Effectiveness of papain gel in venous ulcer treatment: randomized clinical trial

OBJECTIVE:

to assess the effectiveness of 2% papain gel compared to 2% carboxymethyl cellulose in the treatment of chronic venous ulcer patients.

METHOD:

randomized controlled clinical trial with 12-week follow-up. The sample consisted of 18 volunteers and 28 venous ulcers. In the trial group, 2% papain gel was used and, in the control group, 2% carboxymethyl cellulose gel.

RESULTS:

the trial group showed a significant reduction in the lesion area, especially between the fifth and twelfth week of treatment, with two healed ulcers and a considerable increase in the amount of epithelial tissue in the wound bed.

CONCLUSION:

2% papain gel demonstrated greater effectiveness in the reduction of the lesion area, but was similar to 2% carboxymethyl cellulose gel regarding the reduction in the amount of exudate and devitalized tissue. Multicenter research is suggested to evidence the effectiveness of 2% papain gel in the healing of venous ulcers. UTN number: U1111-1157-2998     

Effect of Hominis Placenta on cutaneous wound healing in normal and diabetic mice

BACKGROUND/OBJECTIVES

The number of diabetic patients has recently shown a rapid increase, and delayed wound healing is a major clinical complication in diabetes. In this study, the wound healing effect of Hominis placenta (HP) treatment was investigated in normal and streptozotocin-induced diabetic mice.

MATERIALS/METHODS

Four full thickness wounds were created using a 4 mm biopsy punch on the dorsum. HP was injected subcutaneously at the middle region of the upper and lower wounds. Wounds were digitally photographed and wound size was measured every other day until the 14th day. Wound closure rate was analyzed using CANVAS 7SE software. Wound tissues were collected on days 2, 6, and 14 after wounding for H/E, immunohistochemistry for FGF2, and Masson''s trichrome staining for collagen study.

RESULTS

Significantly faster wound closure rates were observed in the HP treated group than in normal and diabetes control mice on days 6 and 8. Treatment with HP resulted in reduced localization of inflammatory cells in wounded skin at day 6 in normal mice and at day 14 in diabetic mice (P < 0.01). Expression of fibroblast growth factor (FGF) 2 showed a significant increase in the HP treated group on day 14 in both normal (P < 0.01) and diabetic mice (P < 0.05). In addition, HP treated groups showed a thicker collagen layer than no treatment groups, which was remarkable on the last day, day 14, in both normal and diabetic mice.

CONCLUSIONS

Taken together, HP treatment has a beneficial effect on acceleration of cutaneous wound healing via regulation of the entire wound healing process, including inflammation, proliferation, and remodeling.     

Higher persistence with valsartan compared with enalapril in daily practice

Objective

To compare persistence with valsartan and enalapril in daily practice.

Methods

The PHARMO Record Linkage System includes various data registries including drug dispensing and hospitalizations for ≥2 million subjects in the Netherlands. Patients newly treated with valsartan or enalapril in the period of 1999–2002 were selected. Persistence was calculated by summing up the number of days of continuous treatment. Patients who remained on therapy with valsartan or enalapril for 12 or 24 months were defined as persistent at 1 or 2 years, respectively.

Results

3364 patients received valsartan and 9103 patients received enalapril. About 62% of patients treated with valsartan and 55% of patients treated with enalapril remained on therapy at 12 months after the initial dispensing, while 48% of patients treated with valsartan and 43% of patients treated with enalapril were persistent at 24 months. Patients treated with valsartan were about 20% more likely to stay on treatment than patients treated with enalapril (1 year RR_adj: 1.23, 95% CI: 1.16–1.32; 2 years RR_adj: 1.16, 95% CI: 1.11–1.23).

Conclusions

Real-life persistence is higher with valsartan than with enalapril. The results of this and other studies on persistence in daily practice should be taken into account when deciding upon drug treatment for hypertension.     

