- Email: [email protected]
Safety of Dental Extractions During Uninterrupted Single or Dual Antiplatelet Treatment
Safety of Dental Extractions During Uninterrupted Single or Dual Antiplatelet Treatment Theodoros Lillis, DDSa, Antonios Ziakas, MDb, Konstantinos Koskinas, MDb, Anastasios Tsirlis, DDSa, and George Giannoglou, MDb,* Optimal dental management in patients on long-term antiplatelet treatment is not clearly defined. Antiplatelet discontinuation increases the risk of thrombotic complications, whereas uninterrupted antiplatelet therapy, which is the currently recommended approach, is assumed to increase the bleeding hazard after dental procedures. We sought to prospectively compare the risk of immediate and late postextraction bleeding in patients receiving uninterrupted single or dual antiplatelet therapy. We recruited 643 consecutive patients referred for dental extractions. In total 111 (17.3%) were on clinically indicated antiplatelet therapy: aspirin (n ⴝ 42), clopidogrel (n ⴝ 36), and aspirin and clopidogrel (n ⴝ 33). Controls (n ⴝ 532, 82.7%) were not on antiplatelet treatment. Immediate and late bleeding complications were recorded. Compared to controls the risk of prolonged immediate bleeding was higher in patients on dual antiplatelet therapy (relative risk [RR] 177.3, 95% confidence interval [CI] 43.5 to 722, p <0.001) but not in patients on aspirin alone (RR ⴝ 6.3, 95% CI 0.6 to 68.4, p ⴝ 0.2) or clopidogrel alone (RR ⴝ 7.4, 95% CI 0.7 to 79.5, p ⴝ 0.18); however, all immediate bleeding complications in all treatment groups were successfully managed with local hemostatic measures. No patient developed any late hemorrhage. In conclusion, dental extractions may be safely performed in patients receiving single or dual antiplatelet therapy when appropriate local hemostatic measures are taken, thus averting thrombotic risk of temporary antiplatelet discontinuation. © 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:964 –967) The purpose of this study was to prospectively assess the risk of immediate and late-onset bleeding complications during uninterrupted single or dual antiplatelet therapy in patients undergoing dental extractions. Methods The study was conducted from October 2009 through April 2010 at the Aristotle University Dental School, Thessaloniki, Greece. All consecutive patients referred for dental extractions were prospectively screened for study participation. We excluded patients with hematologic, renal, or liver disease; bone marrow disorders; alcoholism; or any concurrent medication affecting hemostasis such as oral or parenteric anticoagulants or anti-inflammatory drugs. Patients who needed extractions of deciduous teeth, surgical extractions, extractions in deferent quadrants, or multiple extractions (⬎3 teeth) were excluded based on previous studies assessing the bleeding risk of multiple extractions in orally anticoagulated patients.1 Based on their medications, study participants were categorized as a treatment group receiving uninterrupted aspirin and/or clopidogrel and a control group receiving no antiplatelets. The study protocol was approved
a
Department of Dentoalveolar Surgery, Implant Surgery and Radiology, Aristotle University Dental School, Thessaloniki, Greece; b1st Cardiology Department, AHEPA University Hospital, Aristotle University Medical School, Thessaloniki, Greece. Manuscript received January 23, 2011; revised manuscript received and accepted May 9, 2011. *Corresponding author: Tel/fax: 30-2310-994-837. E-mail address: [email protected] (G. Giannoglou). 0002-9149/11/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2011.05.029
