Biomedical subjects

Arvind Shah

Publications and source records attributed to Arvind Shah.

9 recordsLinked to original sources

PubMed2006

Comparison of the lipid-modifying efficacy and safety profiles of ezetimibe coadministered with simvastatin in older versus younger patients with primary hypercholesterolemia: a post Hoc analysis of subpopulations from three pooled clinical trials.

BACKGROUND: Despite the need for effective and well-tolerated lipid-lowering therapies for primary hypercholesterolemia in older patients, there is a relative paucity of published data on such treatments in this population. OBJECTIVE: We conducted a post hoc analysis to examine the lipid-modifying efficacy and safety profile of simvastatin (SIMVA) monotherapy, and the coadministration of ezetimibe (EZE) and SIMVA (EZE/SIMVA) in older (ie, aged>or=65 years) versus younger (ie, aged<65 years) patients with primary hypercholesterolemia. METHODS: We analyzed pooled data from 3 previously published, similarly designed, randomized, double-blind, placebo-controlled studies in patients with primary hypercholesterolemia. After a 6- to 8-week washout, a 4-week dietary stabilization period, and a 4-week placebo run-in period, patients with low-density lipoprotein cholesterol (LDL-C) of 145 to 250 mg/dL were randomized to EZE/SIMVA 10/10, 10/20, 10/40, or 10/80 mg; SIMVA 10, 20, 40, or 80 mg; EZE 10 mg; or placebo for 12 weeks. In this post hoc analysis, the percent change from baseline to week 12 in LDL-C, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoprotein B (apo B), triglycerides (TG), and high-sensitivity C-reactive protein (hs-CRP) for EZE/SIMVA (pooled across doses) versus SIMVA alone (pooled across doses) was compared between older and younger patients with primary hypercholesterolemia. Tolerability was assessed by adverse event reports and laboratory and vital signs assessments throughout the study. RESULTS: A total of 3083 patients aged 20 to 87 years were included in the 3 studies (2320 were aged<65 years and 763 were aged>or=65 years). Baseline lipid values and patient characteristics were similar among all treatment groups for patients aged<65 years versus those aged>or=65 years except that there was a higher percentage of females (62% vs 50%) and patients with hypertension (46% vs 29%) in the older versus younger subgroup (both, P<0.001). EZE/SIMVA was associated with greater improvements than SIMVA alone in LDL-C, non-HDL-C, apo B, TG, and hs-CRP (all, P<0.001); these effects did not appear to differ between the older and younger sub-groups (all, P=NS). Changes in HDL-C did not differ significantly between the EZE/SIMVA and SIMVA groups. More patients receiving EZE/SIMVA than SIMVA monotherapy achieved the target LDL-C level<100 mg/dL (P<0.001), regardless of age subgroup (77% vs 41% for patients aged<65 years and 85% vs 48% for patients aged>or=65 years). In the younger sub-group, the incidence of creatinine phosphokinase (CK) elevations>or=10x the upper limit of normal (ULN) was or=10x ULN were reported. In younger patients, the incidence of consecutive alanine amino-transferase or aspartate aminotransferase levels>or=3x ULN was 0% for placebo and EZE, <1% for SIMVA, and 2% for EZE/SIMVA; in older patients, it was 1% for placebo and EZE, <1% for SIMVA, and 0% for EZE/SIMVA. CONCLUSION: This post hoc analysis of pooled data from 3 previously published large clinical trials suggests that EZE/SIMVA was well tolerated and associated with improved lipid profiles in both older and younger patients with primary hypercholesterolemia.

Adult↗

PubMed2006

The age related decrease in testosterone is significantly exacerbated in obese men with the metabolic syndrome. What are the implications for the relatively high incidence of erectile dysfunction observed in these men?

