Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website http://www.cardiologyres.org

Review

Volume 10, Number 5, October 2019, pages 255-267

The Impact of Antithrombotic Regimens on Clinical Outcomes After Endovascular Intervention and Bypass Surgery for Infrapopliteal Artery Disease

**Table 1.** Drugs and Mechanism of Actions
Drugs	Mechanism of actions
PDE: phosphodiesterase; ADP: adenosine diphosphate.
Antiplatelet
Aspirin	Thromboxane A2 inhibitors
Cilostazol	Phosphodiesterase inhibitors
Clopidogrel	P2Y12/ADP receptor inhibitors
Lipo-ecraprost	Prostaglandin E1 analog
Ticagrelor	P2Y12/ADP receptor inhibitors
Ticlopidine	P2Y12/ADP receptor inhibitors
Dipyridamole	PDE inhibitors
Anticoagulant
Batroxobin	Defibrinating agents
Warfarin	Inhibiting the synthesis factors II, VII, IX and X, as well as the regulatory factors protein C, protein S, and protein Z
Heparin	Inactivating thrombin and factor Xa
Dabigatran	Preventing thrombin-mediated activation of coagulation factors
Rivaroxaban and apixaban	Inhibiting free factor Xa and factor Xa bound in the prothrombinase complex

Table 1. Drugs and Mechanism of Actions

Drugs

Mechanism of actions

PDE: phosphodiesterase; ADP: adenosine diphosphate.

Antiplatelet

Aspirin

Thromboxane A2 inhibitors

Cilostazol

Phosphodiesterase inhibitors

Clopidogrel

P2Y12/ADP receptor inhibitors

Lipo-ecraprost

Prostaglandin E1 analog

Ticagrelor

P2Y12/ADP receptor inhibitors

Ticlopidine

P2Y12/ADP receptor inhibitors

Dipyridamole

PDE inhibitors

Anticoagulant

Batroxobin

Defibrinating agents

Warfarin

Inhibiting the synthesis factors II, VII, IX and X, as well as the regulatory factors protein C, protein S, and protein Z

