Emerging Cardiovascular Disease Biomarkers and Incident Diabetes Mellitus Risk in Statin-Treated Patients With Coronary Artery Disease (from the Treating to New Targets [TNT] Study).

Whether biomarkers associated with cardiovascular disease risk also predict incident diabetes mellitus (DM) is unknown. Our objective was to determine if a panel of 18 biomarkers previously associated with risk of cardiovascular disease also predicts incident DM in statin-treated patients with coronary artery disease (CAD). The Treating to New Targets (TNT) study is a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of coronary heart disease events. Fasting plasma levels of standard lipids and of 18 emerging CAD risk biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg in a random sample of 1,424 TNT patients. After exclusion of patients with DM at baseline (n = 253), 101 patients developed DM during the median follow-up of 4.9 years. Patients with incident DM had lower levels of total and high-molecular weight adiponectin, lipoprotein-associated phospholipase A2 (Lp-PLA2), soluble receptor of advanced glycation end products, and vitamin D compared with patients without incident DM. In contrast, insulin, soluble CD40 ligand, and soluble intercellular adhesion molecule-1 levels were higher in patients with incident DM compared with those without. Plasma levels of C-reactive protein, cystatin C, lipoprotein(a), monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, neopterin, N-terminal fragment of pro-B-type natriuretic peptide, osteopontin, and soluble vascular cell adhesion molecule-1 were comparable in patients with and without incident DM. After multivariate adjustment, total and high-molecular weight adiponectin as well as Lp-PLA2 were negatively associated with incident DM. Results of this study suggest that plasma lipids and some emerging CAD risk biomarkers, such as adiponectin and Lp-PLA2, may be useful for predicting incident DM in statin-treated patients with stable CAD.

Relation Between Change in Renal Function and Cardiovascular Outcomes in Atorvastatin-Treated Patients (from the Treating to New Targets [TNT] Study).

Statins may have nephroprotective as well as cardioprotective effects in patients with cardiovascular disease. In the Treating to New Targets (TNT) study (NCT00327691), patients with coronary heart disease (CHD) were randomized to atorvastatin 10 or 80 mg/day and followed for 4.9 years. The relation between intrastudy change in estimated glomerular filtration rate (eGFR) from baseline and the risk of major cardiovascular events (MCVEs, defined as CHD death, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke) was assessed among 9,500 patients stratified by renal function: improving (change in eGFR more than +2 ml/min/1.73 m(2)), stable (-2 to +2 ml/min/1.73 m(2)), and worsening (less than -2 ml/min/1.73 m(2)). Compared with patients with worsening renal function (1,479 patients, 15.6%), the rate of MCVEs was 28% lower in patients with stable renal function (2,241 patients, 23.6%) (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.60 to 0.87; p = 0.0005) and 64% lower in patients with improving renal function (5,780 patients, 60.8%; HR 0.36; 95% CI 0.30 to 0.43; p <0.0001). For each 1 ml/min/1.73 m(2) increase in eGFR, the absolute reduction in the rate of MCVEs was 2.7% (HR 0.973; 95% CI 0.967 to 0.980; p <0.0001). An absolute MCVE rate reduction per 1 ml/min/1.73 m(2) increase in eGFR of 2.0% was reported with atorvastatin 10 mg and 3.3% with atorvastatin 80 mg. In conclusion, intrastudy stabilization or increase in eGFR in atorvastatin-treated patients with CHD from the TNT study was associated with a reduced rate of MCVEs. Statin-treated CHD patients with progressive renal impairment are at high risk for future cardiovascular events.

The effect of conjugated estrogens/bazedoxifene therapy on body weight of postmenopausal women: pooled analysis of five randomized, placebo-controlled trials.