Determinants of outcome in patients eligible for thrombolysis for ischemic stroke

Objectives

Eligibility criteria for thrombolysis in ischemic stroke have been clearly defined. However, not all eligible patients benefit from this treatment. This study aimed to assess the determinants for clinical outcome in consecutive, eligible patients with ischemic stroke treated with thrombolysis in a single-center study.

Methods

Consecutive patients with ischemic stroke were treated with tissue plasminogen activator (t-PA) following the established eligibility National Institute of Neurological Disorders and Stroke (NINDS) and European Stroke Initiative (EUSI) criteria. Risk factors including blood pressure and pre-treatment glycemia were properly managed. Death and disability at 3 months were the study outcomes. Disability was evaluated by the Rankin-scale. Favorable outcome was defined as 0–2 and adverse outcome as 3–6 including death.

Results

Seventy-eight patients were included in the study in a single stroke unit. The mean age was 70.9 ± 13.2 years (range 36–94). Follow-up at 3 months was completed in 73 patients. A favorable outcome was observed in 37 patients (50%) and adverse outcome in 36 (36%). Nine patients (12.3%) died within 3 months. The presence of an occluded carotid artery was a strong predictor for adverse outcome (p < 0.0001). A low NIH Stroke Scale-Score (NIHSS) at admission was a associated with a favorable outcome, while history of diabetes mellitus led to an unfavorable outcome.

Conclusion

Among patients eligible for thrombolysis, many do not benefit from this treatment. These include patients with carotid occlusion and diabetes.     

Effect of candesartan cilexetil on diabetic and non-diabetic hypertensive patients: meta-analysis of five randomized double-blind clinical trials

Objective

To study the effect of candesartan cilexetil (CC) in the management of blood pressure (BP) in diabetic and non-diabetic hypertensive patients.

Methods

A selection of five randomized double-blind clinical trials in which patients were treated for hypertension with CC was analyzed. All of these were similar in design: i) a 4-week placebo run-in period, ii) a 4-to 6-week period (V1) with CC 8 mg once daily (od), after which the dosage was doubled if BP was not normalized (BP >140/90 or BP >130/80 mmHg in diabetes), and iii) a 4- to 6-week period (V2) with CC 8 or 16 mg od. Efficacy was measured at V1 and V2.

Results

702 patients were screened. The population consisted of 397 males (56.6%) with a mean age of 60 ± 11 years, with 153 diabetic (21.8%) and 549 non-diabetic (78.2%) patients. At baseline, mean BP values were 160/94/65 mmHg for SPB, DBP, and pulse pressure (PP) respectively, with differences between diabetic and non-diabetic patients. SBP, DBP, and PP values showed a significant reduction at V1 (p < 0.001) and V2 (p < 0.001) compared with baseline for all hypertensive patients. Mean changes at V2 in SBP and PP values were higher in diabetic than non-diabetic patients (p < 0.001), and to a lesser degree on DBP values (p = 0.034).

Conclusions

CC was effective in lowering BP in diabetic and non-diabetic hypertensive patients. CC is a promising therapy to manage hypertensive diabetic patients, as demonstrated by the significant BP reduction.

Short abstract

The effect of candesartan cilexetil (CC) on controlling blood pressure (BP) in hypertensive diabetic and non-diabetic patients was analyzed. Five randomized double-blind trials were pooled treating hypertension by CC (n = 702), including 153 diabetic (21.8%) and 549 non-diabetic (78.2%) patients. After treatment with CC (8–16 mg), significant reductions in SBP, DBP, and pulse pressure (PP) values were observed after 4–6 weeks (p < 0.001) and after 8–12 weeks (p < 0.001) compared with baseline for all hypertensive patients. Mean BP reductions after 8–12 weeks were higher in diabetic patients than non-diabetic (p < 0.001). CC is a promising therapy to treat hypertensive patients, both diabetic and non-diabetic.     

