Tuesday February 19 2008
Statins are used to lower cholesterol levels
Statins, which are used for lowering cholesterol, could help restore a regular heartbeat, reports The Times. Not only do these drugs reduce the risk of heart attacks and heart disease, but they “could help reduce risk of irregular heartbeat (medically known as atrial fibrillation), a condition that affects one in 20 people over the age of 70”, the newspaper said.
This news article is based on a systematic review and pooling of six studies of statins in about 3,500 people who were at risk of developing atrial fibrillation. Although the review indicates that statins may reduce the risk of atrial fibrillation in some people, limitations to the findings mean that it can’t be concluded that the benefits can be found across all patient groups, nor can the level of benefit be determined.
Where did the story come from?
Dr Laurent Fauchier and colleagues from the Centre Hospitalier Universitaire Trousseau in Tours, France, carried out this research. No sources of funding for this study were reported. It was published in the peer-reviewed medical journal: Journal of the American College of Cardiology.
What kind of scientific study was this?
This was a systematic review and meta-analysis which looked at the effects of statins on the risk of atrial fibrillation. The researchers searched an electronic database of research, looking for randomised controlled trials that compared statins with a placebo or a control treatment published between January 1980 and June 2007. The researchers also looked for studies that were mentioned in reference lists, other reviews and studies, or that were presented at three cardiology conferences between 2001 and 2007.
In order to be included, the studies needed to examine whether participants developed atrial fibrillation, and to follow patients for at least three weeks. The researchers then assessed the quality of the relevant studies using accepted criteria. The results from all the studies were pooled (meta-analysed) using statistical methods that took into account the fact that studies had different (heterogeneous) results.
What were the results of the study?
The researchers identified six randomised controlled trials that met their inclusion criteria. These trials included a total of around 3,500 people. Five of the trials used the statin atorvastatin and one used pravastatin. Four of the trials compared the statin with a placebo, and two compared the effects of adding the statin to a standard treatment regimen with the standard treatment regimen alone.
In three trials the participants were receiving treatment for persistent atrial fibrillation or had experienced episodes of atrial fibrillation in the past. The other three trials included people who were at risk of developing atrial fibrillation because they had had heart surgery or had a particular type of heart disease called acute coronary syndrome. The trials followed up participants for between three and 26 weeks.
When results were pooled for all studies, about 9% of people in the statin group experienced atrial fibrillation during follow-up compared with 12% in the control group. This represented a significant reduction of 61% in the calculated odds ratio of developing atrial fibrillation.
What interpretations did the researchers draw from these results?
The researchers concluded that statins reduced the risk of atrial fibrillation in people with a history of atrial fibrillation or in those who had heart surgery or acute coronary syndrome.
What does the NHS Knowledge Service make of this study?
There are a number of points that should be kept in mind when interpreting the results of this systematic review:
- In a meta-analysis it is important to consider whether the studies are similar enough to be combined in a meaningful way. There were statistical differences between the study results, which were still there even when the authors used complex calculations that took differences into account. This suggests that the pooled results should be interpreted with caution, as it indicates that there are differences in the effects of statins in the individual studies that make them too different to pool meaningfully. One possible reason is that the studies were carried out in different populations (people with a history of atrial fibrillation, acute coronary syndrome, or who have had heart surgery) and statins may have different effects on these different populations. In general, the studies were too small to estimate the effect of statins in the different populations.
- The authors used a particular measure to compare the risk of atrial fibrillation in the two groups, called the "odds ratio". This is used to give an estimate of how many times more or less likely an event is in one group than another (in other words, the relative risk of an event). It gives a good estimate of this value when the risk of an event is low, but when the risk is high, it tends to overestimate the difference between the groups. In this case, if the actual relative risk were calculated, the reduction in the risk of atrial fibrillation with statins would still be significant, but the reduction in risk would be less than 61%.
- Studies with non-significant results are less likely to be published than studies with significant results, known as "publication bias". If publication bias exists, it can affect the results of a meta-analysis, tending to make the overall result more significant. By looking at the spread of the results, the authors found no evidence of "major" publication bias, but it can be difficult to tell whether such a bias does exist.
- The period of follow-up after statin treatment was started was short, so it isn’t possible to be certain about the effects of statins in the longer term.
- People involved in these trials were often taking several different types of treatment, and if the groups were receiving different medications, this could affect the results. The authors report that use of other medications was similar in the groups, but figures for the individual groups in each study were not presented, and so it’s difficult to assess this based on the information provided.
- The authors included one study published as a conference abstract only, and this study included the majority of patients in this analysis (3,086 people with acute coronary syndrome). On its own, this study didn’t find a significant difference in atrial fibrillation with the statins, while the smaller published studies tended to find a reduction in the risk of atrial fibrillation. Studies published as conference abstracts have not been through the same rigorous checking process as studies published in peer-reviewed journals, and often the abstract does not provide enough information for a full assessment of the quality and results of the study. In this case, the authors report that the study was of high quality according to an accepted scale, and had this study been excluded, the results would still show a significant reduction in atrial fibrillation with the statins.
The results of this study do suggest that statins may offer a reduction in risk of atrial fibrillation among certain populations. However, as the authors acknowledge, larger randomised controlled trials are needed to confirm these results.
Sir Muir Gray adds...
Good drugs, statins.