by the institutional ethical committee, and all study participants provided informed consent. All patients were treated in morning sessions. Maxillary and anterior mandibular teeth were extracted under local anesthetic infiltration in the buccal and palatal or lingual aspect of the teeth. Posterior mandibular teeth were extracted under a combination of inferior alveolar nerve block anesthesia and anesthesia infiltration buccally and lingually. Each extraction site was infiltrated with lidocaine solution 2% 1.8 ml with epinephrine 1:80,000 to ensure similar local hemostatic effects of epinephrine. Wound management included removal of granulation tissue, sharp bony edges, or foreign bodies. After extractions patients were instructed to bite on a pressure pack for 30 minutes. If bleeding was still present, it was by our definition considered prolonged postextraction bleeding. In these cases, a piece of oxidized cellulose gauze (Surgicel; Ethicon Inc, Somerville, New Jersy) was sutured over the inlet of the postextraction socket (3-0 silk sutures); patients then bit on a pressure pack for 30 minutes for a second time and were evaluated before leaving the clinic. All patients were given appropriate postoperative instructions and were advised to immediately report any hemorrhagic complication. Patients were interviewed by telephone at the end of the day of extraction, and complaints of bleeding were recorded. Sutures, if placed, were removed at 6 days. Postextraction bleeding complications were categorized according to time of occurrence as immediate, occurring during the extraction session at the clinic, or late, occurring any time thereafter. Prolonged immediate bleeding was dewww.ajconline.org
Coronary Artery Disease/Antiplatelets and Dental Extractions
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Table 1 Patients’ baseline demographic and procedural characteristics Variable
Age (years) Men Number of teeth extracted Indication for extraction* Periodontitis Radicular lesion Severe decay Other
Aspirin (n ⫽ 42)
Clopidogrel (n ⫽ 36)
Aspirin and Clopidogrel (n ⫽ 33)
Controls (n ⫽ 532)
66.6 ⫾ 7.5 26 (62%) 56
66.5 ⫾ 6.8 20 (56%) 59
63.2 ⫾ 7.9 23 (70%) 54
26 (46%) 4 (7%) 25 (45%) 1 (2%)
25 (42%) 3 (5%) 30 (51%) 1 (2%)
24 (45%) 11 (20%) 19 (35%) 0
p Value Control vs Aspirin
Controls vs Clopidogrel
Controls vs Aspirin and Clopidogrel
62 ⫾ 9.5 281 (53%) 734
⬍0.001 0.27
0.003 0.87
0.29 0.07
363 (49%) 88 (12%) 269 (37%) 14 (2%)
0.68 0.38 0.25 0.70
0.30 0.14 0.06 0.63
0.30 0.09 0.88 —
Data are expressed as mean ⫾ SD or number (percentage). * Indicates number of extracted teeth. Table 2 Indications for antiplatelet therapy Indication
Acute coronary syndrome Percutaneous coronary intervention Coronary bypass Atrial fibrillation Stroke Primary prevention Other
Aspirin (n ⫽ 42)
Clopidogrel (n ⫽ 36)
Aspirin and Clopidogrel (n ⫽ 33)
1 (2%) 5 (12%) 7 (17%) 1 (2%) 6 (14%) 20 (48%) 2 (5%)
5 (14%) 6 (17%) 7 (19%) 1 (3%) 0 16 (44%) 1 (3%)
5 (15%) 22 (67%) 4 (12%) 2 (6%) 0 0 0
p Value Aspirin vs Clopidogrel
Clopidogrel vs Aspirin and Clopidogrel
Aspirin vs Aspirin and Clopidogrel
0.09 0.75 0.77 1.00 — 0.82 1.00
1.00 0.001 0.52 0.6 — — —
0.08 0.001 0.75 0.58 — — —
Data are expressed as mean ⫾ SD or number (percentage).
