Sabin Allemann

Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis

BACKGROUND Whether the two drug-eluting stents approved by the US Food and Drug Administration-a sirolimus-eluting stent and a paclitaxel-eluting stent-are associated with increased risks of death, myocardial infarction, or stent thrombosis compared with bare-metal stents is uncertain. Our aim was to compare the safety and effectiveness of these stents. METHODS We searched relevant sources from inception to March, 2007, and contacted investigators and manufacturers to identify randomised controlled trials in patients with coronary artery disease that compared drug-eluting with bare-metal stents, or that compared sirolimus-eluting stents head-to-head with paclitaxel-eluting stents. Safety outcomes included mortality, myocardial infarction, and definite stent thrombosis; the effectiveness outcome was target lesion revascularisation. We included 38 trials (18,023 patients) with a follow-up of up to 4 years. Trialists and manufacturers provided additional data on clinical outcomes for 29 trials. We did a network meta-analysis with a mixed-treatment comparison method to combine direct within-trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. FINDINGS Mortality was similar in the three groups: hazard ratios (HR) were 1.00 (95% credibility interval 0.82-1.25) for sirolimus-eluting versus bare-metal stents, 1.03 (0.84-1.22) for paclitaxel-eluting versus bare-metal stents, and 0.96 (0.83-1.24) for sirolimus-eluting versus paclitaxel-eluting stents. Sirolimus-eluting stents were associated with the lowest risk of myocardial infarction (HR 0.81, 95% credibility interval 0.66-0.97, p=0.030 vs bare-metal stents; 0.83, 0.71-1.00, p=0.045 vs paclitaxel-eluting stents). There were no significant differences in the risk of definite stent thrombosis (0 days to 4 years). However, the risk of late definite stent thrombosis (>30 days) was increased with paclitaxel-eluting stents (HR 2.11, 95% credibility interval 1.19-4.23, p=0.017 vs bare-metal stents; 1.85, 1.02-3.85, p=0.041 vs sirolimus-eluting stents). The reduction in target lesion revascularisation seen with drug-eluting stents compared with bare-metal stents was more pronounced with sirolimus-eluting stents than with paclitaxel-eluting stents (0.70, 0.56-0.84; p=0.0021). INTERPRETATION The risks of mortality associated with drug-eluting and bare-metal stents are similar. Sirolimus-eluting stents seem to be clinically better than bare-metal and paclitaxel-eluting stents.

Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis

Objective To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus. Design Collaborative network meta-analysis. Data sources Electronic databases (Medline, Embase, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, book chapters, and proceedings of advisory panels for the US Food and Drug Administration. Manufacturers and trialists provided additional data. Review methods Network meta-analysis with a mixed treatment comparison method to combine direct within trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. Overall mortality was the primary safety end point, target lesion revascularisation the effectiveness end point. Results 35 trials in 3852 people with diabetes and 10 947 people without diabetes contributed to the analyses. Inconsistency of the network was substantial for overall mortality in people with diabetes and seemed to be related to the duration of dual antiplatelet therapy (P value for interaction 0.02). Restricting the analysis to trials with a duration of dual antiplatelet therapy of six months or more, inconsistency was reduced considerably and hazard ratios for overall mortality were near one for all comparisons in people with diabetes: sirolimus eluting stents compared with bare metal stents 0.88 (95% credibility interval 0.55 to 1.30), paclitaxel eluting stents compared with bare metal stents 0.91 (0.60 to 1.38), and sirolimus eluting stents compared with paclitaxel eluting stents 0.95 (0.63 to 1.43). In people without diabetes, hazard ratios were unaffected by the restriction. Both drug eluting stents were associated with a decrease in revascularisation rates compared with bare metal stents in people both with and without diabetes. Conclusion In trials that specified a duration of dual antiplatelet therapy of six months or more after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes.

