Dental extraction without stopping single or dual antiplatelet therapy: results of a retrospective cohort study

Int. J. Oral Maxillofac. Surg. 2016; 45: 1293–1298 http://dx.doi.org/10.1016/j.ijom.2016.02.010, available online at http://www.sciencedirect.com

Clinical Paper Oral Surgery

Dental extraction without stopping single or dual antiplatelet therapy: results of a retrospective cohort study

S.-Y. Lu1, C.-Y. Tsai1, L.-H. Lin1, S.-N. Lu2 1

Oral Pathology and Family Dentistry Section, Department of Dentistry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Division of HepatoGastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

S.-Y. Lu, C.-Y. Tsai, L.-H. Lin, S.-N. Lu: Dental extraction without stopping single or dual antiplatelet therapy: results of a retrospective cohort study. Int. J. Oral Maxillofac. Surg. 2016; 45: 1293–1298. # 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Abstract. The aim of this study was to investigate the incidence of bleeding after dental extraction without stopping antiplatelet therapy. Postoperative bleeding was assessed in a total of 1271 patients who were divided into two groups: a study group comprising 183 patients on antiplatelet therapy (aspirin 125 patients/185 occasions; clopidogrel 42 patients/65 occasions; dual therapy 16 patients/24 occasions) who underwent 548 dental extractions on 274 occasions, and a control group comprising 1088 patients who were not receiving any antiplatelet or anticoagulant therapy and underwent 2487 dental extractions on 1472 occasions. The incidence of postoperative bleeding was higher in the study group (5/274, 1.8%) than in the control group (10/1472, 0.7%), and also in the dual antiplatelet subgroup (1/24, 4.2%) than in the single antiplatelet subgroups (clopidogrel: 2/65, 3.1%; aspirin: 2/ 185, 1.1%); however, these differences were not significant. Postoperative bleeding was managed successfully by repacking with Gelfoam impregnated with tranexamic acid powder in 12 patients and by resuturing in three of the control patients undergoing extraction of impacted teeth with flap elevation. These findings indicate that there is no need to interrupt antiplatelet drugs before dental extraction.

It is not uncommon for physicians and dentists to routinely stop a patient’s antiplatelet therapy for 7 to 10 days, or for at least 3 days, prior to dental extraction in order to avoid the risk of bleeding. However, the interruption of antiplatelet therapy is associated with a progressive recovery of platelet function and the potential risk of a rebound of thrombotic arterial events.1 0901-5027/01001293 + 06

Excessive thromboxane A2 activity and decreased fibrinolysis have been noted following aspirin interruption, thereby exposing the patient to a higher risk of recurrent thrombosis, stroke, myocardial infarction (MI), or other coronary event.2 Although the risk is small, it outweighs the risk of oral bleeding.3,4 Clinically, the present researchers have witnessed two strokes

Key words: extraction; antiplatelet; aspirin; clopidogrel. Accepted for publication 18 February 2016 Available online 11 March 2016

occurring in two Chinese female patients with hypertension and diabetes who had been taking aspirin for the prevention of cardiovascular disease (CVD). Both had been instructed to stop taking aspirin 7 days before a single dental extraction procedure at a dental clinic and experienced cerebrovascular events 2 days later. The chronological link between aspirin withdrawal and

# 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

1294

Lu et al.

