ORIGINAL CONTRIBUTIONS
ARTICLE 2
Clopidogrel is not associated with increased bleeding complications after full-mouth extraction A retrospective study Hesham R. Omar, MD; Stephanie M. Socias, BS; R. Andrew Powless, DMD; Collin Sprenker, BS; Rachel Karlnoski, PhD; Devanand Mangar, MD; Enrico M. Camporesi, MD
M
anagement of antiplatelet and anticoagulant medications before dental surgery remains a matter of controversy and requires further research. The decision to continue the use of antiplatelets to avoid cardiac events or to withhold them to reduce blood loss is challenging. Although some evidence supports the continued use of anticoagulants before undergoing simple dental extractions because topical hemostatic agents are effective in preventing operative bleeding,1,2 the results of national surveys show that more than one-half of hematologists and oral and maxillofacial surgeons interrupt the patient’s use of anticoagulant medications before the patient undergoes these procedures.3 Fullmouth extraction is associated with a high risk of bleeding with no available results from controlled studies regarding perioperative antiplatelet management, and this absence of results has created significant variation in practice. The increased prevalence of cardiovascular and cerebrovascular disease and the advent of percutaneous intervention (PCI) and dual antiplatelet therapy (DAPT) created a notable rise in the number of patients taking antiplatelet medications. Although the use of such therapies
This article has an accompanying online continuing education activity available at: http://jada.ada.org/ce/home Copyright ª 2015 American Dental Association. All rights reserved.
ABSTRACT Background. To the authors’ knowledge, the effect of clopidogrel on bleeding complications during full-mouth extraction has not been studied. The authors aimed to determine the safety of continued use of clopidogrel during full-mouth extraction. Methods. The authors performed a retrospective study of consecutive patients undergoing full-mouth extraction who were taking aspirin, clopidogrel, a combination of aspirin and clopidogrel, or neither. The main study outcomes in the 4 study groups were estimated blood loss, transfusion requirements, and complications. The authors also examined the correlation between the number of teeth extracted and estimated blood loss in various groups. Results. Seventy-one patients underwent full-mouth extraction with removal of an average of 19 teeth. The authors excluded 3 patients owing to lack of data regarding blood loss. Of the remaining 68 patients, 25 were using aspirin, 12 were using clopidogrel, 9 were using both aspirin and clopidogrel, and 22 had discontinued the use of antiplatelets. There was no significant difference in the number of teeth extracted (P ¼ .283) and estimated blood loss (P ¼ .111) among the 4 groups. The authors found a significant moderate correlation between the number of teeth extracted and estimated blood loss in the group using aspirin (r ¼ 0.537; P ¼ .006) and in the group using clopidogrel, whether alone or in combination with aspirin (r ¼ 0.535; P ¼ .012), but not in the group who discontinued the use of antiplatelets. There was no need for blood transfusion in any patient. Conclusions. The results of this study provide limited evidence to suggest that continuation of clopidogrel during full-mouth extraction and preprosthetic surgery may be safe and does not appear to be associated with a significant risk of bleeding. Practical Implications. Clopidogrel therapy during full-mouth extraction is not associated with significant bleeding complications and may be continued in patients who have a high risk of experiencing a cardiac event. Key Words. Full-mouth extraction; clopidogrel; dual antiplatelet; preprosthetic surgery. JADA 2015:146(5):303-309 http://dx.doi.org/10.1016/j.adaj.2015.01.002
JADA 146(5)
http://jada.ada.org
May 2015 303
ORIGINAL CONTRIBUTIONS
reduces patients’ risk of experiencing cardiac adverse events, they also may increase the risk of postoperative bleeding.4 The decision to continue the use of these therapies by a patient undergoing full-mouth extraction, usually is made on a case-by-case basis after collaboration among the patient’s dentist, primary care physician, and cardiologist. At our institution, we adopted a conservative approach—allowing the continuation of antiplatelet therapy during full-mouth extraction while providing adequate local hemostatic measures—with good results.5 We hypothesized that there would be no significant difference in blood loss and need for blood transfusion between groups of patients continuing antiplatelet therapy and those suspending them before full-mouth extraction and preprosthetic surgery. The purpose of this study was to compare blood loss in patients undergoing full-mouth extraction when various antiplatelet regimens were continued or suspended. METHODS
We conducted this observational study of consecutive patients who had full-mouth extractions at Tampa General Hospital (TGH; Tampa, FL) from March 2012 through December 2013. The institutional review board at the University of South Florida (Tampa, FL) approved the study and waived the need for patient consent. We reviewed the charts of 71 patients who used various antiplatelet therapy regimens and who underwent full-mouth extraction. We studied only cases performed in the hospital setting owing to the availability of accurate data regarding blood loss. The dental surgeon (R.A.P.) deemed these cases to have a high risk of experiencing complications, and therefore these patients were admitted to the hospital rather than having this surgery in the office setting. These patients included those with multiple comorbidities, significant cardiac history, and an expected high risk of experiencing bleeding complications, as well as those who were frail or who had a high level of anxiety. For some cases, the patient’s primary care physician or cardiologist had recommended that the patient discontinue the use of antiplatelet medications, and in some cases—especially women—the patient independently decided to discontinue the antiplatelets because of concern about excessive bleeding. We excluded from the study patients who were concomitantly taking anticoagulant medications with an international normalized ratio (INR) greater than 1.3. Two of these excluded patients had INRs of 1.4 and 2.1. We divided patients into 4 subgroups: patients who used only aspirin, patients who used only clopidogrel, patients who used a combination of aspirin and clopidogrel, and patients who used neither aspirin or clopidogrel. We collected data pertaining to patient demographics, comorbidities, dose and type of antiplatelet medications, number of teeth extracted, surgical complications, and estimated blood loss (EBL). We
304 JADA 146(5) http://jada.ada.org
May 2015
classified patients as having stopped antiplatelet therapy if the last dose had been administered 5 or more days before surgery. At a minimum, each patient’s diagnosis included dental caries as a contributing factor for undergoing full-mouth extraction. A single dental surgeon (R.A.P.) performed all of the surgeries at a single site, TGH. The main study outcomes among the 4 study groups were EBL, transfusion requirements, procedurerelated complications, and cardiac complications. We also evaluated the strength of the correlation between the number of teeth extracted and the EBL in patients using aspirin therapy, patients using clopidogrel therapy (whether alone or in combination with aspirin) and those not using any antiplatelet medications. Surgical and local hemostatic technique. All patients received general anesthetic with endotracheal intubation and presurgical trigeminal blocks as indicated via infiltration with 1% lidocaine hydrochloride and epinephrine 1:100,000 (approximately 10 milliliters per mouth quadrant). We used normal saline in 60-mL syringes with a plastic needle to irrigate the mouth. We subtracted the volume of normal saline used from the final EBL. In addition, the preprosthetic surgical preparation required smoothing of alveolar surfaces and raising submucosal flaps to remove tori when present. After we extracted the teeth, we placed running chromic sutures in all patients’ maxilla and mandible, we packed tooth sockets with gel foam, and we instructed patients to bite on gauze after they regained alertness and orientation after receiving anesthetic. We completed a total blood loss measurement at the time the patient was transferred to the recovery room. We measured blood loss for each procedure using techniques to ensure maximum accuracy. We used a 40-mL Lukens trap to obtain precise blood loss measurements, and we weighed all sponges, x-ray–detectable gauze sponges (Raytec), linen goods, and throat packs before and after surgery to account for blood absorption. After the procedure, we gave patients doses of morphine and fentanyl for pain control. On awakening, patients received oxycodone 5 milligrams with acetaminophen 325 mg once or twice before discharge. Most patients returned home on the same day of the procedure. Because of concern for potential late bleeding, which can occur up to 4 to 7 days after this surgery, we asked all patients to follow up with the dental surgeon (R.A.P.) 5 days after surgery (or whenever uncontrollable bleeding reoccurred) for an examination and possible removal of stitches. Patients also had a follow-up appointment with the dentist 20-35 days after surgery for prosthesis fitting.
