Periprocedural Antithrombotic Therapy: A Practical Guide for Clinical Practice

Article Citation:

JoEllyn C. Moore, Tamara Langeberg, Lena Elizabeth Trager, Charles C. Gornick, Nedaa Skeik, Mario Gössl, Karol Mudy, and William Katsiyiannis (2017) Periprocedural Antithrombotic Therapy: A Practical Guide for Clinical Practice. Journal of the Minneapolis Heart Institute Foundation: January 2017, Vol. 1, No. 1, pp. 24-29.

Original Article

JoEllyn C. Moore, MD, Tamara Langeberg, NP, Lena Elizabeth Trager, BA, Charles C. Gornick, MD, Nedaa Skeik, MD, Mario Gössl, MD, Karol Mudy, MD, and William Katsiyiannis, MD

Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis, MN

Address for correspondence:
JoEllyn Carol Moore, MD
Minneapolis Heart Institute
920 E 28th Street #300
Minneapolis, Minnesota 55407
Tel: 612-863-3900

E-mail: joellyn.moore@allina.com

ABSTRACT

More than 6 million patients are on anticoagulant therapy and more than one third of adults take antiplatelet therapy in the United States, many of whom will require a surgical procedure while on treatment. The answers to questions regarding periprocedural thrombotic therapy are not at all straightforward and there is tremendous variability in practice across the country and across specialties. While there will always be nuances in clinical care that necessitate variation in practice patterns, algorithms for care allow for less ambiguity and they provide guidelines that are consistent with the most recent evidence in the literature. In this review, we provide: 1) a framework for periprocedureal antithrombotic therapy around the time of surgical procedures, 2) an approach for considering the risk of bleeding at the time of surgery as well as the risk of a thrombotic or thromboembolic event should the antithrombotic therapy be stopped, and 3) a strategy for managing periprocedural bridging therapy.

Keywords: periprocedural anticoagulation, antithrombotic therapy, thrombosis, bleeding risk, oral anticoagulation

IS ANTITHROMBOTIC THERAPY REQUIRED?

Answering a question regarding antithrombotic therapy should start with the consideration of whether or not the anticoagulation is still indicated in the first place. However, assuming the patient still has an indication for anticoagulation (and assuming a non-emergent surgery), the next question involves answering questions regarding surgical bleeding risk and the risk of thrombosis/thromboembolism if therapy is withheld.

BLEEDING RISK

One of the major risk-stratifications in assessing bleeding risk involves the risk inherent to the surgery or procedure. There is minimal data to guide decisions regarding procedural bleeding risk. The 2 main factors that impact bleeding risk are the type of procedure and the patient factors that interfere with hemostasis. A frequently cited reference with regard to surgical bleeding is from the American College of Chest Physicians,1 which used expert consensus to generate a list of high-risk procedures. Interestingly, the major reference for surgical bleeding risk dates back to a meta-analysis of perioperative subcutaneous heparin use for the prevention of pulmonary embolism in 1988.2 Table 1 includes a list of high-risk procedures compiled from these consensus guidelines as well as another recent review.1,3 In general, this list comprises surgeries that involve highly vascular organs or large incisions. An extensive list of surgical procedures and their associated risk has also been compiled as an appendix to a recent review on periprocedural antithrombotic therapy4 (also based on expert opinion).

TABLE 1
Procedures with high bleeding risk.

There are several validated nonprocedural factors that increase bleeding risk and these include abnormal renal function, nonsteroidal anti-inflammatory medications, low platelet count, and liver disease/coagulopathy. These factors have been combined into a variety of bleeding risk scores: (1) HEMORR2HAGES (hepatic or renal disease, ethanol abuse, malignancy, older age [≥75 years], reduced platelet count or function, rebleeding risk, hypertension [uncontrolled], anemia, genetic factors [CYP2C9 single nucleotide polymorphism], excessive fall risk, stroke, maximum score);5 (2) Shireman;6(3) HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly);7 and (4) ATRIA (anticoagulation and risk factors in atrial fibrillation).8 As summarized in Table 2, many of the risk factors that increase risk of a thromboembolic event—such as increasing age, hypertension, prior stroke and history of diabetes—are associated with increased risk of bleeding as well. In general, if the surgery is low-risk for bleeding and the patient is high-risk for a thromboembolic event, antithrombotic treatment should be continued. Furthermore, there is increasing consensus that there are many procedures that can be routinely performed on warfarin as long as the international normalized ratio (INR) is 2.5 to 3.5 for anticoagulated patients with mechanical mitral valves and 2 to 3 for all other indications (Table 3).9,10

TABLE 2
Bleeding risk scores.

TABLE 3
Procedures that may allow for uninterrupted warfarin.