the acute thromboembolic events may not have been a matter of chance. Antiplatelet therapy has been reported to have reduced the overall mortality from vascular disease by 15% and non-fatal vascular complications by 30%.1 Lowdose aspirin remains the cornerstone of oral antiplatelet therapy. Prophylactic aspirin use in the USA has been estimated at 33% in high-risk individuals (e.g., those with coronary artery disease (CAD), MI, stroke, or peripheral vascular disease), 16% in those with multiple CVD risk factors, and 12–49% in those with diabetes.5 Diabetes is a complex metabolic disease with increased macrovascular and microvascular complications, which are responsible for 65% of deaths in patients with type 2 diabetes.6 Atrial fibrillation (AF) is the most common sustained arrhythmia. Among patients with AF, the annual rate of stroke without any preventive treatment is approximately 5%, 2- to 7-fold higher than the rate in those with sinus rhythm.7 Such cardioembolic strokes are often fatal or severely disabling. Stroke prevention in AF requires the use of oral anticoagulants (OAC), with antiplatelet therapy only having a weak efficacy.7 The OAC warfarin has been the primary therapy for stroke prevention in AF due to its efficacy in therapeutic range, convenience of once-daily dosing, and relatively low cost. However, warfarin use is associated with a number of limitations, including an unpredictable dose– response and excessive bleeding when not controlled adequately. Novel oral anticoagulants (NOAC), including dabigatran, rivaroxaban, and apixaban, have now been proved to provide a significant reduction in stroke risk without increasing the risk of intracranial haemorrhage, although dabigatran has been shown to increase the relative risk of MI by 33% when compared to warfarin.7 In Taiwan, half of AF patients (54.3%) take antiplatelet agents alone.8–10 Although a national representative cohort study has shown a progressive increase in the use of warfarin among Taiwan Chinese patients over time, usage rates (24.7%) are still low when compared with Western populations (39–65%).10 Randomized trials have shown that warfarin reduces the relative risk of stroke by 64%, while antiplatelet agents only reduce this by 22%.8–10 It is clear that anticoagulation management among Chinese patients is suboptimal.8–10 Under circumstances of poor anticoagulation control, the cessation of antiplatelet medications prior to dental surgery will, most likely, expose the patient to a fatal risk of thromboembolism.

Therefore, the routine perioperative withdrawal of antiplatelet therapy in these patients may have devastating consequences. Aspirin begins irreversibly inhibiting thromboxane A2-induced platelet aggregation within 1 h of ingestion, and clopidogrel selectively inhibits adenosine diphosphate (ADP)-induced platelet aggregation within 2 h; this lasts for 7–10 days of the mean platelet life.11,12 Dual therapies with aspirin and clopidogrel have a synergistic antiplatelet effect, as the two drugs affect platelet aggregation by different mechanisms. Compared with aspirin alone, dual oral antiplatelet therapy can provide an additional 20% reduction in the relative risk of MI or stroke.11–13 Dual antiplatelet therapy and newer antiplatelet agents are associated with greater antithrombotic efficacy, but also with a higher bleeding risk than aspirin. However, studies have reported that no patients taking non-aspirin or dual antiplatelet regimens have had bleeding complications while undergoing dental surgery that have required more than local haemostatic measures.14–16 Most Western studies have reported that single antiplatelet therapy should not be stopped prior to dental surgical procedures and that patients on dual antiplatelet therapy may need to be referred to a hospitalbased dental clinic.14,15 In Taiwan, the debate about continuing or stopping antiplatelet therapy prior to dental extraction has been going on for a long time, with opinions varying between institutions and doctors. In over 25 years of clinical practice, the present researchers have not withheld antiplatelet therapy in any of their patients seeking dental extraction. Perioperative bleeding has been shown not to differ significantly between patients who continue antiplatelet therapy and those who stop it of their own accord. Sufficient haemostasis can be obtained using local measures.3,16 The aim of this retrospective study was to evaluate the incidence of postoperative bleeding after dental extraction in patients without interruption of single or dual antiplatelet therapy. (Table 1 provides a list Table 1. Descriptions of all related acronyms and abbreviations. Acronym AF AHA CAD CVA CVD OAC MI NOAC

Description Atrial fibrillation American Heart Association Coronary artery disease Cerebrovascular accident Cardiovascular disease Oral anticoagulant Myocardial infarction Novel oral anticoagulant

of all acronyms and abbreviations related to this study, for reading convenience.) Patients and methods

The study was approved by the necessary institutional review board and comprised a total of 1363 consecutive subjects who underwent dental extractions performed by the same qualified dentist (the corresponding author) in the family dentistry department of the study hospital between January 2010 and June 2014. Data were retrieved from the chart notes made at each visit, and the following factors were investigated: patient clinico-demographic parameters (sex, age, dental disease, and medical illness), history of antiplatelet therapy (aspirin, clopidogrel, dual therapy), number and types of tooth extraction (simple or complicated extraction), and incidence of postoperative bleeding. Patients with a history of alcoholism, concomitant anticoagulant therapy, platelet counts below 60  109/l, interrupted antiplatelet therapy, liver dysfunction, or any systemic disease affecting postoperative bleeding or coagulopathies were excluded from the study. A total of 92 patients were excluded from the study because of warfarin therapy (65 patients), platelet counts below 60  109/l (two patients), and interruption of antiplatelet therapy by the individual him/herself (25 patients). The remaining 1271 patients who underwent 3035 dental extractions on 1746 occasions were divided into two groups (Table 2). A convenience sample of 1088 consecutive patients who had never been on antiplatelet therapy comprised the control group. The study group comprised 183 patients, of whom 125 were on aspirin (100 mg/day), 42 were on clopidogrel (75 mg/day), and 16 were on dual therapy (100 mg aspirin plus 75 mg clopidogrel) (Table 2). The antiplatelet agents were being used for CAD (76 patients), cerebrovascular accident (CVA) (58 patients), AF (15 patients), hypertension (11 patients), primary prevention in diabetes (nine patients), peripheral artery disease or deep vein thrombosis (five patients), heart valve replacement (four patients), and organ transplantation (five patients). All were dental outpatients and had been advised against interrupting antiplatelet therapy in any way before dental extraction. In accordance with the American Heart Association (AHA) guidelines, an appropriate regimen of antibiotic prophylaxis was administered to patients with cardiac valvular disease or an organ transplant.17 All procedures were planned with the patient’s informed consent.