ABBREVIATION KEY. ADP: Adenosine diphosphate. DAPT: Dual antiplatelet therapy. EBL: Estimated blood loss. INR: International normalized ratio. PCI: Percutaneous intervention. TGH: Tampa General Hospital.
ORIGINAL CONTRIBUTIONS
Statistical analysis. We used the KolmogorovSmirnov test to assess the normality of the distribution of the investigated variables. We expressed continuous data as means and standard deviations, and we compared the data across the four study groups using analysis of variance (ANOVA). We compared categorical variables using the c2 test. We examined the strength of the association between the number of teeth extracted and EBL in various groups using Pearson product moment correlation. We considered a P value < .05 to be significant. We analyzed data using statistical software (IBM SPSS Statistics for Windows, Version 21.0, IBM). RESULTS
Patient characteristics. We found 71 patients who underwent full-mouth extraction involving the removal of 5 to 31 teeth (average, 19 teeth) during the study period. We excluded 3 patients owing to lack of accurate perioperative antiplatelet management data. These 3 patients had no complications and the EBL was approximately 30 mL. Of the remaining 68 patients, 25 were using aspirin, 12 were using clopidogrel, 9 were using both aspirin and clopidogrel, and 22 had discontinued the use of antiplatelet medications. Those who continued using clopidogrel were taking 75 mg daily. Most patients who continued aspirin therapy, whether alone or in combination with clopidogrel, were receiving aspirin 81 mg (26 patients), and 8 patients were taking aspirin 325 mg daily. Table 1 lists baseline demographics and clinical characteristics of the 4 groups. Patients in the groups who continued using clopidogrel either alone or in combination with aspirin had a significantly higher previous incidence of PCI (P ¼ .001) and a trend toward having a higher previous incidence of coronary artery disease (P ¼ .071) and myocardial infarction (P ¼ .061) than patients in the other groups. The rest of baseline parameters were comparable across the 4 study groups. Blood loss data. Average blood loss in the aspirin, clopidogrel, aspirin and clopidogrel, and no-antiplatelet groups was 32.2 mL, 45.6 mL, 33.1 mL, and 37.3 mL, respectively. The EBL in 3 patients was more than 50 mL (2 patients from the clopidogrel group and 1 from the aspirin and clopidogrel group), 1 of whom lost more than 100 mL (118 mL) from the clopidogrel group. Figures 1 and 2 illustrate the mean EBL and average number of teeth extracted in the four study subgroups, respectively. ANOVA showed no significant difference in blood loss (P ¼ .111) or teeth extracted (P ¼ .283) across the 4 groups. We examined the strength of the correlation between the number of teeth extracted and the EBL in the 4 study groups. Among the 21 patients taking clopidogrel either alone or in combination with aspirin therapy, there was a significant moderate correlation between the number of teeth extracted and EBL (r ¼ 0.535; P ¼ .012). Among the 25 patients using aspirin therapy, there was also a
significant moderate correlation between the number of teeth extracted and EBL (r ¼ 0.537; P ¼ .006). We did not find this correlation to be significant in the 22 patients who discontinued antiplatelet medications (r ¼ 0.398; P ¼ .067) (Table 2). Complications. Perioperative complications were minimal, and none of the patients required blood transfusions. There were no incidents of stent thrombosis. Two patients required extended hospital stay; the first patient, a 60-year-old man who continued aspirin therapy before undergoing full-mouth extraction, had no issues during the surgery itself, but because of postoperative uncontrolled blood pressure, he was discharged 4 days after surgery. The second patient, a 63-year-old woman who had continued the use of clopidogrel therapy, experienced postoperative chest pain, atrial flutter, and non-ST segment elevation myocardial infarction. A postoperative clinical work-up revealed a normal cardiac stress test, and the patient was discharged 5 days after surgery. There were no cases of late postoperative bleeding. DISCUSSION
Performing oral surgery on patients taking antiplatelet medications requires a risk-benefit assessment to balance concerns of excessive bleeding and the risk of experiencing cardiovascular events. The absence of specific recommendations owing to a lack of published results from randomized controlled trials adds to the complexity of making this decision and allows for taking a more individualized rather than an evidence-based approach. Dentists making the choice to continue or suspend a patient’s use of antiplatelet medications should take into consideration the type and dose of the drug, the patient’s cardiac history (including previous myocardial infarctions, onset, and type of deployed stent, if any), concomitant administration of anticoagulant drugs, other comorbidities that can increase risk of bleeding (such as liver failure and renal failure), the level of difficulty of the procedure, the number of teeth to be extracted, the skills of the operating dentist, and the availability of transfusion products and hospital bed if needed. The results of our study confirm that continued use of clopidogrel either alone or in addition to aspirin did not significantly increase bleeding during full-mouth extractions. Although we noted a trend for patients in the group using clopidogrel to have a slightly higher level of mean EBL compared with participants in the other groups, this result was not significant and did not translate into a negative outcome. None of the patients in our study required blood transfusion. Our experience with full-mouth extractions and the employment of local hemostatic tools has contributed to this clinical success. Although the investigators of few studies have examined continuing antiplatelet therapy in patients who had fewer than 6 teeth extracted, we found
JADA 146(5)
http://jada.ada.org
May 2015 305
ORIGINAL CONTRIBUTIONS
TABLE 1
Baseline demographics and clinical characteristics among 68 patients who had full-mouth extractions from March 2012 through December 2013. CHARACTERISTIC
ASPIRIN
CLOPIDOGREL
No. (%)
25 (36.8)
12 (17.6)
Age (Mean [Standard Deviation])
59 (13)
62 (11)
Female, n (%)
13 (52) 8 (32)
Coronary Artery Disease, n (%)
ASPIRIN AND CLOPIDOGREL 9 (13.2) 58 (6)
NO USE OF ANTIPLATELETS
P VALUE
22 (32.4)
Not applicable
56 (10)
.409
7 (58.3)
6 (66.7)
18 (81.8)
.186
6 (50)
7 (77.8)
7 (31.8)
.071
Diabetes Mellitus, n (%)
11 (44)
7 (58.3)
6 (66.7)
11 (50)
.651
Hypertension, n (%)
19 (76)
12 (100)
9 (100)
19 (86.3)
.126
Previous Percutaneous Coronary Intervention, n (%)
2 (8)
6 (50)
4 (44.4)
1 (4.5)
.001*
Previous Pacemaker, n (%)
2 (8)
2 (16.7)
3 (33.3)
2 (9.1)
.239
Myocardial Infarction, n (%)
4 (16)
3 (25)
5 (55.6)
3 (13.6)
.061
Stroke, n (%)
8 (32)
2 (16.7)
2 (22.2)
5 (22.7)
.754
* Statistically significant.
