Post-marketing surveillance study of the safety and efficacy of sildenafil prescribed in primary care to erectile dysfunction patients

In order to investigate the safety and efficacy of sildenafil prescribed in primary care, a post-marketing surveillance study was undertaken. A total of 651 men with erectile dysfunction (ED) were enrolled from 31 family physicians in Korea from December 1999 to July 2002. Patients were regularly followed up to ascertain the safety and efficacy of sildenafil. Of the 651 patients enrolled, 572 (87.9%) returned for safety evaluation and efficacy assessment. In all, 458 (80.1%) of 572 patients reported improved erectile function with sildenafil. Hypertension, diabetes and low-dose sildenafil were associated with poor efficacy. A total of 71 adverse events were reported among 56 patients (8.6%), with the most frequent being hot flushes (5.6%), followed by headache (2.6%), palpitation (1.0%), anxiety (0.5%) and elevated ALT (0.5%). Only six patients (1.0%) discontinued sildenafil as a direct result of adverse events. These results suggest that sildenafil prescribed by primary care physicians was well tolerated and improved erectile function in patients with ED.     

Cardiovascular morbidity and mortality after orthotopic liver transplantation

BACKGROUND: Hyperlipidemia and hypertension have been reported in liver allograft recipients and contribute to an increased risk of ischemic heart disease (IHD) after orthotopic liver transplantation (OLT). The aims of the study were (1) to determine the prevalence of risk factors for IHD in these patients and (2) to compare the observed incidence of cardiovascular events and related mortality in allograft recipients with a matched population. METHODS: One hundred ten consecutive adults (50 male) who attended for review after OLT (median follow-up 3.9 years; range 0.1-17.9) were assessed for cardiovascular risk factors using current blood pressure, diabetic status, and smoking history and measurements of total cholesterol, high-density lipoprotein cholesterol, and triglyceride concentrations. Cardiovascular events and cardiovascular mortality data were collected from the prospective database of all adult liver allograft recipients and compared to matched data from myocardial infarction registries and Office for National Statistics data, respectively. RESULTS: Raised serum cholesterol (>5.0 mmol/L) was found in 48 (44%) patients (18 male), and systolic hypertension (>140 mmHg) was found in 69 (63%) patients (27 male). The relative risk of ischemic cardiac events was 3.07 (95% [confidence interval] CI, 1.98-4.53) and the relative risk for cardiovascular deaths was 2.56 (95% CI, 1.52-4.05) in allograft recipients compared to an age-matched population without transplants. CONCLUSIONS: Liver allograft recipients have a greater risk of cardiovascular deaths and ischemic events than an age- and sex-matched population. The prevalence of raised cholesterol concentrations in patients after OLT is similar to those in previous reports. Moderate hypertension and hyperlipidemia may be more detrimental in patients after OLT compared to non-transplant patients without these risk factors.     

Natural history of the ectatic aorta

OBJECTIVES: To define the natural history of ectatic abdominal aortas and to assess the clinical need for follow-up. DESIGN: Abdominal aortas were considered ectatic if they were diffusely and irregularly dilated with a diameter less than 3 cm. Ectatic aortas were identified either by AAA screening or as incidental findings. Patients who had only one scan were excluded from the study. Clinical data were analysed. SETTING: Two district general hospitals in Wales and England. SUBJECTS: 116 patients (90 men). RESULTS: : The median age of patients was 71 years (range 48-90). Co-existing risk factors included hypertension (75), IHD (22), PVD (8), diabetes (3), COAD (14), stroke (5), popliteal aneurysm (1), malignant disease (3) and 4 had a family history of AAA. The median follow-up was 24 months (range 5-72). The median and maximum growth rate of the ectatic aortas were 0.65 and 14.4 mm/year respectively. In three patients the expansion rate was more than 5 mm/year. In 22 patients the ectatic aorta became aneurysmal, reaching a diameter greater than 3 cm. There were no ruptures and no elective repairs. Two deaths occurred due to IHD. CONCLUSIONS: : This study demonstrates that if ectatic aortas do expand they do so very slowly. However, 22 of the 116 (19%) became aneurysmal in a follow-up of two years. Once identified ectatic aortas should be scanned at intervals of three years.     