Extraction without stopping antiplatelet therapy

1295

Table 2. Tooth extractions in the control group of patients (not taking antiplatelet or warfarin therapy) and the study group of outpatients on continuing antiplatelet therapy. Study group (n = 183) Sex Male Female Age, years, mean (range) Number of tooth extractions (occasions) Number of tooth extractions (postoperative bleeding) Number of simple extractions Number of complicated extractions Mean number of teeth extracted per case Reason for extraction (postoperative bleeding) Periodontitis Deep caries or residual roots Impaction Postoperative bleeding (number of patients/occasions) Aspirin Clopidogrel Aspirin + clopidogrel a b

Control group (n = 1088)

P-value 0.79

110 73 72.0 (20–94) 548 (274) 548 (5) 489 (5) 59 (0) 2.0

513 575 48.9 (9–95) 2487 (1472) 2487 (10) 1669 (7) 818 (3) 1.7

190 (3) 350 (2) 8 (0) 5/274 (1.8%) 2/185 (1.1%) 2/65 (3.1%) 1/24 (4.2%)

576 (5) 1298 (2) 613 (3) 10/1472 (0.7%)

0.94 0.81 0.80 0.98 0.03a 0.26 0.40 0.07b 0.49 0.50 0.43

Postoperative bleeding was significantly higher in patients with periodontitis (P = 0.03). No significant difference in the incidence of postoperative bleeding was found between the study group and the control group (P = 0.07).

Before dental extraction, all patients received local anaesthesia using 2% (20 mg/ml) lidocaine hydrochloride with 1/80,000 (12.5 mg/ml) epinephrine. The tooth extraction was performed with minimal invasion, and inflamed granulation tissue was curetted completely. The extraction was considered complicated when the tooth was removed using additional surgical procedures such as mucoperiosteal flap reflection, tooth separation, and bone cutting. The standard haemostatic measures for each extraction involved packing the site with Gelfoam, followed by biting on a dry gauze pad. Suturing was not performed routinely unless indicated, depending on the extent of the wound. Immediate bleeding was recorded if haemostasis was not achieved by dry gauze compression for 10 min; in such cases the socket was repacked with Gelfoam impregnated with tranexamic acid (TXA) powder. If this failed, sutures were inserted and the patient was kept under observation for the next 30 min before being discharged. Patients were given a leaflet outlining the usual post-extraction instructions and a 24-h on-call emergency telephone number to contact if any serious bleeding occurred Patients during non-office hours. experiencing bleeding 1 h after extraction and having to return to the hospital were considered as having delayed bleeding; patients who were able to manage the bleeding themselves at home were not included. All patients were reviewed by telephone call 24 h later or at clinical follow-up 7 days postoperatively if they were able to return to the hospital, in order to check on the following: the occurrence

of any delayed bleeding, adequacy of the gauze pressure packing in stopping bleeding, and need for professional help. Data were analyzed using IBM SPSS Statistics version 19.0 software (IBM Corp., Armonk, NY, USA). One-way analysis of variance (ANOVA) was used to analyze age and the mean number of extracted teeth. Categorical data such as the extraction type and the incidence of postoperative bleeding in relation to single or dual antiplatelet therapy between the two groups were analyzed using Fisher’s exact test or the x2 test, as appropriate. Statistical significance was set at a P-value of less than 0.05. Results