Heparin

Inactivating thrombin and factor Xa

Dabigatran

Preventing thrombin-mediated activation of coagulation factors

Rivaroxaban and apixaban

Inhibiting free factor Xa and factor Xa bound in the prothrombinase complex

**Table 2.** Antiplatelets and Anticoagulants Treatments Following Endovascular Intervention
Study/type	Procedure	Treatment/follow-up duration	Endpoints	Treatment groups and endpoint rates	Significance	Notes
RCT: randomized clinical trial; MAPT: mono-antiplatelet treatment; DAPT: dual antiplatelet treatment; EVT: endovascular therapy; TLR: target lesion revascularization; MACE: major adverse cardiac event; MCE: major cardiac event; n.s.: not significant; n.m.: not measured.
Placebo versus MAPT
Nehler [21], 2007/RCT	n.m.	Placebo vs. lipoecraprost (6 months)	Major amputation	Placebo (n = 41)	Lipo-ecraprost (n = 30)	n.s.	1) Included data for both bypass surgery and endovascular intervention, 2) major amputation was the only specific data reported for endovascular intervention. For combined results (bypass and endovascular), there were no differences for mortality rates or MCE
				12%	17%
MAPT vs. DAPT
Soga [23], 2017/RCT	Balloon angioplasty	Aspirin vs. aspirin + cilostazol (3 months)		Aspirin (100 mg/day) (n = 25)	Aspirin (100 mg/day) + cilostazol
			Restenosis	81%	82%	n.s.
			Major amputation	4%	4%	n.s.
			MACEs	4%	4%	n.s.
			Mortality	4%	0%	n.s.
			Bleeding events	0%	4%	n.s.
Antiplatelet group vs. antiplatelet group
Soga [22], 2012/retrospective	(Angioplasty), selection of an EVT approach was left to the discretion of the operator	Non-cilostazol group vs. cilostazol group (3 months)		Non-cilostazol group (n = 31)	Cilostazol group (n = 32)		Non-cilostazol group (aspirin (n = 14), thienopyridine (n = 2) alone, aspirin + thienopyridine (n=15)), cilostazol group (cilostazol (n = 3), aspirin + cilostazol (n = 16), thienopyridine + cilostazol (n = 3), aspirin + thienopyridine + cilostazol (n = 10))
			Restenosis	86%	56.8%	P = 0.001
			Reocclusion	42.1%	20.50%	P = 0.02
			TLR	49.1%	27.50%	P = 0.01
			MACEs	0%	0%	n.s.
			Mortality	0%	0%	n.s.
			Bleeding events	0%	0%	n.s.
Lejay [24], 2013/retrospective	Angioplasty with or without stenting	Aspirin + clopidogrel, followed by long-term clopidogrel (non-compliant) vs. aspirin + clopidogrel, followed by long-term clopidogrel (compliant); mean follow-up (30.3 ± 20.2 months)		Aspirin + clopidogrel, followed by long-term clopidogrel (non-compliant) (n = 10)	Aspirin + clopidogrel, followed by long-term clopidogrel (compliant) (n = 15)		1) Treatment doses were not specified, 2) statistics presented here for univariate analysis, 3) infrapopliteal procedure had a negative effect on non-compliant group, 4) bleeding events were not evaluated
			Survival	n.m.	n.m.	n.s.
			Primary patency	n.m.	n.m.	P < 0.01
			Limb salvage	n.m.	n.m.	n.s.
MAPT vs. anticoagulant
Wang [26], 2011/RCT	Angioplasty (intraluminal/subintimal)	Aspirin vs. aspirin + batroxobin (3 months)		Aspirin (100 mg/d) for minimum 12 months if no side effects (n = 206)	Aspirin (as control group) + batroxobin (5 IU/0.5 mL), two doses before and four doses after the procedure (n = 173)		1) Included combined data for infrapopliteal and femoropopliteal artery segments, 2) subgroup analysis for infrapopliteal was performed for reocclusion only, 3) for the comparison for combined infrapopliteal and femoropopliteal surgeries: a) rates were better for cumulative rate of major amputation or death and for limb salvage and survival rates, b) there were no differences for restenosis, reocclusion, major amputation, and mortality, and C) no differences for bleeding events
			Reocclusion	42.7%	27.7%	P = 0.0026
Wang [25], 2010/RCT (pilot)	Angioplasty (intraluminal/subintimal)	Aspirin vs. aspirin + batroxobin (12 months)		Aspirin (100 mg/d) for 12 months from admission if no side effects (n = 26)	Aspirin (control group) + batroxobin (5 IU/0.5 mL), two doses before and four doses after the procedure (n = 26)		1) No differences for serious bleeding events, 2) amputation-free rates are for major and minor amputation
			Restenosis/reocclusion	45%	26%	P = 0.0353
			Limb salvage rate	92.3%	96.2%	n.s.
			Amputation	15.4%	15.4%	n.s.

Table 2. Antiplatelets and Anticoagulants Treatments Following Endovascular Intervention

Study/type

Procedure

Treatment/follow-up duration

Endpoints

Treatment groups and endpoint rates

Significance

Notes

RCT: randomized clinical trial; MAPT: mono-antiplatelet treatment; DAPT: dual antiplatelet treatment; EVT: endovascular therapy; TLR: target lesion revascularization; MACE: major adverse cardiac event; MCE: major cardiac event; n.s.: not significant; n.m.: not measured.

Placebo versus MAPT

Nehler [21], 2007/RCT

n.m.

Placebo vs. lipoecraprost (6 months)

Major amputation

Placebo (n = 41)

Lipo-ecraprost (n = 30)

n.s.

1) Included data for both bypass surgery and endovascular intervention, 2) major amputation was the only specific data reported for endovascular intervention. For combined results (bypass and endovascular), there were no differences for mortality rates or MCE

12%

17%

MAPT vs. DAPT

Soga [23], 2017/RCT

Balloon angioplasty

Aspirin vs. aspirin + cilostazol (3 months)

Aspirin (100 mg/day) (n = 25)

Aspirin (100 mg/day) + cilostazol

Restenosis

81%

82%

n.s.

Major amputation

n.s.

MACEs

n.s.

Mortality

n.s.

Bleeding events

n.s.

Antiplatelet group vs. antiplatelet group

Soga [22], 2012/retrospective

(Angioplasty), selection of an EVT approach was left to the discretion of the operator

Non-cilostazol group vs. cilostazol group (3 months)

Non-cilostazol group (n = 31)

Cilostazol group (n = 32)

Non-cilostazol group (aspirin (n = 14), thienopyridine (n = 2) alone, aspirin + thienopyridine (n=15)), cilostazol group (cilostazol (n = 3), aspirin + cilostazol (n = 16), thienopyridine + cilostazol (n = 3), aspirin + thienopyridine + cilostazol (n = 10))

Restenosis

86%

56.8%

P = 0.001

Reocclusion

42.1%

20.50%

P = 0.02

TLR

49.1%

27.50%

P = 0.01

MACEs

n.s.