fined by the need to use hemostatic gauze when blood extended beyond the tooth socket after 30 minutes of biting on a pressure pack. Late bleeding complications were defined as clinically significant when they extended beyond 12 hours, made the patient call or return to the dental practitioner or to an emergency department, resulted in a hematoma or ecchymosis within the oral soft tissues, or required blood transfusion.2 Statistical analyses were performed with SPSS 17.0 (SPSS, Inc., Chicago, Illinois). Continuous variables are presented as mean ⫾ SD and categorical variables as actual number and percentage. Continuous variables were tested for normality of distribution by Kolmogorov–Smirnov test and were compared by Student’s t test or Mann– Whitney test between 2 study groups and by analysis of variance or Kruskal–Wallis test among ⬎2 study groups. Categorical variables such as incidence of bleeding were compared by chi-square test or Fisher’s exact test, as appropriate. Relative risk (RR), defined as the ratio of bleeding incidence between 2 groups, and corresponding 95% confidence interval (CI) are reported for comparison of bleeding risk between groups. All statistical tests were 2-sided and were considered statistically significant at the 0.05 level. The authors had full access to and take responsibility for the integrity of the data. All authors have read and agreed to the report as written.
Results During the study period 1,262 consecutive patients were screened, and 643 patients meeting the inclusion and exclusion criteria were enrolled, undergoing 903 dental extractions. One hundred eleven patients (17.3%) were on longterm antiplatelet therapy with aspirin and/or clopidogrel. Patients’ demographic and procedural characteristics and indications for antiplatelet treatment are presented in Tables 1 and 2, respectively. To account for the intraindividual heterogeneity of procedural indications in patients with ⬎1 extracted tooth, we compared numbers of teeth, and not patients, with different extraction indications across study groups (Table 1). Prolonged immediate bleeding occurred in 2 patients (0.4%) in the control group, 1 patient (2.4%) receiving aspirin, 1 patient (2.8%) on clopidogrel, and 22 patients (66.7%) on dual antiplatelet treatment. Compared to controls risk of prolonged immediate bleeding was significantly higher in patients on dual antiplatelet therapy (RR 177.3, 95% CI 43.5 to 722, p ⬍0.001) but not in patients on aspirin alone (RR 6.3, 95% CI 0.6 to 68.4, p ⫽ 0.2) or clopidogrel alone (RR 7.4, 95% CI 0.7 to 79.5, p ⫽ 0.18). Bleeding risk was higher in patients on dual antiplatelets compared to those on aspirin only (RR 28, 95% CI 4 to 197, p ⬍0.001) or clopidogrel only (RR 24, 95% CI 3.4 to 168.3, p ⬍0.001). All immediate bleedings were successfully treated with local hemostatic measures as described earlier.
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Patients with immediate bleeding did not significantly differ in gender, age, and number or type of extracted teeth across different treatment groups. The indication for extraction in all controls and patients on single treatment who developed immediate bleeding was periodontitis. In patients on dual therapy who developed prolonged immediate bleeding, extraction was performed for periodontitis (n ⫽ 16, 73%), radicular lesion (n ⫽ 5, 23%), and severe decay (n ⫽ 1, 4%). Notably, all patients on dual antiplatelet therapy who had periodontitis developed prolonged postextraction bleeding. None of the controls or patients on single antiplatelet treatment developed any late hemorrhagic complication. One patient on dual therapy developed immediate bleeding and received hemostatic gauze and suturing after extraction and reported bleeding after consumption of hard food on the fifth postextraction day, but bleeding stopped spontaneously after 10 minutes and thus did not meet the criteria of significant late bleeding.2 Discussion The optimal treatment strategy for dental extractions, the most frequent minor surgical procedure, in the expanding population of patients receiving long-term antiplatelet therapy is a challenging issue; the documented thrombotic risk of antiplatelet withdrawal3 needs to be balanced against the putative hemorrhagic risk of uninterrupted antiplatelet treatment. Uninterrupted dual antiplatelet therapy is currently recommended in patients with drug-eluting stents who undergo dental procedures, although prospective studies specifically assessing the safety of this approach are missing.4 The present study is the first, to our knowledge, to prospectively assess the safety of dental extractions in patients on uninterrupted single or dual antiplatelet therapy. Our realworld cohort included patients receiving single, dual, or no antiplatelets, all treated by the same protocol, such that the RR of each antiplatelet regimen could be directly compared. Our results support the safety of dental extractions on uninterrupted single and dual antiplatelet treatment with appropriate local hemostatic measures. Antiplatelet monotherapy did not increase the risk of immediate postextraction bleeding. Prolonged bleeding that required local hemostatic treatment occurred in 2.4% of patients on aspirin and 2.8% on clopidogrel and was comparable to the RR in controls. Previous studies using similar criteria of immediate postextraction bleeding in aspirinreceiving patients reported an incidence of 0% to 3.8%.5,6 Consistent with our prospective results, serious or lifethreatening postextraction bleeding complications associated with antiplatelet therapy are extremely rare, with only few reports in the literature.7,8 No patient on single antiplatelet therapy developed clinically significant late hemorrhage. Cardona-Tortajada et al9 reported late-onset (⬎24 hours) postextraction bleeding in 17% of their 155 antiplatelet-treated patients; these complications, however, were mostly mild and self-controlled. The higher frequency of late bleeding events in that study may be associated with short (10 minutes) postextraction monitoring, whereas patients in our study were monitored for ⱖ30 minutes and then treated appropriately, if needed.
