Journals Watch - Warfarin, BCG and bronchiolitis

Too busy to read all the journals? Let Dr Simon Hunter keep you up to date with the latest research.

Oral thromboprophylaxis Lancet 2009; 373: 1,673-80
The risk of DVT post major joint surgery is well established, as is the use of heparin post op to reduce the risk. At least 10 days of heparin usage post op is recommended. Given shorter hospital stays, this introduces the inconvenience of giving a regular injection at home.

Angiogram of a DVT: oral rivaroxaban was shown to be more effective in preventing DVT than enoxaparin

This study compared subcutaneous enoxaparin 30mg every 12 hours against the new drug oral rivaroxaban 10mg once daily. Rivaroxaban directly inhibits factor Xa, an enzyme of the coagulation cascade involved in the formation of thrombin.

The authors looked at the number of episodes of venous thrombosis and safety outcomes (bleeding). In the rivaroxaban group, 6.9 per cent had venous thrombosis compared with 10.1 per cent in the enoxaparin group, an absolute risk reduction of 3.2 per cent. There was an insignificant increase in bleeding on rivaroxaban.

The next question is can this be used instead of warfarin for the treatment of DVTs?

Duration of anticoagulation Ann Intern Med 2009; 150: 577-85
Residual thrombosis on ultrasound when warfarin is withdrawn is associated with a substantial increase in risk of recurrence of venous thromboembolism (VTE), while prolonged anticoagulation is associated with an increased risk of bleeding.

This study took patients who had received three months of warfarin post-DVT and randomised them into two groups.

The first had their warfarin stopped if they had a secondary DVT or had an extra three months warfarin if it was an unprovoked DVT.

The second group's length of warfarinisation was guided by ultrasonography. If the vein was recanalised, warfarin was stopped, otherwise it was continued for up to nine months for a secondary DVT or up to 21 months for unprovoked DVT.

The rate of confirmed DVT was measured over 33 months.

Of the fixed duration group, 17.2 per cent had a recurrent DVT compared with 11.9 per cent of the flexible group, hazard ratio 0.64. This seems like a good method if the extra ultrasonography could be provided outside a research setting.

Also of note is the recurrence rate - one in five. We really need to be on our guard for recurrence of DVT.

Adding clopidogrel to aspirin post stroke N Engl J Med 2009; 360: 2,066-78
Warfarin is frequently recommended after a stroke because it can reduce recurrence by 64 per cent compared with 22 per cent for aspirin, which is used where warfarin is unsuitable.

This trial (supported by grants from Sanofi-Aventis and Bristol Myers Squibb) examined the effect of adding clopidogrel to aspirin for patients with increased risk of stroke.

A total of 7,554 patients, with an average age of 70, were recruited and followed up for 3.5 years. The aspirin and placebo group had a re-stroke rate of 3.3 per cent a year while the aspirin and clopidogrel group's rate was 2.4 per cent; the relative risk with clopidogrel, 0.72.

The addition of clopidogrel caused a relative risk reduction to 0.78 for MI (0.7 vs 0.9 per cent) and 0.89 for any major vascular events (6.8 vs 7.6 per cent), both significant. However, the addition of clopidogrel led to a relative risk increase of a major bleed to 1.57 (2.0 vs 1.3 per cent).

Protective effect of BCG Arch Dis Child 2009; 94: 392-3
In Ireland, there is significant regional variation in the use of BCG vaccination, and in Cork it is given on parental request.

In March 2007, there was a TB outbreak in two childcare centres in Cork with children exposed to two workers with smear-positive TB, one with cavitating disease on X-ray. Both cases were Irish born.

A total of 268 children were exposed and 18 cases were diagnosed. Of these, only 66 per cent were Mantoux positive.

The most significant observation was that all 18 cases were in the non-immunised population. No child who had received the BCG contracted TB.

In the UK, routine BCG has been stopped despite 7,000 (and rising) new cases a year and an ever more mobile world population. The Mantoux test does not seem that reliable and I wonder if we have made the right decision to stop routine BCG.

Temperature and age appropriate heart rates Arch Dis Child 2009; 94: 361-5
NICE recommends that heart rate should be part of the assessment of a febrile child, despite acknowledging there are no suitable reference data. The current reference charts, while age-specific, do not take into account temperature, a factor that is known to increase heart rate.

In this paper, charts have been constructed for children aged three months to 10 years at various temperatures caused by non-serious infections - typically URTIs or non-specific viral infections.

The trend was that heart rate increases by 9.9-14.1 bpm for each 1 degsC rise of temperature. The charts can then be used as part of the assessment of a febrile child to see if the heart rate falls outside the reference values, raising suspicion of a more significant illness.

They are only part of the clinical picture but I think I will keep the charts on my desk.

Adrenaline + dexamethasone for bronchiolitis N Engl J Med 2009; 360: 2,079-89
A number of studies have looked at the effect of nebulised adrenaline or corticosteroids alone to treat bronchiolitis, but not in combination.

The study on infants had four arms: nebulised adrenaline in the emergency department and oral dexamethasone for six days, adrenaline and placebo oral treatment, placebo nebuliser and oral dexamethasone, and lastly placebo nebuliser and placebo oral treatment.

The outcome measure was hospital admission within seven days.

By seven days, 17.1 per cent of the adrenaline + dexamethasone group, 23.7 per cent of the adrenaline group, 25.6 per cent of the dexamethasone group and 26.4 per cent of the placebo group were admitted.

The addition of adrenaline seems to produce a synergistic affect, whereas dexamethasone on its own seems surprisingly disappointing on the results of this study.

  • Dr Hunter is a GP in Bishop's Waltham, Hampshire and a member of our team who regularly review the journals.

The quick study

  • Rivaroxaban reduced the risk of venous thrombosis compared with enoxaparin.
  • Post-VTE treatment with warfarin does not exclude risk of recurrence.
  • Clopidogrel combined with aspirin reduced the risk of a stroke or MI.
  • BCG vaccination prevented children contracting TB in a recent outbreak but not all children had been immunised.
  • Heart rate increases by 9.9-14.1 bpm for each 1 degsC rise of temperature in children.
  • Bronchiolitis treatment outcomes were improved when adrenaline was combined with dexamethasone.

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