Mortality

n.s.

Bleeding events

n.s.

Lejay [24], 2013/retrospective

Angioplasty with or without stenting

Aspirin + clopidogrel, followed by long-term clopidogrel (non-compliant) vs. aspirin + clopidogrel, followed by long-term clopidogrel (compliant); mean follow-up (30.3 ± 20.2 months)

Aspirin + clopidogrel, followed by long-term clopidogrel (non-compliant) (n = 10)

Aspirin + clopidogrel, followed by long-term clopidogrel (compliant) (n = 15)

1) Treatment doses were not specified, 2) statistics presented here for univariate analysis, 3) infrapopliteal procedure had a negative effect on non-compliant group, 4) bleeding events were not evaluated

Survival

n.m.

n.s.

Primary patency

n.m.

P < 0.01

Limb salvage

n.m.

n.s.

MAPT vs. anticoagulant

Wang [26], 2011/RCT

Angioplasty (intraluminal/subintimal)

Aspirin vs. aspirin + batroxobin
(3 months)

Aspirin (100 mg/d) for minimum 12 months if no side effects (n = 206)

Aspirin (as control group) + batroxobin (5 IU/0.5 mL), two doses before and four doses after the procedure (n = 173)

1) Included combined data for infrapopliteal and femoropopliteal artery segments, 2) subgroup analysis for infrapopliteal was performed for reocclusion only, 3) for the comparison for combined infrapopliteal and femoropopliteal surgeries: a) rates were better for cumulative rate of major amputation or death and for limb salvage and survival rates, b) there were no differences for restenosis, reocclusion, major amputation, and mortality, and C) no differences for bleeding events

Reocclusion

42.7%

27.7%

P = 0.0026

Wang [25], 2010/RCT (pilot)

Angioplasty (intraluminal/subintimal)

Aspirin vs. aspirin + batroxobin (12 months)

Aspirin (100 mg/d) for 12 months from admission if no side effects (n = 26)

Aspirin (control group) + batroxobin (5 IU/0.5 mL), two doses before and four doses after the procedure (n = 26)

1) No differences for serious bleeding events, 2) amputation-free rates are for major and minor amputation

Restenosis/reocclusion

45%

26%

P = 0.0353

Limb salvage rate

92.3%

96.2%

n.s.

Amputation

15.4%

n.s.