RISK OF A THROMBOEMBOLIC EVENT IF TREATMENT IS STOPPED

Atrial Fibrillation

While the CHA2DS2-VASc (congestive heart failure [or Left ventricular systolic dysfunction], hypertension: blood pressure consistently above 140/90 mm Hg [or treated hypertension on medication], Age ≥75 years, diabetes mellitus, prior stroke or TIA or thromboembolism, vascular disease [eg, peripheral artery disease, myocardial infarction, aortic plaque],age 65–74 years, sex category [ie, female sex]) has replaced the CHADS2 (congestive heart failure, hypertension: blood pressure consistently above 140/90 mm Hg [or treated hypertension on medication], age ≥75 years, diabetes mellitus, prior Stroke or TIA or thromboembolism) score for assessing stroke risk in the national guidelines, for patients with atrial fibrillation, the data and guidelines regarding periprocedural risk are still based on the CHADS2 score.1,4,9,11 In general, patients with a CHADS2 score of 0 to 1 (annual stroke risk < 5%) may discontinue anticoagulation for the procedure without bridging anticoagulation (see below for timing). For patients with a score >4 (annual stroke risk >12%), bridging anticoagulation is recommended. For patients with an intermediate risk score of 2 to 3, bridging should likely be used if the patient has a prior history of thromboembolism within the previous 12 weeks, but all others can likely have interrupted anticoagulation based on the recent bridging anticoagulation in patients who require temporary interruption of warfarin therapy for an elective invasive procedure or surgery (BRIDGE) trial that demonstrated no difference in arterial thromboembolism but a significantly higher risk of bleeding in those patients who were bridged with low molecular weight heparin (LMWH).11Recent History of Venous Thromboembolism and History of Severe Thrombophilia

Based on expert opinion,1 patients with a venous thromboembolism within the previous 3 months have a high risk of recurrent thromboembolism and should have bridging therapy. There are also select patients with a severe thrombophilia (such as a deficiency of protein C, protein S, or antithrombin) who would also warrant bridging anticoagulation in consultation with a vascular medicine specialist or hematologist.Mechanical Valves

Mechanical mitral valves carry a high risk for thrombosis with interrupted anticoagulation as do caged-ball or tilting disc aortic valves, and these cases warrant bridging anticoagulation.1Direct Oral Anticoagulants (DOACs) Versus Warfarin

Most studies evaluating bridging anticoagulation to date have been performed with populations on warfarin. However, a recent prospective registry of >2,100 patients on the DOACs provides additional evidence that bridging anticoagulation should only be used for patients with a high risk for thromboembolism.12 Like the BRIDGE trial, they found that while heparin bridging of patients on DOACs did not decrease cardiovascular events, it did increase the risk of bleeding significantly (2.7%; 95% confidence interval [CI] 1.1–5.5) compared with no bridging (0.5%; 0.1–1.4; P = 0.010). Consistent with this finding, the most recent European Heart Rhythm Guidelines recommend against bridging if the patient is on a DOAC.13History of Percutaneous Coronary Intervention

Patients who have had a bare metal stent placed within the past 6 weeks or a drug-eluting stent placed in the past 6 months are at significantly elevated risk for stent thrombosis if dual antiplatelet therapy is withheld. In this context, the general recommendation is that elective surgeries should be postponed.1 In patients who have a drug-eluting stent who are between 6 months and 1 year after their last intervention and are in need of an urgent, high-bleeding risk procedure, there is some data to support continuing aspirin only for the perioperative period.14 Beyond these windows, it would be reasonable to hold the clopidogrel/prasugrel/ticagrelor 5 days prior and continue aspirin only perioperatively.History of Myocardial Infarction or Severe Peripheral Vascular Disease

There is mixed evidence for whether or not to continue aspirin in the perioperative period. The CHEST (American College of Chest Physicians) guidelines1 recommend that patients who are receiving aspirin for secondary prevention of cardiovascular disease should continue aspirin at the time of surgery. This recommendation was called into question by the recent randomized, placebo-controlled trial that evaluated the safety and efficacy of aspirin at the time of noncardiac surgery.15 The primary endpoint was a composite of death or nonfatal myocardial infarction within 30 days of surgery. They found that while there was a significantly higher rate of bleeding in the aspirin group (4.6% versus 3.8%; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P = 0.04), the primary endpoint was not statistically different between groups (approximately 7% for both). While it was a large trial with over 10,000 patients, only 4.7% had prior percutaneous coronary intervention (PCI) and 1% had drug eluting stents; thus, generalization to this population is not possible. However, based on this trial, it seems reasonable to hold aspirin for 7 days prior to surgery for patients not having coronary artery bypass grafting except for in the case of PCI as above.

HOW TO BRIDGE?

If a decision has been made that a surgical procedure is high-risk for bleeding and that the patient is high risk for a thromboembolic event, we propose the following management strategy, based on a synthesis of national guidelines and our own institutional experience (Table 4). In general, warfarin is discontinued 5 days prior to surgery and either subcutaneous LMWH or intravenous heparin is initiated when the INR drops <2. Warfarin is restarted the night after the surgery and the timing of the reinitiation of LMWH or heparin is guided by the bleeding risk of surgery. Direct oral anticoagulants should be held for 1 to 3 days prior to surgery with no need for bridging and timing of re-initiation is again guided by the surgical bleeding risk.

TABLE 4
Perioperative antithrombotic management scheme.

CONCLUSIONS

In summary, management of periprocedural antithrombotic therapy requires complex decision-making that can be streamlined by an algorithmic approach in many cases (Figure 1). We recommend: (1) starting with consideration of whether or not anticoagulation is even indicated; (2) consideration of the surgical bleeding risk as well as the potential patient factors that would increase bleeding; (3) bridging anticoagulation for patients with a CHADS2 score of 4 or higher; (4) holding aspirin for 7 days prior to a noncardiac surgery when it has been prescribed for primary prevention; and (5) continuing aspirin at the time of surgery when the patient has any history of prior PCI. Nonetheless, despite the above discussion and any institutional algorithms that may exist, direct communication between the surgeon and cardiologist is critical in order to provide the most appropriate management for any individual patient.

FIGURE 1
Approach to periprocedural anticoagulation. Reprinted from Journal of the American College of Cardiology, Rechenmacher et al., 2015;66:1392–1403 with permission from Elsevier.

Periprocedural antithrombotic therapy requires complex decision-making that can be streamlined by an algorithmic approach.

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