Statin use after acute myocardial infarction by patient complexity: Are the rates right?

Reprinted with permission of the publisher.Background: Guidelines suggest statin use after acute myocardial infarction (AMI) should be close to universal in patients without safety concerns yet rates are much lower than recommended, decline with patient complexity, and display substantial geographic variation. Trial exclusions have resulted in little evidence to guide statin prescribing for complex patients. Objective: Assess the benefits and risks associated with higher rates of statin use after AMI by baseline patient complexity. Research Design: Sample includes Medicare fee-for-service patients with AMIs in 2008-2009. Instrumental variable estimators using variation in local area prescribing patterns by statin-intensity as instruments were used to assess the association of higher statin prescribing rates by statin-intensity on 1-year survival, adverse events, and cost by patient complexity. Results: Providers appear to have individualized statin use across patients based on potential risks. Higher statin rates for non-complex AMI patients were associated with increased survival rates with little added adverse event risk. Higher statin rates for complex AMI patients were associated with tradeoffs between higher survival rates and higher rates of adverse events. Conclusions: Higher rates of statin use for non-complex AMI patients are associated with outcome rate changes similar to existing evidence. For the complex patients in our study, who were least represented in existing trials, higher statin-use rates were associated with survival gains and higher adverse event risks not previously documented. Policy interventions promoting higher statin-use rates for complex patients may need to be re-evaluated taking careful consideration of these tradeoffs.This project was supported by an Agency for Healthcare Research and Quality grant (1R21HS019574-01) under the American Recovery and Reinvestment Act of 2009

Does sticky blood predict a sticky end? Associations of blood viscosity, haematocrit and fibrinogen with mortality in the West of Scotland

There is increasing evidence that blood viscosity and its major determinants (haematocrit, plasma viscosity and fibrinogen) are associated with an increased risk of incident cardiovascular events; however, their associations with mortality are not established. We therefore studied the associations of these variables with cardiovascular events and total mortality in 1238 men and women aged 25-64 years, followed for 13 years in the first North Glasgow MONICA (MONItoring CArdiovascular disease) survey and West of Scotland centres in the Scottish Heart Health Study. After adjustment for age and sex, increasing whole blood viscosity, plasma viscosity, haematocrit and fibrinogen (analysed by both von Clauss and heat precipitation assays) were significantly associated with mortality. Only the association for fibrinogen (von Clauss assay) remained significant after adjustment for major cardiovascular risk factors. We conclude that clottable fibrinogen may be independently associated with mortality. However, the significance of this association, and the extent to which viscosity is associated with mortality, remain to be established in larger studies and meta-analyses

N-terminal Pro-B-type natriuretic peptide, vascular disease risk, and cholesterol reduction among 20,536 patients in the MRC/BHF heart protection study.

OBJECTIVES: We sought to assess the ability of N-terminal pro-B-type natriuretic peptide (N-BNP) to predict vascular events in high-risk people and to test whether statins benefit people with high levels of N-BNP. BACKGROUND: The predictive value of N-BNP for occlusive vascular events and the effects of statins in people with high N-BNP levels are uncertain. METHODS: A total of 20,536 people were assigned randomly to simvastatin 40 mg daily or placebo for an average of 5 years. Five baseline N-BNP groups were defined ( andlt; 386; 386 to 1,171; 1,172 to 2,617; 2,618 to 5,758; and > or =5,759 pg/ml). RESULTS: Baseline N-BNP was strongly predictive of future vascular events independently of other characteristics. Compared with participants with N-BNP andlt; 386 pg/ml, those with levels > or =5,759 pg/ml had adjusted relative risks for major vascular events (MVEs) (i.e., major coronary events [MCE] [nonfatal myocardial infarction or coronary death], stroke, or revascularization) of 2.26, for MCE of 3.09, for stroke of 1.80, and for heart failure (hospitalization or death) of 9.23 (all p andlt; 0.0001). Overall, simvastatin allocation reduced the relative risk of MVE by 24% (95% confidence interval 19 to 28). There was a trend toward smaller (but still significant) proportional reductions in MVE among participants with greater baseline N-BNP levels, but the absolute benefits of simvastatin allocation were similar at all N-BNP levels. Simvastatin allocation was also associated with a 14% (95% confidence interval 0 to 25) proportional reduction in heart failure. No excess risk of other vascular and nonvascular outcomes was observed with simvastatin allocation among participants with greater baseline values of N-BNP. CONCLUSIONS: In this study, N-BNP levels were strongly predictive not only of heart failure but also of MVEs. In people with high N-BNP levels consistent with heart failure, statin allocation significantly reduced vascular risk, with no evidence of hazard. (http://www.controlledtrials.com/ISRCTN48489393/48489393)