Self-monitoring of blood glucose in non-insulin treated patients with type 2 diabetes: a systematic review and meta-analysis

Abstract Objective: To assess the effect of self-monitoring of blood glucose (SMBG) on glycaemic control in non-insulin treated patients with type 2 diabetes by means of a systematic review and meta-analysis. Research design and methods: MEDLINE and the Cochrane Controlled Trials Register were searched from inception to January 2009 for randomised controlled trials comparing SMBG with non-SMBG or more frequent SMBG with less intensive SMBG. Electronic searches were supplemented by manual searching of reference lists and reviews. The comparison of SMBG with non-SMBG was the primary, the comparison of more frequent SMBG with less intensive SMBG the secondary analysis. Stratified analyses were performed to evaluate modifying factors. Main outcome measures: The primary endpoint was glycated haemoglobin A1c (HbA1c), secondary outcomes included fasting glucose and the occurrence of hypoglycaemia. Using random effects models a weighted mean difference (WMD) was calculated for HbA1c and a risk ratio (RR) was calculated for hypoglycaemia. Due to considerable heterogeneity, no combined estimate was computed for fasting glucose. Results: Fifteen trials (3270 patients) were included in the analyses. SMBG was associated with a larger reduction in HbA1c compared with non-SMBG (WMD −0.31%, 95% confidence interval −0.44 to −0.17). The beneficial effect associated with SMBG was not attenuated over longer follow-up. SMBG significantly increased the probability of detecting a hypoglycaemia (RR 2.10, 1.37 to 3.22). More frequent SMBG did not result in significant changes of HbA1c compared with less intensive SMBG (WMD −0.21%, 95% CI −0.57 to 0.15). Conclusions: SMBG compared with non-SMBG is associated with a significantly improved glycaemic control in non-insulin treated patients with type 2 diabetes. The added value of more frequent SMBG compared with less intensive SMBG remains uncertain.

Efficacy of drug eluting stents in patients with and without diabetes mellitus: indirect comparison of controlled trials

Objective: To examine whether polymer based coronary stents eluting sirolimus or paclitaxel are equally effective in patients with and without diabetes. Methods: Systematic review and meta-analysis by indirect comparison of randomised controlled trials comparing stents eluting sirolimus or paclitaxel with conventional bare metal stents. The overall study population and patients with and without diabetes were analysed separately by using the ratio of incidence rate ratios (RIRR). Results: The analysis was based on 10 trials (six with sirolimus, four with paclitaxel), 4513 patients (1146 patients with diabetes), 5755 years of follow up, and 2464 events. In patients without diabetes sirolimus eluting stents were superior to paclitaxel eluting stents with respect to in-stent (RIRR 0.21, 95% confidence interval (CI) 0.10 to 0.48, p < 0.001) and in-segment restenosis (RIRR 0.47, 95% CI 0.24 to 0.92, p  =  0.027), target lesion revascularisation (RIRR 0.54, 95% CI 0.30 to 0.99, p  =  0.045), and major adverse cardiac events (RIRR 0.46, 95% CI 0.26 to 0.83, p  =  0.010). In patients with diabetes the two drug eluting stents did not differ significantly in any of these end points. Meta-regression analysis showed a significant difference between patients with and without diabetes (tests for interaction for in-stent and in-segment restenosis, p  = 0.036 and p  =  0.016). Conclusion: Indirect evidence indicates that sirolimus eluting stents are superior to paclitaxel eluting stents in patients without diabetes but not in patients with diabetes.