ESTIMATED BLOOD LOSS (MILLILITERS)
0.4% of the patients in the control group (P < .001), and this was 120 * controlled successfully with local measures. 100 Park and colleagues8 studied 100 matched pairs of patients with 80 drug-eluting stents who * had 1 to 6 tooth extrac60 tions while receiving antiplatelet therapy; 40 they noted excessive bleeding in 2 patients in the continued drug 20 therapy group and 1 patient in the control 0 group. Interestingly, Aspirin No Clopidogrel Aspirin and excessive bleeding Clopidogrel Antiplatelets occurred in patients INTERVENTION who had 3 or fewer extractions, and no transfusion was needed. Figure 1. Mean estimated blood loss among the 4 groups whose participants received full-mouth extractions at Tampa General Hospital (from March 2012 through December 2013) according to their antiplatelet regimen. In our study results, P ¼ .111. : Outlier. *: Extreme outlier. we found no correlation between the number of no studies whose investigators evaluated the safety of teeth extracted and EBL in the group whose participants using antiplatelets during full-mouth extraction and discontinued the use of antiplatelet medications; howmajor dental procedures.6 Lillis and colleagues7 evaluated ever, in the groups whose participants received aspirin 643 patients undergoing 3 or fewer dental extractions and clopidogrel, either alone or in combination with during uninterrupted single-antiplatelet therapy or aspirin, we found a significant moderate correlation. DAPT; they found no significant difference in blood loss However, the difference in blood loss was not clinically among members of the control group and members of significant, and blood transfusion was not required. the single-antiplatelet therapy group with either aspirin Nonetheless, this result might suggest that a clinician or clopidogrel, but they noted prolonged bleeding in who needs to remove a large number of teeth from a 66.7% of patients who received DAPT compared with patient should perform the tooth extractions over several
306 JADA 146(5) http://jada.ada.org
May 2015
ORIGINAL CONTRIBUTIONS
NUMBER OF TEETH EXTRACTED
sessions, especially if the patient uses antiplatelet therapy. Cardona35 Tortajada and col9 30 leagues prospectively evaluated 155 patients 25 who were using antiplatelet therapy for 20 dental extractions and found a statistically 15 significant correlation between the number 10 of teeth extracted and 5 bleeding. Despite reporting no major 0 hemorrhages, the authors recommended –5 that no more than 3 Clopidogrel Aspirin and Aspirin No teeth be extracted at Clopidogrel Antiplatelets a time for patients INTERVENTION continuing antiplatelet 9 therapy. A review by Wahl10 in 2014 identified Figure 2. Average number of teeth extracted among the 4 groups who received full-mouth extraction (from March 2012 through December 2013) according to their antiplatelet regimen. P ¼ .283. 23 published studies whose investigators had explored the continuation of antiplatelet ther- TABLE 2 apy in 1,129 patients The correlation between the number of teeth extracted undergoing 1,916 dental and estimated blood loss in patients not using antiplatelets, extractions; Wahl found patients taking aspirin, and patients taking clopidogrel, a rate of 1.6% posteither alone or in combination with aspirin. operative bleeding. Conversely, Wahl10 CHARACTERISTIC NO. OF TEETH EBL,† mL‡ CORRELATION (r) P VALUE found 10 published PATIENTS EXTRACTED (MEAN [SD]) (MEAN [SD*]) studies that involved a No Antiplatelet 22 17.1 (6.7) 37.3 (11.5) 0.398 .067 total of 322 patients, Aspirin 25 20.5 (6.8) 32.2 (10.6) 0.537 .006§ in whom there had 21 17.5 (7.0) 40.2 (23.9) 0.535 .012§ Clopidogrel and Aspirin been 372 cessations of Group in Combination antiplatelet therapy with With Clopidogrel Group an incidence of 5% * SD: Standard deviation. of patients who ex† EBL: Estimated blood loss. ‡ mL: Milliliters. perienced thromboem§ Statistically significant. bolic complications. Similarly, Partridge and colleagues11 performed a prospective observational study with patients undergoing continued clopidogrel therapy is related mostly to cardentoalveolar lavage who were taking aspirin, nonstediac surgery; therefore, the American Heart Association12 roidal anti-inflammatory drugs, or clopidogrel. The recommends discontinuing the use of clopidogrel 5 days experimental group whose participants used antiplatelet before planned coronary artery bypass graft surgery therapy lost a mean of 1.78 grams of blood compared unless the benefit of continuing clopidogrel therapy with 1.96 g in participants in the control group (not a outweighs the risk of excessive bleeding. Studies whose investigators have tested antiplatelet management in significant difference).11 Wahl10 and Partridge and colleagues11 recommended continuation of antiplatelet noncardiac surgeries have produced results similar to our therapy for dental procedures. study. Stone and colleagues13 concluded that patients undergoing peripheral arterial surgery who continued Clinicians should note that the main evidence of increased postoperative bleeding complications from using clopidogrel either alone or as a part of DAPT did
JADA 146(5)
http://jada.ada.org
May 2015 307
ORIGINAL CONTRIBUTIONS
not experience more bleeding compared with patients using no antiplatelet therapy or using aspirin alone. The investigators of a study on the safety of antithrombotics and general thoracic surgery found that patients taking clopidogrel who have a coronary stent can safely undergo general thoracic surgery without increased bleeding.14 Similarly, investigators found perioperative clopidogrel use during major lung resection and hip fracture surgery to be safe.15,16 In a summary of management of antithrombotic medications, the American Academy of Neurology17 affirmed that the continuation of aspirin or heparin is unlikely to increase clinically important bleeding in dental procedures. Clopidogrel affects platelet activation by selectively and irreversibly blocking a subunit of the adenosine diphosphate (ADP) receptor, providing an antiplatelet action additive to the inhibition of the thromboxane A2 pathway by aspirin therapy. Despite the fact that platelet function completely recovers 7 days after clopidogrel cessation,18,19 the optimal time delay from the last clopidogrel dose to the onset of surgery is not clear. Price and colleagues20 compared the offset of the antiplatelet effects of prasugrel and clopidogrel and found that in the clopidogrel group, at least 50% of patients returned to baseline reactivity by washout day 3, at least 75% of patients had returned to baseline reactivity by day 5, and at least 90% of patients had returned to baseline reactivity by day 6; these authors concluded that most patients who were treated with clopidogrel (87%) recovered platelet function by 5 days after drug cessation. This finding is consistent with guidelines regarding the recommended waiting period for surgery after clopidogrel discontinuation. Accordingly, in our study we used a cutoff value of 5 days to identify groups of patients who continued or discontinued clopidogrel therapy. This study is subject to all limitations inherent in a nonrandomized study. The design is retrospective, the number of patients is rather small, and a single provider performed all of the full-mouth extractions. Therefore, clinicians should extrapolate the results to other centers with caution and realize the need for these results to be verified by investigators of larger prospective trials. Potential confounding variables that are difficult to control might have been present. We did not account for the administration of other medicines that might affect platelet function, such as nonsteroidal anti-inflammatory drugs or proton pump inhibitors, which have been shown to reduce the antiplatelet effect of clopidogrel. Also we did not account for the wide interindividual variability in the capacity of clopidogrel to inhibit ADP-induced platelet aggregation. CONCLUSION
