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Monday, May 11, 2009

STATINS CUTS RISK OF DVT

11 may 2009--Taking a common heart drug “halves the risk of death from DVT,” reports the Daily Express. The newspaper says that a commonly prescribed statin pill “slashes the risk of the killer condition deep vein thrombosis by more than half.”

These results come from research into use cholesterol-lowering statin drug by apparently healthy people. In this publication researchers focused on the role the drug plays in preventing venous thromboembolism (the development of clots in the veins of the legs or lungs). DVT can be caused by sitting still during long-haul air travel or being confined to bed for long periods.

The well-conducted study provides good evidence that the statin can reduce risk of DVT in apparently healthy people, and that this effect is not simply a result of statins reducing the chance of heart-related illness, which can raise the risk of DVT. The researchers imply that this research offers a new reason for prescribing the drug.

However, the participants in this study had to meet a number of criteria, and although apparently healthy, they were all at higher risk of a cardiovascular event than the general population. The results may not apply to the wider population, and more research will be needed before statins can be widely used to prevent DVT as suggested.

Where did the story come from? This research was conducted by Dr Robert Glynn and colleagues from Brigham and Women’s Hospital in Boston, Universidade Federal de Sao Paulo, McGill University Health Centre in Montreal, and other academic and medical institutions in Denmark, Argentina and Scotland.

The research was funded by the AstraZeneca pharmaceutical company, and by a grant from the National Institutes on Aging. It was published in the peer-reviewed medical journal, the New England Journal of Medicine.

What kind of scientific study was this? This study was a large randomised controlled trial that reported on the effects of statin use on occurrence of venous thromboembolism (deep vein thrombosis and pulmonary embolism). Apparently healthy individuals were randomly allocated to receive rosuvastatin (20mg daily) or a placebo.

This study used data from the large ‘Jupiter trial’, which was originally set up to assess the role of rosuvastatin for primary prevention of cardiovascular events in people with higher C-reactive protein (CRP) levels. CRP is a protein that is produced in reaction to inflammatory processes in the body, and it is thought to be a marker of increased risk of diabetes and cardiovascular diseases. The occurrence of venous thromboembolism was a secondary outcome from this initial Jupiter study.

Although statins such as rosuvastatin are used for managing cholesterol levels, it is also thought that they reduce inflammation, with observational studies showing a 22% to 50% cut in risk. This study is one of the first randomised studies to report on any possible anti-inflammatory effects of statins.

A total of 17,802 people were randomised within this study. To be eligible for inclusion, they had to meet the following criteria:

Be aged at least 50 years for males or 60 years for females.
Have no known cardiovascular diseases at an initial screening visit.
Have a low-density lipoprotein (LDL) cholesterol level of less than 3.4 mmol/L, and a high-sensitivity C-reactive protein (CRP) level of 2.0 mg/L or more.

Between March 2003 and December 2006, participants were randomised into either an active group, receiving a daily 20mg dose of rosuvastatin, or a placebo. They were followed-up for an average of 60 months after randomisation, with regular visits to the study team for interim interviews that assessed the occurrence of outcomes.

Any reported venous thromboembolism was confirmed using a venous ultrasonogram or venogram for DVT. For confirmation of pulmonary embolism, angiograms, computed tomographic scans or ventilation–perfusion scans were used.

The Jupiter trial on rosuvastatin was stopped in March 2008 because evidence of efficacy of the statin’s effectiveness was convincing. Events up to this date were included in the analysis. To account for the fact that thromboembolism often occurs around the time of cardiovascular events, the researchers performed separate analyses for venous thromboembolism and for primary cardiovascular events.

What were the results of the study? A pulmonary embolism or DVT occurred in 94 participants, with 34 in the statin group and 60 in the placebo group. Rosuvastatin reduced the combined risk of these outcomes by 43% (HR 0.57, 95% CI 0.37 to 0.86). There was a similar-sized effect of statin on prevention of either a primary cardiovascular event or a venous thromboembolism (HR 0.56, 95% CI 0.47 to 0.68).

Venous thromboembolism was more common in those people over 70 years with a high BMI and large waist circumference. Cholesterol levels at time of entry to the study (baseline) did not have any effect on the efficacy of the drug. The researchers do not discuss the side effects of statin use in this publication.

What interpretations did the researchers draw from these results? The researchers report that 20mg of rosuvastatin a day reduces the risk of symptomatic venous thromboembolism in apparently healthy people. They say that this reduction in risk appears to be an independent benefit of statin use, in that it does not depend on the reduction in risk of heart attacks or strokes.

They go on to say that as a result of this newly observed benefit of statins, the research goal should be widened from preventing arterial thrombosis to preventing venous thromboembolism and death too.

What does the NHS Knowledge Service make of this study? This randomised control trial found that daily rosuvastatin reduces the risk of venous thromboembolism: the study was large and well-conducted and offers robust evidence for the successful treatment of DVT with this drug.

This study only assessed the role of statin treatment in outcomes of symptomatic venous thromboembolism. The researchers say that because asymptomatic venous thromboembolism is common too, the study may have underestimated the beneficial effects of the drug by not assessing this outcome as well.

It should be noted that the selection of participants who took part in this study make it harder to apply the findings to the general population. In particular:

Only people with higher levels of CRP were entered into this study, meaning that although none of them had yet had a cardiovascular event, they were at a higher risk of having one than the general population.
In both the rosuvastatin and placebo groups, 37.6% of the subjects were obese, with a BMI of more than 30.
41.7% of the participants had metabolic syndrome, another marker of increased risk.

It should also be noted that despite higher-than-average risk of venous thromboembolism, the absolute number of events in this group of people was low, with only 94 episodes among all the 17,802 participants.

In general, this large randomised trial confirms previous findings from observational studies, but also raises further questions about who exactly should be offered treatment with these drugs. Further analysis of the subgroups results from this study, as well as repeated trial in groups with normal CRP levels will be required before new indications for statin use can be confirmed.