Weekend hospitalization and additional risk of death: an analysis of inpatient data

Objective

To assess whether weekend admissions to hospital and/or already being an inpatient on weekend days were associated with any additional mortality risk.

Design

Retrospective observational survivorship study. We analysed all admissions to the English National Health Service (NHS) during the financial year 2009/10, following up all patients for 30 days after admission and accounting for risk of death associated with diagnosis, co-morbidities, admission history, age, sex, ethnicity, deprivation, seasonality, day of admission and hospital trust, including day of death as a time dependent covariate. The principal analysis was based on time to in-hospital death.

Participants

National Health Service Hospitals in England.

Main Outcome Measures

30 day mortality (in or out of hospital).

Results

There were 14,217,640 admissions included in the principal analysis, with 187,337 in-hospital deaths reported within 30 days of admission. Admission on weekend days was associated with a considerable increase in risk of subsequent death compared with admission on weekdays, hazard ratio for Sunday versus Wednesday 1.16 (95% CI 1.14 to 1.18; P < .0001), and for Saturday versus Wednesday 1.11 (95% CI 1.09 to 1.13; P < .0001). Hospital stays on weekend days were associated with a lower risk of death than midweek days, hazard ratio for being in hospital on Sunday versus Wednesday 0.92 (95% CI 0.91 to 0.94; P < .0001), and for Saturday versus Wednesday 0.95 (95% CI 0.93 to 0.96; P < .0001). Similar findings were observed on a smaller US data set.

Conclusions

Admission at the weekend is associated with increased risk of subsequent death within 30 days of admission. The likelihood of death actually occurring is less on a weekend day than on a mid-week day.     

Compliance, clinical outcome, and quality of life of patients with stable angina pectoris receiving once-daily betaxolol versus twice daily metoprolol: a randomized controlled trial

Background

A randomized, controlled trial was conducted in an outpatient setting to examine the effect of beta-blocker dosing frequency on patient compliance, clinical outcome, and health-related quality of life in patients with stable angina pectoris.

Methods

One hundred and twelve beta-blockers-naive outpatients with stable angina pectoris were randomized to receive betaxolol, 20 mg once daily or metoprolol tartrate, 50 mg twice daily for 8 weeks. The principal outcome measure was overall compliance measured electronically, whereas secondary outcome measures were drug effectiveness and health-related quality of life.

Results

The overall compliance was 86.5 ± 21.3% in the betaxolol group versus 76.1 ± 26.3% in the metoprolol group (p < 0.01), and the correct number of doses was taken on 84.4 ± 21.6% and 64.0 ± 31.7% of treatment days, respectively (p < 0.0001). The percentage of missed doses was 14.5 ± 21.5% in the once-daily group and 24.8 ± 26.4% in the twice-daily group (p < 0.01). The percentage of doses taken in the correct time window (58.6% vs 42.0%, p = 0.01), correct interdose intervals (77.4% v 53.1%, p < 0.0001), and therapeutic coverage (85.6% vs 73.7%, p < 0.001) were significantly higher in the once-daily group. Both studied drugs had similar antianginal effectiveness. Health-related quality of life improved in both groups, but this increase was more pronounced in the betaxolol arm in some dimensions.

Conclusions

The study demonstrates that patient compliance with once-daily betaxolol is significantly better than with twice daily metoprolol. Similarly, this treatment provides better quality of life. These results demonstrate possible therapeutic advantages of once-daily over twice-daily beta-blockers in the treatment of stable angina pectoris.     

Traditional male circumcision in eastern and southern Africa: a systematic review of prevalence and complications

Objective

To systematically review studies on the prevalence and complications of traditional male circumcision (i.e. circumcision by a traditional provider with no formal medical training), whose coverage and safety are unclear.

Methods

We systematically searched databases and reports for studies on the prevalence and complications of traditional male circumcision in youth 10–24 years of age in eastern and southern Africa, and also determined the ages at which traditional circumcision is most frequently performed.