To our knowledge, this is the first study to compare blood loss owing to various antiplatelet regimens during
308 JADA 146(5) http://jada.ada.org
May 2015
full-mouth extraction and preprosthetic surgery. None of the 21 patients in the cohorts receiving clopidogrel, either alone or in combination with aspirin, experienced significant postsurgical bleeding after multiple extractions of their remaining (17.5 [standard deviation ¼ 7]) teeth and preprosthetic surgery. The results of this study provide limited evidence to suggest that continuation of clopidogrel therapy during full-mouth extraction and preprosthetic surgery may be safe and is not associated with significant risk of bleeding. It is also reasonable to accept the minor risk of blood transfusion rather than the consequences of perioperative adverse cardiac events. We therefore propose that patients undergoing fullmouth extraction who have a high risk of experiencing cardiac complications may continue antiplatelet therapy perioperatively. The risk of bleeding appears to be minimal and should be managed with appropriate local hemostatic measures rather than antiplatelet therapy suspension. n Dr. Omar is an internal medicine physician, Internal Medicine Department, Mercy Medical Center – Clinton, 1410 N. Fourth St., Clinton, IA 52732, e-mail [email protected]. Address correspondence to Dr. Omar. Ms. Socias is a research assistant, Department of Research, Florida Gulfto-Bay Anesthesiology Associates, Tampa, FL. Dr. Powless is vice chief, Dental and Maxillofacial Surgery, Tampa General Hospital, Tampa, FL. Mr. Sprenker is a research assistant, Department of Research, Florida Gulf-to-Bay Anesthesiology Associates, Tampa, FL. Dr. Karlnoski is the director of quality and research, Department of Research, Florida Gulf-to-Bay Anesthesiology Associates, Tampa, FL. Dr. Mangar is an anesthesiologist and chief executive officer, Florida Gulfto-Bay Anesthesiology Associates, Tampa, FL; chief of anesthesia, Tampa General Hospital, Tampa, FL; and regional medical director, TEAMHealth, Tampa, FL. Dr. Camporesi is a professor of surgery and anesthesiology and molecular pharmacology and physiology, University of South Florida, Tampa, FL; an attending anesthesiologist, Florida Gulf-to-Bay Anesthesiology Associates, Tampa, FL; and the research director, TEAMHealth, Tampa, FL. Disclosure. None of the authors reported any disclosures. The authors presented selected results of this study at the annual meeting of the American Society of Anesthesiology, held October 11-15, 2014, in New Orleans, LA. 1. Aframian DJ, Lalla RV, Peterson DE. Management of dental patients taking common hemostasis-altering medications. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(suppl):S45.e1-S45.e11. 2. Madrid C, Sanz M. What influence do anticoagulants have on oral implant therapy? A systematic review. Clin Oral Implants Res. 2009; 20(suppl 4):96-106. 3. Lim W, Wang M, Crowther M, Douketis J. The management of anticoagulated patients requiring dental extraction: a cross-sectional survey of oral and maxillofacial surgeons and hematologists. J Thromb Haemost. 2007;5(10):2157-2159. 4. Pototski M, Amenabar JM. Dental management of patients receiving anticoagulation or antiplatelet treatment. J Oral Sci. 2007; 49(4):253-258. 5. Powless RA, Omar HR, Mangar D, Camporesi EM. Management of antithrombotic therapy before full-mouth extraction. J Calif Dent Assoc. 2013;41(6):417-420. 6. van Diermen DE, Aartman IH, Baart JA, Hoogstraten J, van der Waal I. Dental management of patients using antithrombotic drugs: critical appraisal of existing guidelines. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107(5):616-624.
ORIGINAL CONTRIBUTIONS
7. 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(7):964-967. 8. Park MW, Her SH, Kwon JB, et al. Safety of dental extractions in coronary drug-eluting stenting patients without stopping multiple antiplatelet agents. Clin Cardiol. 2012;35(4):225-230. 9. Cardona-Tortajada F, Sainz-Gómez E, Figuerido-Garmendia J, 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(11):e588-e592. 10. Wahl MJ. Dental surgery and antiplatelet agents: bleed or die. Am J Med. 2014;127(4):260-267. 11. Partridge CG, Campbell JH, Alvarado F. The effect of platelet-altering medications on bleeding from minor oral surgery procedures. J Oral Maxillofac Surg. 2008;66(1):93-97. 12. Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA focused update of the guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline): a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines [published corrections appear in Circulation. 2011;123(22):e625-e626 and in Circulation. 2011;124(12):e337-e340]. Circulation. 2011;123(18):2022-2060. 13. Stone DH, Goodney PP, Schanzer A, et al; Vascular Study Group of New England. Clopidogrel is not associated with major bleeding
complications during peripheral arterial surgery. J Vasc Surg. 2011;54(3): 779-784. 14. Cerfolio RJ, Minnich DJ, Bryant AS. General thoracic surgery is safe in patients taking clopidogrel (Plavix). J Thorac Cardiovasc Surg. 2010; 140(5):970-976. 15. Ceppa DP, Welsby IJ, Wang TY, et al. Perioperative management of patients on clopidogrel (Plavix) undergoing major lung resection. Ann Thorac Surg. 2011;92(6):1971-1976. 16. Feely MA, Mabry TM, Lohse CM, Sems SA, Mauck KF. Safety of clopidogrel in hip fracture surgery. Mayo Clin Proc. 2013;88(2):149-156. 17. Armstrong MJ, Gronseth G, Anderson D, et al. Summary of evidencebased guideline: periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease—report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013;80(22):2065-2069. 18. Angiolillo DJ, Ueno M, Goto S. Basic principles of platelet biology and clinical implications. Circ J. 2010;74(4):597-607. 19. Weber AA, Braun M, Hohlfeld T, Schwippert B, Tschöpe D, Schrör K. Recovery of platelet function after discontinuation of clopidogrel treatment in healthy volunteers. Br J Clin Pharmacol. 2001;52(3):333-336. 20. Price MJ, Walder JS, Baker BA, et al. Recovery of platelet function after discontinuation of prasugrel or clopidogrel maintenance dosing in aspirin-treated patients with stable coronary disease: the recovery trial. J Am Coll Cardiol. 2012;59(25):2338-2343.
