Research highlights – 25 March 2011

Research questions “Research highlights” is a weekly round-up of research papers appearing in the print BMJ. We start off with this week’s research questions, before providing more detail on some individual research papers and accompanying articles.

Comparative cardiovascular effects of thiazolidinediones
Last October rosiglitazone was withdrawn from the European market in response to mounting concerns about its cardiovascular safety, regulatory failures (see the BMJ’s investigation, BMJ 2010;341:c4848), and a belated recommendation from the European Medicines Agency (BMJ 2010;341:c727). Yet the drug is still on the market in the US, albeit with prescribing restrictions. 

What about pioglitazone? There have been no long term trials directly comparing the cardiovascular harms of  the two thiazolidinediones. But observational studies, including two in the BMJ (BMJ 2009;339:b2942, BMJ 2009;339:b4731) have suggested that pioglitazone is safer than rosiglitazone. And now Yoon Kong Loke and colleagues’ meta-analysis of 16 observational studies with 810, 000 mostly older patients adds much weight to this message. Numbers needed to treat to harm, depending on the population at risk, suggest 170 excess myocardial infarctions, 649 excess cases of heart failure, and 431 excess deaths for every 100, 000 patients who receive rosiglitazone rather than pioglitazone.

Reviewing the rosiglitazone saga, editorialists Victor Montori and Nilay Shah from the Mayo Clinic in the United States ask, “Has the corruption of healthcare advanced so far that it is unreasonable, even naive, to expect responsible drug companies, enlightened regulators, and thoughtful prescribers?” And they warn that inadequate regulation of the newest diabetes agents, dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 agonists, could lead to a similar mess.

Supplementing parenteral nutrition with glutamine or selenium

Many critically ill patients have gastrointestinal dysfunction and so require parenteral nutrition. However, standard parenteral nutrition formulations are lacking in glutamine and selenium, both necessary for optimal immune function and recovery from disease. Several small trials have suggested that supplementing parenteral nutrition with glutamine or selenium can reduce mortality and new infections, but the results are not conclusive.

The SIGNET Trials Group has conducted a large randomised controlled trial (reported by Peter Andrews and colleagues) to test whether the inclusion of glutamine, selenium, or both in a standard preparation of parenteral nutrition influenced the rate of new infections and mortality in 502 critically ill patients. The primary (intention to treat) analysis found no difference in either outcome with the trial interventions, but a preplanned subgroup analysis of those patients who received at least five days of parenteral nutrition found a significant reduction in new infections with selenium supplementation. The authors acknowledge that this result, from only a subset of the randomised participants, requires confirmation.

Parenteral nutrition is also discussed in this week’s clinical review by Geert Wanten and colleagues; in this case its use at home for patients with long term intestinal failure. Although glutamine and selenium deficiency can develop over time, the main problems stem from complications related to venous access, particularly infections, and from liver dysfunction and altered bone mineralisation.

Long term statins and atrial fibrillation
Atrial fibrillation is a common problem, and likely to become more so as the life expectancies of populations increase. Some have looked to statins as a potential solution, attractive by virtue of their falling costs and good safety profiles as well as their effectiveness against a wide range of cardiovascular conditions. And indeed, the findings of some studies suggest that the drugs do have a protective effect against atrial fibrillation.

Kazem Rahimi and colleagues reviewed the evidence in search of a conclusive answer. They found that while shorter term studies supported the use of statins to prevent atrial fibrillation, longer term and larger trials showed no protective effect. The meta-analysis, say the authors, does not completely exclude a real reduction in risk, but “casts doubt over the existence of any sustained and clinically relevant beneficial effect.”

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