Findings

Six studies reported the prevalence of traditional male circumcision, which had been practised in 25–90% of all circumcised male study participants. Most circumcisions were performed in boys 13–20 years of age. Only two of the six studies on complications reported overall complication rates (35% and 48%) following traditional male circumcision. The most common complications were infection, incomplete circumcision requiring re-circumcision and delayed wound healing. Infection was the most frequent cause of hospitalization. Mortality related to traditional male circumcision was 0.2%.

Conclusion

Published studies on traditional male circumcision in eastern and southern Africa are limited; thus, it is not possible to accurately assess the prevalence of complications following the procedure or the impact of different traditional practices on subsequent adverse events. Also, differences in research methods and the absence of a standard reporting format for complications make it difficult to compare studies. Research into traditional male circumcision procedures, practices and complication rates using standardized reporting formats is needed.     

Eliminating the category II retreatment regimen from national tuberculosis programme guidelines: the Georgian experience

Problem

The category II retreatment regimen for management of tuberculosis in previously treated patients was first introduced in the early 1990s. It consists of 8 months of total therapy with the addition of streptomycin to standard first-line medications. A review of 6500 patients on category II therapy in Georgia showed poor outcomes and high rates of streptomycin resistance.

Approach

The National Tuberculosis Program used an evidence-based analysis of national data to convince policy-makers that category II therapy should be eliminated from national guidelines in Georgia.

Local setting

The World Health Organization tuberculosis case-notification rate in Georgia is 102 per 100 000 population. All patients receive culture and drug susceptibility testing as a standard part of tuberculosis diagnosis. In 2009, routine surveillance found multidrug-resistant tuberculosis in 10.6% of newly diagnosed patients and 32.5% of previously treated cases.

Relevant changes

Category II retreatment regimen is no longer used in Georgia. Treatment is guided by results of drug susceptibility testing – using rapid, molecular tests where possible – for all previously treated tuberculosis patients.

Lessons learnt

There was little resistance to policy change because the review was initiated and led by the National Tuberculosis Program. This experience can serve as a successful model for other countries to make informed decisions about the use of category II therapy.     

Surveillance of anti-tuberculosis drug resistance in the world: an updated analysis, 2007-2010

Objective

To present a global update of drug-resistant tuberculosis (TB) and explore trends in 1994–2010.

Methods

Data on drug resistance among new and previously treated TB patients, as reported by countries to the World Health Organization, were analysed. Such data are collected through surveys of a representative sample of TB patients or surveillance systems based on routine drug susceptibility testing. Associations between multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection and sex were explored through logistic regression.

Findings

In 2007–2010, 80 countries and 8 territories reported surveillance data. MDR-TB among new and previously treated cases was highest in the Russian Federation (Murmansk oblast, 28.9%) and the Republic of Moldova (65.1%), respectively. In three former Soviet Union countries and South Africa, more than 10% of the cases of MDR-TB were extensively drug-resistant. Globally, in 1994 to 2010 multidrug resistance was observed in 3.4% (95% confidence interval, CI: 1.9–5.0) of all new TB cases and in 19.8% (95% CI: 14.4–25.1) of previously treated TB cases. No overall associations between MDR-TB and HIV infection (odds ratio, OR: 1.4; 95% CI: 0.7–3.0) or sex (OR: 1.1; 95% CI: 0.8–1.4) were found. Between 1994 and 2010, MDR-TB rates in the general population increased in Botswana, Peru, the Republic of Korea and declined in Estonia, Latvia and the United States of America.

Conclusion

The highest global rates of MDR-TB ever reported were documented in 2009 and 2010. Trends in MDR-TB are still unclear in most settings. Better surveillance or survey data are required, especially from Africa and India.     

Influence of albuminuria and glomerular filtration rate on blood pressure response to antihypertensive drug therapy

Background

Albuminuria and glomerular filtration rate (GFR), two factors linked to kidney and vascular function, may influence longitudinal blood pressure (BP) responses to complex antihypertensive drug regimens.