Persistent postextraction evaluation may therefore facilitate adequate hemostatic control and increase procedural safety in the setting of antiplatelet monotherapy. An intriguing result of our study is the safety of dental extractions even in patients on uninterrupted dual antiplatelet treatment when appropriate local hemostatic measures are taken. Patients receiving aspirin and clopidogrel were clearly at a higher risk of immediate postextraction bleeding, but all cases were successfully controlled by suturing and application of oxidized cellulose gauze. Importantly, the incidence of late hemorrhage did not increase in this putatively high-risk bleeding-prone population. Overall, although postextraction bleeding events are likely to occur under uninterrupted combined antiplatelet therapy, these are limited in the immediate postprocedure time frame, occurring within the safe environment of a dental clinic, and are controllable with appropriate local hemostatic treatment. Our results agree with those of Napeñas et al10 who reported no episodes of prolonged bleeding in their 29 patients receiving dual antiplatelet treatment; that study was limited, however, by the retrospective design, absence of direct assessment of perioperative bleeding, and absence of a control arm of patients not receiving antiplatelets. Hemorrhagic complications mostly occurred in the setting of periodontitis. Local inflammation in relation to local hyperemia and possibly fragility of the blood vessels might predispose to postextraction bleeding. Presence of periodontitis could thus enable risk stratification of patients who are more likely to develop hemorrhage while receiving antiplatelets to ensure a higher index of suspicion and prompt appropriate hemostatic measures. Our study would have benefited from a larger study population. Based on current recommendations4 we did not include patients with antiplatelet interruption; our study was therefore not designed to directly compare hemorrhagic risk in continuous versus interrupted antiplatelet treatment. We did not obtain a platelet count; thus we could not assess the potential role of platelet count in hemorrhagic risk. Considering the recognized variable response to antiplatelet drugs11 we did not use platelet function testing to assess antiplatelet resistance; hence, we could not determine whether patients with bleeding might have been “hyperresponders.” The safety of antiplatelet drugs other than aspirin and clopidogrel was not assessed. 1. Pototski M, Amenábar JM. Dental management of patients receiving anticoagulation or antiplatelet treatment. J Oral Sci 2007;49: 253–258. 2. Lockhart PB, Gibson J, Pond SH, Leitch J. Dental management considerations for the patient with an acquired coagulopathy. Part 1: coagulopathies from systemic disease. Br Dent J 2003;195:439 – 445. 3. Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, Airoldi F, Chieffo A, Montorfano M, Carlino M, Michev I, Corvaja N, Briguori C, Gerckens U, Grube E, Colombo A. Incidence, predictors, and outcome of thrombosis after successful implantation of drugeluting stents. JAMA 2005;293:2126 –2130. 4. Grines CL, Bonow RO, Casey DE Jr, Gardner TJ, Lockhart PB, Moliterno DJ, O’Gara P, Whitlow P; American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, American Dental Association, American College of Physicians. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart
Coronary Artery Disease/Antiplatelets and Dental Extractions
5. 6. 7. 8.
Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation 2007;115:813– 818. Krishnan B, Shenoy NA, Alexander M. Exodontia and antiplatelet therapy. J Oral Maxillofac Surg 2008;66:2063–2066. Morimoto Y, Niwa H, Minematsu K. Hemostatic management of tooth extractions in patients on oral antithrombotic therapy. J Oral Maxillofac Surg 2008;66:51–57. Foulke CN. Gingival hemorrhage related to aspirin ingestion. A case report. J Periodontol 1976;47:355–357. Thomason JM, Seymour RA, Murphy P, Brigham KM, Jones P. Aspirin-induced post-gingivectomy haemorrhage: a timely reminder. J Clin Periodontol 1997;24:136 –138.
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9. Cardona-Tortajada F, Sainz-Gómez E, Figuerido-Garmendia J, de Robles-Adsuar AL, Morte-Casabó A, Giner-Muñoz F, ArtázcozOsés J, Vidán-Lizari J. 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 – e592. 10. Napeñas JJ, Hong CH, Brennan MT, Furney SL, Fox PC, Lockhart PB. The frequency of bleeding complications after invasive dental treatment in patients receiving single and dual antiplatelet therapy. J Am Dent Assoc 2009;140:690 – 695. 11. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 2009;360:354 –362.
a
Department of Dentoalveolar Surgery, Implant Surgery and Radiology, Aristotle University Dental School, Thessaloniki, Greece; b1st Cardiology Department, AHEPA University Hospital, Aristotle University Medical School, Thessaloniki, Greece. Manuscript received January 23, 2011; revised manuscript received and accepted May 9, 2011. *Corresponding author: Tel/fax: 30-2310-994-837. E-mail address: [email protected] (G. Giannoglou). 0002-9149/11/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2011.05.029
by the institutional ethical committee, and all study participants provided informed consent. All patients were treated in morning sessions. Maxillary and anterior mandibular teeth were extracted under local anesthetic infiltration in the buccal and palatal or lingual aspect of the teeth. Posterior mandibular teeth were extracted under a combination of inferior alveolar nerve block anesthesia and anesthesia infiltration buccally and lingually. Each extraction site was infiltrated with lidocaine solution 2% 1.8 ml with epinephrine 1:80,000 to ensure similar local hemostatic effects of epinephrine. Wound management included removal of granulation tissue, sharp bony edges, or foreign bodies. After extractions patients were instructed to bite on a pressure pack for 30 minutes. If bleeding was still present, it was by our definition considered prolonged postextraction bleeding. In these cases, a piece of oxidized cellulose gauze (Surgicel; Ethicon Inc, Somerville, New Jersy) was sutured over the inlet of the postextraction socket (3-0 silk sutures); patients then bit on a pressure pack for 30 minutes for a second time and were evaluated before leaving the clinic. All patients were given appropriate postoperative instructions and were advised to immediately report any hemorrhagic complication. Patients were interviewed by telephone at the end of the day of extraction, and complaints of bleeding were recorded. Sutures, if placed, were removed at 6 days. Postextraction bleeding complications were categorized according to time of occurrence as immediate, occurring during the extraction session at the clinic, or late, occurring any time thereafter. Prolonged immediate bleeding was dewww.ajconline.org
Coronary Artery Disease/Antiplatelets and Dental Extractions
965
Table 1 Patients’ baseline demographic and procedural characteristics Variable
Age (years) Men Number of teeth extracted Indication for extraction* Periodontitis Radicular lesion Severe decay Other
Aspirin (n ⫽ 42)
Clopidogrel (n ⫽ 36)
Aspirin and Clopidogrel (n ⫽ 33)
Controls (n ⫽ 532)
66.6 ⫾ 7.5 26 (62%) 56
66.5 ⫾ 6.8 20 (56%) 59
63.2 ⫾ 7.9 23 (70%) 54
26 (46%) 4 (7%) 25 (45%) 1 (2%)
25 (42%) 3 (5%) 30 (51%) 1 (2%)