OBJECTIVE: This post hoc analysis compared body weight, body mass index (BMI), and BMI category changes in postmenopausal women treated with conjugated estrogens/bazedoxifene (CE/BZA) versus placebo in the Selective Estrogens, Menopause, and Response to Therapy (SMART) trials. METHODS: Data were pooled from five randomized, double-blind, placebo- and active-controlled studies in postmenopausal women aged 40 to 75 years with a uterus given CE 0.45 mg/BZA 20 mg (n = 1,607), CE 0.625 mg/BZA 20 mg (n = 1,598), or placebo (n = 1,256) for at least 12 weeks and up to 2 years. Changes from baseline in body weight, BMI (kg/m(2)), and World Health Organization BMI category (underweight <18.5; normal 18.5 to <25; overweight 25 to <30; obese ≥30) during treatment were evaluated. RESULTS: Mean body weight increased less than 0.9 kg and mean BMI increased less than 0.4 kg/m(2) in all treatment groups at all time points. There were no statistically significant between-group differences, except for significantly greater increases in weight (P = 0.015) and BMI (P = 0.014) with placebo versus CE 0.625 mg/BZA 20 mg at month 12. Approximately, 10% of women in the CE/BZA groups and 11% in the placebo group had increases in body weight greater than 7% of baseline. The majority of BMI changes were within ±7%, and there were no statistically significant between-group differences in BMI category distributions during treatment. CONCLUSIONS: Significant increases in body weight or BMI were not observed in postmenopausal women receiving CE 0.45 mg/BZA 20 mg or CE 0.625 mg/BZA 20 mg for up to 2 years in the Selective Estrogens, Menopause, and Response to Therapy trials.

Incidence and Timing of Taper/Posttherapy-Emergent Adverse Events Following Discontinuation of Desvenlafaxine 50 mg/d in Patients With Major Depressive Disorder.

OBJECTIVE: The purpose of this post hoc analysis was to evaluate the incidence and timing of taper/posttherapy-emergent adverse events (TPAEs) following discontinuation of long-term treatment with desvenlafaxine (administered as desvenlafaxine succinate). METHOD: This was a phase 4, randomized, double-blind, placebo-controlled study conducted at 38 research centers within the United States between March 2010 and February 2011. Adult outpatients with major depressive disorder (MDD; DSM-IV-TR criteria) who completed 24 weeks of open-label treatment with desvenlafaxine 50 mg/d were randomly assigned to 1 of 3 groups for the double-blind taper phase: desvenlafaxine 50 mg/d for 4 weeks (no discontinuation), desvenlafaxine 25 mg/d for 1 week followed by placebo for 3 weeks (taper), or placebo for 4 weeks (abrupt discontinuation). The primary endpoint, Discontinuation-Emergent Signs and Symptoms Scale (DESS) score over the first 2 weeks of the taper phase, was described previously. Secondary assessments included incidence and timing of TPAEs (any adverse event that started or increased in severity during the double-blind phase) and the percentage of patients who could not continue the taper phase due to discontinuation symptoms. The Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) assessed MDD status. RESULTS: A total of 480 patients enrolled in the open-label phase; the full analysis set included 357 patients (taper, n = 139; abrupt discontinuation, n = 146; no discontinuation, n = 72). TPAEs occurred in all groups through week 4. The incidence of any TPAE was lower for taper versus abrupt discontinuation at week 1 (P < .001), similar at week 2, and lower for taper versus abrupt discontinuation at weeks 3 and 4 (P ≤ .034). The most common TPAEs (incidence ≥ 3%) in the taper group were nausea and headache (3% each) at week 1 and dizziness (5%) and headache (4%) at week 2. The most common TPAEs in the abrupt discontinuation group were dizziness (8%), headache (8%), nausea (4%), irritability (3%), and diarrhea (3%) at week 1 and headache (3%) at weeks 2 and 3. The most common TPAE in the no discontinuation group was nausea (6%) at week 2. CONCLUSION: The overall incidence of any TPAE was lower in the taper versus abrupt discontinuation groups. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01056289.

Effect of high-dose atorvastatin on renal function in subjects with stroke or transient ischemic attack in the SPARCL trial.