Methods

We reviewed the clinic records of 459 patients with hypertension in an urban, academic practice.

Results

Mean patient age was 57-years, 89% of patients were African American, and 69% were women. Mean patient systolic/diastolic BP (SBP/DBP) at baseline was 171/98 mmHg while taking an average of 3.3 antihypertensive medications. At baseline, 27% of patients had estimated (e)GFR <60 ml/min/1.73², 28% had micro-albuminuria (30–300 mg/g) and 16% had macro-albuminuria (>300 mg/g). The average longitudinal BP decline over the observation period (mean 7.2 visits) was 25/12 mmHg. In adjusted regression models, macro-albuminuria predicted a 10.3 mmHg lesser longitudinal SBP reduction (p < 0.001) and a 7.9 mmHg lesser longitudinal DBP reduction (p < 0.001); similarly eGFR <60 ml/min/1.73² predicted an 8.4 mmHg lesser longitudinal SBP reduction (p < 0.001) and a 4.5 lesser longitudinal DBP reduction (p < 0.001). Presence of either micro- or macro-albuminuria, or lower eGFR, also significantly delayed the time to attainment of goal BP.

Conclusions

These data suggest that an attenuated decline in BP in drug-treated hypertensives, resulting in higher average BP levels over the long-term, may mediate a portion of the increased risk of cardiovascular-renal disease linked to elevated urinary albumin excretion and reduced eGFR.     

Effects of early treatment with zofenopril in patients with myocardial infarction and metabolic syndrome: the SMILE Study

Objective

To evaluate the clinical efficacy of the early administration of zofenopril in a group of patients with and without metabolic syndrome (MS+ and MS−) and anterior myocardial infarction enrolled in the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study.

Methods

Patients were randomized double-blind to zofenopril (n = 719) or placebo (n = 699) for 6 weeks. The primary end point was the effect of treatment on the 6-week combined occurrence of death and severe congestive heart failure. The secondary end point was the 1-year mortality rate.

Results

Of the 1418 patients included in this post-hoc analysis, 686 (48.3%) had MS. After 6 weeks of treatment zofenopril significantly reduced the incidence of all-cause death and severe congestive failure (risk reduction: 69%, 95% CI: 7–78; 2p = 0.002) in MS+ patients. This was the case for 1-year mortality, too (29%, 95% CI: 4–41; 2p = 0.048). Zofenopril was effective also in MS− patients but the amount of relative risk reduction was less than in MS+ for both the primary (−11%; 2p = 0.61) and secondary endpoint (−19%; 2p = 0.025).

Conclusions

Results of this post-hoc analysis of the SMILE Study demonstrate the striking benefit of early administration of zofenopril in MS+ patients with acute anterior myocardial infarction.     

Shift work increases the frequency of duodenal ulcer in H pylori infected workers

Aim

To evaluate whether shift work is associated with an increased rate of peptic ulcer in H pylori infected workers.

Methods

During a two year period, consecutive dyspeptic workers underwent non‐invasive evaluation of H pylori status by means of urea ¹³C breath test or stool testing. Those testing positive were included in the study and divided into two main categories: day‐time workers and shift workers. An upper gastrointestinal endoscopy was performed in all workers, and biopsy specimens were taken from the stomach to confirm the presence of H pylori infection (culture and histology).

Results

A total of 247 day‐time workers and 101 shift workers were included. The prevalence of duodenal ulcer was significantly higher in shift workers than in day‐time workers (29 of 101 v 23 of 247; OR = 3.92, 95% CI 2.13 to 7.21), and persisted after multivariate analysis, taking into account possible confounding factors (OR = 3.96, 95% CI 2.10 to 7.47).

Conclusion

Shift work increases the ulcerogenic potential of H pylori infection and should be considered a risk factor for duodenal ulcer in infected shift workers. Treatment of infection in this high risk group may improve the health of workers and may reduce the economic impact of peptic ulcer.     