24 (45%) 11 (20%) 19 (35%) 0
p Value Control vs Aspirin
Controls vs Clopidogrel
Controls vs Aspirin and Clopidogrel
62 ⫾ 9.5 281 (53%) 734
⬍0.001 0.27
0.003 0.87
0.29 0.07
363 (49%) 88 (12%) 269 (37%) 14 (2%)
0.68 0.38 0.25 0.70
0.30 0.14 0.06 0.63
0.30 0.09 0.88 —
Data are expressed as mean ⫾ SD or number (percentage). * Indicates number of extracted teeth. Table 2 Indications for antiplatelet therapy Indication
Acute coronary syndrome Percutaneous coronary intervention Coronary bypass Atrial fibrillation Stroke Primary prevention Other
Aspirin (n ⫽ 42)
Clopidogrel (n ⫽ 36)
Aspirin and Clopidogrel (n ⫽ 33)
1 (2%) 5 (12%) 7 (17%) 1 (2%) 6 (14%) 20 (48%) 2 (5%)
5 (14%) 6 (17%) 7 (19%) 1 (3%) 0 16 (44%) 1 (3%)
5 (15%) 22 (67%) 4 (12%) 2 (6%) 0 0 0
p Value Aspirin vs Clopidogrel
Clopidogrel vs Aspirin and Clopidogrel
Aspirin vs Aspirin and Clopidogrel
0.09 0.75 0.77 1.00 — 0.82 1.00
1.00 0.001 0.52 0.6 — — —
0.08 0.001 0.75 0.58 — — —
Data are expressed as mean ⫾ SD or number (percentage).
fined by the need to use hemostatic gauze when blood extended beyond the tooth socket after 30 minutes of biting on a pressure pack. Late bleeding complications were defined as clinically significant when they extended beyond 12 hours, made the patient call or return to the dental practitioner or to an emergency department, resulted in a hematoma or ecchymosis within the oral soft tissues, or required blood transfusion.2 Statistical analyses were performed with SPSS 17.0 (SPSS, Inc., Chicago, Illinois). Continuous variables are presented as mean ⫾ SD and categorical variables as actual number and percentage. Continuous variables were tested for normality of distribution by Kolmogorov–Smirnov test and were compared by Student’s t test or Mann– Whitney test between 2 study groups and by analysis of variance or Kruskal–Wallis test among ⬎2 study groups. Categorical variables such as incidence of bleeding were compared by chi-square test or Fisher’s exact test, as appropriate. Relative risk (RR), defined as the ratio of bleeding incidence between 2 groups, and corresponding 95% confidence interval (CI) are reported for comparison of bleeding risk between groups. All statistical tests were 2-sided and were considered statistically significant at the 0.05 level. The authors had full access to and take responsibility for the integrity of the data. All authors have read and agreed to the report as written.
Results During the study period 1,262 consecutive patients were screened, and 643 patients meeting the inclusion and exclusion criteria were enrolled, undergoing 903 dental extractions. One hundred eleven patients (17.3%) were on longterm antiplatelet therapy with aspirin and/or clopidogrel. Patients’ demographic and procedural characteristics and indications for antiplatelet treatment are presented in Tables 1 and 2, respectively. To account for the intraindividual heterogeneity of procedural indications in patients with ⬎1 extracted tooth, we compared numbers of teeth, and not patients, with different extraction indications across study groups (Table 1). Prolonged immediate bleeding occurred in 2 patients (0.4%) in the control group, 1 patient (2.4%) receiving aspirin, 1 patient (2.8%) on clopidogrel, and 22 patients (66.7%) on dual antiplatelet treatment. Compared to controls risk of prolonged immediate bleeding was significantly higher in patients on dual antiplatelet therapy (RR 177.3, 95% CI 43.5 to 722, p ⬍0.001) but not in patients on aspirin alone (RR 6.3, 95% CI 0.6 to 68.4, p ⫽ 0.2) or clopidogrel alone (RR 7.4, 95% CI 0.7 to 79.5, p ⫽ 0.18). Bleeding risk was higher in patients on dual antiplatelets compared to those on aspirin only (RR 28, 95% CI 4 to 197, p ⬍0.001) or clopidogrel only (RR 24, 95% CI 3.4 to 168.3, p ⬍0.001). All immediate bleedings were successfully treated with local hemostatic measures as described earlier.
