Young, Annie (2011)
Ph.D. thesis, University of Birmingham.
This thesis focuses on a nurse-led trial assessing the thromboprophylactic utility of warfarin in cancer patients (n=1590) with central venous catheters and designed following a UK survey of practice.
Clinicians who were ‘uncertain’ of the benefits of warfarin, randomised patients to no warfarin vs fixed dose warfarin of 1mg (FDW) vs dose adjusted warfarin (DAW) to maintain the international normalised ratio (INR) between 1.5 and 2.0. Clinicians, who were ‘certain’, randomised patients between FDW and DAW. The primary endpoint was the number of symptomatic catheter-related thrombotic events (CRT).
Compared to no warfarin, warfarin (79% FDW; 21% DAW) did not reduce CRT [5.9% vs 5.9%; relative risk (RR) 0.99, (95% Confidence Interval (CI) 0.57-1.72), p=0.98]. However, compared to FDW, DAW was superior in preventing CRT [2.8% vs 7.2%; RR 0.38, (95%CI 0.20-0.71), p=0.002]. Major bleeding events were rare; an excess was observed with warfarin compared to no warfarin (7 vs 1, p=0.07) and with DAW compared to FDW (16 vs 7, p=0.09).
There is no benefit in using low dose warfarin in CRT prophylaxis. DAW shows benefit over FDW but at a cost of major bleeding events. Subsequent meta-analysis confirmed the primary finding. This research has changed clinical practice internationally.
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