). In patients receiving spironolactone, there was a significant positive correlation between the change in cortisol and the change in HbA1(c) (r = 0.489, P = .003). In contrast, in patients receiving eplerenone (n = 73), plasma levels of adiponectin, HbA1(c) and cortisol did not change. CONCLUSION: These findings indicated that the metabolic effect of eplerenone differed from that of spironolactone and that eplerenone had a superior metabolic effect especially on HbA1(c) in CHF patients.

A study of cycle control, side effects and client's satisfaction of a low dose combined contraceptive containing ethinylestradiol/drospirenone (24/4 regimen).

OBJECTIVE: To study cycle control, side effects, and satisfaction of low dose 24-day combined contraceptive containing 20 microg of Ethinylestradiol and 3 mg of Drospirenone. MATERIAL AND METHOD: This was an open label, non-comparative study. The healthy females from the family planning clinic at King Chulalongkorn Memorial Hospital were assigned to receive six cycles of combined oral contraceptive containing 20 microg of ethinylestradiol and 3 mg of drospirenone administered daily for 24 days followed by 4-day hormone-free interval. Data were collected on cycle control, side effects, and satisfaction. Data were analyzed using descriptive statistics for descriptive data and Paired t test for comparison. RESULTS: One hundred fifty four women were assigned the study medication, including one (0.64%) who did not start medication. In the second reference period, the occurrence of frequent and infrequent bleeding was low (2.1% and 4.9%). Only one woman (0.65%) discontinued medication because of irregular bleeding. There was no pregnancy reported during the present study. Overall, the study medication was well tolerated and five subjects (3.24%) discontinued study because of side effects. No serious side effects related to the study medication were reported. The majority of women (84.2%) were satisfied and very satisfied with the treatment and most (73.3%) would continue the medication if it were available. CONCLUSION: The low dose combined contraceptive containing Ethinylestradiol/Drospirenone (24/4 regimen) has acceptable cycle control and good tolerability.

Comparative effects of conventional vs. novel hormone replacement therapy on blood pressure in postmenopausal women.

Menopause is commonly characterized by an increase in blood pressure. Higher blood pressure may partially explain the elevated risk for cardiovascular events observed in postmenopausal women. There is a graded relationship between blood pressure and cardiovascular risk which extends to levels of blood pressure well below 140/90 mmHg, the classical established blood pressure limit for the diagnosis of hypertension. Despite this knowledge and the wide availability of consensus treatment guidelines for hypertension, high blood pressure remains untreated or poorly treated in many postmenopausal patients. It is clear that novel and innovative population strategies for lowering blood pressure in postmenopausal women are warranted. Clinical trials suggest that oral estrogen administration may produce either a neutral effect or a small increase in blood pressure in postmenopausal women. Transdermal estrogen administration has not been studied as extensively but may produce a decrease in blood pressure. The mechanisms for the differences observed between oral and transdermal estrogen have not been completely elucidated. Drospirenone (DRSP) is a novel progestin with aldosterone receptor antagonist activity that has been developed for hormone therapy as DRSP/17beta-estradiol (DRSP/E2). In several clinical trials, DRSP/E2 has demonstrated a significant antihypertensive effect as well an additive effect when combined with existing antihypertensive therapy. Despite the wide availability of treatment guidelines, a wide array of antihypertensive agents, and the introduction of hormone replacement therapy that can lower blood pressure, optimizing blood pressure control remains a serious issue confronting the physician who cares for the postmenopausal woman.

Medical therapy of adrenocortical tumors.

Medical therapy is but one of a multiarm, multispecialty approach that is needed in order to successfully treat adrenocortical tumors. The role of surgery, radiation therapy, radiofrequency ablation, and the need for a team approach for the care of the patient cannot be over-emphasized. In this article current and potential future medical therapies for adrenocortical tumors are reviewed.

Abiraterone and spironolactone in prostate cancer: a combination to avoid.

Objectives: Disease progression in metastatic castration-resistant prostate cancer (mCRPC) is dependent on androgen signaling. This case describes the complex adaptive androgen signaling mechanisms in mCRPC and illustrates that caution should be exercised when treating these patients with drugs influencing the androgen axis.Methods: Single case report and review of the literature.Results: We report the case of an 86-year-old man with mCRPC, treated with the secondary antihormonal agent abiraterone acetate. Following association of spironolactone to deal with symptoms related to mineralocorticoid excess, biochemical and radiographic disease progression occurred. Spironolactone was discontinued and 8 months after withdrawal, the patient continues to show a biochemical response to abiraterone.Conclusions: Although spironolactone generally exerts anti-androgenic effects, experimental evidence exists that it acts as an androgen receptor agonist in an androgen-depleted environment, capable of inducing prostate cancer proliferation. This is supported by the observations described in this case report. Therefore, spironolactone should be avoided in prostate cancer patients suffering from treatment-associated side effects of abiraterone.