PURPOSE: We examined pooled baseline data from 2 lipid treatment studies to evaluate the relationship among total serum testosterone levels, obesity and the metabolic syndrome in aging men. MATERIALS AND METHODS: Baseline total serum testosterone, lipid, glycemic and anthropometric data were obtained from 864 men (mean age 52 years) participating in 2 lipid treatment studies. Inclusion criteria for the 2 studies included low-density lipoprotein cholesterol 130 to 160 mg/dl and triglycerides 350 mg/dl or less. RESULTS: For all patients as well as the nonmetabolic syndrome and the metabolic syndrome cohorts, testosterone decreased with increasing body mass index (p < 0.0001 for Pearson correlation coefficient in all 3 cohorts). Mean baseline total serum testosterone levels in obese and severely obese aging men with the metabolic syndrome were around 150 and 300 ng/dl, respectively, less than that in aging, lean men with no metabolic syndrome. The relative contributions of each of the individual National Cholesterol Education Program Adult Treatment Panel III components of the metabolic syndrome to low serum testosterone in aging men was examined using multiple linear regression modeling. Based on these analyses the presence of diabetes or fasting serum glucose greater than 110 mg/dl, body mass index 30 kg/m or greater, and triglycerides 150 mg/dl or greater each appeared to have a clinically relevant association with low serum testosterone. CONCLUSIONS: This study demonstrated that aging men with obesity and the metabolic syndrome have a significant decrease in total serum testosterone levels compared to aging, metabolically healthy men. These data suggest that the well established association between erectile dysfunction and pre-diabetes/diabetes (particularly in obese pre-diabetic/diabetic patients) may involve a hormonal component.

Age Factors↗

PubMed2006

Consistency of lipid-altering effects of ezetimibe/simvastatin across gender, race, age, baseline low density lipoprotein cholesterol levels, and coronary heart disease status: results of a pooled retrospective analysis.

BACKGROUND: The combination tablet containing ezetimibe and simvastatin (EZE/SIMVA), inhibits both the intestinal absorption and endogenous production of cholesterol, providing significantly greater low-density lipoprotein cholesterol (LDL-C) lowering than EZE or SIMVA alone. The purpose of this pooled analysis was to evaluate the consistency of efficacy (i.e., between-treatment difference) of EZE/SIMVA versus SIMVA within several selected subgroups of patients with primary hypercholesterolemia. METHODS: For the present analysis, data were pooled from three similarly designed, 12-week, randomized, double-blind, placebo-controlled factorial studies consisting of 3083 patients with primary hypercholesterolemia (n = 311 in placebo group; n = 302 in EZE group; n = 1234 in pooled SIMVA group; n = 1236 in pooled EZE/SIMVA group). In these clinical studies, primary hypercholesterolemia was defined as an LDL-C value between 145 and 250 mg/dL inclusive and a triglyceride (TG) level of less than 350 mg/dL. The results for the pooled SIMVA and pooled EZE/SIMVA groups were used for the present analyses. The pooled analyses focused on the consistency of the between-treatment differences (i.e., incremental effect) for EZE/SIMVA (pooled across doses) versus SIMVA (pooled across doses) on various lipid and non-lipid parameters within different patient subgroups defined according to gender, race (Caucasian, Non-Caucasian), baseline age (< 65, > or = 65 years), baseline LDL-C (< 160, > or = 160 mg/dL), and coronary heart disease (CHD) history. Tolerability was also examined for pooled EZE/SIMVA and pooled SIMVA within these selected subgroups. In a modified intention-to-treat analysis, an ANOVA model was used for testing the consistency of pooled treatment effects on lipid and non-lipid parameters within each selected subgroup. RESULTS: For the entire cohort, baseline lipid profiles were similar for the patients in the pooled EZE/SIMVA group compared with those in the pooled SIMVA group. Treatment with EZE/SIMVA led to significant (p < 0.001) incremental improvements in LDL-C, non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, TG and high sensitivity C-reactive protein compared to SIMVA, across the entire cohort. These changes were consistent within each of the selected subgroups. Moreover, more patients attained LDL-C goal levels < 100 mg/dL with EZE/SIMVA than with SIMVA in the entire cohort and this was consistent across all subgroups, except baseline LDL-C. In this pooled retrospective analysis, treatment with EZE/SIMVA was generally well tolerated across subgroups, with a safety profile similar to SIMVA monotherapy. Although this pooled analysis was performed on a large cohort of patients with primary hypercholesterolemia, the results of this analysis were specific for this select patient population and generalizations to other populations should be applied with caution. CONCLUSION: The enhanced lipid-altering effects of EZE/SIMVA versus those of SIMVA observed in the entire cohort were consistent within all subgroups examined. EZE/SIMVA represents an effective and well-tolerated therapeutic option for the treatment of a wide range of patient subgroups with primary hypercholesterolemia.

