Yes, warfarin is effective in the secondary prevention of venous thromboembolic events (VTEs) for patients positive for lupus anticoagulant or anticardiolipin antibody (also known as antiphospholipid antibodies [aPL]) (strength of recommendation [SOR]: B, single cohort study, extrapolation from other RCTs). Patients should be treated for at least a year (SOR: C, consensus statement), and possibly indefinitely, with warfarin (SOR: B, small clinical trials and cohort studies). Moderate-intensity therapy (international normalized ratio [INR] range, 2.0-3.0) appears to be the best balance between risks and benefits (SOR: B, based on meta-analysis of 2 small randomized control trials

Jamieson, Barbara

Mazzone, Michael F.

University of Missouri: MOspace

	 vol	56,	No	4	/	april	2007	 309www.jfponline.comCliniCal iNquiries From the Family Physicians Inquiries NetworkDoes warfarin prevent  venous thromboembolic events in aPL-positive patients?Michael F. Mazzone, MD Waukesha Family Medicine    Residency Program,  Waukesha; Department of  Family and Community  Medicine, Medical College of        Wisconsin, MilwaukeeBarbara Jamieson, MlSMedical College of Wisconsin, MilwaukeeEvidence-based answerYes,	warfarin	is	effective	in	the	secondary	prevention	of	venous	thromboembolic	events	(vTes)	for	patients	positive	for	lupus	anticoagulant	or	anticardiolipin	antibody	(also	known	as	antiphospholipid	antibodies	[apl])	(strength	of	recommendation	[sor]:	B,	single	cohort	study,	extrapolation	from	other	rCTs).	patients	should	be	treated	for	at	least	a	year	(sor:	C,	consensus	statement),	and	possibly	indefinitely,	with	warfarin	(sor:	B,	small	clinical	trials	and	cohort	studies).	Moderate-intensity	therapy	(international	normalized	ratio	[iNr]	range,	2.0–3.0)	appears	to	be	the	best	balance	between	risks	and	benefits	(sor:	B,	based	on	meta-analysis	of	2	small	randomized	control	trials).		 little	evidence	exists	regarding	primary	prevention	for	patients	with	an	incidental	finding	of	either	apl.	For	these	individuals,	the	risks	of	warfarin	may	outweigh	any	benefits.	Many	experts	recommend	primary	prevention	with	aspirin	for	those	individuals	who	are	apl	positive	and	who	do	not	have	contraindications	to	aspirin	or	another	compelling	reason	for	warfarin	use	(malignancy,	family	history,	or	accompanying	hypercoagulable	state)	(sor:	C,	expert	opinion).Clinical commentaryConsider this syndrome when  a younger patient has had an idiopathic thromboembolism episodeantiphospholipid	antibodies	have	a	prevalence	rate	of	1%	to	5%	in	the	general	population,	and	12%	to	34%	among	patients	with	systemic	lupus	erythematosus.1	The	prevalence	of	antiphospholipid	antibodies	increases	with	age,	especially	among	elderly	patients	with	coexistent	chronic	illness.		 patients	with	antiphospholipid	antibodies	are	not	always	symptomatic.	Common	manifestations	may	include	arterial	and	venous	thromboembolic	events,	frequent	miscarriage,	thrombocytopenia,	hemolytic	anemia,	and	livedo	reticularis.2	 Family	physicians	should	consider	this	syndrome	when	a	patient	≤50	years	old	has	had	an	episode	of	idiopathic	thromboembolism,	or	an	unexplained	elevated	activated	partial-thromboplastin	time,	or	a	history	of	miscarriage.	a	previous	study3	reported	that	presence	of	lupus	anticoagulant	is	associated	with	increased	risk	of	recurrent	thromboembolic	events.Therefore,	it’s	reasonable	to	continue	anticoagulation	with	warfarin	indefinitely	for	these	patients,	after	their	first	episode	of	a	thromboembolic	event.Vincent lo, MDsan	Joaquin	General	Hospital,	French	Camp,	CalifCoNT iNueDfast trackModerate-intensity warfarin (to an INR of 2–3) appears  to be the best balance between risks and benefitsC pyright® Dowden Health Media  For personal use onlyFor mass reproduction, content licensing and permissions contact Dowden Health Media.fast track310 vol	56,	No	4	/	april	2007		ThE Journal of family PraCTiCECliniCal iNquiriesz Evidence summaryLupus anticoagulant and anticardio-lipin antibodies are known to increase risk of both arterial and venous throm-boembolic events. One study prospectively followed patients ≥15 years old recruited from 16 hospitals in Sweden, who had their first or second episode of a VTE. Patients with malignancy or a known congenital deficiency of an inhibitor of coagula-tion were excluded. These patients were followed for 4 years. Each received at least 6 months of warfarin therapy (INR=2.0–2.85) after initial diagnosis of a VTE. After treatment, the 4-year re-currence rate for VTEs was 29% for patients with aPL (20/68) vs 14% for patients without (47/344) (relative risk [RR]=2.1; 95% confidence interval [CI], 1.3–3.3). The risk of death for those patients with aPL was 15% (10/68) vs 6% for those without (20/324) (RR=1.8; 95% CI, 0.9–3.6). In the same study, those with an aPL and a second clot were random-ized to a second 6 months of therapy vs indefinite therapy (INR=2.0–2.85). After 4 years, their risk of another re-currence was 20% (3/15) with 6 months of therapy vs 5% (1/19) with indefinite therapy. This underpowered study did not show a statistical difference under intention-to-treat analysis; however, the single failure in the treatment group had stopped the warfarin prior to the event.4Moderate intensity therapy  does the jobTwo recent randomized