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

Rosuvastatin for primary prevention in patients with European systematic coronary risk evaluation risk ≥5% or Framingham risk >20%: post hoc analyses of the JUPITER trial requested by European health authorities

Aims: On the basis of the JUPITER trial, European health authorities recently approved the use of rosuvastatin to reduce first major cardiovascular events among ‘high' global risk primary prevention patients defined either by Framingham risk score >20% or European systematic coronary risk evaluation (SCORE) ≥5%. However, as these are post hoc analyses, data describing these subgroups have not previously been available to the clinical community. Methods and results: We randomized 17 802 apparently healthy men aged ≥50 and women ≥60 with low-density lipoprotein cholesterol (LDL-C) 20% or SCORE risk ≥5%. During 1.8-year median follow-up (maximum 5 years) of patients with Framingham risk >20%, the rate of myocardial infarction/stroke/cardiovascular death was 9.4 and 18.2 per 1000 person-years in rosuvastatin and placebo-allocated patients, respectively [hazard ratio (HR): 0.50, 95% confidence interval (CI): 0.27–0.93, P = 0.028]. Among patients with SCORE risk ≥5%, the corresponding rates were 6.9 and 12.0 using a model extrapolating risk for age ≥65 years (HR: 0.57, 95% CI: 0.43–0.78, P = 0.0003) and rates were 5.9 and 12.7 when risk for age was capped at 65 years (HR: 0.47, 95% CI: 0.32–0.68, P 20% or SCORE risk ≥5%), but LDL-C levels not requiring pharmacologic treatment, rosuvastatin 20 mg significantly reduced major cardiovascular events. ClinicalTrial.gov Identifier: NCT0023968

Lipid-lowering for lower limb atherosclerosis

Background: Lipid-lowering therapy is recommended for secondary prevention in people with coronary artery disease. It may also reduce cardiovascular events and/or local disease progression in people with lower limb peripheral arterial disease (PAD). Objectives: To assess the effects of lipid-lowering therapy on all-cause mortality, cardiovascular events and local disease progression in patients with PAD of the lower limb. Search methods: The authors searched The Cochrane Peripheral Vascular Diseases Group's Specialised Register (last searched February 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 2, 2007) for publications describing randomised controlled trials of lipid-lowering therapy in peripheral arterial disease of the lower limb. Selection criteria: Randomised controlled trials of lipid-lowering therapy in patients with PAD of the lower limb. Data collection and analysis: Three authors independently assessed trial quality and extracted data. Main results: Eighteen trials were included, involving a total of 10,049 participants. Trials differed considerably in their inclusion criteria, outcomes measured, and type of lipid-lowering therapy used. Only one trial (PQRST) reported a detrimental effect of active treatment on blood lipid/lipoprotein levels. The pooled results from all eligible trials indicated that lipid-lowering therapy had no statistically significant effect on overall mortality (Odds Ratio (OR) 0.86; 95% Confidence Interval (CI) 0.49 to 1.50) or on total cardiovascular events (OR 0.8; 95% CI 0.59 to 1.09). However, subgroup analysis which excluded PQRST showed that lipid-lowering therapy significantly reduced the risk of total cardiovascular events (OR 0.74; CI 0.55 to 0.98). This was primarily due to a positive effect on total coronary events (OR 0.76; 95% CI 0.67 to 0.87). Greatest evidence of effectiveness came from the use of simvastatin in people with a blood cholesterol ≥ 3.5 mmol/litre (HPS). Pooling of the results from several small trials on a range of different lipid-lowering agents indicated an improvement in total walking distance (Mean Difference (MD) 152 m; 95% CI 32.11 to 271.88) and pain-free walking distance (WMD 89.76 m; 95% CI 30.05 to 149.47) but no significant impact on ankle brachial index (WMD 0.04; 95% CI -0.01 to 0.09). Authors' conclusions: Lipid-lowering therapy is effective in reducing cardiovascular mortality and morbidity in people with PAD. It may also improve local symptoms. Until further evidence on the relative effectiveness of different lipid-lowering agents is available, use of a statin in people with PAD and a blood cholesterol level ≥ 3.5 mmol/litre is most indicated.Output Type: Revie

Modulation of endogenous antioxidant defense and the progression of kidney disease in multi-heritage groups of patients with type 2 diabetes: PRospective EValuation of Early Nephropathy and its Treatment (PREVENT).

