Antithrombotic therapy in patients treated with oral anticoagulation undergoing coronary artery stenting. An expert consensus document with focus on atrial fibrillation

Figures & data

Table

AF	atrial fibrillation
INR	international normalized ratio
OAC	oral anticoagulation
PCI-S	percutaneous coronary intervention with stent implantation

Table I.  Design and outcome evaluation in the published studies reporting on patients treated with oral anticoagulation and undergoing coronary artery stenting.

Author	Design of the study	Outcomes evaluated	Outcome comparisons	Time of outcome evaluation
Orford JL et al. 5	retrospective, single-center	bleeding, MACE	none	30 days
Mattichak SJ et al. 7	retrospective, single-center	bleeding, stroke, MACE	versus contemporary pts on dual antiplatelet	6 and 12 months
Khurram Z et al. 8	retrospective, single-center	bleeding	versus contemporary pts on dual antiplatelet	12 months
Porter A et al. 9	retrospective, single-center	bleeding	none	30 days
Lip GYH & Karpha M 10	retrospective, single-center	bleeding	within population	30 days
Karjalainen PP et al. 11	retrospective, multi-center	bleeding, stroke, MACE	versus contemporary pts on dual antiplatelet, and within population	in-hospital/12 months
DeEugenio D et al. 12	retrospective, single-center	bleeding	versus contemporary pts on dual antiplatelet	6 months
Rubboli A et al. 13	retrospective, single-center	bleeding, thromboembolism, MACE	within population	30 days
Nguyen MC et al. 14	prospective (post-hoc analysis), multi-center (GRACE registry)	MACE, stroke (bleeding, MI, shock, heart failure, stroke)	within population	6 months (in-hospital)
Wang TY et al. 15	prospective (post-hoc analysis), multi-center (CRUSADE registry)	bleeding, transfusion, MI, heart failure	within population	in-hospital
Ruiz-Nodar JM et al. 16	retrospective, two-center	bleeding, thromboembolism MACE	within population	∼ 20 months
Rogacka R et al. 17	retrospective, two-center	bleeding, MACE, cerebrovascular events, stent thrombosis	none	∼ 21 months

MACE = major adverse cardiac events (death, myocardial infarction, repeat revascularization); MI = myocardial infarction; pts = patients.

Table II.  Epidemiological and procedural characteristics in the published studies on patients treated with oral anticoagulation undergoing coronary artery stenting.

				Indication for PCI-S				Antithrombotic therapy at discharge
Author	N° of pts	Age (yrs) ^a	Prevalence of AF	STEMI	NSTE ACS	Elective	Implantation of DES	TT	DAT	OAC + ASA	OAC + clopidogrel
Orford JL et al. 5	66	74	39%	14%	75%	NR	NR	100%	–	–	–
Mattichak SJ et al. 7	40	67	43%	100%	–	–	NR	100%	–	–	–
Khurram Z et al. 8	107	69	80%	NR	NR	NR	50%	100%	–	–	–
Porter A et al. 9	180	65	37%	46%	37%	17%	NR	100%	–	–	–
Lip GYH & Karpha M 10	35	71	100%	31%	63%	6%	14%	17%	71%	6%
Karjalainen PP et al. 11	239	70	70%	9%	44%	NR	42%	48%	16%	15%	21%
DeEugenio D et al. 12	97	70	60%	NR	NR	NR	25%	100%	–	–	–
Rubboli A et al. 13	49	69	60%	31%	29%	40%	2%	41%	45%	14%	–
Nguyen MC et al. 14	800	65	37%	61%	39%	–	25%	73%	–	13%	14%
Wang TY et al. 15	1247	76	NR	NR	NR	NR	77%	60%	31%	3%	3%
Ruiz-Nodar JM et al. 16	426	72	100%	20%	64%	16%	40%	50%	41%	2%	4%
Rogacka R et al. 17	127	70	59%	3%	23%	47%	56%	100%	–	–	–

^a mean/median.

AF = atrial fibrillation; ASA = aspirin; DAT = dual antiplatelet therapy of aspirin and clopidogrel; DES = drug eluting stent; GP = glycoprotein; NR = not reported; NSTE ACS = non-ST-elevation acute coronary syndrome; OAC = oral anticoagulation; PCI-S = percutaneous coronary intervention with stent; STEMI = ST-elevation myocardial infarction; TT = triple therapy of warfarin, aspirin, and clopidogrel; pts = patients.

