Research highlights – 6 May 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.

Angiotensin receptor blockers and risk of myocardial infarction
Seven years ago, an unexpected result of the valsartan antihypertensive long term use evaluation (VALUE) trial in the Lancet led editorialists in the BMJ to say that angiotensin receptor blockers “may increase myocardial infarction—and patients may need to be told” (BMJ 2004;329:1248-9).

Sripal Bangalore and colleagues’ meta-analysis of individual trial summary data now strongly refutes the hypothesis, ruling out even a 0.3% absolute increase in the risk of myocardial infarction. This analysis also found that, while angiotensin receptor blockers do not actually protect against myocardial infarction or cardiovascular death, they do lower blood pressure (compared with placebo) and reduce the risk of stroke, heart failure, and diabetes (compared with active treatment or placebo). On Medscape’s website, Dr Bangalore said that “many people are still spooked by a somewhat controversial editorial in BMJ in 2004, which suggested that ARBs might increase the risk of MI. This article was the subject of much ‘bad press’ at the time, he says, and although many doctors were split on this issue, with some pooh-poohing the link, others have been nervous, and ‘there has been no other news since to counter the argument.’”

Back in the BMJ, editorialist Richard Hobbs muses that “it would be interesting to know how many clinicians have debated the speculative risk of myocardial infarction related to ARBs with their patients since the controversy emerged.” He concludes that doctors can now discuss with patients the modest relative benefits of these drugs, and also notes that most commonly prescribed ARBs are already generic or will be by 2012.

Levothyroxine dose and risk of fractures in older adults
About a fifth of older people in Canada are on long term levothyroxine replacement therapy for hypothyroidism. But the need for levothyroxine falls naturally with ageing, leading to overtreatment if doses aren’t adjusted. Marci Turner and colleagues’ study indicates that this may be associated with an increased risk of fractures. The authors analysed anonymised linked health records of more than 200 000 men and women aged 70-105 in Ontario, Canada, and found a strong dose-response relation between current use of levothyroxine and any fracture over the next 3.8 years. In all, 10% of current levothyroxine users had a fracture (most of them women) and among them 15.0% were on low doses, 53.2% on medium doses, and 31.8% on high doses.
In a linked editorial Graham P Leese and Robert V Flynn recommend that serum TSH should be regularly monitored in older patients and that the reference ranges (usually 0.4-4.0 mU/L) should be reappraised for this age group.

Reporting eligibility criteria for trials participants
Despite the publication of several iterations of the CONSORT statement since 1996 to improve the quality of reporting of clinical trials, problems still remain. One aspect of concern is the reporting of the eligibility criteria used to select trial participants. Precise definition of a trial’s study population is necessary for assessment of how widely the results are applicable to other patients with the same condition.

Anette Blümle and colleagues examined research protocols submitted to the research ethics committee of the University of Freiburg, Germany, in 2000 and linked them to any subsequent published reports of randomised controlled trials. Of the 52 completed trials with published reports, all had discrepancies between the participants’ eligibility criteria prespecified in the protocols and those listed in the publications. In total, about half of the prespecified eligibility criteria were either modified or not reported in the publications. The authors acknowledge that they don’t know the reasons for the observed differences, which could include real changes to the eligibility criteria made during the course of the studies. However, such discrepancies make it more difficult to accurately assess the applicability of trial results in a wider context, and in their full paper the authors call for trial protocols to be made publicly accessible.

Arsenic and cardiovascular disease
Yu Chen and colleagues’ cohort study found that in Bangladesh, exposure to arsenic in drinking water was adversely associated with mortality from heart disease, especially among smokers.

Antibiotic prophylaxis for prevention of infective endocarditis
In 2008, a clinical guideline from the UK National Institute for Health and Clinical Excellence recommended the cessation of antibiotic prophylaxis before invasive dental procedures for patients at risk of infective endocarditis. Martin Thornhill and colleagues report the effect of this guidance on prescribing of antibiotic prophylaxis and incidence of infective endocarditis.