Long-term efficacy and safety of oral Viagra (sildenafil citrate) in men with erectile dysfunction and the effect of randomised treatment withdrawal

The long-term efficacy and safety of oral Viagra (sildenafil citrate), a selective phosphodiesterase 5 inhibitor, and the effect of withdrawing treatment were evaluated in men with erectile dysfunction (ED). In 233 men with ED of psychogenic or mixed organic/psychogenic aetiology, 16 weeks of open-label, flexible-dose sildenafil treatment (10-100 mg) was followed by eight weeks of double-blind, fixed-dose, randomised withdrawal to placebo or continued treatment with sildenafil. Sildenafil was taken as needed (not more than once daily) approximately 1 h prior to sexual activity. The main outcome measures were a global efficacy question, a sexual function questionnaire, an event log of erections, and adverse event recording. In the open-label phase, 200 of 216 patients (93%) reported improved erections with sildenafil; 28 patients (12%) discontinued treatment. In the double-blind phase, the significant improvements in the frequency and duration of erections were maintained in the sildenafil group but returned to pre-treatment values in patients on placebo (P values < 0.0001 versus placebo). The most frequent adverse events in the sildenafil group during the double-blind phase were flushing (7%), headache (6%), and dyspepsia (5%). Of the 192 patients enrolled in the 1-y extension, 90% completed the study; only two patients (1%) were withdrawn due to lack of efficacy. In men with ED of psychogenic or mixed aetiology, oral sildenafil is effective and well-tolerated both at the initiation of therapy and during long-term treatment. For most patients, sildenafil treatment must be continued for improvements in erectile function to be maintained.     

Cardiac diseases in maintenance hemodialysis patients: results of the HEMO Study

BACKGROUND: Cardiac disease is a common cause of death in chronic hemodialysis patients. A subanalysis of the data on cardiac diseases in the Hemodialysis (HEMO) Study was performed. The specific objectives were: (1) to analyze the prevalence of cardiac disease at baseline; (2) to characterize the incidence of various types of cardiac events during follow-up; (3) to examine the association of cardiac events during follow-up with baseline cardiac diseases; and (4) to examine the effect of dose and flux interventions on various types of cardiac events. METHODS: The HEMO Study is a randomized multi-center trial on 1846 chronic hemodialysis patients at 15 clinical centers comprising 72 dialysis units. The scheduled maximum follow-up duration was 0.9 to 6.6 years, with the mean actual follow-up of 2.84 years. The interventions were standard-dose versus high-dose and low-flux versus high-flux hemodialysis in a 2 x 2 factorial design. RESULTS: At baseline, 80% of patients had cardiac diseases, including ischemic heart disease (IHD) (39%), congestive heart failure (40%), arrhythmia (31%), and other heart diseases (63%). There were a total of 1685 cardiac hospitalizations, with angina and acute myocardial infarction accounting for 42.7% of these hospitalizations. There were 343 cardiac deaths during follow-up, accounting for 39.4% of all deaths. IHD was implicated in 61.5% of the cardiac deaths. Any cardiac disease at baseline was highly predictive of cardiac death during follow-up [relative risk (RR) 2.57; 95% CI 1.73-3.83]. There were no significant effects of dose or flux assignments on the primary outcome of all-cause mortality or the main secondary cardiac composite outcome of first cardiac hospitalization or all-cause mortality. Assignment to high-flux dialysis was, however, associated with decreased cardiac mortality and the composite outcome of first cardiac hospitalization or death from cardiac causes. CONCLUSION: The HEMO Study identified IHD to be a major cause of cardiac hospitalizations and cardiac deaths. Future strategies for the prevention of cardiac diseases in the maintenance hemodialysis population should focus on this entity. Although high-flux dialysis did not reduce all-cause mortality, it might improve cardiac outcomes. This hypothesis needs to be further examined.     

Efficacy, tolerability and satisfaction with sildenafil citrate 100-mg titration compared with continued 50-mg dose treatment in men with erectile dysfunction

OBJECTIVE

To evaluate the efficacy, tolerability, and treatment satisfaction after initiating treatment with sildenafil 50 mg and later titrating to 100 mg, compared with continuing treatment with sildenafil 50 mg, in men with erectile dysfunction (ED).