Early seizures in patients with acute stroke: frequency, predictive factors, and effect on clinical outcome

Background

Early seizure (ES) may complicate the clinical course of patients with acute stroke. The aim of this study was to assess the rate of and the predictive factors for ES as well the effects of ES on the clinical outcome at hospital discharge in patients with first-ever stroke.

Patients and methods

A total of 638 consecutive patients with first-ever stroke (543 ischemic, 95 hemorrhagic), admitted to our Stroke Unit, were included in this prospective study. ES were defined as seizures occurring within 7 days from acute stroke. Patients with history of epilepsy were excluded.

Results

Thirty-one patients (4.8%) had ES. Seizures were significantly more common in patients with cortical involvement, severe and large stroke, and in patient with cortical hemorrhagic transformation of ischemic stroke. ES was not associated with an increase in adverse outcome (mortality and disability). After multivariate analysis, hemorrhagic transformation resulted as an independent predictive factor for ES (OR = 6.5; 95% CI: 1.95–22.61; p = 0.003).

Conclusion

ES occur in about 5% of patients with acute stroke. In these patients hemorrhagic transformation is a predictive factor for ES. ES does not seem to be associated with an adverse outcome at hospital discharge after acute stroke.     

Revisiting an ancient treatment for transphincteric fistula-in-ano ‘There is nothing new under the sun’ Ecclesiastes 1v9

Objective

The history of treatments for fistula-in-ano can be traced back to ancient times. Current treatment of transphincteric fistulae is controversial, with many options available. We reviewed the history of treatment using cutting setons and present our series of transphincteric fistulae in the light of the series in the literature.

Design

Literature review and case series.

Setting

Hospital based coloproctology service

Participants

140 consecutive patients presenting with fistula-in-ano were included.

Main Outcome Measures

The literature pertaining to treatment of transphincteric fistula was reviewed, along with the outcome of various treatment methods for this condition. Data were collected for 140 consecutive patients presenting with fistula- in-ano were assessed for fistula healing, recurrence and complications.

Results

A total of 140 consecutive patients with fistula-in-ano were identified, of which 111 were cryptoglandular (79.3%). Eighty-one of these 111 were transphincteric (73.0%). At a median follow-up of 35 months (range, 2–83 months), 70 transphincteric fistulae had healed (86.4%), 10 were still undergoing treatment (12.3%) and one patient was lost to follow-up prior to treatment (1.2%). Two patients in this group required a stoma (2.5%), six patients developed recurrence (7.4%); three ‘true’ recurrences (3.7%). One (1.2%) developed a chronic fissure. There were no reported cases of incontinence.

Conclusions

The management of transphincteric fistula-in-ano is complex and controversial, for which no clear surgical procedure has gained acceptance as the gold standard. This study demonstrates that transphincteric fistulae can be successfully treated using cutting setons. A high healing rate (86.4%), low recurrence rate (7.4%) and a low complication rate (3.7%) are shown, which compares favourably with published rates over a long follow-up.     

Ethnic and social disparity in glycaemic control in type 2 diabetes; cohort study in general practice 2004-9

Objective

To determine whether ethnic group differences in glycated haemoglobin (HbA1c) changed over a 5-year period in people on medication for type 2 diabetes.

Design

Open cohort in 2004–9.

Setting

Electronic records of 100 of the 101 general practices in two inner London boroughs.

Participants

People aged 35 to 74 years on medication for type 2 diabetes.

Main outcome measures

Mean HbA1c and proportion with HbA1c controlled to ≤7.5%.

Results

In this cohort of 24,111 people, 22% were White, 58% South Asian and 17% Black African/Caribbean. From 2004 to 2009 mean HbA1c improved from 8.2% to 7.8% for White, from 8.5% to 8.0% for Black African/Caribbean and from 8.5% to 8.0% for South Asian people. The proportion with HbA1c controlled to 7.5% or less, increased from 44% to 56% in White, 38% to 53% in Black African/Caribbean and 34% to 48% in South Asian people. Ethnic group and social deprivation were independently associated with HbA1c. South Asian and Black African/Caribbean people were treated more intensively than White people.