BACKGROUND AND PURPOSE: Higher low-density lipoprotein cholesterol is associated with more rapid chronic kidney disease progression; reduction in cholesterol with statins, in conjunction with statins' pleiotropic effects, such as decreasing inflammation, may be renoprotective. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial assessed the effect of statin treatment on the risk of nonfatal and fatal stroke in subjects with a noncardioembolic stroke or transient ischemic attack, no known coronary heart disease, and low-density lipoprotein cholesterol between 2.6 and 4.9 mmol/L (100-190 mg/dL). METHODS: We explored the effect of randomization to atorvastatin 80 mg/d or placebo on the change in estimated glomerular filtration rate (eGFR; using the 4-component Modification of Diet in Renal Disease Study equation) in SPARCL subjects (n=4731) with (eGFR, <60 mL/min per 1.73 m2; n=3119) and without (eGFR, ≥60 mL/min per 1.73 m2; n=1600) chronic kidney disease overall and by glycemic status at baseline. RESULTS: Mean baseline eGFR was similar between treatment groups (65.5±0.26 versus 65.6±0.26 mL/min per 1.73 m2 atorvastatin versus placebo; 33% versus 34% had chronic kidney disease, respectively; P=0.55). After 60 months, eGFR increased 3.46±0.33 mL/min per 1.73 m2 in those randomized to atorvastatin versus 1.42±0.34 mL/min per 1.73 m2 in those randomized to placebo (P<0.001) independent of baseline renal function. In the subgroup with diabetes mellitus at randomization, eGFR increased 1.12±0.92 mL/min per 1.73 m2 in the atorvastatin group and decreased 1.69±0.92 mL/min per 1.73 m2 in placebo group during a period of 60 months (P=0.016). CONCLUSIONS: This post hoc analysis suggests that atorvastatin treatment may improve renal function in patients with prior stroke or transient ischemic attack with and without chronic kidney disease, and that atorvastatin treatment may prevent eGFR decline in patients with stroke and diabetes mellitus. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00147602.

Menopause-specific quality of life across varying menopausal populations with conjugated estrogens/bazedoxifene.

OBJECTIVE: Describe the effects of conjugated estrogens/bazedoxifene (CE/BZA), a new treatment for vasomotor symptoms (VMS) and osteoporosis prevention, on menopause-specific quality of life (MSQOL) across different patient population types in phase 3 clinical trials. DESIGN: MSQOL was prospectively evaluated in 4 randomized, double-blind, placebo-controlled studies. The populations studied included healthy, non-hysterectomized postmenopausal women with symptomatic VMS or vulvar-vaginal atrophy (VVA) and general postmenopausal women (eligible regardless of symptoms). Menopause-specific Quality of Life (MENQOL) questionnaire total and domain scores for CE 0.625 mg/BZA 20mg and CE 0.45 mg/BZA 20mg were evaluated and compared with established thresholds for clinically important differences (CID). RESULTS: Significant improvements compared with placebo were found with both CE/BZA doses in MENQOL vasomotor domain (-0.61 to -2.23 over 3-24 months) and total scores (-0.24 to -0.94) in the general and symptomatic VMS/VVA populations. Significant improvement compared with placebo in sexual domain (-0.11 to -0.72) was observed with the higher dosage for all populations, and with the lower dosage in the VVA (-0.71 at month 3) and general populations (-0.4 at months 12 and 24). Improvements in vasomotor domain exceeded the CID with both doses in symptomatic VMS populations and with the higher dosage in women with symptomatic VVA; for total MENQOL, the CID was exceeded with the higher dose in symptomatic VMS populations. CONCLUSIONS: CE/BZA significantly improved overall and vasomotor-related MSQOL across populations of postmenopausal women with varying baseline symptom statuses. Women with greater menopausal symptoms at baseline were more likely to experience clinically meaningful changes.

Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study.

OBJECTIVE: Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design. RESEARCH DESIGN AND METHODS: This multicenter study included 6 week single-blind pregabalin CR treatment followed by 13 week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330-495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as <30% pain reduction relative to single-blind baseline or discontinuation owing to lack of efficacy or adverse event (AE). Secondary endpoints included measures of pain severity, global assessment, functional status, tiredness/fatigue, and sleep. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01271933. RESULTS: A total of 441 patients entered the single-blind phase, and 63 were randomized to pregabalin CR and 58 to placebo. The median time to LTR (Kaplan-Meier analysis) was significantly longer in the pregabalin CR group than placebo (58 vs. 22 days, p = 0.02). By trial end, 34/63 (54.0%) pregabalin CR and 41/58 (70.7%) placebo patients experienced LTR. Significantly more patients reported 'benefit from treatment' (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant. Most AEs were mild to moderate in severity (most frequent: dizziness, somnolence). The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%). CONCLUSIONS: Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response. Pregabalin CR was well tolerated in most patients. Generalizability may be limited by study duration and selective population.

Abrupt discontinuation compared with a 1-week taper regimen in depressed outpatients treated for 24 weeks with desvenlafaxine 50 mg/d.