PATIENTS AND METHODS

A multicentre, parallel‐group trial was conducted in two 4‐week periods. In period 1, patients received 50‐mg doses of sildenafil single‐blinded for 4 weeks. In period 2, patients were randomized to double‐blind, placebo‐controlled treatment with sildenafil 50 mg or sildenafil 100 mg for 4 weeks. All patients were aged ≥18 years with a documented clinical diagnosis of ED (score of ≤25 on the International Index of Erectile Function, IIEF, Erectile Function, EF, domain), and met the prescribing criteria for sildenafil 50 mg and 100 mg.

RESULTS

Of 492 enrolled patients (mean age 53 years, sd 11), 476 (97%) completed period 1 and 473 (96%) completed period 2. Patients receiving sildenafil 50 mg in period 1 had an increase in the mean (sd ) baseline EF domain score from 12.8 (5.2) to 22.5 (6.6) (P < 0.001), and improved scores on the Quality of Erection Questionnaire (QEQ) and Sexual Experience Questionnaire (SEX‐Q). The IIEF EF domain scores were similar in the two groups at baseline and randomization. Patients titrated to the 100‐mg dose (237 men) showed a significantly greater improvement than those who continued on the 50‐mg dose (240; P < 0.001). There was a significant increase in QEQ and SEX‐Q scores in patients titrated to sildenafil 100 mg compared with patients continuing at sildenafil 50 mg. At either sildenafil dose, headache, flushing and hot flushes were the most common adverse events. Neither the frequency nor the severity of adverse events increased with titration to sildenafil 100 mg.

CONCLUSIONS

After initial treatment with sildenafil 50 mg, patients titrated to 100 mg showed further increases in efficacy and satisfaction with no increase in the number or severity of adverse events than in those remaining on the starting dose.     

Clinical efficacy and safety of sildenafil citrate (Viagra) in a multi-racial population in Singapore: A retrospective study of 1520 patients

BACKGROUND: Sildenafil citrate (Viagra), a selective inhibitor of cGMP-specific phosphodiesterase type-5, has been used as an oral therapeutic drug for erectile dysfunction. The present paper is a clinical study of the success rate and side-effects of the use of sildenafil in a multi-racial population in Singapore. METHODS: From April 1999 to May 2000, 1520 patients were given sildenafil citrate. Of these, 912 patients (mean age, 54.6 years; age range, 22-99 years) were followed up and evaluated for clinical efficacy and safety of the drug. The mean duration of erectile dysfunction (ED) and follow-up periods were 31.5 and 3.0 months, respectively. RESULTS: Satisfactory erections assessed by single global efficacy question (GEQ) occurred in 83% of patients, major side-effects in the form of flushing (3.48%), headache (1.97%), blurred vision (1.25%), giddiness (1.18%), warmth (1.11%) and others (4.92%) were recorded in 127 patients (13.9%). Racially, Chinese men with ED had higher efficacy (85.7%), compared to Indian men (74.2%) and Malay men (72.8%). With respect to comorbid profiles, an efficacy of 77.8% (n = 271), 83.9% (n = 292), 86.4% (n = 44) and 83.3% (n = 199) was recorded in diabetic, hypertensive, ischemic heart disease patients and in benign prostatic hyperplasia patients, respectively. Patients who smoked (n = 135) and drank alcohol (n = 118) showed an efficacy of 80%. Baseline hormonal profiles of luteinizing hormone, follicle stimulating hormone, testosterone and prolactin did not affect the success rates of sildenafil citrate. Many patients had earlier received other forms of treatment (medicated urethral suppository for erection (MUSE; 84.9%); vacuum devices (86.8%), traditional medicines (100%) and other oral medications (89.2%)), but this did not influence the success rate of sildenafil citrate. But patients previously treated with prostaglandin-E intracavernosal injections were less successful on sildenafil citrate (77.3%). In the total cohort, 50 mg sildenafil citrate was an effective dose in 49% of patients and 46.5% patients needed 100 mg sildenafil citrate, while 4.1% of the total cohort needed only 25 mg sildenafil citrate. CONCLUSION: Oral sildenafil citrate has been shown to be an effective, safe and well tolerated drug in Singaporean men with ED, as in men from other parts of the world.     