Table III.  Incidence of major bleedings in patients receiving triple therapy of warfarin, aspirin, and clopidogrel after coronary artery stent implantation.

Author	At 30 days	At 6 months	At ≥12 months
Orford JL et al. 5	2/66 pts (3.1%)	NR	NR
Mattichak SJ et al. 7	NR	5/40 pts (12.5%)	8/40 pts (21%)
Khurram Z et al. 8	NR	NR	7/107 pts (6.6%)
Porter A et al. 9	2/180 pts (1.1%)	NR	NR
Lip GYH & Karpha M 10	0/6 pts (0%)	NR	NR
Karjalainen PP et al. 11	NR	NR	7/106 pts (6.6%)
DeEugenio D et al. 12	NR	14/97 pts (14%)	NR
Rubboli A et al. 13	3/20 pts (15%)	NR	NR
Nguyen MC et al. 14	NR (34/580 pts; 5.9%) ^a	NR	NR
Wang TY et al. 15	NR	NR	NR
Ruiz-Nodar JM et al. 16	NR	NR	NR (36/242 pts; 14.9%) ^b
Rogacka R et al. 17	NR	NR	6/127 pts (4.7%)
Total	7/272 pts (2.6%)	19/137 pts (13.9%)	28/380 pts (7.4%)
	(39/852 pts; 4.6%, including ref. (14))		(64/622 pts; 10.3%, including ref. (16))

^aOccurring in-hospital.

^bOccurring in all anticoagulated patients: triple therapy, oral anticoagulant plus single antiplatelet agent, and oral anticoagulant monotherapy.

NR = not reported; pts = patients.

Table IV.  Stroke risk according to CHADS₂ score (1).

Score	Annual risk (%)
0	1.9
1	2.8
2	4.0
3	5.9
4	8.5
5	12.5
6	18.2

CHADS₂ risk score: 1 point each for congestive heart failure, hypertension, age ≥75 years, Diabetes; 2 points for prior stroke.

Table V.  Bleeding risk according to outpatient bleeding risk index (22).

Score	Annual risk (%)
0	3
1–2	8–12
3–4	30–48

Outpatient bleeding risk index score: 1 point each for age ≥65 years, prior stroke, history of bleeding; and 1 point for any of the following: hematocrit <30%, serum creatinine >1.5 mg/dL, or diabetes.

Table VI.  Recommended antithrombotic strategies following coronary artery stenting in patients with atrial fibrillation at intermediate or high thromboembolic risk (in whom oral anticoagulation therapy is required).

Hemorrhagic risk	Clinical setting	Stent implanted	Recommendations
Low or intermediate	Elective	Bare-metal	1 month: triple therapy of warfarin (INR 2.0–3.0) + aspirin ≤100 mg/day + clopidogrel 75 mg/day + PPI
			lifelong: warfarin (INR 2.0–3.0) alone
	Elective	Drug-eluting	3 (-olimus group) to 6 (paclitaxel) months: triple therapy of warfarin (INR 2.0–3.0) + aspirin ≤100 mg/day + clopidogrel 75 mg/day + PPI
			up to 12th month: combination of warfarin (INR 2.0–3.0) + clopidogrel 75 mg/day ^a
			lifelong: warfarin (INR 2.0–3.0) alone
	ACS	Bare-metal/drug-eluting	6 months: triple therapy of warfarin (INR 2.0–3.0) + aspirin ≤100 mg/day + clopidogrel 75 mg/day + PPI
			up to 12th month: combination of warfarin (INR 2.0–3.0) + clopidogrel 75 mg/day ^a
			lifelong: warfarin (INR 2.0–3.0) alone
High	Elective	Bare-metal ^b,c	2 to 4 weeks: triple therapy of warfarin (INR 2.0–3.0) + aspirin ≤100 mg/day + clopidogrel 75 mg/day + PPI
			lifelong: warfarin (INR 2.0–3.0) alone
	ACS	Bare-metal ^b,d	2 to 4 weeks: triple therapy of warfarin (INR 2.0–3.0) + aspirin ≤100 mg/day + clopidogrel 75 mg/day + PPI
			up to 12th month: combination of warfarin (INR 2.0–3.0) + clopidogrel 75 mg/day ^a
			lifelong: warfarin (INR 2.0–3.0) alone

^aCombination of warfarin (INR 2.0–3.0) + aspirin ≤100 mg/day + PPI may be considered as an alternative.