BACKGROUND: Diabetes is the western world's leading cause of end-stage renal disease. Glucose-dependent, oxidative stress is linked to the development of renal inflammation and sclerosis, which, in animal models of diabetes, can be prevented by anti-oxidative treatment. Patients of non-Caucasian heritage have low activity of the selenoprotein, antioxidant enzyme, glutathione peroxidase (GPx) and its co-factor vitamin E, which may be linked to their increased propensity to developing end-stage renal disease. RESEARCH DESIGN AND METHODS: We have designed a double-blind, randomized, placebo controlled study with selenium and/or vitamin E versus placebo as the interventions for patients with type 2 diabetes and chronic kidney disease (CKD) stages 1-3. A 2 × 2 factorial design will allow a balanced representation of the heritage groups exposed to each intervention. The primary biochemical outcome is change in GPx activity, and clinical outcome measure is the actual, rate of-and/or percentage change in estimated glomerular filtration rate (eGFR) from baseline. Analysis will be with a marginal model for longitudinal data using Generalized Estimating Equations corrected for measures of baseline serum antioxidant enzyme activities (GPx, superoxide dismutase and catalase), micronutrient levels (vitamins E and C), measures of inflammation (interleukin 6, c-reactive protein and monocyte chemoattractant protein-1) and markers of oxidative damage (plasma 8-isoprostaglandin F2α and urinary 8-hydroxydeoxyguanosine). EXPECTED RESULTS: The study will assess the relationship between GPx activity, oxidative stress, inflammation and eGFR. It will test the null hypothesis that antioxidant therapy does not influence the activity of GPx or other antioxidant enzymes and/or alter the rate of change in eGFR in these patient groups. CONCLUSIONS: Outcome data on the effect of antioxidants in human diabetic renal disease is limited. Previous post hoc analyses have not shown a beneficial effect of vitamin E on renal function. A recent trial of a pharmaceutical antioxidant agent, improved eGFR, but in patients with advanced diabetes-related chronic kidney disease its use was associated with an increased incidence of cardiovascular events. We will explore whether the nutritional antioxidants, vitamin E and selenium alone, or in combination in patients at high risk of renal disease progression, forestalls a reduction in eGFR. The study will describe whether endogenous antioxidant enzyme defenses can be safely modified by this intervention and how this is associated with changes in markers of oxidative stress. Trial registration ISRCTN 97358113. Registered 21st September 2009

Lp-PLA2 activity is associated with increased risk of diabetic retinopathy:a longitudinal disease progression study

Aims/hypothesis: The aim of the study was to examine the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) activity levels and incident diabetic retinopathy and change in retinopathy grade.Methods: This was a cohort study of diabetic participants with serum collected at baseline and routinely collected diabetic retinal screening data. Participants with type 2 diabetes from the GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland) cohort were used. This cohort is composed of individuals of white Scottish ancestry from the Tayside region of Scotland. Survival analysis accounting for informative censoring by modelling death as a competing risk was performed for the development of incident diabetic retinopathy from a disease-free state in a 3 year follow-up period (n = 1364) by stratified LpPLA2 activity levels (in quartiles). The same analysis was performed for transitions to more severe grades.Results: The hazard of developing incident diabetic retinopathy was 2.08 times higher (95% CI 1.64, 2.63) for the highest quartile of Lp-PLA2 activity compared with the lowest. Higher Lp-PLA2 activity levels were associated with a significantly increased risk for transitions to all grades. The hazards of developing observable (or more severe) and referable (or more severe) retinopathy were 2.82 (95% CI 1.71, 4.65) and 1.87 (95% CI 1.26, 2.77) times higher for the highest quartile of Lp-PLA2 activity compared with the lowest, respectively.Conclusions/interpretation: Higher Lp-PLA2 levels are associated with increased risk of death and the development of incident diabetic retinopathy, as well as transitions to more severe grades of diabetic retinopathy. These associations are independent of calculated LDL-cholesterol and other traditional risk factors. Further, this biomarker study shows that the association is temporally sensitive to the proximity of the event to measurement of Lp-PLA2

Post-Prandial Lipid Levels for Assessing Target Goal Achievement in Type 2 Diabetic Patients Taking Statin

It is inconvenient to perform serum lipid analysis in fasting state in diabetic patients with drug treatment. In patients with statin treatment and Asian diet, it has not been clearly known whether non-fasting values could be used for the clinical decision making in diabetic patients. In this study, fasting and post-prandial plasma lipid profiles of hospitalized type 2 diabetic patients taking statin, were measured in whom standard diabetic breakfast in traditional Korean style were provided. In repeated-measures ANOVA, there were no significant differences among fasting, post-prandial 2 and 4 hr low-density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol values. When compared to fasting levels, both post-prandial 2 hr and 4 hr LDL cholesterol levels were misclassified as not achieved target goal only in 4% of patients. Post-prandial HDL cholesterol matched with fasting values in women, without exception. In conclusion, the fasting and post-prandial LDL and HDL cholesterol levels are not significantly different each other and can be used in the assessment of achieving target goal in type 2 diabetes taking statin after Korean diet