Detection of carotid stenosis in African Americans with ischemic heart disease

OBJECTIVES: This study was conducted to define the frequency of internal carotid stenosis in African American patients with ischemic heart disease (IHD). METHODS: We recruited 101 African American patients with IHD from a university medical center for carotid duplex examination. RESULTS: The frequency of >30%, >50%, and >70% stenosis was 21%, 11%, and 5%, respectively. Age >60 years (21% vs 3%, P < .01) and diabetes mellitus (22% vs 5%, P < .01) were predictors of unilateral stenosis of >50% and remained significant on multivariate testing. CONCLUSION: African American patients with established IHD have higher rates of extracranial carotid stenosis than community dwelling African American subjects and comparable rates with other populations.     

The incidence of ischemic heart disease in white South Africans cremated in Pretoria, 1978-1985

The prevalence of ischaemic heart disease was studied in a population selected on the basis of an application for cremation by the next of kin. In the age group 35-44 years 15.2% of the deaths were ascribed to ischaemic heart disease (IHD), while the corresponding figure in the general population was 27.2%. In females in the age group 45-54 years IHD was responsible for 9.3% of the deaths; the corresponding prevalence in the general population was 18.3%. The figures for all age groups and both sexes were 22% for the cremation group and 24.5% for the general population. In the economically active group (20-65) years, the figures were 20.0% for the cremation group and 30% for the general population. There was no significant difference in the IHD deaths between Afrikaans-speakers and other language groups. These findings are not necessarily applicable to the general population, as the cremation group is not truly representative, but the consistently lower prevalence of IHD suggests that there is over-reporting of this disease in unmonitored death certification.     

Changing epidemiology of acute post-streptococcal glomerulonephritis in Northeast Florida: a comparative study

The objective of this study was to review the epidemiological patterns of acute post-streptococcal glomerulonephritis (APSGN) in a pediatric population. We compared incidence, pathogenesis, clinical presentation and outcomes in two APSGN pediatric patient cohorts in northeastern Florida. Retrospective medical records were reviewed of children who were admitted to our institution with a diagnosis of APSGN. Patients admitted between 1999 and 2006 (recent cohort) were compared with a previously reported cohort of patients admitted between 1957 and 1973 (earlier cohort). The recent cohort comprised 45 children with APSGN of whom 87% were male and 13% were female; the median age was 7 years, and there was an average incidence of 6.4 patients per year. The earlier cohort comprised 153 children with APSGN of whom 62% were male and 38% were female; the median age 4.25 years, and there was an average incidence of 10.9 patients per year. The recent cohort was predominantly White-American (62%) and the earlier cohort predominately African American (87%). In the recent cohort, 64% of patients had antecedent pharyngitis, and in the earlier cohort, 66% of patients had antecedent pyoderma. In the recent cohort, 11% of APSGN cases occurred between August to October, and in the earlier cohort, 50% occurred during these months. In the recent cohort, symptoms of APSGN at presentation were milder and all cases recovered, but in the earlier cohort two deaths (1.3% mortality) were reported. In conclusion, there has been a decline in the incidence and severity of APSGN at our institute in recent decades. Pharyngitis has replaced impetigo as the predominant cause of APSGN. The etiological agent for impetigo has changed over the last decade, which has impacted the incidence, racial distribution, seasonal variation and severity of APSGN.     

Efficacy and safety of sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men in Egypt and South Africa

The efficacy of sildenafil citrate (Viagra), an oral agent for the treatment of erectile dysfunction (ED), has been demonstrated in global studies. This 12-week randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study assessed the efficacy and safety of sildenafil to treat ED in men in Egypt and South Africa. Men with ED of varied etiology were randomized to receive sildenafil 50 mg (n=128) or placebo (n=126); doses could be adjusted to 100 or 25 mg. Questions from the International Index of Erectile Function (IIEF) assessing the ability to achieve (Q3) and maintain (Q4) erections demonstrated a significant improvement with sildenafil compared with placebo (P<0.0001). Improved erections were reported by 74% of patients receiving sildenafil and 27% of those receiving placebo (P<0.0001). Headache, dyspepsia, and flushing were the most common adverse events in sildenafil-treated patients. These results are consistent with clinical trials in other countries. We conclude that sildenafil is an efficacious and well-tolerated treatment for men with ED in Egypt and South Africa.