JADA 146(5)
http://jada.ada.org
May 2015 309
ARTICLE 2
Clopidogrel is not associated with increased bleeding complications after full-mouth extraction A retrospective study Hesham R. Omar, MD; Stephanie M. Socias, BS; R. Andrew Powless, DMD; Collin Sprenker, BS; Rachel Karlnoski, PhD; Devanand Mangar, MD; Enrico M. Camporesi, MD
M
anagement of antiplatelet and anticoagulant medications before dental surgery remains a matter of controversy and requires further research. The decision to continue the use of antiplatelets to avoid cardiac events or to withhold them to reduce blood loss is challenging. Although some evidence supports the continued use of anticoagulants before undergoing simple dental extractions because topical hemostatic agents are effective in preventing operative bleeding,1,2 the results of national surveys show that more than one-half of hematologists and oral and maxillofacial surgeons interrupt the patient’s use of anticoagulant medications before the patient undergoes these procedures.3 Fullmouth extraction is associated with a high risk of bleeding with no available results from controlled studies regarding perioperative antiplatelet management, and this absence of results has created significant variation in practice. The increased prevalence of cardiovascular and cerebrovascular disease and the advent of percutaneous intervention (PCI) and dual antiplatelet therapy (DAPT) created a notable rise in the number of patients taking antiplatelet medications. Although the use of such therapies
This article has an accompanying online continuing education activity available at: http://jada.ada.org/ce/home Copyright ª 2015 American Dental Association. All rights reserved.
ABSTRACT Background. To the authors’ knowledge, the effect of clopidogrel on bleeding complications during full-mouth extraction has not been studied. The authors aimed to determine the safety of continued use of clopidogrel during full-mouth extraction. Methods. The authors performed a retrospective study of consecutive patients undergoing full-mouth extraction who were taking aspirin, clopidogrel, a combination of aspirin and clopidogrel, or neither. The main study outcomes in the 4 study groups were estimated blood loss, transfusion requirements, and complications. The authors also examined the correlation between the number of teeth extracted and estimated blood loss in various groups. Results. Seventy-one patients underwent full-mouth extraction with removal of an average of 19 teeth. The authors excluded 3 patients owing to lack of data regarding blood loss. Of the remaining 68 patients, 25 were using aspirin, 12 were using clopidogrel, 9 were using both aspirin and clopidogrel, and 22 had discontinued the use of antiplatelets. There was no significant difference in the number of teeth extracted (P ¼ .283) and estimated blood loss (P ¼ .111) among the 4 groups. The authors found a significant moderate correlation between the number of teeth extracted and estimated blood loss in the group using aspirin (r ¼ 0.537; P ¼ .006) and in the group using clopidogrel, whether alone or in combination with aspirin (r ¼ 0.535; P ¼ .012), but not in the group who discontinued the use of antiplatelets. There was no need for blood transfusion in any patient. Conclusions. The results of this study provide limited evidence to suggest that continuation of clopidogrel during full-mouth extraction and preprosthetic surgery may be safe and does not appear to be associated with a significant risk of bleeding. Practical Implications. Clopidogrel therapy during full-mouth extraction is not associated with significant bleeding complications and may be continued in patients who have a high risk of experiencing a cardiac event. Key Words. Full-mouth extraction; clopidogrel; dual antiplatelet; preprosthetic surgery. JADA 2015:146(5):303-309 http://dx.doi.org/10.1016/j.adaj.2015.01.002
JADA 146(5)
http://jada.ada.org
May 2015 303
ORIGINAL CONTRIBUTIONS
reduces patients’ risk of experiencing cardiac adverse events, they also may increase the risk of postoperative bleeding.4 The decision to continue the use of these therapies by a patient undergoing full-mouth extraction, usually is made on a case-by-case basis after collaboration among the patient’s dentist, primary care physician, and cardiologist. At our institution, we adopted a conservative approach—allowing the continuation of antiplatelet therapy during full-mouth extraction while providing adequate local hemostatic measures—with good results.5 We hypothesized that there would be no significant difference in blood loss and need for blood transfusion between groups of patients continuing antiplatelet therapy and those suspending them before full-mouth extraction and preprosthetic surgery. The purpose of this study was to compare blood loss in patients undergoing full-mouth extraction when various antiplatelet regimens were continued or suspended. METHODS
We conducted this observational study of consecutive patients who had full-mouth extractions at Tampa General Hospital (TGH; Tampa, FL) from March 2012 through December 2013. The institutional review board at the University of South Florida (Tampa, FL) approved the study and waived the need for patient consent. We reviewed the charts of 71 patients who used various antiplatelet therapy regimens and who underwent full-mouth extraction. We studied only cases performed in the hospital setting owing to the availability of accurate data regarding blood loss. The dental surgeon (R.A.P.) deemed these cases to have a high risk of experiencing complications, and therefore these patients were admitted to the hospital rather than having this surgery in the office setting. These patients included those with multiple comorbidities, significant cardiac history, and an expected high risk of experiencing bleeding complications, as well as those who were frail or who had a high level of anxiety. For some cases, the patient’s primary care physician or cardiologist had recommended that the patient discontinue the use of antiplatelet medications, and in some cases—especially women—the patient independently decided to discontinue the antiplatelets because of concern about excessive bleeding. We excluded from the study patients who were concomitantly taking anticoagulant medications with an international normalized ratio (INR) greater than 1.3. Two of these excluded patients had INRs of 1.4 and 2.1. We divided patients into 4 subgroups: patients who used only aspirin, patients who used only clopidogrel, patients who used a combination of aspirin and clopidogrel, and patients who used neither aspirin or clopidogrel. We collected data pertaining to patient demographics, comorbidities, dose and type of antiplatelet medications, number of teeth extracted, surgical complications, and estimated blood loss (EBL). We
304 JADA 146(5) http://jada.ada.org
May 2015
classified patients as having stopped antiplatelet therapy if the last dose had been administered 5 or more days before surgery. At a minimum, each patient’s diagnosis included dental caries as a contributing factor for undergoing full-mouth extraction. A single dental surgeon (R.A.P.) performed all of the surgeries at a single site, TGH. The main study outcomes among the 4 study groups were EBL, transfusion requirements, procedurerelated complications, and cardiac complications. We also evaluated the strength of the correlation between the number of teeth extracted and the EBL in patients using aspirin therapy, patients using clopidogrel therapy (whether alone or in combination with aspirin) and those not using any antiplatelet medications. Surgical and local hemostatic technique. All patients received general anesthetic with endotracheal intubation and presurgical trigeminal blocks as indicated via infiltration with 1% lidocaine hydrochloride and epinephrine 1:100,000 (approximately 10 milliliters per mouth quadrant). We used normal saline in 60-mL syringes with a plastic needle to irrigate the mouth. We subtracted the volume of normal saline used from the final EBL. In addition, the preprosthetic surgical preparation required smoothing of alveolar surfaces and raising submucosal flaps to remove tori when present. After we extracted the teeth, we placed running chromic sutures in all patients’ maxilla and mandible, we packed tooth sockets with gel foam, and we instructed patients to bite on gauze after they regained alertness and orientation after receiving anesthetic. We completed a total blood loss measurement at the time the patient was transferred to the recovery room. We measured blood loss for each procedure using techniques to ensure maximum accuracy. We used a 40-mL Lukens trap to obtain precise blood loss measurements, and we weighed all sponges, x-ray–detectable gauze sponges (Raytec), linen goods, and throat packs before and after surgery to account for blood absorption. After the procedure, we gave patients doses of morphine and fentanyl for pain control. On awakening, patients received oxycodone 5 milligrams with acetaminophen 325 mg once or twice before discharge. Most patients returned home on the same day of the procedure. Because of concern for potential late bleeding, which can occur up to 4 to 7 days after this surgery, we asked all patients to follow up with the dental surgeon (R.A.P.) 5 days after surgery (or whenever uncontrollable bleeding reoccurred) for an examination and possible removal of stitches. Patients also had a follow-up appointment with the dentist 20-35 days after surgery for prosthesis fitting.