**Table 3.** Antiplatelet and Anticoagulant Treatments Following Below-Knee Bypass Surgery
Study/type	Procedure	Treatment/follow-up duration	Endpoints	Treatment groups and endpoint rates	Significance	Notes
MAPT: mono-antiplatelet treatment; DAPT: dual antiplatelet treatment; i.v.: intravenous; s.c.: subcutaneous; RCT: randomized control trial; INR: international normalized ratio; LMWH: low molecular weight heparin; MACEs: major adverse cardiac events; MCE: major cardiac event; PTFE: polytetrafluoroethylene; n.s.: not significant; n.m.: not mentioned; HR: hazard ratio; SE: standard error.
Placebo vs. MAPT
Becquemin [27], 1997/RCT	Venous grafts	Placebo vs. ticlopidine (24 months)		Placebo (325 mg/day) (n = 121)	Ticlopidine (250 mg twice a day for 24 months) (n = 122)		100% of the bypass grafts were below the knee
			Primary patency	51%	66%	P = 0.02
			Secondary patency	55%	69%	P = 0.03
			Cumulative secondary patency			P = 0.02
			Amputation	7%	2%	P = 0.05
			Mortality rate	15%	15%	n.s.
			MACEs	12%	10%	n.s.
			Bleeding events (hematoma)	3%	1.64%	n.s.
			Other bleeding events	1.70%	0.8%	n.s.
No treatment vs. DAPT
Clyne [29], 1987/RCT	Venous and prosthetic grafts	No treatment vs. aspirin + dipyridamole (12 months)		No treatment (total grafts, n = 70; autogenous grafts, n = 44; prosthetic grafts, n = 26)	Dipyridamole (started before surgery) followed by 300 mg aspirin and 200 mg dipyridamole twice per day for 6 weeks (total grafts, n = 78; autogenous grafts, n = 49; prosthetic grafts, n = 29)		1) For patency, 100% of the grafts were below the knee as stratified by the study, 2) for amputation, death, and MCE, 80% of the grafts were infrapopliteal
			Graft patency
			All grafts	68%	83%	n.s.
			Autogenous	73%	83%	n.s.
			Prosthetic graft	53%	85%	P = 0.005
			Amputation (all grafts)	17%	10%	n.s.
			Death (all grafts)	11%	14%	n.s.
			MACEs (all grafts)	3%	6%	n.s.
MAPT vs. DAPT
Belch [28], 2010/RCT	Venous and prosthetic grafts	Aspirin vs. aspirin + clopidogrel (24 months)		Placebo + aspirin (75 - 100 mg/day) (total grafts, n = 426; venous grafts, n = 301; prosthetic grafts, n = 125)	Aspirin (same as control) + clopidogrel (75 mg/day) (total grafts, n = 425; venous grafts, n = 297; prosthetic grafts, n = 128)		100% of the grafts were below the knee, bleeding follow-up duration was not specified
			Graft occlusion
			All grafts	22.77%	21.88%	HR 0.94 (0.71 - 1.25)
			Venous	12.62%	17.51%	HR 1.45 (0.95 - 2.20)
			Prosthetic	47.20%	32.03%	HR 0.63 (0.42 - 0.93), P = 0.021
			Amputation
			All grafts	10.56%	7.29%	HR 0.68 (0.43 - 1.08)
			Venous	6.98%	6.40%	HR 0.93 (0.50 - 1.72)
			Prosthetic	19.20%	9.38%	HR 0.48 (0.24 - 0.96), P = 0.034
			Death
			All grafts	3.99%	5.65%	HR 1.44 (0.77 - 2.68)
			Venous	4.32%	6.06%	HR 1.43 (0.70 - 2.91)
			Prosthetic	3.20%	4.69%	HR 1.51 (0.42 - 5.33)
			Bleeding	(n = 422)	(n = 426)
			Total	7.04%	16.67%	P < 0.001
			Severe	1.18%	2.12%	n.s.
Antiplatelet vs. antiplatelet + anticoagulant
Sarac [30], 1998/RCT	Venous grafts	Aspirin vs. aspirin + warfarin (up to 36 months)		Aspirin (325 mg/day) (n = 24)	Aspirin (same as control) + warfarin (adjusted to maintain INR between 2 and 3) (n = 32)		1) > 90% of the bypass grafts were below the knee, 2) mortality and bleeding were measured perioperatively (1 month from operation), 3) other parameters are measured as cumulative for 3 years
			Cumulative primary patency	51%	74%	P = 0.04
			Cumulative primary assisted patency	56%	77%	P = 0.05
			Cumulative secondary patency	56%	81%	P = 0.02
			Cumulative limb salvage rate	31%	81%	P = 0.01
			Mortality rate	0%	3%	n.s.
			Bleeding events (hematoma)	4%	32%	0.004
			Other bleeding events	17%	15.63%	n.s.
Anticoagulant vs. anticoagulant
Aurshina [31], 2018/retrospective	PTFE graft	Traditional heparin-warfarin vs. direct oral anticoagulants (dabigatran, rivaroxaban, apixaban) (6 months)		Traditional heparin-warfarin (n = 100)	Direct oral anticoagulants (dabigatran, rivaroxaban, apixaban) (n = 19)		1) 100% below the knee bypass, 2) doses were not mentioned, 3) heparin started 24 h postoperatively and switch to warfarin was undertaken when INR was therapeutic
			Graft patency	93%	100%	n.s.
			Major adverse events	0%	0%	n.s.
			Bleeding events (hematoma)	3%	0%	n.s.
Logason [32], 2001/RCT	Venous and prosthetic grafts	Dextran 70 vs. LMWH (3 months)		Dextran 70 (total dose of 2,500 mL) (total grafts, n = 138; venous graft, n = 73; prosthetic graft, n = 65)	LMWH (40 mg s.c. eight doses) (total grafts, n = 131; venous graft, n = 68; prosthetic graft, n = 63)		1) Dextran possesses antithrombotic and flow-promoting properties, 2) approximately 70% of the bypass grafts were below the knee
			Graft patency
			All graft	88%	83%	n.s.
			Autogenous graft	90%	79%	n.s.
			Prosthetic graft	86%	87%	n.s.
			Death (all grafts)	4%	3%	n.s.
			MACEs (all grafts)	17%	5%	P < 0.05
			Bleeding events (all grafts)	6.90%	2.30%	n.s.
Samama [33], 1995/RCT	Venous and prosthetic grafts	Unfractionated heparin vs. LMWH (1 month)		Unfractionated heparin (50 IU/kg i.v. then 150 IU/kg s.c. twice a day for 10 days) (n = 100)	LMWH (75 IU/kg i.v. then 75 IU/kg s.c. twice a day for 10 days) (n = 99)		90% of the bypass grafts were below the knee
			Graft occlusion	24%	11%	P = 0.025
			Perioperative death	9%	5%	n.s.
			MACEs (all grafts)	2%	1%	n.s.
			Major bleeding events	12%	12%	n.s.
LeCroy [34], 2005/retrospective	PTFE graft	Warfarin (subtherapeutic) vs. warfarin (therapeutic) (up to 5 years)		Warfarin (subtherapeutic) (n = 40)	Warfarin (therapeutic) (n = 37)		1) Subtherapeutic INR (≤ 1.9), therapeutic INR (≥ 2.0), 2) median primary patency of 29.9 months (SE = 2.23) for therapeutic group vs. 6.8 months (SE = 2.34) for non-therapeutic group
			Patency	n.m.	n.s.	P = 0.0007
			Graft occlusion	60%	18.92%	P = 0.0002
			Bleeding events	3%	11%	n.d.