Patient clinico-demographic data and the results of the study are summarized in Table 2. A total of 1271 patients were included in the study and divided into two groups: (1) study group, n = 183 (110 male and 73 female, mean age

72.0 years, range 20–94 years); (2) control group, n = 1088 (513 male and 575 female, mean age 48.9 years, range 9–95 years). There was no significant difference in sex distribution, mean age, or in the types or number of teeth extracted between the two groups. Aspirin was the most used antiplatelet drug (68.3% of the study patients), followed by clopidogrel (23.0%) and dual therapy (8.7%) (Table 3). Most patients were taking single antiplatelet therapy for the prevention of primary or secondary CVD, including 14 out of 15 patients with AF receiving aspirin alone. Dual therapy was assumed in 14 patients with coronary drug-eluting stents, one AF patient, and one CVA patient. A total number of 3035 extractions were performed on 1746 occasions in all patients. In the control group, 2487 teeth were extracted on 1472 occasions (mean 1.7 per occasion, range 1–12), whereas in the study group, 548 teeth were extracted on 274 occasions (mean 2.0 per occasion,

Table 3. Main indications for antiplatelet drug prescription in the study group. Main indication

Aspirin

Coronary artery disease Cerebrovascular accident Atrial fibrillation Hypertension Diabetes (primary prevention) PAD/DVT Heart valve replacement Transplantation (liver, renal, heart) Total %

51 35 14 10 7 3 2 3 125 68.3%

Clopidogrel 11 22 0 1 2 2 2 2 42 23.0%

PAD, peripheral arterial disease; DVT, deep vein thrombosis.

Dual therapy

Total patients, n (%)

14 1 1 0 0 0 0 0 16 8.7%

76 58 15 11 9 5 4 5 183 100%

(41.5%) (31.7%) (8.2%) (6.0%) (4.9%) (2.7%) (2.2%) (2.7%)

1296

Lu et al.

Fig. 1. Numbers of teeth extracted and occasions of extraction. Postoperative bleeding was not associated with the number of tooth extractions. (*Immediate postoperative bleeding occurred once.).

range 1–7). The distribution of teeth extracted on each occasion is shown in Fig. 1. Immediate postoperative bleeding occurred in 10 patients in the control group (patients who underwent 1–6 tooth extractions) and in five patients in the study group (patients who underwent 1–3 tooth extractions). However, none of the patients reported any delayed bleeding necessitating a return to the hospital. In the telephone records, 24 patients (six patients (3%) from the study group and 18 patients (2%) from the control group) reported mild bleeding, which they had simply controlled by biting on a new dry gauze. The incidence of postoperative bleeding was higher in the study group (5/274, 1.8%) than in the control group (10/1472, 0.7%), but the difference was not significant (P = 0.07) (Table 2). In the study group, the incidence of postoperative bleeding was higher in patients on dual therapy (1/24, 4.2%) than in those on aspirin alone (2/185, 1.1%) or clopidogrel alone (2/65, 3.1%); however, the differences were not significant. The incidence of postoperative bleeding in the two groups was not associated with the number of tooth extractions, the types of extraction, or single or dual antiplatelet therapy (all P-values >0.05, Table 2). Among the 15 patients who developed immediate postoperative bleeding, eight cases involved periodontitis that was complicated by either acute inflammation or alveolar abscess. With respect to the reasons for extraction, periodontitis was found to be associated with postoperative bleeding in both groups (P < 0.05). Local haemostasis with Gelfoam sponge was sufficient in most patients. Immediate postoperative bleeding occurred in

five confirmed cases in the study group and seven cases in the control group and could be managed by repacking with Gelfoam impregnated with TXA powder followed by pressure; suturing was not necessary. The wounds were sutured only in those patients who had undergone surgical extractions of teeth with flap elevation, including three patients in the control group with immediate postoperative bleeding. Discussion

Planning dental extractions for patients on antiplatelet therapy implies facing a decision to either stop the drugs and bring about a possible lethal thrombosis, or continue the drugs and confront the eventuality of excessive bleeding. The risk of a thromboembolic event is difficult to estimate, but is probably 0.005%.1,4 Mounting evidence supports a platelet rebound phenomenon after abrupt antiplatelet withdrawal.2 This rebound period is characterized by increased thromboxane production, decreased fibrinolysis, and a resultant clinical prothrombotic state.2 The mean platelet life-span being 7–10 days, about 50% of normally functioning platelets are recovered within 5 days after aspirin withdrawal, while platelet thromboxane biosynthesis recovers more rapidly, with its urinary thromboxane metabolites close to normal levels after 3 days.4 The mean delay in stroke and MI after aspirin cessation is approximately 10 days (range 4–17 days), which is consistent with the time interval of the platelet rebound effect.12 Ferrari et al. reported that 51 of 383 CAD patients were admitted for acute coronary syndrome events within 1 month (mean 10 days) after stopping aspirin therapy, for an incidence among