Adult↗

PubMed2005

LDL-C goal attainment with ezetimibe plus simvastatin coadministration vs atorvastatin or simvastatin monotherapy in patients at high risk of CHD.

AIMS: To compare the proportion of patients at high risk for coronary heart disease (CHD) achieving the recommended low-density lipoprotein cholesterol (LDL-C) treatment goal of < 100 mg/dL and the optional LDL-C target of < 70 mg/dL with coadministration of ezetimibe and simvastatin (EZE/SIMVA) vs either atorvastatin or simvastatin monotherapy. PATIENTS: Patients with established CHD or CHD risk equivalent according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria with baseline LDL-C = 130 mg/dL and triglycerides (TG) < or = 350 mg/dL. METHODS: A post hoc analysis from 2 separate studies assessed the percentage of high-risk patients achieving the LDL-C targets (< 100 and < 70 mg/dL) after 6 weeks on the usual recommended starting doses of the following treatments: EZE/SIMVA (10/20 mg) vs atorvastatin (10 mg) or simvastatin (20 mg). Depending on the study, EZE/SIMVA 10/10 or 10/40 mg was also compared with either atorvastatin 10 mg or simvastatin 20 mg. Percent change in other lipid parameters from baseline to study endpoint was also examined. RESULTS: In both studies, the proportions of patients achieving an LDL-C of < 100 mg/dL were significantly (P < .001) greater for EZE/SIMVA 10/10, 10/20, or 10/40 mg vs either atorvastatin 10 mg or simvastatin 20 mg after 6 weeks. The percentage reaching the optional LDL-C treatment target of < 70 mg/dL was also significantly higher with EZE/SIMVA compared with either atorvastatin or simvastatin. Percent reduction in LDL-C was significantly (P < .001) larger with all doses of EZE/SIMVA (46% to 59%) compared with either atorvastatin 10 mg (37%) or simvastatin 20 mg (38%) monotherapy after 6 weeks. Changes in other lipid parameters consistently favored EZE/SIMVA vs statin monotherapy. All treatments were well tolerated in both studies. CONCLUSION: Patients at high risk for CHD are more likely to attain LDL-C treatment targets with the usual recommended starting dose of EZE/SIMVA (10 or 20 mg) therapy than with that of atorvastatin (10 mg) or simvastatin (20 mg) monotherapy.

Aged↗

PubMed2004

Identification of the antibacterial component of an ethanolic extract of the Australian medicinal plant, Eremophila duttonii.

Activity-guided fractionation was used to determine the antibacterial component of an ethanolic extract of the leaves of an Australian native medicinal plant, Eremophila duttonii F. Muell. (Myoporaceae). The extract, previously shown to have activity against Gram positive bacteria, was shown to have activity against additional Gram positive bacteria, including Clostridium perfringens, C. sporogenes and Listeria monocytogenes. Thin layer chromatography (TLC) was used to separate the extract into seven coloured fractions in visible light, one of which was shown by bioautography to contain antibacterial activity. Recovery of the component from the TLC plate and testing for antibacterial activity using a plate-hole diffusion assay supported this result. The purity of the component was verified by high-performance liquid chromatography and a time-kill experiment indicated that the purified component showed identical bactericidal activity to the whole extract. TLC spray reagents indicated that the component was a sterol, terpene or sugar but not a flavonoid, while the pigmented nature suggested a carotenoid.

Anti-Bacterial Agents↗

PubMed2004

Efficacy and safety of simvastatin in Asian and non-Asian coronary heart disease patients: a comparison of the GOALLS and STATT studies.