Table 3. Antiplatelet and Anticoagulant Treatments Following Below-Knee Bypass Surgery

Study/type

Procedure

Treatment/follow-up duration

Endpoints

Treatment groups and endpoint rates

Significance

Notes

MAPT: mono-antiplatelet treatment; DAPT: dual antiplatelet treatment; i.v.: intravenous; s.c.: subcutaneous; RCT: randomized control trial; INR: international normalized ratio; LMWH: low molecular weight heparin; MACEs: major adverse cardiac events; MCE: major cardiac event; PTFE: polytetrafluoroethylene; n.s.: not significant; n.m.: not mentioned; HR: hazard ratio; SE: standard error.

Placebo vs. MAPT

Becquemin [27], 1997/RCT

Venous grafts

Placebo vs. ticlopidine (24 months)

Placebo (325 mg/day) (n = 121)

Ticlopidine (250 mg twice a day for 24 months) (n = 122)

100% of the bypass grafts were below the knee

Primary patency

51%

66%

P = 0.02

Secondary patency

55%

69%

P = 0.03

Cumulative secondary patency

P = 0.02

Amputation

P = 0.05

Mortality rate

15%

n.s.

MACEs

12%

10%

n.s.

Bleeding events (hematoma)

1.64%

n.s.

Other bleeding events

1.70%

0.8%

n.s.

No treatment vs. DAPT

Clyne [29], 1987/RCT

Venous and prosthetic grafts

No treatment vs. aspirin + dipyridamole (12 months)

No treatment (total grafts, n = 70; autogenous grafts, n = 44; prosthetic grafts, n = 26)

Dipyridamole (started before surgery) followed by 300 mg aspirin and 200 mg dipyridamole twice per day for 6 weeks (total grafts, n = 78; autogenous grafts, n = 49; prosthetic grafts, n = 29)

1) For patency, 100% of the grafts were below the knee as stratified by the study, 2) for amputation, death, and MCE, 80% of the grafts were infrapopliteal

Graft patency

All grafts

68%

83%

n.s.

Autogenous

73%

83%

n.s.

Prosthetic graft

53%

85%

P = 0.005

Amputation (all grafts)

17%

10%

n.s.

Death (all grafts)

11%

14%

n.s.

MACEs (all grafts)

n.s.

MAPT vs. DAPT

Belch [28], 2010/RCT

Venous and prosthetic grafts

Aspirin vs. aspirin + clopidogrel (24 months)

Placebo + aspirin (75 - 100 mg/day) (total grafts, n = 426; venous grafts, n = 301; prosthetic grafts, n = 125)

Aspirin (same as control) + clopidogrel (75 mg/day) (total grafts, n = 425; venous grafts, n = 297; prosthetic grafts, n = 128)

100% of the grafts were below the knee, bleeding follow-up duration was not specified

Graft occlusion

All grafts

22.77%

21.88%

HR 0.94 (0.71 - 1.25)

Venous

12.62%

17.51%

HR 1.45 (0.95 - 2.20)