Effect of eplerenone in patients with heart failure and reduced ejection fraction: potential effect modification by abdominal obesity. Insight from the EMPHASIS-HF trial.

AIMS: An excessive production of aldosterone influences outcome in patients with heart failure (HF) and in obese patients. Findings from laboratory studies suggest that chronic aldosterone blockade maybe more beneficial in abdominally obese HF-prone rats. In the current study, we investigated if the clinical response to a mineralocorticoid receptor antagonist in mildly symptomatic HF patients varied by abdominal obesity. METHODS AND RESULTS: A total of 2587 NYHA class II, reduced ejection fraction HF (HFrEF) patients enrolled in the EMPHASIS-HF trial were randomly assigned to eplerenone and placebo. In this post hoc analysis, patients were categorized according to waist circumference (WC) (normal if WC < 102 cm in men and < 88 cm in women; abdominal obesity if WC ≥ 102 cm in men and ≥ 88 cm women). The potential statistical interaction between the treatment and WC was assessed on the primary endpoint of death from cardiovascular causes or hospitalization for HF and other secondary endpoints. Over a median follow-up of 21 months, a significant benefit of eplerenone for the primary outcome was noted in both normal [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61-0.98, P = 0.03] and increased (HR 0.48, 95% CI 0.37-0.63, P < 0.0001) WC subgroups, but the latter patients appeared to receive greater benefit than patients with normal WC (P for interaction = 0.01). This suggests a significant quantitative (treatment effect varies in magnitude by subgroup, but is always in same direction) rather than a qualitative interaction (direction of the treatment effect varies by subgroup) between eplerenone and WC in the adjusted analysis. Mean doses of eplerenone, blood pressure and serum potassium changes and adverse events were similar between WC subgroups. CONCLUSION: In EMPHASIS-HF, eplerenone improved outcomes in HFrEF patients with and without abdominal obesity, although the benefit appeared to be more pronounced among those with abdominal obesity. The findings are potentially hypothesis generating and need to be replicated in other HFrEF populations.

The effects of thiazide and thiazide-potassium sparing diuretics on fibrinolytic system parameters.

OBJECTIVE: This study investigates whether the combination of thiazides with an aldosterone antagonist can decrease their negative effects on the fibrinolytic activity. METHODS: Twenty-eight hypertensive patients (20 men, 8 women) visiting our hypertension unit were included in the study. The control group consisted of age- and gender-matched 9 normotensive healthy individuals. The patients in the 1st group (7 men, 2 women, mean age 48.55+/-6.14 years) were given 50 mg hydrochlorothiazide (HCT), whereas patients in the 2nd group (7 men, 2 women, mean age 48+/-6.3 years) received a combination of 50 mg HCT and 5 mg amyloride and the 3rd group (7 men, 3 women, mean age 48.2+/-7.25 years) took 50 mg HCT and 50 mg spironolactone for a period of 2 weeks. The plasminogen activator inhibitor (PAI)-I, tissue plasminogen activator (t-PA) and PAI-I/t-PA ratio were assessed before and after treatment. RESULTS: Treatment with HCT-spironolactone caused an increase in PAI-I (p<0.001) and t-PA ( p<0.001), while no changes were observed in PAI-I/t-PA (P>0.05). In patients treated with HCT-spironolactone, PAI-I increase rate was lower than in those treated with HCT and HCT-amyloride (p<0.001). Hydrochlorothiazide, HCT-amyloride and HCT-spironolactone treatments caused a significant decrease in the baseline blood pressure values (p<0.001). Uric acid levels had increased after treatment with HCT (p<0.01) and HCT-amyloride (p<0.001), but no changes were observed in individuals receiving HCT-spironolactone (p>0.05). CONCLUSION: Thiazides have a negative effect on the endogenous fibrinolytic activity, which is already impaired in the hypertensive patients. Their use in combination with an aldosterone antagonist such as spironolactone can decrease their hypofibrinolytic effects and metabolic side effects.

Long-Term Effects of Low-Dose Spironolactone on Chronic Dialysis Patients: A Randomized Placebo-Controlled Study.