^bDrug-eluting stents must not be implanted.

^cImplantation of a carbon-coated stent associated with the combination of warfarin (INR 2.0–3.0) + aspirin ≤100 mg/day + PPI for 1 month, followed by warfarin (INR 2.0–3.0) lifelong, should be considered.

^dImplantation of a carbon-coated stent associated with the combination of warfarin (INR 2.0–3.0) + aspirin ≤100 mg/day + PPI for up to 6 months, followed by warfarin (INR 2.0–3.0) lifelong, should be considered.

ACS = acute coronary syndrome; INR = international normalized ratio; PPI = proton pump inhibitors.

Orford JL, Fasseas P, Melby S, Burger K, Steinhubl SR, Holmes DR, et al. Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement in patients with an indication for anticoagulation. Am Heart J. 2004; 147: 463–7

 PubMed Web of Science ®Google Scholar

Mattichak SJ, Reed PS, Gallagher MJ, Boura JA, O'Neill WW, Kahn JK. Evaluation of safety of warfarin in combination with antiplatelet therapy for patients treated with coronary stents for acute myocardial infarction. J Interven Cardiol. 2005; 18: 163–6

 Google Scholar

Khurram Z, Chou E, Minutello R, Bergman G, Parikh M, Naidu S, et al. Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding. J Invasive Cardiol. 2006; 18: 162–4

 PubMedGoogle Scholar

Porter A, Konstantino Y, Iakobishvili Z, Shachar L, Battler A, Hasdai D. Short-term triple therapy with aspirin, warfarin, and a thienopyridine among patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv. 2006; 68: 56–61

 Google Scholar

Lip GYH, Karpha M. Anticoagulant and antiplatelet therapy use in patients with atrial fibrillation undergoing percutaneous coronary intervention: the need for consensus and a management guideline. Chest. 2006; 130: 1823–7

 PubMed Web of Science ®Google Scholar

Karjalainen PP, Porela P, Ylitalo A, Vikman S, Nyman K, Vaittinen MA, et al. Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting. Eur Heart J. 2007; 28: 726–32

 PubMed Web of Science ®Google Scholar

DeEugenio D, Kolman L, DeCaro M, Andrel J, Chervoneva I, Duong P, et al. Risk of major bleeding with concomitant dual antiplatelet therapy after percutaneous coronary intervention in patients receiving long-term warfarin therapy. Pharmacotherapy. 2007; 27: 691–6

 Google Scholar

Rubboli A, Colletta M, Herzfeld J, Sangiorgio P, Di Pasquale G. Periprocedural and medium-term antithrombotic strategies in patients with an indication for long-term anticoagulation undergoing coronary angiography and intervention. Coron Artery Dis. 2007; 18: 193–9

 Google Scholar

Nguyen MC, Lim YL, Walton A, Lefkovits J, Agnelli G, Goodman SG, et al. Combining warfarin and antiplatelet therapy after coronary stenting in the Global Registry of Acute Coronary Events: is it safe and effective to use just one antiplatelet agent?. Eur Heart J. 2007; 28: 1717–22

 PubMed Web of Science ®Google Scholar

Wang TY, Robinson LA, Ou F-S, Roe MT, Ohman EM, Gibler B, et al. Discharge antithrombotic strategies among patients with acute coronary syndrome previously on warfarin anticoagulation: physician practice in the CRUSADE registry. Am Heart J. 2008; 155: 361–8

 PubMed Web of Science ®Google Scholar

Ruiz-Nodar JM, Marin F, Hurtado JA, Valencia J, Pinar E, Pineda J, et al. Anticoagulant and antiplatelet therapy use in 426 patients with atrial fibrillation undergoing percutaneous coronary intervention and stent implantation. J Am Coll Cardiol. 2008; 51: 818–25

 PubMed Web of Science ®Google Scholar

Rogacka R, Chieffo A, Michev I, Airoldi F, Latib A, Cosgrave J, et al. Dual antiplatelet therapy after percutaneous coronary intervention with stent implantation in patients taking chronic oral anticoagulation. J Am Coll Cardiol Intv. 2008; 1: 56–61

 Google Scholar