BACKGROUND: Asians are thought to be more responsive to the lipid-lowering effects of statins than non-Asians although there are no head-to-head trials that examine this perception. OBJECTIVE: To compare the results of the GOALLS and STATT studies that used similar titrate-to-goal protocols with 20 mg up to 80 mg simvastatin in Asian and non-Asian coronary heart disease (CHD) patients. METHODS: GOALLS (N = 198; included non-Asians and Asians) and STATT (N = 133; included Asians only) were both multi-center, open-label 14-week studies in CHD patients with serum low density lipoprotein cholesterol (LDL-C) levels 115 mg/dL-180 mg/dL and triglycerides (TG) levels < or = 400 mg/dL. Simvastatin was titrated from 20 mg/day up to 80 mg/day in order to achieve the National Cholesterol Education Program (NCEP) LDL-C target < or = 100 mg/dL. The primary efficacy variable was the percentage of patients attaining the NCEP LDL-C target at Week 14. Secondary endpoints included proportion of patients achieving the European Society of Cardiology/European Atherosclerosis Society/European Society of Hypertension (European) LDL-C target < or = 115 mg/dL at Week 14 and percentage change in lipid parameters. Safety and tolerability were assessed by monitoring adverse experiences and safety laboratory tests. Fifteen Asian patients were part of the GOALLS cohort and their data were compared separately with results of non-Asians from GOALLS and Asians from the STATT study. RESULTS: After 14 weeks of simvastatin treatment, 87.1% of GOALLS non-Asians, 85.7% of GOALLS Asians, and 78.2% of STATT patients attained the NCEP LDL-C target. At Week 14, 94.4%, 92.9%, and 91.7% of the GOALLS non-Asians, GOALLS Asians, and STATT patients achieved the European LDL-C target, respectively. The average treatment doses to attain NCEP and European targets were comparable among groups. The percentage reductions in lipid parameters from baseline to week 14 were similar among groups except, changes in high density lipoprotein cholesterol and apolipoprotein A-I favored Asian subjects. There was also a greater reduction in TG in the STATT study, but this was not consistent with TG reductions experienced by Asians in the GOALLS study. In both studies, simvastatin was generally well tolerated by all patients across the dosage range of 20 mg-80 mg. No cases of rhabdomyolysis or myopathy were reported in either study. CONCLUSIONS: A great majority of CHD patients is able to achieve LDL-C treatment goals (up to 90%) on simvastatin regardless of racial background. Simvastatin treatment at doses of 20 mg-80 mg is well-tolerated in Asian and non-Asian CHD patients. This side-by-side comparison provides evidence that Asian and non-Asian CHD populations respond similarly to comparable doses of simvastatin.

Asia↗

PubMed2004

Effects of ezetimibe added to on-going statin therapy on the lipid profile of hypercholesterolemic patients with diabetes mellitus or metabolic syndrome.

OBJECTIVE: To conduct a post-hoc assessment of the lipid-modifying effects of adding the cholesterol absorption inhibitor, ezetimibe, to on-going statin therapy in patients with diabetes mellitus (DM) or metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS: This was a post-hoc analysis of data from a randomized, double-blind, placebo-controlled trial designed to evaluate the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy and safety of adding ezetimibe 10 mg/day versus placebo to ongoing, open-label statin treatment for 8 weeks in hypercholesterolemic patients. Qualifying LDL-C levels and target LDL-C goals were based on National Cholesterol Education Program risk categories. The DM subgroup were patients who entered the study with a prior diagnosis of DM. Patients were classified as having MetS if they met 3 or more of the following criteria at baseline: triglycerides (TG) > or = 150 mg/dL (1.69 mmol/L); high-density lipoprotein cholesterol (HDL-C) < 40 mg/dL (1.04 mmol/L) for men or < 50 mg/dL (1.29 mmol/L) for women; fasting serum glucose (FSG) > or = 110 mg/dL (> or = 6.1 mmol/L); a diagnosis of hypertension or taking hypertension medication or blood pressure > or = 130/> or = 85 mmHg; waist circumference > 88 cm (women) or > 102 cm (men). DM patients were excluded from the MetS subgroup analysis. MAIN OUTCOME MEASURES: The objectives were to assess the effects of treatment on plasma concentrations of LDL-C and other lipid variables, and on the percentage of patients achieving LDL-C target levels at the end of the study. RESULTS: Of 769 patients enrolled in the original study, there were 191 (24.8%) with DM and 195 (25.4%) with MetS. Regardless of subgroup, ezetimibe + statin was significantly more effective than statin alone at lowering plasma levels of LDL-C, non-HDL-C, total cholesterol, apolipoprotein B, and triglycerides (between-group p < 0.001 for all). For all lipid parameters, the relative treatment effects were generally consistent regardless of DM or MetS status. Significantly more ezetimibe than placebo patients in all subgroups achieved prespecified LDL-C goals (p < 0.001 for all), and although more patients in the DM and MetS groups, respectively, achieved the goal compared with their non-DM and non-MetS counterparts [83.6% (DM) versus 67.2 (non-DM) and 71.8% (MetS) versus 65.6% (non-MetS)], these differences were not significant after adjusting for differences in baseline LDL-C levels. Ezetimibe was well-tolerated and had a favorable safety profile in all subgroups. CONCLUSIONS: The co-administration of ezetimibe with statins, a therapeutic regimen that inhibits both the absorption and synthesis of cholesterol, offers a well-tolerated and efficacious treatment to lower LDL-C in patients with DM and MetS.