The purpose of this 2-year multicentric, randomized, placebo-controlled study was to evaluate the long-term effects and adverse effects of spironolactone on chronic dialysis patients. A total of 253 non-heart failure dialysis patients with end-stage renal disease were randomly assigned to 2-year treatment with spironolactone (25 mg once daily, n=125) or a matching placebo (n=128) as add-on therapy. The primary outcome was a composite of death from cardiocerebrovascular (CCV) events, aborted cardiac arrest, and sudden cardiac death, and the secondary outcome was death from all causes. Other CCV-related indexes such as left ventricular mass index, left ventricular ejection fraction, heart rate variability, vascular endothelial function, and blood pressure-lowering effect were analyzed for patients who completed the whole 2-year follow-up study. Sociodemographic, clinical, and relevant laboratory data were also collected. During the 2-year follow-up, the primary outcome occurred less frequently in the spironolactone group vs the control group (7.2% vs 18.0%; adjusted hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.26-0.78). Death from CCV events occurred in 4.0% of patients in the spironolactone group and in 11.7% of patients in the control group. Neither aborted cardiac arrest nor sudden cardiac death was significantly reduced by spironolactone treatment. The secondary outcome occurred less frequently in the spironolactone group vs the control group (9.6% vs 19.5%; adjusted HR, 0.52; 95% CI, 0.29-0.94). Other CCV-related indexes except for heart rate variability were significantly improved. This study demonstrates that use of low-dose spironolactone in non-heart failure dialysis patients can effectively reduce the risks of both CCV morbidity and mortality with few side effects. Moreover, the beneficial effect was mediated through improving the endothelial function or reducing left ventricular size independent of blood pressure changes, rather than mediation through changes in salt or potassium handling in the kidney.

Long-term, dose-dependent effects of spironolactone on left ventricular function and exercise tolerance in patients with chronic heart failure.

OBJECTIVES: This study was designed to assess the effects of spironolactone (SP) on left ventricular (LV) function and exercise tolerance in patients with chronic heart failure (CHF). BACKGROUND: In severe heart failure (HF), SP improves survival, but the underlying mechanisms are not clear. METHODS: We randomized 106 outpatients with HF to SP (12.5 to 50 mg/day) (group 1) or control (group 2). Complete echocardiography and cardiopulmonary exercise testing were performed at baseline and 12 months after randomization. RESULTS: Left ventricular end-systolic volume at baseline and at follow-up was 188 +/- 94 ml and 171 +/- 97 ml in group 1 and 173 +/- 71 ml and 168 +/- 79 ml in group 2 (treatment group-by-time interaction, p = 0.03). Left ventricular ejection fraction at baseline and at follow-up was 33 +/- 7% and 36 +/- 9% in group 1 and 34 +/- 7% and 34 +/- 9% in group 2 (treatment group-by-time interaction, p = 0.02). At baseline, 9 patients in group 1 and 3 patients in group 2 had a restrictive mitral filling pattern, a marker of severe diastolic dysfunction; at follow-up, 3 patients in group 1 and no patient in group 2 improved their pattern. No patient in group 1 and 4 patients in group 2 worsened their pattern (chi-square, p = 0.02). Peak oxygen consumption increased significantly in patients treated with 50 mg of SP and decreased in group 2 (17.7 +/- 5.2 vs. 18.5 +/- 5.9 and 19.1 +/- 5.6 vs. 17.9 +/- 5.3, respectively; analysis of variance, p = 0.01). CONCLUSIONS: Spironolactone improves LV volumes and function; furthermore, it improves exercise tolerance at the highest administered dose. Our data might explain the mortality reduction during aldosterone antagonism in patients with HF.

Comparison between theophylline and spironolactone in the management of cirrhotic ascites: a randomized controlled study.

BACKGROUND: It has been suggested that adenosine is involved in the renal haemodynamic and tubular abnormalities observed in cirrhosis. Low-dose theophylline is an adenosine antagonist and recent studies have shown that this drug can improve renal blood flow and sodium excretion in cirrhotic patients. METHODS: Fifteen patients with newly diagnosed cirrhotic ascites were randomized to receive either 100 mg spironolactone daily for 7 days or 250 mg theophylline on days 1, 2, 4 and 6. Baseline clinical and urinary and serum biochemical data were collected and compared following therapy. RESULTS: After 7 days of spironolactone there were increases in urinary sodium excretion (43.5 +/- 15.6 vs. 106.8 +/- 34.7 mmol/day; P < 0.05) and urine volume (769.1 +/- 206.5 vs. 1541.6 +/- 342.6 mL/day; P < 0.05). No changes in the patients' weight, creatinine clearance or serum electrolytes were observed. No change was detected in any of these parameters following theophylline therapy. CONCLUSION: Adenosine antagonism in the form of low-dose theophylline is less efficacious than spironolactone in the management of cirrhotic ascites.