Prosthetic

47.20%

32.03%

HR 0.63 (0.42 - 0.93), P = 0.021

Amputation

All grafts

10.56%

7.29%

HR 0.68 (0.43 - 1.08)

Venous

6.98%

6.40%

HR 0.93 (0.50 - 1.72)

Prosthetic

19.20%

9.38%

HR 0.48 (0.24 - 0.96), P = 0.034

Death

All grafts

3.99%

5.65%

HR 1.44 (0.77 - 2.68)

Venous

4.32%

6.06%

HR 1.43 (0.70 - 2.91)

Prosthetic

3.20%

4.69%

HR 1.51 (0.42 - 5.33)

Bleeding

(n = 422)

(n = 426)

Total

7.04%

16.67%

P < 0.001

Severe

1.18%

2.12%

n.s.

Antiplatelet vs. antiplatelet + anticoagulant

Sarac [30], 1998/RCT

Venous grafts

Aspirin vs. aspirin + warfarin (up to 36 months)

Aspirin (325 mg/day) (n = 24)

Aspirin (same as control) + warfarin (adjusted to maintain INR between 2 and 3) (n = 32)

1) > 90% of the bypass grafts were below the knee, 2) mortality and bleeding were measured perioperatively (1 month from operation), 3) other parameters are measured as cumulative for 3 years

Cumulative primary patency

51%

74%

P = 0.04

Cumulative primary assisted patency

56%

77%

P = 0.05

Cumulative secondary patency

56%

81%

P = 0.02

Cumulative limb salvage rate

31%

81%

P = 0.01

Mortality rate

n.s.

Bleeding events (hematoma)

32%

0.004

Other bleeding events

17%

15.63%

n.s.

Anticoagulant vs. anticoagulant

Aurshina [31], 2018/retrospective

PTFE graft

Traditional heparin-warfarin vs. direct oral anticoagulants (dabigatran, rivaroxaban, apixaban) (6 months)

Traditional heparin-warfarin (n = 100)

Direct oral anticoagulants (dabigatran, rivaroxaban, apixaban) (n = 19)

1) 100% below the knee bypass, 2) doses were not mentioned, 3) heparin started 24 h postoperatively and switch to warfarin was undertaken when INR was therapeutic

Graft patency

93%

100%

n.s.

Major adverse events

n.s.

Bleeding events (hematoma)

n.s.

Logason [32], 2001/RCT

Venous and prosthetic grafts

Dextran 70 vs. LMWH (3 months)

Dextran 70 (total dose of 2,500 mL) (total grafts, n = 138; venous graft, n = 73; prosthetic graft, n = 65)

LMWH (40 mg s.c. eight doses) (total grafts, n = 131; venous graft, n = 68; prosthetic graft, n = 63)

1) Dextran possesses antithrombotic and flow-promoting properties, 2) approximately 70% of the bypass grafts were below the knee

Graft patency

All graft

88%

83%

n.s.

Autogenous graft

90%

79%

n.s.

Prosthetic graft

86%

87%

n.s.

Death (all grafts)

n.s.

MACEs (all grafts)

17%

P < 0.05

Bleeding events (all grafts)

6.90%

2.30%

n.s.

Samama [33], 1995/RCT

Venous and prosthetic grafts

Unfractionated heparin vs. LMWH (1 month)

Unfractionated heparin (50 IU/kg i.v. then 150 IU/kg s.c. twice a day for 10 days) (n = 100)

LMWH (75 IU/kg i.v. then 75 IU/kg s.c. twice a day for 10 days) (n = 99)

90% of the bypass grafts were below the knee

Graft occlusion

24%

11%

P = 0.025

Perioperative death

n.s.

MACEs (all grafts)

n.s.

Major bleeding events

12%

n.s.

LeCroy [34], 2005/retrospective

PTFE graft

Warfarin (subtherapeutic) vs. warfarin (therapeutic) (up to 5 years)

Warfarin (subtherapeutic) (n = 40)

Warfarin (therapeutic) (n = 37)

1) Subtherapeutic INR (≤ 1.9), therapeutic INR (≥ 2.0), 2) median primary patency of 29.9 months (SE = 2.23) for therapeutic group vs. 6.8 months (SE = 2.34) for non-therapeutic group

Patency

n.m.

n.s.

P = 0.0007

Graft occlusion

60%

18.92%

P = 0.0002

Bleeding events

11%

n.d.