CAD patients of 13% and an overall incidence of 4% (51 of 1236 patients).12 Collet et al. reported that nine of 475 MI patients (1.9%) had discontinued aspirin therapy within 15 days prior to intended surgery.4 The present researchers have witnessed two diabetic females who were rescued from a stroke at 2 days after tooth extraction because their aspirin had been stopped for 7 days prior to their procedures. These data suggest that aspirin cessation might lead to lethal thrombosis, particularly in patients with prior CVD and indications for aspirin treatment. Although the risk is low, the outcome is serious. As early as 1987, Salzman stated that the haemostatic defect induced by aspirin in patients with otherwise normal haemostasis is usually minor.18 A number of studies have shown no difference in the incidence of bleeding after invasive oral surgical procedures between patients receiving single and dual antiplatelet therapy.3,15 Wahl reported that of 1283 patients on single or dual antiplatelet agents who experienced 2308 dental extractions on 1334 occasions, no more than 35 (2.7% of patients and 2.6% of occasions) had bleeding complications, and only two patients (0.2%) required more than local measures for haemostasis.3 Park et al. reported that dental extractions were safe without stopping dual or triple antiplatelet agents in coronary drug-eluting stent patients; only two of 100 (2%) had postoperative bleeding, which could be controlled easily with the application of pressure.19 However, the risk of stent thrombosis in drug-eluting stents is increased in the perioperative setting and is strongly associated with the cessation of antiplatelet therapy. Based on the evidence that post-extraction bleeding problems in patients on antiplatelet therapy are not more severe than those in patients with normal coagulation, it appears logical to continue antiplatelet therapy for dental surgery. From the results of this study, it is clear that postoperative bleeding was not a problem following dental extraction for patients whose single or dual antiplatelet medications were not stopped and who were treated under local anaesthesia on an outpatient basis. None of the patients with immediate bleeding required a blood transfusion, parenteral TXA, or the administration of vitamin K, or needed to stop antiplatelet agents. Postoperative haemostasis can be managed successfully by repacking with Gelfoam plus TXA powder, which is safe, simple, and less troublesome than continuing TXA mouthwash

Extraction without stopping antiplatelet therapy for days.20 Sutures were not considered to be necessary; sutures were made only on a case-by-case basis and depending on the extent of the trauma. In fact, this remains the standard of care in the authors’ daily practice. Among the 15 cases of postoperative bleeding, 12 were simple extractions rather than invasive dental procedures, eight of which involved periodontitis. Many dental studies have reported local haemostasis to be less successful when acute inflammation is present, which is compatible with the present results.14,21,22 Platelet function is commonly assessed using the cutaneous bleeding test.23 Aspirin can double the baseline bleeding time, but this can still be within or just outside the normal range. Only 20–25% of patients using low-dose aspirin have an abnormal bleeding time.24 Clopidogrel as a more potent antiplatelet agent can prolong the bleeding time by 1.5–3-times normal, but no single antiplatelet drug (aspirin, clopidogrel, triflusal, or ticlopidine) appears to promote haemorrhage more than any other.25,26 As a correlation between bleeding time test results and the rate of surgical bleeding complications has not yet been established, the cutaneous bleeding time test should not be used to estimate the bleeding risk in patients on antiplatelet therapy; moreover the test has no role in the prediction of bleeding in the dental setting.23,24 The American Diabetes Association and AHA have confirmed the prophylactic effects of aspirin and other antiplatelet agents in the prevention of thrombotic CVDs.27,28 However, the American College of Cardiology and AHA suggest that warfarin or dual antiplatelet therapy should be the first choice of antithrombotic agent among patients with AF or CAD with drug-eluting stents.13,19,29,30 Although aspirin is less efficacious than warfarin or newer antiplatelet agents, it has been found to be the most used agent.10,11,27 In this study, aspirin was also found to be the most used antiplatelet drug (68.3%), and 14 out of 15 patients with AF were receiving aspirin alone (Table 3). These findings coincide with the observations of other studies.10,26,27 It is clear that an efficacious antithrombotic therapy to prevent stroke remains underused in Taiwan Chinese patients and that most AF patients have not been treated appropriately. A large national representative cohort study from Taiwan showed that there was no difference between antiplatelet therapy and warfarin with regard to the risk of ischaemic stroke, while for bleeding, aspirin had a lower risk compared to