ABBREVIATION KEY. ADP: Adenosine diphosphate. DAPT: Dual antiplatelet therapy. EBL: Estimated blood loss. INR: International normalized ratio. PCI: Percutaneous intervention. TGH: Tampa General Hospital.
ORIGINAL CONTRIBUTIONS
Statistical analysis. We used the KolmogorovSmirnov test to assess the normality of the distribution of the investigated variables. We expressed continuous data as means and standard deviations, and we compared the data across the four study groups using analysis of variance (ANOVA). We compared categorical variables using the c2 test. We examined the strength of the association between the number of teeth extracted and EBL in various groups using Pearson product moment correlation. We considered a P value < .05 to be significant. We analyzed data using statistical software (IBM SPSS Statistics for Windows, Version 21.0, IBM). RESULTS
Patient characteristics. We found 71 patients who underwent full-mouth extraction involving the removal of 5 to 31 teeth (average, 19 teeth) during the study period. We excluded 3 patients owing to lack of accurate perioperative antiplatelet management data. These 3 patients had no complications and the EBL was approximately 30 mL. Of the remaining 68 patients, 25 were using aspirin, 12 were using clopidogrel, 9 were using both aspirin and clopidogrel, and 22 had discontinued the use of antiplatelet medications. Those who continued using clopidogrel were taking 75 mg daily. Most patients who continued aspirin therapy, whether alone or in combination with clopidogrel, were receiving aspirin 81 mg (26 patients), and 8 patients were taking aspirin 325 mg daily. Table 1 lists baseline demographics and clinical characteristics of the 4 groups. Patients in the groups who continued using clopidogrel either alone or in combination with aspirin had a significantly higher previous incidence of PCI (P ¼ .001) and a trend toward having a higher previous incidence of coronary artery disease (P ¼ .071) and myocardial infarction (P ¼ .061) than patients in the other groups. The rest of baseline parameters were comparable across the 4 study groups. Blood loss data. Average blood loss in the aspirin, clopidogrel, aspirin and clopidogrel, and no-antiplatelet groups was 32.2 mL, 45.6 mL, 33.1 mL, and 37.3 mL, respectively. The EBL in 3 patients was more than 50 mL (2 patients from the clopidogrel group and 1 from the aspirin and clopidogrel group), 1 of whom lost more than 100 mL (118 mL) from the clopidogrel group. Figures 1 and 2 illustrate the mean EBL and average number of teeth extracted in the four study subgroups, respectively. ANOVA showed no significant difference in blood loss (P ¼ .111) or teeth extracted (P ¼ .283) across the 4 groups. We examined the strength of the correlation between the number of teeth extracted and the EBL in the 4 study groups. Among the 21 patients taking clopidogrel either alone or in combination with aspirin therapy, there was a significant moderate correlation between the number of teeth extracted and EBL (r ¼ 0.535; P ¼ .012). Among the 25 patients using aspirin therapy, there was also a
significant moderate correlation between the number of teeth extracted and EBL (r ¼ 0.537; P ¼ .006). We did not find this correlation to be significant in the 22 patients who discontinued antiplatelet medications (r ¼ 0.398; P ¼ .067) (Table 2). Complications. Perioperative complications were minimal, and none of the patients required blood transfusions. There were no incidents of stent thrombosis. Two patients required extended hospital stay; the first patient, a 60-year-old man who continued aspirin therapy before undergoing full-mouth extraction, had no issues during the surgery itself, but because of postoperative uncontrolled blood pressure, he was discharged 4 days after surgery. The second patient, a 63-year-old woman who had continued the use of clopidogrel therapy, experienced postoperative chest pain, atrial flutter, and non-ST segment elevation myocardial infarction. A postoperative clinical work-up revealed a normal cardiac stress test, and the patient was discharged 5 days after surgery. There were no cases of late postoperative bleeding. DISCUSSION
Performing oral surgery on patients taking antiplatelet medications requires a risk-benefit assessment to balance concerns of excessive bleeding and the risk of experiencing cardiovascular events. The absence of specific recommendations owing to a lack of published results from randomized controlled trials adds to the complexity of making this decision and allows for taking a more individualized rather than an evidence-based approach. Dentists making the choice to continue or suspend a patient’s use of antiplatelet medications should take into consideration the type and dose of the drug, the patient’s cardiac history (including previous myocardial infarctions, onset, and type of deployed stent, if any), concomitant administration of anticoagulant drugs, other comorbidities that can increase risk of bleeding (such as liver failure and renal failure), the level of difficulty of the procedure, the number of teeth to be extracted, the skills of the operating dentist, and the availability of transfusion products and hospital bed if needed. The results of our study confirm that continued use of clopidogrel either alone or in addition to aspirin did not significantly increase bleeding during full-mouth extractions. Although we noted a trend for patients in the group using clopidogrel to have a slightly higher level of mean EBL compared with participants in the other groups, this result was not significant and did not translate into a negative outcome. None of the patients in our study required blood transfusion. Our experience with full-mouth extractions and the employment of local hemostatic tools has contributed to this clinical success. Although the investigators of few studies have examined continuing antiplatelet therapy in patients who had fewer than 6 teeth extracted, we found
JADA 146(5)
http://jada.ada.org
May 2015 305
ORIGINAL CONTRIBUTIONS
TABLE 1
Baseline demographics and clinical characteristics among 68 patients who had full-mouth extractions from March 2012 through December 2013. CHARACTERISTIC
ASPIRIN
CLOPIDOGREL
No. (%)
25 (36.8)
12 (17.6)
Age (Mean [Standard Deviation])
59 (13)
62 (11)
Female, n (%)
13 (52) 8 (32)
Coronary Artery Disease, n (%)
ASPIRIN AND CLOPIDOGREL 9 (13.2) 58 (6)
NO USE OF ANTIPLATELETS
P VALUE
22 (32.4)
Not applicable
56 (10)
.409
7 (58.3)
6 (66.7)
18 (81.8)
.186
6 (50)
7 (77.8)
7 (31.8)
.071
Diabetes Mellitus, n (%)
11 (44)
7 (58.3)
6 (66.7)
11 (50)
.651
Hypertension, n (%)
19 (76)
12 (100)
9 (100)
19 (86.3)
.126
Previous Percutaneous Coronary Intervention, n (%)
2 (8)
6 (50)
4 (44.4)
1 (4.5)
.001*
Previous Pacemaker, n (%)
2 (8)
2 (16.7)
3 (33.3)
2 (9.1)
.239
Myocardial Infarction, n (%)
4 (16)
3 (25)
5 (55.6)
3 (13.6)
.061
Stroke, n (%)
8 (32)
2 (16.7)
2 (22.2)
5 (22.7)
.754
* Statistically significant.