Association of 1,5-Anhydroglucitol and 2-h Postprandial Blood Glucose in Type 2 Diabetic Patients

OBJECTIVE—To assess the association of 1,5-anhydroglucitol (1,5-AG) with 2-h postprandial glucose values in type 2 diabetic patients followed over 12 months in an outpatient setting. RESEARCH DESIGN AND METHODS—In 55 patients, we examined self-measured postprandial blood glucose values for correlations with 1,5-AG values over prespecified preceding time periods (3 days, 1 week, and weekly up to 12 weeks). RESULTS—The correlation coefficients for postprandial glucose values were −0.34 (P < 0.05) for 3 days, −0.38 (P < 0.001) for 1 week, and −0.40 (P < 0.001) for 2 weeks preceding the measurement of 1,5-AG. Correlations declined for time periods >2 weeks before measurement of 1,5-AG. The correlation was lower with fasting/preprandial plasma glucose levels. There was no time dependency for the correlation between A1C and fasting or postprandial glucose. CONCLUSIONS—1,5-AG best reflected the 2-h postprandial glucose values of the 2 previous weeks.

Differential Effects of Antihypertensive Treatment on the Retinal Microcirculation. An Anglo-Scandinavian Cardiac Outcomes Trial Substudy

Changes in the retinal microcirculation are associated with hypertension and predict cardiovascular mortality. There are few data describing the impact of antihypertensive therapy on retinal vascular changes. This substudy of the Anglo-Scandinavian Cardiac Outcomes Trial compared the effects of an amlodipine-based regimen (373 patients) with an atenolol-based regimen (347 patients) on retinal microvascular measurements made from fundus photographs. The retinal photographs were taken at a stage in the trial when treatments were stable and blood pressure was well controlled. Amlodipine-based treatment was associated with a smaller arteriolar length:diameter ratio than atenolol-based treatment (13.32 [10.75 to 16.04] versus 14.12 [11.27 to 17.81], median [interquartile range]; P<0.01). The association remained significant after adjustment for age, sex, cholesterol, systolic and diastolic blood pressures, body mass index, smoking, and statin treatment. This effect appeared to be largely attributable to shorter retinal arteriolar segment lengths in the amlodipine-treated group and is best explained by the vasodilator effects of amlodipine causing the visible emergence of branching side vessels. Photographic assessment of the retinal vascular network may be a useful approach to evaluating microvascular structural responses in clinical trials of antihypertensive therapy.

Long-term cardiovascular and non- cardiovascular mortality in women and men with type 1 and type 2 diabetes mellitus: A 30-year follow-up in Switzerland

BACKGROUND While studies from other countries have shown an excess mortality in diabetic individuals when compared with the general population, comparable long-term data is not available for Switzerland. AIMS To assess gender-specific cardiovascular and non-cardiovascular mortality of patients with type 1 and type 2 diabetes compared with the general Swiss population between 1974 and 2005. DESIGN 533 patients (225 type 1, 308 type 2 diabetes, 52.2% men) were followed for 30 years (10349 person-years). RESULTS Diabetic patients had an increased all-cause mortality compared with the general population (SMR [95% CI] 3.8 [3.5-4.3]). Standardised mortality ratio (SMR) was higher for type 1 compared with type 2 diabetic patients (4.5 [3.8-5.3] vs 3.5 [3.1-4.0], p = 0.032). For cardiovascular and non-cardiovascular deaths SMRs were 5.6 (95% CI 4.8-6.6) and 2.7 (2.3-3.1) and did not differ according to type of diabetes. SMRs for all-cause and cardiovascular mortality were significantly higher in women compared with men in type 1 (p <0.05 and p <0.01) and type 2 diabetes (p <0.001 and p <0.01). In both types of diabetes, SMRs significantly decreased during the last two decades (p for trend 0.004 and 0.002). CONCLUSIONS Patients with type 1 and type 2 diabetes had an increased long-term mortality compared with the general Swiss population. Excess mortality was higher in type 1 compared with type 2 diabetes and in women compared with men for both types of diabetes, but steadily decreased over the last two decades.