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The American Journal of Cardiology (www.ajconline.org)
Patients with immediate bleeding did not significantly differ in gender, age, and number or type of extracted teeth across different treatment groups. The indication for extraction in all controls and patients on single treatment who developed immediate bleeding was periodontitis. In patients on dual therapy who developed prolonged immediate bleeding, extraction was performed for periodontitis (n ⫽ 16, 73%), radicular lesion (n ⫽ 5, 23%), and severe decay (n ⫽ 1, 4%). Notably, all patients on dual antiplatelet therapy who had periodontitis developed prolonged postextraction bleeding. None of the controls or patients on single antiplatelet treatment developed any late hemorrhagic complication. One patient on dual therapy developed immediate bleeding and received hemostatic gauze and suturing after extraction and reported bleeding after consumption of hard food on the fifth postextraction day, but bleeding stopped spontaneously after 10 minutes and thus did not meet the criteria of significant late bleeding.2 Discussion The optimal treatment strategy for dental extractions, the most frequent minor surgical procedure, in the expanding population of patients receiving long-term antiplatelet therapy is a challenging issue; the documented thrombotic risk of antiplatelet withdrawal3 needs to be balanced against the putative hemorrhagic risk of uninterrupted antiplatelet treatment. Uninterrupted dual antiplatelet therapy is currently recommended in patients with drug-eluting stents who undergo dental procedures, although prospective studies specifically assessing the safety of this approach are missing.4 The present study is the first, to our knowledge, to prospectively assess the safety of dental extractions in patients on uninterrupted single or dual antiplatelet therapy. Our realworld cohort included patients receiving single, dual, or no antiplatelets, all treated by the same protocol, such that the RR of each antiplatelet regimen could be directly compared. Our results support the safety of dental extractions on uninterrupted single and dual antiplatelet treatment with appropriate local hemostatic measures. Antiplatelet monotherapy did not increase the risk of immediate postextraction bleeding. Prolonged bleeding that required local hemostatic treatment occurred in 2.4% of patients on aspirin and 2.8% on clopidogrel and was comparable to the RR in controls. Previous studies using similar criteria of immediate postextraction bleeding in aspirinreceiving patients reported an incidence of 0% to 3.8%.5,6 Consistent with our prospective results, serious or lifethreatening postextraction bleeding complications associated with antiplatelet therapy are extremely rare, with only few reports in the literature.7,8 No patient on single antiplatelet therapy developed clinically significant late hemorrhage. Cardona-Tortajada et al9 reported late-onset (⬎24 hours) postextraction bleeding in 17% of their 155 antiplatelet-treated patients; these complications, however, were mostly mild and self-controlled. The higher frequency of late bleeding events in that study may be associated with short (10 minutes) postextraction monitoring, whereas patients in our study were monitored for ⱖ30 minutes and then treated appropriately, if needed.