ESTIMATED BLOOD LOSS (MILLILITERS)
0.4% of the patients in the control group (P < .001), and this was 120 * controlled successfully with local measures. 100 Park and colleagues8 studied 100 matched pairs of patients with 80 drug-eluting stents who * had 1 to 6 tooth extrac60 tions while receiving antiplatelet therapy; 40 they noted excessive bleeding in 2 patients in the continued drug 20 therapy group and 1 patient in the control 0 group. Interestingly, Aspirin No Clopidogrel Aspirin and excessive bleeding Clopidogrel Antiplatelets occurred in patients INTERVENTION who had 3 or fewer extractions, and no transfusion was needed. Figure 1. Mean estimated blood loss among the 4 groups whose participants received full-mouth extractions at Tampa General Hospital (from March 2012 through December 2013) according to their antiplatelet regimen. In our study results, P ¼ .111. : Outlier. *: Extreme outlier. we found no correlation between the number of no studies whose investigators evaluated the safety of teeth extracted and EBL in the group whose participants using antiplatelets during full-mouth extraction and discontinued the use of antiplatelet medications; howmajor dental procedures.6 Lillis and colleagues7 evaluated ever, in the groups whose participants received aspirin 643 patients undergoing 3 or fewer dental extractions and clopidogrel, either alone or in combination with during uninterrupted single-antiplatelet therapy or aspirin, we found a significant moderate correlation. DAPT; they found no significant difference in blood loss However, the difference in blood loss was not clinically among members of the control group and members of significant, and blood transfusion was not required. the single-antiplatelet therapy group with either aspirin Nonetheless, this result might suggest that a clinician or clopidogrel, but they noted prolonged bleeding in who needs to remove a large number of teeth from a 66.7% of patients who received DAPT compared with patient should perform the tooth extractions over several
306 JADA 146(5) http://jada.ada.org
May 2015
ORIGINAL CONTRIBUTIONS
NUMBER OF TEETH EXTRACTED
sessions, especially if the patient uses antiplatelet therapy. Cardona35 Tortajada and col9 30 leagues prospectively evaluated 155 patients 25 who were using antiplatelet therapy for 20 dental extractions and found a statistically 15 significant correlation between the number 10 of teeth extracted and 5 bleeding. Despite reporting no major 0 hemorrhages, the authors recommended –5 that no more than 3 Clopidogrel Aspirin and Aspirin No teeth be extracted at Clopidogrel Antiplatelets a time for patients INTERVENTION continuing antiplatelet 9 therapy. A review by Wahl10 in 2014 identified Figure 2. Average number of teeth extracted among the 4 groups who received full-mouth extraction (from March 2012 through December 2013) according to their antiplatelet regimen. P ¼ .283. 23 published studies whose investigators had explored the continuation of antiplatelet ther- TABLE 2 apy in 1,129 patients The correlation between the number of teeth extracted undergoing 1,916 dental and estimated blood loss in patients not using antiplatelets, extractions; Wahl found patients taking aspirin, and patients taking clopidogrel, a rate of 1.6% posteither alone or in combination with aspirin. operative bleeding. Conversely, Wahl10 CHARACTERISTIC NO. OF TEETH EBL,† mL‡ CORRELATION (r) P VALUE found 10 published PATIENTS EXTRACTED (MEAN [SD]) (MEAN [SD*]) studies that involved a No Antiplatelet 22 17.1 (6.7) 37.3 (11.5) 0.398 .067 total of 322 patients, Aspirin 25 20.5 (6.8) 32.2 (10.6) 0.537 .006§ in whom there had 21 17.5 (7.0) 40.2 (23.9) 0.535 .012§ Clopidogrel and Aspirin been 372 cessations of Group in Combination antiplatelet therapy with With Clopidogrel Group an incidence of 5% * SD: Standard deviation. of patients who ex† EBL: Estimated blood loss. ‡ mL: Milliliters. perienced thromboem§ Statistically significant. bolic complications. Similarly, Partridge and colleagues11 performed a prospective observational study with patients undergoing continued clopidogrel therapy is related mostly to cardentoalveolar lavage who were taking aspirin, nonstediac surgery; therefore, the American Heart Association12 roidal anti-inflammatory drugs, or clopidogrel. The recommends discontinuing the use of clopidogrel 5 days experimental group whose participants used antiplatelet before planned coronary artery bypass graft surgery therapy lost a mean of 1.78 grams of blood compared unless the benefit of continuing clopidogrel therapy with 1.96 g in participants in the control group (not a outweighs the risk of excessive bleeding. Studies whose investigators have tested antiplatelet management in significant difference).11 Wahl10 and Partridge and colleagues11 recommended continuation of antiplatelet noncardiac surgeries have produced results similar to our therapy for dental procedures. study. Stone and colleagues13 concluded that patients undergoing peripheral arterial surgery who continued Clinicians should note that the main evidence of increased postoperative bleeding complications from using clopidogrel either alone or as a part of DAPT did
JADA 146(5)
http://jada.ada.org
May 2015 307
ORIGINAL CONTRIBUTIONS
not experience more bleeding compared with patients using no antiplatelet therapy or using aspirin alone. The investigators of a study on the safety of antithrombotics and general thoracic surgery found that patients taking clopidogrel who have a coronary stent can safely undergo general thoracic surgery without increased bleeding.14 Similarly, investigators found perioperative clopidogrel use during major lung resection and hip fracture surgery to be safe.15,16 In a summary of management of antithrombotic medications, the American Academy of Neurology17 affirmed that the continuation of aspirin or heparin is unlikely to increase clinically important bleeding in dental procedures. Clopidogrel affects platelet activation by selectively and irreversibly blocking a subunit of the adenosine diphosphate (ADP) receptor, providing an antiplatelet action additive to the inhibition of the thromboxane A2 pathway by aspirin therapy. Despite the fact that platelet function completely recovers 7 days after clopidogrel cessation,18,19 the optimal time delay from the last clopidogrel dose to the onset of surgery is not clear. Price and colleagues20 compared the offset of the antiplatelet effects of prasugrel and clopidogrel and found that in the clopidogrel group, at least 50% of patients returned to baseline reactivity by washout day 3, at least 75% of patients had returned to baseline reactivity by day 5, and at least 90% of patients had returned to baseline reactivity by day 6; these authors concluded that most patients who were treated with clopidogrel (87%) recovered platelet function by 5 days after drug cessation. This finding is consistent with guidelines regarding the recommended waiting period for surgery after clopidogrel discontinuation. Accordingly, in our study we used a cutoff value of 5 days to identify groups of patients who continued or discontinued clopidogrel therapy. This study is subject to all limitations inherent in a nonrandomized study. The design is retrospective, the number of patients is rather small, and a single provider performed all of the full-mouth extractions. Therefore, clinicians should extrapolate the results to other centers with caution and realize the need for these results to be verified by investigators of larger prospective trials. Potential confounding variables that are difficult to control might have been present. We did not account for the administration of other medicines that might affect platelet function, such as nonsteroidal anti-inflammatory drugs or proton pump inhibitors, which have been shown to reduce the antiplatelet effect of clopidogrel. Also we did not account for the wide interindividual variability in the capacity of clopidogrel to inhibit ADP-induced platelet aggregation. CONCLUSION