controlled tri-als have shown that moderate-inten-sity warfarin therapy (INR=2.0–3.0) is equally efficacious to high-intensity therapy (INR=3.0–4.0).5,6 In these small studies, those with aPL were random-ized to moderate-intensity vs high- intensity therapy and followed for ap-proximately 3 years. A meta-analy-sis of these studies (done in conjunc-tion with the second study) remained insufficiently powered to show any significant differences between high- and moderate-intensity therapy, but there was a trend towards increased thrombosis and bleeding events in the high-intensity groups.6 Of note, the relative risk for developing a VTE was lower in these studies than in those with time-limited treatment, suggesting that indefinite treatment may be indicated. Warfarin probably isn’t best  for primary preventionWahl et al7 constructed a decision analysis of antithrombotic therapy for patients with systemic lupus erythema-tosus with and without aPL. They com-pared observation alone with aspirin and with warfarin for the primary pre-vention of VTE. Using a decision analy-sis based on the best available efficacy rates, they recommended that the ben-efits of prophylactic aspirin outweigh the risks. However, due to high com-plication rates, warfarin’s benefits are outweighed by the risks. This analysis has not been validated in an actual pa-tient population and remains theoreti-cal in nature, but is the best available evidence regarding primary prevention of VTE for patients with aPL.Recommendations from othersGuidelines from the American College of Chest Physicians recommend at least 12 months of treatment with warfarin and suggest indefinite treatment for pa-tients with a VTE and antiphospholipid antibodies. The guidelines also suggest a target INR of 3.0 (range, 2.5–3.5) for pa-tients with recurrent VTEs or additional risk factors, and a therapeutic INR of 2.5 (range, 2.0–3.0) for patients with a VTE and lupus anticoagulant but no addition-al risk factors.8The Thrombosis Interest Group of Canada also recommends considering in-definite treatment for those with a VTE and a positive test for any of the antiphos-pholipid antibodies.9 nAmerican College of Chest Physicians advisory:  12 months of  warfarin, and  indefinite therapy if a VTE patient has antiphospholipid antibodiesWarfarin to prevent VTEs in aPl-positive patientswww.jfponline.com 	 vol	56,	No	4	/	april	2007	 311references	 1.	 	petri	M.	epidemiology	of	the	antiphospolipid	anti-body	syndrome.	J Autoimmune 2000;	15:145–151.	 2.	 	levine	Js,	Branch	DW,	rauch	J.	The	antiphospho-lipid	syndrome.	N Engl J Med	2002;	346:752-63.	 3.	 	Kearon	C,	 Gent	M,	 Hirsh	 J,	 et	 al.	 a	 comparison	of	 three	months	of	anticoagulation	with	extended	anticoagulation	 for	 a	 first	 episode	 of	 idiopathic	venous	 thromboembolism.	 N Engl J Med	 1999;	340:901–907.	 4.	 	schulman	 s,	 svenungsson	 e,	Granqvist	 s.	 anti-cardiolipin	 antibodies	 predict	 early	 recurrence	 of	thromboembolism	and	death	among	patients	with	venous	 thromboembolism	 following	anticoagulant	therapy.	 Duration	 of	 anticoagulant	 study	 Group.	Am J Med	1998;	104:332–338.	 5.	 	Crowther	Ma,	Ginsberg	Js,	Julian	J,	et	al.	a	com-parison	of	two	intensities	of	wararin	for	the	preven-tion	 of	 recurrent	 thrombosis	 in	 patients	 with	 an-tiphospholipid	antibody	syndrome.	N Engl J Med	2003;	349:1133–1138.	 6.	 	Finazzi	G,	Marchioli	r,	Brancaccio	v,	et	al.	a	ran-domized	clinical	 trial	of	high-intensity	warfarin	vs.	conventional	 antithrombotic	 therapy	 for	 the	 pre-vention	of	recurrent	thrombosis	in	patients	with	the	antiphospholipid	 syndrome.	 J Thromb Haemost 2005;	3:848–353.	 7.	 	Wahl	DG,	Bounameaux	H,	de	Moerloose	p,	sarasin	F.	prophylactic	antithrombotic	therapy	for	patients	with	 systemic	 lupus	 erythematosus	 with	 or	 with-out	 antiphospholipid	 antibodies.	Arch Intern Med	2000;	160:2042–2048.	 8.	 	Hirsh	J,	Guyatt	G,	albers	G,	schunemann	H.	The	seventh	aCCp	Conference	on	antithrombotic	and	Thromboyltic	Therapy:	evidence	Based	Guidelines.	Chest 2004;	126:172s–173s.		 9.	 	Carter	C.	 The	 antiphospholipid	 syndrome.	 The	Thrombosis	 interest	 Group	 of	 Canada	 web	 site.	updated	 June	 2004.	 available	 at:	 www.tigc.org/eguidelines/antiphoslipid04.htm.	 accessed	 on	March	7,	2007.Warfarin to prevent VTEs in aPl-positive patients CMEEvidence-Based Practice“Do you EBP?”Evidence-based medicine from a team  you trust—a monthly newsletter published by and for family physiciansz Transforming Practice, plus updates  When the evidence points to a change in practice,  we explain whyz Editor’s News Alert  Keep up with the latest in the world of healthcare, always staying focused on the evidencez The Help Desk Answers series Concise answers to your relevant clinical questionsz Drug Profile  Objective reviews of the drug messages  targeting physicians and patients in the media  and on the Internet PLUS z Behavioral Health Matters z Ever-expanding exclusive content z 3 CME credits monthlyIndependently brought to you every month by theFamily Physicians Inquiries NetworkPhone: 573-256-2066Email: ebp@fpin.orgVisit www.ebponline.net to subscribe online or to request FREE sample issues

Does warfarin prevent venous thromboembolic events in aPL-positive patients?

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