warfarin.10 This may reflect poor anticoagulation control, highlighting opportunities for improved stroke prevention with alternative strategies, such as the NOACs, and the importance of continuous antiplatelet therapy throughout the perioperative period of dental surgery. For patients with established CVD, especially those taking aspirin or other antiplatelet agents for thrombotic prophylaxis, this should be considered a critical therapy. The dentist today is seeing an increasing number of patients on antiplatelet drugs to prevent thrombosis who require dental surgery. The findings of the present study suggest that there is no need to stop single or dual antiplatelet therapy prior to dental extraction. It is time to teach patients and dentists, as well as physicians, that antiplatelet withdrawal preoperatively may invite a remote but fatal risk of thromboembolism. Bleeding complications, while inconvenient, do not carry the same risks as thromboembolic complications. Local haemostatic measures are sufficient to control bleeding for those receiving continuous antiplatelet medications, and good surgical techniques must be employed in all oral surgical procedures. Funding

The study was supported in part by a CMRP research grant from the Chang Gung Memorial Hospital, Kaohsiung, Taiwan (CMRPG8C0642 to Shin-Yu Lu) after proper Institutional Review Board approval. Competing interests

The authors whose names are listed certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript. Ethical approval

The study was approved by the Institutional Review Board of Chang Gung Memorial Hospital (102-2101B to Shin-Yu Lu). Patient consent

Not required.

1297

References 1. Collet JP, Montalescot G. Premature withdrawal and alternative therapies to dual oral antiplatelet therapy. Eur Heart J 2006;8: 46–52. 2. Gerstein NS, Schulman PM, Gerstein WH, Petersen TR, Tawil I. Should more patients continue aspirin therapy perioperatively? Clinical impact of aspirin withdrawal syndrome. Ann Surg 2012;255:811–9. 3. Wahl MJ. Dental surgery and antiplatelet agents: bleed or die. Am J Med 2014;127: 260–7. 4. Collet JP, Himbert D, Steg PG. Myocardial infarction after aspirin cessation in stable coronary artery disease patients. Int J Cardiol 2000;76:257–8. 5. Brennan MT, Valerin MA, Noll JL, Napen˜as JJ, Kent ML, Fox PC, et al. Aspirin use and post-operative bleeding from dental extractions. J Dent Res 2008;87:740–4. 6. White Jr JR, Davis SN, Cooppan R, Davidson MB, Mulcahy K, Manko GA, et al. Clarifying the role of insulin in type 2 diabetes management. Clin Diabetes 2003;21: 14–21. 7. Bassand JP. Review of atrial fibrillation outcome trials of oral anticoagulant and antiplatelet agents. Europace 2012;14:312–24. 8. Lin LJ, Cheng MH, Lee CH, Wung DC, Cheng CL, Kao Yang YH. Compliance with antithrombotic prescribing guidelines for patients with atrial fibrillation—a nationwide descriptive study in Taiwan. Clin Ther 2008;30:1726–36. 9. Lee CH, Liu PY, Tsai LM, Tsai WC, Ho MT, Chen JH, et al. Characteristics of hospitalized patients with atrial fibrillation in Taiwan: a nationwide observation. Am J Med 2007;120:819e1–7. 10. Chen PC, Lip GY, Yeh G, Lin HJ, Chien KL. Risk of bleeding and stroke with oral anticoagulation and antiplatelet therapy in patients with atrial fibrillation in Taiwan: a nationwide cohort study. PLOS ONE 2015;10:e0125257. 11. Meritt JC, Bhatt DL. The efficacy and safety of perioperative antiplatelet therapy. J Thromb Thrombolysis 2002;13:97–103. 12. Ferrari E, Benhamou M, Cerboni P, Marcel B. Coronary syndromes following aspirin withdrawal: a special risk for late thrombosis. J Am Coll Cardiol 2005;45:456–9. 13. Raji MA, Lowery M, Lin YL, Kuo YF, Baillargeon J, Goodwin JS. National utilization patterns of warfarin use in older patients with atrial fibrillation: a population-based study of Medicare Part D beneficiaries. Ann Pharmacother 2013;47:35–42. 14. Kumar AJ, Kumari MM, Arora N, Haritha A. Is anti-platelet therapy interruption a real clinical issue? Its implications in dentistry and particularly in periodontics. J Indian Soc Periodontol 2009;13:121–5. 15. Napen˜as JJ, Hong CH, Brennan MT, Furney SL, Fox PC, Lockhart PB. The frequency of

1298

16.