To our knowledge, this is the first study to compare blood loss owing to various antiplatelet regimens during
308 JADA 146(5) http://jada.ada.org
May 2015
full-mouth extraction and preprosthetic surgery. None of the 21 patients in the cohorts receiving clopidogrel, either alone or in combination with aspirin, experienced significant postsurgical bleeding after multiple extractions of their remaining (17.5 [standard deviation ¼ 7]) teeth and preprosthetic surgery. The results of this study provide limited evidence to suggest that continuation of clopidogrel therapy during full-mouth extraction and preprosthetic surgery may be safe and is not associated with significant risk of bleeding. It is also reasonable to accept the minor risk of blood transfusion rather than the consequences of perioperative adverse cardiac events. We therefore propose that patients undergoing fullmouth extraction who have a high risk of experiencing cardiac complications may continue antiplatelet therapy perioperatively. The risk of bleeding appears to be minimal and should be managed with appropriate local hemostatic measures rather than antiplatelet therapy suspension. n Dr. Omar is an internal medicine physician, Internal Medicine Department, Mercy Medical Center – Clinton, 1410 N. Fourth St., Clinton, IA 52732, e-mail [email protected]. Address correspondence to Dr. Omar. Ms. Socias is a research assistant, Department of Research, Florida Gulfto-Bay Anesthesiology Associates, Tampa, FL. Dr. Powless is vice chief, Dental and Maxillofacial Surgery, Tampa General Hospital, Tampa, FL. Mr. Sprenker is a research assistant, Department of Research, Florida Gulf-to-Bay Anesthesiology Associates, Tampa, FL. Dr. Karlnoski is the director of quality and research, Department of Research, Florida Gulf-to-Bay Anesthesiology Associates, Tampa, FL. Dr. Mangar is an anesthesiologist and chief executive officer, Florida Gulfto-Bay Anesthesiology Associates, Tampa, FL; chief of anesthesia, Tampa General Hospital, Tampa, FL; and regional medical director, TEAMHealth, Tampa, FL. Dr. Camporesi is a professor of surgery and anesthesiology and molecular pharmacology and physiology, University of South Florida, Tampa, FL; an attending anesthesiologist, Florida Gulf-to-Bay Anesthesiology Associates, Tampa, FL; and the research director, TEAMHealth, Tampa, FL. Disclosure. None of the authors reported any disclosures. The authors presented selected results of this study at the annual meeting of the American Society of Anesthesiology, held October 11-15, 2014, in New Orleans, LA. 1. Aframian DJ, Lalla RV, Peterson DE. Management of dental patients taking common hemostasis-altering medications. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(suppl):S45.e1-S45.e11. 2. Madrid C, Sanz M. What influence do anticoagulants have on oral implant therapy? A systematic review. Clin Oral Implants Res. 2009; 20(suppl 4):96-106. 3. Lim W, Wang M, Crowther M, Douketis J. The management of anticoagulated patients requiring dental extraction: a cross-sectional survey of oral and maxillofacial surgeons and hematologists. J Thromb Haemost. 2007;5(10):2157-2159. 4. Pototski M, Amenabar JM. Dental management of patients receiving anticoagulation or antiplatelet treatment. J Oral Sci. 2007; 49(4):253-258. 5. Powless RA, Omar HR, Mangar D, Camporesi EM. Management of antithrombotic therapy before full-mouth extraction. J Calif Dent Assoc. 2013;41(6):417-420. 6. van Diermen DE, Aartman IH, Baart JA, Hoogstraten J, van der Waal I. Dental management of patients using antithrombotic drugs: critical appraisal of existing guidelines. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107(5):616-624.
ORIGINAL CONTRIBUTIONS
7. 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(7):964-967. 8. Park MW, Her SH, Kwon JB, et al. Safety of dental extractions in coronary drug-eluting stenting patients without stopping multiple antiplatelet agents. Clin Cardiol. 2012;35(4):225-230. 9. Cardona-Tortajada F, Sainz-Gómez E, Figuerido-Garmendia J, 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(11):e588-e592. 10. Wahl MJ. Dental surgery and antiplatelet agents: bleed or die. Am J Med. 2014;127(4):260-267. 11. Partridge CG, Campbell JH, Alvarado F. The effect of platelet-altering medications on bleeding from minor oral surgery procedures. J Oral Maxillofac Surg. 2008;66(1):93-97. 12. Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA focused update of the guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline): a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines [published corrections appear in Circulation. 2011;123(22):e625-e626 and in Circulation. 2011;124(12):e337-e340]. Circulation. 2011;123(18):2022-2060. 13. Stone DH, Goodney PP, Schanzer A, et al; Vascular Study Group of New England. Clopidogrel is not associated with major bleeding
complications during peripheral arterial surgery. J Vasc Surg. 2011;54(3): 779-784. 14. Cerfolio RJ, Minnich DJ, Bryant AS. General thoracic surgery is safe in patients taking clopidogrel (Plavix). J Thorac Cardiovasc Surg. 2010; 140(5):970-976. 15. Ceppa DP, Welsby IJ, Wang TY, et al. Perioperative management of patients on clopidogrel (Plavix) undergoing major lung resection. Ann Thorac Surg. 2011;92(6):1971-1976. 16. Feely MA, Mabry TM, Lohse CM, Sems SA, Mauck KF. Safety of clopidogrel in hip fracture surgery. Mayo Clin Proc. 2013;88(2):149-156. 17. Armstrong MJ, Gronseth G, Anderson D, et al. Summary of evidencebased guideline: periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease—report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013;80(22):2065-2069. 18. Angiolillo DJ, Ueno M, Goto S. Basic principles of platelet biology and clinical implications. Circ J. 2010;74(4):597-607. 19. Weber AA, Braun M, Hohlfeld T, Schwippert B, Tschöpe D, Schrör K. Recovery of platelet function after discontinuation of clopidogrel treatment in healthy volunteers. Br J Clin Pharmacol. 2001;52(3):333-336. 20. Price MJ, Walder JS, Baker BA, et al. Recovery of platelet function after discontinuation of prasugrel or clopidogrel maintenance dosing in aspirin-treated patients with stable coronary disease: the recovery trial. J Am Coll Cardiol. 2012;59(25):2338-2343.
JADA 146(5)
http://jada.ada.org
May 2015 309