Anticholesteremic Agents↗

PubMed2004

Reduction of cardiovascular events by simvastatin in nondiabetic coronary heart disease patients with and without the metabolic syndrome: subgroup analyses of the Scandinavian Simvastatin Survival Study (4S).

OBJECTIVE: To assess the effect of simvastatin treatment on the risk of cardiovascular events in nondiabetic patients with coronary heart disease (CHD) with and without the metabolic syndrome, as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP-III). RESEARCH DESIGN AND METHODS: Subgroup analyses were performed on data from 3933 nondiabetic patients with clinically established CHD, serum total cholesterol level 5.5-8.0 mmol/l, and serum triglyceride level <or=2.5 mmol/l who were participating in the Scandinavian Simvastatin Survival Study (4S), a randomized, placebo-controlled trial. End points were total mortality, coronary mortality, major CHD event, myocardial revascularization, any CHD event, stroke, and any atherosclerotic event. RESULTS: Over the 5.4-year median follow-up period, simvastatin produced similar changes in serum lipid levels in 893 patients with the metabolic syndrome and in 3040 patients without the metabolic syndrome. The relative risks of main end points in simvastatin-treated patients compared with placebo-treated patients with the metabolic syndrome were as follows: total mortality 0.54 (95% CI 0.36-0.82), coronary mortality 0.39 (0.23-0.65), major CHD event 0.59 (0.45-0.77), and any atherosclerotic event 0.69 (0.56-0.84). The corresponding RRs in patients without the metabolic syndrome were 0.72 (0.56-0.91), 0.62 (0.45-0.84), 0.71 (0.61-0.82), and 0.76 (0.68-0.85). CONCLUSIONS: Nondiabetic CHD patients with or without the metabolic syndrome realize from simvastatin treatment a similar, substantial relative reduction in the risk of cardiovascular events. The absolute benefit may be greater in patients with the metabolic syndrome because they are at a higher absolute risk.

Cardiovascular Diseases↗

PubMedDate not supplied

Changes in central corneal thickness after laser in situ keratomileusis and photorefractive keratectomy.

PURPOSE: To evaluate changes in corneal thickness after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) in eyes with the same preoperative refraction, correlate these changes to postoperative refractive outcomes, and compare corneal healing process in a standardized subset of patients. METHODS: Central corneal thickness was measured by contact ultrasound pachymetry in 14 eyes of 8 patients with preoperative myopia of -6.00 D who had LASIK, and in 14 eyes of 8 patients with the same preoperative refractive error who had PRK. Measurements were taken preoperatively, and 1 week, 3, and 6 months after surgery. Data were evaluated and compared using the paired Student t-test and Pearson correlation coefficient. RESULTS: Mean preoperative central corneal thickness in the LASIK group was 549.14 +/- 37.4 microm, and in the PRK group, 552.64 +/- 34.9 microm. At 1-week postoperatively, mean central corneal thickness in the LASIK eyes was 467.28 +/- 29 microm and in the PRK eyes, 473.85 +/- 39.2 microm; at 6 months, central corneal thickness had increased in both groups compared to the 1-week values; LASIK eyes had a mean central corneal thickness of 481.42 +/- 23.0 microm and PRK, 481.50 +/- 35.3 microm. Mean postoperative refraction after 6 months was -0.48 +/- 0.30 D in the LASIK group and -0.67 +/- 0.35 D in the PRK group. CONCLUSION: Increase in central corneal thickness between 1 week and 6 months postoperatively occurred in both LASIK and PRK eyes, but differences were not statistically significant. No statistically significant differences were found in myopic regression between the two patient groups.

Adult↗