The objective of this study was to determine whether the occurrence of discontinuation symptoms was equivalent for abrupt discontinuation versus 1-week taper to desvenlafaxine 25 mg/d after a 24-week treatment with desvenlafaxine 50 mg/d (administered as desvenlafaxine succinate) for major depressive disorder. Adult outpatients with major depressive disorder who completed the 24 weeks of open-label treatment with desvenlafaxine 50 mg/d were randomly assigned to no discontinuation (desvenlafaxine 50 mg/d), taper (desvenlafaxine 25 mg/d), or abrupt discontinuation (placebo) groups for the double-blind (DB) taper phase. The primary end point was Discontinuation-Emergent Signs and Symptoms (DESS) scale total score during the first 2 weeks of the DB phase. The null hypothesis that the absolute difference of greater than 2.5 in DESS scores between taper and abrupt discontinuation groups was tested by calculating the 95% 2-sided confidence interval on the mean difference between the 2 groups. Of the 480 patients enrolled in the open-label phase, 357 (≥1 postrandomization DESS record) were included in the primary analysis. Adjusted mean ± SE DESS scores were 4.1 ± 0.72 for no discontinuation (n = 72), 4.8 ± 0.54 for taper (n = 139), and 5.3 ± 0.52 for abrupt discontinuation (n = 146) groups. The difference in adjusted mean DESS total scores between the abrupt discontinuation and taper groups was 0.50 (95% confidence interval, -0.88 to 1.89) within the prespecified margin (±2.5) for equivalence. The number of patients who discontinued because of adverse events or discontinuation symptoms during the DB period was similar between the taper (2.8%) and abrupt discontinuation (2.1%) groups. These findings indicate that an abrupt discontinuation of desvenlafaxine 50 mg/d produces statistically equivalent DESS scores compared with the 1-week taper using 25 mg/d.

Prediction of major vascular events after stroke: the stroke prevention by aggressive reduction in cholesterol levels trial.

BACKGROUND: Identifying patients with recent stroke or transient ischemic attack (TIA) at high risk of major vascular events (MVEs; stroke, myocardial infarction, or vascular death) may help optimize the intensity of secondary preventive interventions. We evaluated the relationships between the baseline Framingham Coronary Risk Score (FCRS) and a novel risk prediction model and with the occurrence of MVEs after stroke or TIA in subjects enrolled in the Stroke Prevention by Aggressive Reduction in Cholesterol Level (SPARCL) trial. METHODS: Data from the 4731 subjects enrolled in the SPARCL study were analyzed. Hazard ratios (HRs) from Cox regression models were used to determine the risk of subsequent MVEs based on the FCRS predicting 20% or more 10-year coronary heart disease risk. The novel risk model was derived based on multivariable modeling with backward selection. Model discrimination (c-statistics) was assessed using the areas under the receiver operating characteristic curves. RESULTS: Of 3969 subjects with complete data, 27% had a baseline FCRS of 20% or more. In multivariable analysis, an FCRS of 20% or more was associated with twice the risk of subsequent MVEs (HR = 1.92, 95% confidence interval [CI]: 1.63-2.27). The novel model based on a multivariable analysis included age (HR = 1.37, 95% CI: 1.25-1.51 per 10 years), diabetes (HR = 1.82, 95% CI: 1.51-2.18), male sex (HR = 1.35, 95% CI: 1.12-1.61), and an apolipoprotein (APO)-B/APO-A1 ratio (HR = 1.56, 95% CI: 1.16-2.11). The c-statistic was .58 (95% CI: .55-.60) for the FCRS of 20% or more and .65 (95% CI: .63-.67) for the novel model. CONCLUSIONS: Both a baseline FCRS of 20% or more and a novel predictive model were associated with future MVEs in SPARCL trial subjects. The novel model needs to be validated, and the benefits of using either the FCRS or the novel model in clinical practice needs to be assessed.

Effect of change in body weight on incident diabetes mellitus in patients with stable coronary artery disease treated with atorvastatin (from the treating to new targets study).