Persistent postextraction evaluation may therefore facilitate adequate hemostatic control and increase procedural safety in the setting of antiplatelet monotherapy. An intriguing result of our study is the safety of dental extractions even in patients on uninterrupted dual antiplatelet treatment when appropriate local hemostatic measures are taken. Patients receiving aspirin and clopidogrel were clearly at a higher risk of immediate postextraction bleeding, but all cases were successfully controlled by suturing and application of oxidized cellulose gauze. Importantly, the incidence of late hemorrhage did not increase in this putatively high-risk bleeding-prone population. Overall, although postextraction bleeding events are likely to occur under uninterrupted combined antiplatelet therapy, these are limited in the immediate postprocedure time frame, occurring within the safe environment of a dental clinic, and are controllable with appropriate local hemostatic treatment. Our results agree with those of Napeñas et al10 who reported no episodes of prolonged bleeding in their 29 patients receiving dual antiplatelet treatment; that study was limited, however, by the retrospective design, absence of direct assessment of perioperative bleeding, and absence of a control arm of patients not receiving antiplatelets. Hemorrhagic complications mostly occurred in the setting of periodontitis. Local inflammation in relation to local hyperemia and possibly fragility of the blood vessels might predispose to postextraction bleeding. Presence of periodontitis could thus enable risk stratification of patients who are more likely to develop hemorrhage while receiving antiplatelets to ensure a higher index of suspicion and prompt appropriate hemostatic measures. Our study would have benefited from a larger study population. Based on current recommendations4 we did not include patients with antiplatelet interruption; our study was therefore not designed to directly compare hemorrhagic risk in continuous versus interrupted antiplatelet treatment. We did not obtain a platelet count; thus we could not assess the potential role of platelet count in hemorrhagic risk. Considering the recognized variable response to antiplatelet drugs11 we did not use platelet function testing to assess antiplatelet resistance; hence, we could not determine whether patients with bleeding might have been “hyperresponders.” The safety of antiplatelet drugs other than aspirin and clopidogrel was not assessed. 1. Pototski M, Amenábar JM. Dental management of patients receiving anticoagulation or antiplatelet treatment. J Oral Sci 2007;49: 253–258. 2. Lockhart PB, Gibson J, Pond SH, Leitch J. Dental management considerations for the patient with an acquired coagulopathy. Part 1: coagulopathies from systemic disease. Br Dent J 2003;195:439 – 445. 3. Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, Airoldi F, Chieffo A, Montorfano M, Carlino M, Michev I, Corvaja N, Briguori C, Gerckens U, Grube E, Colombo A. Incidence, predictors, and outcome of thrombosis after successful implantation of drugeluting stents. JAMA 2005;293:2126 –2130. 4. Grines CL, Bonow RO, Casey DE Jr, Gardner TJ, Lockhart PB, Moliterno DJ, O’Gara P, Whitlow P; American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, American Dental Association, American College of Physicians. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart
Coronary Artery Disease/Antiplatelets and Dental Extractions
5. 6. 7. 8.
Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation 2007;115:813– 818. Krishnan B, Shenoy NA, Alexander M. Exodontia and antiplatelet therapy. J Oral Maxillofac Surg 2008;66:2063–2066. Morimoto Y, Niwa H, Minematsu K. Hemostatic management of tooth extractions in patients on oral antithrombotic therapy. J Oral Maxillofac Surg 2008;66:51–57. Foulke CN. Gingival hemorrhage related to aspirin ingestion. A case report. J Periodontol 1976;47:355–357. Thomason JM, Seymour RA, Murphy P, Brigham KM, Jones P. Aspirin-induced post-gingivectomy haemorrhage: a timely reminder. J Clin Periodontol 1997;24:136 –138.
967
9. Cardona-Tortajada F, Sainz-Gómez E, Figuerido-Garmendia J, de Robles-Adsuar AL, Morte-Casabó A, Giner-Muñoz F, ArtázcozOsés J, Vidán-Lizari J. 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 – e592. 10. Napeñas JJ, Hong CH, Brennan MT, Furney SL, Fox PC, Lockhart PB. The frequency of bleeding complications after invasive dental treatment in patients receiving single and dual antiplatelet therapy. J Am Dent Assoc 2009;140:690 – 695. 11. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 2009;360:354 –362.