25th November 2011, Volume 124 Number 1346

Do hormones protect women from ischaemic heat disease?

Although heart disease mortality increases with age, it was thought to be lower in women than in men because of the protective effects of premenopausal hormone levels. This proposition is examined in this paper which reviews three birth cohorts in England and Wales and the US and their subsequent incidence of death from ischaemic heart disease. They regarded 45 years of age to be the average age of menopause and their findings were that heart disease mortality in women increased exponentially with age, with no acceleration after age 45 years.
On the other hand they report that in men there was a rapid increase during young adulthood followed by a deceleration in mortality rates after age 45 years. They suggest that the early rapid acceleration seen in male heart disease mortality could explain these sex differences rather than menopausal changes in women.
BMJ 2011;343:5170.

Can the anticoagulant effects of rivaroxaban and dabigatran be reversed by prothrombin complex concentrate (PCC)?

Currently dabigatran (a direct thrombin inhibitor) and rivaroxaban (a direct factor Xa inhibitor) are the most extensively evaluated novel anticoagulant agents. Neither of these drugs require monitoring blood tests and neither have significant interactions with other drugs. Their anticoagulant effects are comparable with warfarin. However, to date, no method of reversing their effects has been demonstrated. In this randomised, double-blind, placebo-controlled study, 12 healthy male volunteers received ribaroxaban 20mg twice daily (n=6) or dabigatran 150mg twice daily (n=6) for 2½ days. This was followed by a single bolus of PCC (50 IU/kg) or a similar volume of saline. They report that PCC immediately and completely reverses the anticoagulant effect of rivaroxaban in healthy subjects but has no influence on the anticoagulant action of dabigatran at the PCC dose used in this study. Encouraging.
An editorial writer notes these results but points out that they need to be confirmed in the real life setting—viz will the PCC reverse the bleeding as well as the blood tests? She also points out that there is some variability in different PCC formulations.
Circulation 2011;124:1573-9 & 1508-9.

New guidelines for hypertension management in UK

The recent updated guidelines from the National Institute for Health and Clinical Excellence (NICE) on the management of hypertension in adults are not without interest and are relevant to our situation. They recommend ambulatory or home blood pressure monitoring to avoid the over treatment of people with “white coat” hypertension.
For the first time, targets have been partially relaxed. Admittedly this applies only to people aged 80 or more, in whom a target blood pressure lower than 150/90mmHg is recommended. The previous target of 140/90mmHg is retained for everyone else. Thiazides are no longer recommended as first line drugs unless other indications exist. Calcium channel blockers are preferred first drugs for patients over 55 years and angiotensin converting enzyme inhibitors or angiotensin receptor blockers are recommended for younger patients. It is acknowledged that many patients will need a combination of drugs for optimal management.
BMJ 2011;343:5644.

Chronic obstructive pulmonary disease (COPD) – lifetime risk

This paper from Canada sets the scene by noting that the World Health Organisation has declared chronic obstructive pulmonary disease the fourth most common cause of death worldwide and estimates that it will be the third by 2030. They performed a retrospective longitudinal cohort study from health records in Ontario (population roughly 13 million).
All individuals free of COPD in 1996 were monitored for up to 14 years for three possible outcomes; diagnosis of COPD by a physician, reached 80 years of age, or death. Well over half a million individuals were diagnosed as having COPD over the study period. The precise figure was 27.6% lifetime risk by the age of 80 years. It was higher in men (29.7%) than in women (25.6%). They advocate a more aggressive approach to detection, prevention and management.
Lancet 2011;378:991-6.

Oral teriflunomide for relapsing multiple sclerosis

Teriflunomide, the active metabolite of leflunomide, has been shown in phase 1 and 2 trials to possibly be useful in the management of relapsing multiple sclerosis. This report concerns a phase 3 randomised trial comparing two dosages of teriflunomide with a placebo. 1008 patients with multiple sclerosis who had previously suffered at least one relapse in the previous year or at least two relapses in the previous two years were entered in the trial. They were randomly assigned (in a 1:1:1 ratio) to placebo, 7mg of teriflunomide, or 14mg of teriflunomide once daily for 108 weeks. The primary end point was the annual relapse rate and the secondary end point was disability progression.
Their conclusions were that teriflunomide significantly reduced relapse rates, disability progression (at the higher dose), and MRI evidence of disease activity, as compared with placebo. Diarrhoea, nausea, and hair thinning were more common with teriflunomide than with placebo. However, these events rarely lead to discontinuation of treatment.
N Engl J Med 2011;365:1293-303.