The New England Journal of Medicine has published the results of a randomised controlled study that aimed to quantify any benefits of rosuvastatin in the prevention of venous thromboembolism (VTE). The results have been reported in the general media (BBC).
The study recruited 17,802 participants with a low-density lipoprotein (LDL) cholesterol below 3.4 mmol/L and a high-sensitivity C-reactive protein (hs-CRP) levels of 2.0mg/L or above. Participants were randomly assigned to treatment with rosuvastatin 20mg daily or placebo. Median follow up was approximately 2 years. The primary outcome was symptomatic venous thromboembolism or pulmonary embolism.
During the study the primary outcome occurred in 34 patients taking rosuvastatin and 60 patients taking placebo. This represents a 43% relative risk reduction (Hazard ratio 0.57, 95% Confidence interval 0.37 to 0.86; P=0.007) from a baseline risk of 0.32 events per 100 patient-years based on the placebo arm risk.
44 instances of the primary outcome were classified as ‘provoked‘ because they were associated with cancer or recent trauma, hospital admission or surgery. The risk reduction was similar in both the ‘provoked’ and ‘unprovoked’ subgroups. There was a decreased tendency to pulmonary embolism in the rosuvastatin group but this was not statistically significant.
Although these findings are interesting, further research is required to quantify potential benefits in patients at higher risk of venous thromboembolism. In addition, hs-CRP tests are currently not widely available and the clinical significance of hs-CRP results lacks consensus.
Action: Statins should not be routinely used with the exclusive aim of preventing VTE. Efficacy and safety has not been demonstrated in individuals at high risk.
The absolute risk reduction over the 1.9 years median follow up works out as 0.2921%. This means that 342 people would have to be treated with rosuvastatin 20mg instead of placebo for 1.9 years to prevent one VTE at a cost of just over £400,000.
The National Institute of Health and Clinical Excellence has published new guidance for the month of March.
There is one guideline that may impact on primary care, a public health guideline on long-term sickness absence and incapacity for work.
The guideline is aimed at employers as well as NHS staff in primary care and occupational health. The guidance recommends that employers establish sickness absence policies and appropriate health and safety practices. This will help to ensure that adequate support is given to employees to allow them to return to work as soon as they are able.
Action: Clinicians who are involved in occupational health or who issue sick notes will find this information useful.
The Annals of Internal Medicine has published the results of a post-hoc observational analysis of a randomised controlled trial to assess the optimal dose of aspirin as an anti-thrombotic.
The review assessed the benefits and risks of aspirin at doses of less the 100mg daily and more than 100mg daily. The review found no differences between the two dose classifications in terms of the primary efficacy or primary safety endpoints. In patients who were also taking clopidogrel, there was a trend towards reduced efficacy and increased harm in patients taking more than 100mg of aspirin daily although these results were not statistically significant.
The authors conclude that higher doses of aspirin are associated with “no clear benefit in patients taking aspirin only and possibly with harm in patients taking clopidogrel“.
Action: Clinicians should ensure that aspirin is given at a daily dose of 75mg when intended for use as an anti-thrombotic. Higher doses should be used cautiously after careful assessment of potential risks and benefits.
Thanks to Kevin Ashworth for spotting this article
The National Prescribing Centre (NPC) has published MeReC Extra 38 (PDF).
This MeReC discusses the results of the Veterans Association Diabetes Trial (VADT) and the recently published ACCOMPLISH Study.
VADT involved 1,791 US military veterans with uncontrolled type 2 diabetes (HbA1c >7.5%, baseline median 9.4%). Participants were treated to an intensive or standard targets reaching an HbA1c 6.9% or 8.4% respectively.
Despite the lower HbA1c in the intensive arm there were no differences in major cardiovascular events or deaths from any cause. These results are in keeping with a growing body of evidence; cardiovascular risk in patients with diabetes is best managed with lifestyle interventions, blood pressure control, statins, metformin and aspirin in cases of secondary prevention.
The ACCOMPLISH study compared two strategies for treating hypertension and found that a combination of ACE inhibitor and calcium channel blocker was superior to that of ACE inhibitor and diuretic in terms of the primary composite outcome (a composite of six cardiovascular outcomes). The results were mainly driven by differences in fatal and nonfatal myocardial infarction but there was no difference in rates of cardiovascular or all cause death.
The results are of limited relevance to the UK because the drugs studied are not available on the UK market. In addition there was a small difference in mean blood pressure in the two groups that favoured the superior treatment and this may also explain some of the observed difference. Clinicians are advised to continue to follow the existing NICE guidelines.
Action: Clinicians who see patients with hypertension or diabetes will find this information useful and informative.
The Lancet has published the results of a study conducted by the Clinical Trial Service Unit (CTSU) at the University of Oxford. The results have been reported in the general media (BBC).
This study reviewed data from 57 prospective studies involving 894,576 participants with the aim of assessing the associations between body mass index (BMI) and overall and cause-specific mortality. The studies were mainly conducted in North America and Western Europe. The average age of participants at enrolment was 46 years and 61% were male.
The study found that mortality was lowest in individuals with a BMI in the range of 22.5-25 kg/m2. Overall mortality increased by 30% for each additional 5 kg/m2 increase in BMI.
When mortality was analysed by specific causes a 5 kg/m2 increase in BMI was associated with a 40% increase in vascular mortality, 120% increase in diabetic mortality, 60% increase in renal mortality and 80% increase in hepatic mortality.
A press release issued by CTSU estimates that moderate obesity (BMI 30-35 kg/m2) reduces life expectancy by 3 years and severe obesity (BMI 40-50 kg/m2) by 10 years. A 10 year reduced is equivalent to that seen in lifelong smokers. It was also noted that the additional risks posed by smoking and high BMI were additive.
Action: Clinicians will find this research useful when communicating the risks of obesity to patients. These data show that a severely obese smoker is likely to have a reduction in life expectancy of 20 years.