Biomedical subjects

Alan Meehan

Publications and source records attributed to Alan Meehan.

4 recordsLinked to original sources

PubMed2005

Long-term safety and, tolerability profiles and lipid-modifying efficacy of ezetimibe coadministered with ongoing simvastatin treatment: a multicenter, randomized, double-blind, placebo-controlled, 48-week extension study.

BACKGROUND: Ezetimibe (EZE) is a cholesterol-lowering drug that inhibits absorption of dietary and biliary cholesterol across the intestinal wall without affecting absorption of bile acids, fatty acids, fat-soluble vitamins, or triglycerides. It has a complementary mechanism of action to the statins, which inhibit cholesterol synthesis in the liver. Coadministration of EZE and statins provides inhibition of 2 sources of cholesterol, leading to greater reductions in low-density lipoprotein cholesterol (LDL-C) than with either agent alone. OBJECTIVES: This study evaluated the long-term safety and tolerability profiles and lipid-modifying efficacy of treatment with EZE 10 mg/d plus simvastatin (SIMVA) 10, 20, 40, or 80 mg/d for 48 weeks in patients with primary hypercholesterolemia. METHODS: This was an extension of a multicenter, double-blind, placebo (PBO)-controlled base study in which hypercholesterolemic patients were randomized to receive EZE 10 mg/d or PBO in addition to their current statin for 8 weeks. Patients who successfully completed the base study could enter the extension study if they were willing to switch from their current statin to an approximately equipotent dose of SIMVA for the 54-week study period. After a 6-week open-label SIMVA run-in phase, patients were rerandomized to receive EZE 10 mg/d or PBO in a 4:1 ratio, respectively, for 48 weeks. At each clinic visit, beginning at week 12, the dose of SIMVA was titrated upward until patients reached their National Cholesterol Education Program Adult Treatment Panel II LDL-C goal or the maximum SIMVA dose of 80 mg/d. Safety/tolerability and lipid efficacy parameters were assessed at 12-week intervals. RESULTS: Of 433 patients entering the extension study, 355 were randomized to receive EZE and 78 were randomized to receive PBO. Baseline demographic characteristics and lipid levels were similar between treatment groups. Overall, coadministration of EZE + SIMVA was well tolerated. There were no clinically meaningful differences between the EZE and PBO groups with regard to the incidence of treatment-related adverse events (AEs) (19% vs 17%, respectively), discontinuations due to AEs (7% vs 10%), serious AEs (12% vs 17%), consecutive elevations in liver function tests > or =3 times the upper limit of normal (ULN) (0.3% vs 0%), or elevations in creatine kinase > or =10 times the ULN (both, 0%). As in the base study, LDL-C levels were significantly lower with the addition of EZE to SIMVA compared with the addition of PBO (-24% vs 3%; P < 0.001). CONCLUSION: In these patients with primary hypercholesterolemia, EZE 10 mg/d added to ongoing SIMVA treatment for 48 weeks had a favorable safety and tolerability profile and was more efficacious than SIMVA monotherapy.

Adult↗

PubMed2005

The relationship among lower urinary tract symptoms, prostate specific antigen and erectile dysfunction in men with benign prostatic hyperplasia: results from the proscar long-term efficacy and safety study.

PURPOSE: We evaluated the associations among lower urinary tract symptoms, prostate specific antigen (PSA) and erectile dysfunction (ED) in men with benign prostatic enlargement enrolled in the Proscar (Merck, Whitehouse Station, New Jersey) Long-Term Efficacy and Safety Study. MATERIALS AND METHODS: The Proscar Long-Term Efficacy and Safety Study was a 4-year, randomized, double-blind, placebo controlled study that enrolled 3,040 men with moderate to severe lower urinary tract symptoms and an enlarged prostate gland. Two questions assessed ED. A logistic regression model, including the effect of patient age, was used to examine the relationships among quasi-American Urological Association Symptom Score (AUASS), PSA, and ED at baseline. Changes in ED scores from baseline to study closeout were analyzed with ANOVA. RESULTS: A total of 2,981 patients had baseline data available for analysis. Mean age was 64 years, mean quasi-AUASS was 15, mean PSA was 2.8 ng/ml and mean prostate volume was 55 cm. At baseline every 1 point increase in quasi-AUASS was associated with a 2% increased risk of ED even after controlling for age (p <0.001). At 48 months in placebo but not in finasteride treated men a 1-unit decrease in quasi-AUASS was associated with a slight but statistically significant decrease in ED. No association existed between increasing PSA and ED on baseline or longitudinal analysis. CONCLUSIONS: We found a moderately strong association between baseline quasi-AUASS and the ED rate in men with an enlarged prostate, a finding that was supported by longitudinal data in the placebo arm. The absence of a relationship between PSA and ED highlights the need for further investigation into the mechanisms of benign prostatic hyperplasia related sexual dysfunction.