Features of the metabolic syndrome are independent risk factors for new-onset diabetes mellitus (NODM) related to statin therapy. Obesity is the predominant underlying risk factor for the metabolic syndrome and diabetes mellitus. This study investigated whether change in body weight may predict NODM in statin-treated patients. A total of 7,595 patients without prevalent diabetes mellitus at baseline from the Treating to New Targets (TNT) study were included in this analysis. They were randomized to atorvastatin 10 or 80 mg/day and monitored for a median of 4.9 years. NODM developed in 659 patients (8.1% in the 10-mg group and 9.2% in the 80-mg group). There was a significant increase in body weight (0.9 kg, p <0.01 in both men and women) over 1 year after randomization. The increase in body weight was greater in patients with NODM than those without NODM (1.6 vs 0.9 kg, p <0.001). The association of change in body weight with NODM risk remained significant after adjusting for confounding factors (hazard ratios 1.33, 1.42, and 1.88 for quartiles 2, 3, and 4 compared with quartile 1, respectively). Similar results were obtained in patients with normal fasting glucose level. In conclusion, 1-year change in body weight is predictive of NODM in patients who underwent statin therapy from the TNT trial. Our study highlights the importance of weight control as a lifestyle measure to prevent statin-related NODM.

Association of deferring a quit attempt with smoking cessation success: a secondary analysis.

Several smoking cessation treatments ask smokers to wait to quit to obtain treatment. We report a secondary analysis of whether a later quit attempt is associated with less success. In a placebo-controlled trial of varenicline that allowed smokers to set their quit date within 5 weeks after starting medication, 24% had their first quit attempt during week 1, and 27%, 19%, 18% and 12% in subsequent weeks. Continuous abstinence between 9 and 24 weeks declined over time; that is, from 36% to 37%, 35%, 29%, and 18% across the 5 weeks (p<0.001). The only statistically significant difference was between the last week and prior weeks. Whether a later quit attempt actually causes less success or is a marker for other variables (e.g., low motivation) is unclear.

Pregabalin in patients with inadequately treated painful diabetic peripheral neuropathy: a randomized withdrawal trial.

OBJECTIVES: This study used a randomized withdrawal design to evaluate the efficacy of pregabalin versus placebo for pain relief in patients with painful diabetic peripheral neuropathy inadequately treated by other therapies. METHODS: A total of 665 patients received pregabalin in a 6-week single-blind phase. Two hundred ninety-four patients who achieved a ≥ 30% pain response were randomized to receive pregabalin or placebo in a double-blind phase for a further 13 weeks. The primary endpoint was the change in mean pain score from single-blind baseline to double-blind endpoint for pregabalin versus placebo (last observation carried forward [LOCF]). Secondary endpoints included a baseline observation carried forward (BOCF) analysis of mean pain score; time to loss of pain response; and other assessments of pain, sleep, function, and quality of life (QOL). RESULTS: Pregabalin numerically improved all measures assessed during the single-blind phase. At the end of the double-blind withdrawal phase, there was no significant difference in the primary endpoint of mean pain score (LOCF) between pregabalin and placebo (least squares mean difference, -0.32), although there was a significant difference in the BOCF analysis (least squares mean difference, -0.51). Pregabalin was associated with a significantly longer time to loss of pain response versus placebo during double-blind treatment, and some aspects of sleep and QOL also showed significant improvements with pregabalin. DISCUSSION: This is the first reported placebo-controlled trial of pregabalin in patients with inadequately treated painful diabetic peripheral neuropathy. Although the primary endpoint was not met, pregabalin was associated with clinically relevant improvements versus placebo in this difficult-to-treat population.

Incidence, determinants, and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF).

BACKGROUND: Mineralocorticoid receptor antagonists improve outcomes in patients with systolic heart failure but may induce worsening of renal function (WRF) and hyperkalemia (HK). We assessed the risk factors for mineralocorticoid receptor antagonist-related WRF and for HK, as well as the association between HK and WRF with clinical outcomes in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). METHODS AND RESULTS: Serial changes in estimated glomerular filtration rate and in serum potassium were available in 2737 patients during a median 21-month follow-up. HK variably defined as serum K>4.5, 5, or 5.5 mmol/L occurred in 74.7%, 32.5%, and 8.9% patients enrolled in EMPHASIS-HF, respectively. WRF defined as a decrease in estimated glomerular filtration rate>20% or >30% from baseline occurred in 27% and 14% of patients, respectively. Patients assigned eplerenone displayed modest and early but significant and persistent (1) rise in serum potassium and (2) reduction in estimated glomerular filtration rate when compared with those assigned placebo. In multivariate analyses, eplerenone was associated with a higher incidence of WRF and HK, which were interrelated and also associated with baseline patient characteristics (eg, age≥75 years, hypertension, diabetes mellitus, nonwhite race, ejection fraction<30%, and treatment with an antiarrythmics drug or loop diuretic). Eplerenone retained its survival benefits without any significant interaction with the association between HK>5.5 mmol/L only and WRF and worse outcomes. CONCLUSIONS: In patients with heart failure receiving optimal therapy, WRF and HK were more frequent when eplerenone was added, but their occurrence did not eliminate the survival benefit of eplerenone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.

Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes.

OBJECTIVES: The purpose of this study was to compare the incidence of new-onset diabetes (NOD) with cardiovascular (CV) event reduction at different levels of NOD risk. BACKGROUND: Statins reduce the number of CV events but increase the incidence of NOD. We previously reported that 4 factors independently predicted NOD: fasting blood glucose >100 mg/dl, fasting triglycerides >150 mg/dl, body mass index >30 kg/m(2), and history of hypertension. METHODS: We compared NOD incidence with CV event reduction among 15,056 patients with coronary disease but without diabetes at baseline in the TNT (Treating to New Targets) (n = 7,595) and IDEAL (Incremental Decrease in Endpoints Through Aggressive Lipid Lowering) (n = 7,461) trials. CV events included coronary heart disease death, myocardial infarction, stroke, and resuscitated cardiac arrest. RESULTS: Among 8,825 patients with 0 to 1 of the aforementioned NOD risk factors at baseline, NOD developed in 142 of 4,407 patients in the atorvastatin 80 mg group and in 148 of 4,418 in the atorvastatin 10 mg and simvastatin 20 to 40 mg groups (3.22% vs. 3.35%; hazard ratio [HR]: 0.97; 95% confidence intervals [CI]: 0.77 to 1.22). Among the remaining 6,231 patients with 2 to 4 NOD risk factors, NOD developed in 448 of 3,128 in the atorvastatin 80 mg group and in 368 of 3,103 in the lower-dose groups (14.3% vs. 11.9%; HR: 1.24; 95% CI: 1.08 to 1.42; p = 0.0027). The number of CV events was significantly reduced with atorvastatin 80 mg in both NOD risk groups. CONCLUSIONS: Compared with lower-dose statin therapy, atorvastatin 80 mg/day did not increase the incidence of NOD in patients with 0 to 1 NOD risk factors but did, by 24%, among patients with 2 to 4 NOD risk factors. The number of CV events was significantly reduced with atorvastatin 80 mg in both NOD risk groups.

Vitamin D levels do not predict cardiovascular events in statin-treated patients with stable coronary disease.

BACKGROUND: This post hoc nested case-control analysis of the TNT study was designed to investigate whether baseline vitamin D level is a significant predictor of cardiovascular risk among statin-treated patients and whether changes in vitamin D after treatment with atorvastatin are associated with improved cardiovascular outcomes. METHODS: A total of 10,001 patients with stable coronary heart disease were randomized to atorvastatin 80 or 10 mg for a median of 4.9 years. This analysis included 1,509 patients (497 with a subsequent cardiovascular event and 1,012 without an event) with vitamin D levels determined at baseline and 1 year. Event rates were analyzed by Cox proportional hazard model by baseline vitamin D levels, with vitamin D as a continuous variable, and with change in vitamin D level as the predictor. RESULTS: Vitamin D deficiency (<15 ng/mL) or insufficiency (15- <30 ng/mL) was present in 108 (7.2%) of 1,509 and 625 (41.4%) of 1,509 of patients, whereas 46 (3.0%) of 1,509 had elevated vitamin D. There was no relationship between baseline vitamin D levels or change in vitamin D levels and cardiovascular events or mortality. Modeling of events with vitamin D as a continuous variable similarly showed no relationship of vitamin D to events. These findings held true after adjustment for seasonal variations in vitamin D and other confounders. CONCLUSION: In statin-treated patients with stable coronary heart disease, vitamin D levels did not predict cardiovascular risk. Changes in plasma concentrations of vitamin D after 1 year of treatment made no contribution to the efficacy of atorvastatin therapy.

A comparison of non-HDL and LDL cholesterol goal attainment in a large, multinational patient population: the Lipid Treatment Assessment Project 2.