The Effect of Aerobic Exercise on Intrahepatocellular and Intramyocellular Lipids in Healthy Subjects

Background Intrahepatocellular (IHCL) and intramyocellular (IMCL) lipids are ectopic lipid stores. Aerobic exercise results in IMCL utilization in subjects over a broad range of exercise capacity. IMCL and IHCL have been related to impaired insulin action at the skeletal muscle and hepatic level, respectively. The acute effect of aerobic exercise on IHCL is unknown. Possible regulatory factors include exercise capacity, insulin sensitivity and fat availability subcutaneous and visceral fat mass). Aim To concomitantly investigate the effect of aerobic exercise on IHCL and IMCL in healthy subjects, using Magnetic Resonance spectroscopy. Methods Normal weight, healthy subjects were included. Visit 1 consisted of a determination of VO2max on a treadmill. Visit 2 comprised the assessment of hepatic and peripheral insulin sensitivity by a two-step hyperinsulinaemic euglycaemic clamp. At Visit 3, subcutaneous and visceral fat mass were assessed by whole body MRI, IHCL and IMCL before and after a 2-hours aerobic exercise (50% of VO2max) using 1H-MR-spectroscopy. Results Eighteen volunteers (12M, 6F) were enrolled in the study (age, 37.6±3.2 years, mean±SEM; VO2max, 53.4±2.9 mL/kg/min). Two hours aerobic exercise resulted in a significant decrease in IMCL (−22.6±3.3, % from baseline) and increase in IHCL (+34.9±7.6, % from baseline). There was no significant correlation between the exercise-induced changes in IMCL and IHCL and exercise capacity, subcutaneous and visceral fat mass and hepatic or peripheral insulin sensitivity. Conclusions IMCL and IHCL are flexible ectopic lipid stores that are acutely influenced by physical exercise, albeit in different directions. Trial Registration ClinicalTrial.gov NCT00491582

Exercise capacity in subjects with type 1 diabetes mellitus in eu- and hyperglycaemia

Circumstantial evidence suggests that an increase in plasma glucose availability improves exercise capacity in subjects with type 1 diabetes mellitus. The aim of this study was to assess exercise capacity in eu‐ and hyperglycaemic conditions in subjects with type 1 diabetes.

Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mellitus: meta-analysis of randomised controlled trials

ABSTRACT Objective: To assess the impact of lipid lowering treatment with fibrates on cardiovascular endpoints in patients with type 2 diabetes mellitus. Methods: MEDLINE (from inception to November 2005) and the Cochrane Controlled Trials Register (including Issue 3, 2005) were searched for randomised controlled trials comparing therapy with fibrates to placebo in patients with type 2 diabetes mellitus. Electronic searches were supplemented by manual searching of reference lists, reviews, conference abstracts and specialist journals. Incidence rate ratios (IRRs) were estimated using a fixed effects model. The primary endpoint was the IRR for coronary heart disease (CHD) events (a combination of non fatal myocardial infarction and death due to CHD). Secondary endpoints included: (1) death due to CHD; (2) fatal and non fatal myocardial infarction; and (3) fatal and non fatal stroke. Results: Eight trials and 12 249 patients with type 2 diabetes were included in the analyses. A total of 924 CHD events (418 and 506 in the treatment and placebo groups, respectively) occurred during a follow up of 60 395 person-years (30 106 and 30 289 in treatment and placebo groups). The combined IRR for CHD events was 0.84 (95% confidence interval [CI] 0.74–0.96, p = 0.008). The numbers needed to treat (NNTs) to prevent one CHD event over 10 years were nine and 26 for patients with and without pre-existing CHD, respectively. IRRs for death due to CHD, myocardial infarction and stroke were 0.96 (95% CI 0.77–1.20, p = 0.73), 0.88 (95% CI 0.69–1.12, p = 0.30) and 0.87 (95% CI 0.73–1.05, p = 0.14), respectively. Larger benefits were found when restricting the analysis to trials that were not confounded by unequal provision of additional lipid-lowering therapy. Conclusions: Fibrates are associated with a substantial reduction of CHD events, but their exact role in lipid lowering treatment of patients with type 2 diabetes mellitus remains to be defined.