Conclusion

HbA1c control improved for all ethnic groups between 2004–9. However, South Asian and Black African/Caribbean people had persistently worse control despite more intensive treatment and significantly more improvement than White people. Higher social deprivation was independently associated with worse control.     

Trends in consultant clinical activity and the effect of the 2003 contract change: retrospective analysis of secondary data

Objectives

To explore trends in the clinical activity of hospital specialists in English National Health Service (NHS) hospitals, and test the effect of contract reform.

Design

Retrospective secondary analysis of hospital episode statistics, describing trends and testing for a contract effect using multilevel interrupted time series analysis.

Setting

Ten surgical and medical specialties in English NHS hospitals from 1999 to 2009.

Participants

Hospital consultants on full time or maximum part-time English NHS hospitals.

Intervention

A new contract offered to NHS consultants in October 2003, with higher pay alongside job planning and appraisal.

Main outcome measures

Inpatient finished consultant episodes (FCEs) per consultant per month, with and without accounting for case-mix differences.

Results

In most specialties there was a statistically significant downward trend in FCEs per consultant per month. On average in the surgical specialties, FCEs reduced by 0.14 per month (95% CI −0.16 to −0.11) and in medicine there was a smaller reduction of 0.08 FCEs per month (95% CI −0.1 to −0.06). NHS patients symptoms have increased in severity over time, and the downward trend is reduced after case-mix-adjustment, and reversed in general and geriatric medicine. The effect of the contract on clinical activity was minimal. In five specialties there was no statistically significant effect, but in five specialties there was a statistically significant negative effect.

Conclusions

Consultant clinical activity, as measured by FCEs per month, has shown a general downward trend from 1999 to 2009. The consultant contract was not associated with an increase in consultant clinical activity rates.     

Relationship between glycemic status and progression of carotid intima-media thickness during treatment with combined statin and extended-release niacin in ARBITER 2

Background

We previously reported in a placebo-controlled study that extended-release niacin slowed the progression of carotid atherosclerosis when added to statin monotherapy. This analysis examines the relationship between glycemic status and the effects of niacin on common carotid intima-media thickness (CIMT) and HDL cholesterol.

Methods

Post-hoc, subgroup analysis of ARBITER 2, a randomized, placebo-controlled trial of once-daily extended-release niacin (1000 mg) added to background statin therapy in 167 patients (mean age 67 years) with known coronary heart disease. The primary analysis was a comparison of the primary endpoint, the change in CIMT, between participants with either normal glycemic status, diabetes mellitus (DM) or the metabolic syndrome (MS).

Results

Baseline cardiovascular risk variables were significantly worse in those with abnormal glycemic status, particularly among subjects with MS. Niacin increased HDL-C to a similar degree (∼20%) across normals, DM and MS. Placebo-treated patients had the greatest CIMT progression, regardless of glycemic status. The lowest progression rate was observed in niacin treated patients with normal glycemic status. Among all niacin treated subjects, there was a significant linear relationship between change in CIMT and change in HDL-C (r = −0.16; p = 0.05), which was of similar magnitude in subgroups with normal glycemic status (r = −0.23; p = 0.08) and DM (r = −0.22; p = 0.17). In those with MS, there was no relationship between changes in HDL and CIMT, (r = 0.11; p = 0.44), whereas blood glucose was positive correlated to change in CIMT (r = 0.30; p = 0.04). In multivariable linear models controlling for MS characteristics and blood glucose changes, only the change in HDL independently predicted change in CIMT.

Conclusions

During niacin treatment, increases in HDL-C are related to changes in CIMT in the setting of both normal glycemic status and diabetes mellitus.