Aged↗

PubMed2004

Sustained decrease in incidence of acute urinary retention and surgery with finasteride for 6 years in men with benign prostatic hyperplasia.

PURPOSE: We determined the effect of long-term treatment with finasteride on the incidence of acute urinary retention (AUR) and benign prostatic hyperplasia (BPH) related surgery in men with BPH. MATERIALS AND METHODS: The Proscar (Merck and Co., Inc., Whitehouse Station, New Jersey) Long-Term Efficacy and Safety Study (PLESS) was comprised of 3040 men with enlarged prostates, moderate to severe symptomatic BPH and no clinical evidence of prostate cancer. Patients were randomized to placebo or 5 mg finasteride daily for 4 years. Of the 3016 randomized patients with available efficacy data 62% completed the original 4-year study (1006 on finasteride and 891 on placebo) and 89% of these (908 from the original finasteride arm and 785 from the placebo arm) continued in a 2-year open extension on finasteride. Followup was attempted in discontinued patients. Complete 6-year outcomes data, including 6-year followup in 770 men who had discontinued treatment during years 1 to 6, were available for 2463 (82%) of the 3016 originally randomized patients. RESULTS: For patients on continuous finasteride treatment the decrease in incidence of AUR and/or BPH related surgery in the 4-year base study was sustained during the open extension. In patients who were switched from placebo to finasteride in the extension, the incidence of AUR and/or BPH related surgery was similar to that in the continuous finasteride arm. CONCLUSIONS: The 6-year data from PLESS confirmed and further extended the findings from the original 4-year trial, demonstrating that finasteride treatment led to a sustained decrease in the incidence of AUR and/or BPH related surgery in men with BPH and enlarged prostates.

Acute Disease↗

PubMed2003

Effects of finasteride on serum testosterone and body mass index in men with benign prostatic hyperplasia.

OBJECTIVES: To examine the effect of finasteride on serum testosterone in men with benign prostatic hyperplasia (BPH). METHODS: The Proscar Long-Term Efficacy and Safety Study (PLESS) was a 4-year trial comparing the safety and efficacy of finasteride 5 mg with placebo in 3040 men with moderate to severe symptomatic BPH and enlarged prostates. PLESS included the prospective measurement of annual serum testosterone in a randomly selected subset of patients comprising approximately 10% of the randomized population (n = 301). RESULTS: Finasteride treatment led to a modest, but significant (P <0.001), increase relative to placebo in serum testosterone, with this increase greatest in patients who had low baseline testosterone levels. The larger testosterone increases seen in finasteride-treated patients in the lower baseline testosterone tertiles were associated with significant mean reductions relative to placebo at year 4 in body mass index (BMI), ranging from 0.6 to 0.8 kg/m2. No statistically significant between-group difference was found in BMI in the upper testosterone tertile. The sexual adverse experience profiles for finasteride and placebo were similar across the baseline testosterone cohorts examined. CONCLUSIONS: Finasteride treatment led to a generally modest increase relative to placebo in serum testosterone, with the greatest increases occurring in men with low baseline testosterone levels. The physiologic significance of these changes in men with low baseline testosterone levels is unclear, but the associated reduction in BMI is intriguing and may be related, because BMI is known to be negatively correlated with serum testosterone levels in men.

5-alpha Reductase Inhibitors↗