OBJECTIVE: This study evaluated the success in attaining non-HDL-cholesterol (non-HDL-C) goals in the multinational L-TAP 2 study. METHODS: 9955 patients ≥20 years of age with dyslipidemia on stable lipid-lowering therapy were enrolled from nine countries. RESULTS: Success rates for non-HDL-C goals were 86% in low, 70% in moderate, and 52% in high-risk patients (63% overall). In patients with triglycerides of >200 mg/dL success rates for non-HDL-C goals were 35% vs. 69% in those with ≤200 mg/dL (p < 0.0001). Among patients attaining their LDL-C goal, 18% did not attain their non-HDL-C goal. In those with coronary disease and at least two risk factors, only 34% and 30% attained respectively their non-HDL-C and LDL-C goals. Rates of failure in attaining both LDL-C and non-HDL-C goals were highest in Latin America. CONCLUSIONS: Non-HDL-C goal attainment lagged behind LDL-C goal attainment; this gap was greatest in higher-risk patients.

Comparison of lipid profiles and attainment of lipid goals in patients <65 years versus patients ≥65 years (from the Lipid Treatment Assessment Project [L-TAP] 2).

There is a well-established link between dyslipidemia and cardiovascular events, although this risk is modified by age. Little is known about how treatment of dyslipidemia and low-density lipoprotein (LDL) cholesterol goal attainment differ between older and younger patients. We obtained clinical data from 9,926 dyslipidemic patients across 9 countries in North and Latin America, Europe, and Asia from 2006 through 2007. Multivariate regressions were performed to determine predictors of lipid level goal attainment. The study sample consisted of 5,733 adults <65 and 4,193 adults ≥65 years old. Compared with younger patients, older patients were more likely to have diabetes (32.5% vs 30.0%, p = 0.0014) and hypertension (73.4% vs 57.0%, p <0.0001), to be classified as high risk (68.6% vs 53.2%, p <0.0001), and to be taking a statin (79.1% vs 72.0%, p <0.0001). However, they were less likely to smoke (8.2% vs 17.6%, p <0.0001) or to have metabolic syndrome (29.0% vs 34.4%, p <0.0001). Older patients had lower LDL cholesterol levels (95.1 vs 103.9 mg/dl, p <0.0001) and higher levels of high-density lipoprotein cholesterol (54.2 vs 51.5 mg/dl, p <0.0001). LDL cholesterol goal attainment was 74.7% in older and 71.1% in younger patients (p = 0.036). Older patients were more likely to achieve LDL targets whether low risk (89.8% vs 84.6%, p = 0.002), moderate risk (79.0% vs 71.9%, p = 0.0006), or high risk (70.5% vs 64.4%, p <0.0001). In conclusion, older patients had different risk profiles and better lipid levels compared with their younger counterparts. They were more likely to attain their LDL cholesterol goal, perhaps because of greater statin use, different risk profiles, or survival bias.

Varenicline as a smoking cessation aid in a Greek population: a subanalysis of an observational study.

BACKGROUND: Greece has the highest proportion of smokers in the European Union with 42% of Greeks admitting that they smoke, based on a 2009 survey. This post-hoc analysis of a prospective, observational study evaluated the effectiveness and safety profile of the smoking cessation aid varenicline, as well as potential predictors of quit success in a Greek population. METHODS: Participants were prescribed varenicline according to the recommendations of the European Summary of Product Characteristics (1 mg twice daily). The 7-day point prevalence of abstinence at Week 12 was determined based on verbal reporting using a nicotine use inventory. Abstinence was confirmed by carbon monoxide measurements of exhaled air at the last visit of the study. The safety profile of varenicline was also assessed. RESULTS: At baseline, the Greek subsample (n = 196) had a mean age of 42.6 years, with 54.6% of them being men. Participants had a smoking history of 23.5 years and a Fagerström Test for Nicotine Dependence total score of 6.6. After 12 weeks of varenicline therapy, 70.4% (95% CI, 64.0-76.7) of all participants had quit smoking. This increased to 86.2% among participants who had taken the study medication for 80% of the planned number of treatment days. Age was a significant predictor of quit success. The most frequently observed treatment-emergent adverse event was nausea, occurring in 13.3% of participants. CONCLUSIONS: In this 'real-world' observational study, 70.4% of Greek smokers successfully quit smoking after 12 weeks of varenicline therapy, providing support that varenicline is an effective smoking cessation medication. Further studies with longer follow-up are warranted. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00669240.