17.

18.

19.

20.

21.

22.

Lu et al.

bleeding complications after invasive dental treatment in patients receiving single and dual antiplatelet therapy. J Am Dent Assoc 2009;140:690–5. Lillis T, Ziakas A, Koskinas K, Tsirlis A, Giannoglou G. Safety of dental extractions during uninterrupted single or dual antiplatelet treatment. Am J Cardiol 2011;108:964–7. Miyatake K, Akaishi M, Kawazoe K, Kitamura S, Nakazawa M, Nakamura K, et al. Guidelines for the prevention and treatment of infective endocarditis (JCS2003). Circ J 2003;67(Suppl.):1039–110. Salzman EW. Hemostatic problems in surgical patients. In: Colman RW, Hirsh J, Marder VJ, Salzman EW, editors. Hemostasis and thrombosis: basic principles and clinical practice. 2nd ed. Philadelphia, PA: Lippincott; 1987. p. 920–5. Park MW, Her SH, Kwon JB, Lee JB, Choi MS, Cho JS, et al. Safety of dental extractions in coronary drug-eluting stenting patients without stopping multiple antiplatelet agents. Clin Cardiol 2012;35:225–30. Sindet-Pedersen S, Ramstrom G, Bernvil S, Blomback M. Hemostatic effect of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery. N Engl J Med 1989;320:840–3. Morimoto Y, Niwa H, Minematsu K. Hemostatic management of tooth extractions in patients on oral antithrombotic therapy. J Oral Maxillofac Surg 2008;66:51–7. Samama CM, Bastien O, Forestier F, Denninger MH, Isetta C, Juliard JM, et al. Antiplatelet agents in the perioperative period:

23.

24.

25.

26.

27.

expert recommendations of the French Society of Anesthesiology and Intensive Care (SFAR) 2001—summary statement. Can J Anesth 2002;49:S26–35. Shalom A, Wong L. Outcome of aspirin use during excision of cutaneous lesions. Ann Plast Surg 2003;50:296–8. Harder S, Klinkhardt U, Alvarez JM. Avoidance of bleeding during surgery in patients receiving anticoagulant and/or antiplatelet therapy. Pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinet 2004;43:963–81. Cardona-Tortajada F, Sainz-Go´mez E, Figuerido-Garmendia J, de Robles-Adsuar AL, Morte-Casabo´ A, Giner-Mun˜oz F, et al. Dental extractions in patients on antiplatelet therapy. A study conducted by the Oral Health Department of the Navarre Health Service (Spain). Med Oral Patol Oral Cir Bucal 2009;14:e588–92. Pignone M, Alberts MJ, Colwell JA, Cushman M, Inzucchi SE, Mukherjee D, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Diabetes Care 2010;33:1395–402. Collet JP, Montalescot G, Blanchet B, Tanguy ML, Golmard JL, Choussat R, et al. Impact of prior use or recent withdrawal of oral antiplatelet agents on acute coronary syndromes. Circulation 2004;110:2361–7.

28. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland Jr JC et al. American College of Cardiology/American Heart Association Task Force on Practice Guidelines: 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014;64:e1–76. 29. Connolly SJ, Pogue J, Hart RG, Hohnloser SH, Pfeffer M, Chrolavicius S, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009;360: 2066–78. 30. Ogawa S, Aonuma K, Tse HF, Huang D, Huang JL, Kalman J, et al. The APHRS’s 2013 statement on antithrombotic therapy of patients with nonvalvular atrial fibrillation. J Arrhythm 2013;29:190–200.

Address: Shin-Yu Lu Oral Pathology and Family Dentistry Section Department of Dentistry Kaohsiung Chang Gung Memorial Hospital 123 Dapi Road Niaosong District Kaohsiung 833 Taiwan Tel: +886 7 7317123x2371; Fax: +886 7 7317123x2243 E-mail: [email protected]