Tirofiban has a plasma half-life of 1. It is removed by both renal and biliary excretion. Patients with renal insufficiency require dose adjustment of tirofiban 86 Table 1. Many studies have evaluated the efficacy of i.
Perioperative management of antiplatelet agents is complex, so the team of perioperative clinicians anaesthesiologist, surgeon, and prescribing physician—either neurologist or cardiologist should participate in decision-making. Several factors need to be considered before a decision to continue or stop antiplatelet agents perioperatively. An important factor is the initial indication for antiplatelet therapy and, most importantly, the consequences of stopping the drug before the operation.
Based on the role of platelets in the coagulation cascade, various point-of-care testing devices have been developed. However, there are differences in the sensitivity of these tests in assessing recovery of platelet function after discontinuation of ADP receptor inhibitors and significant interindividual variability in results.
Therefore, the role of these tests in strategies for perioperative management of antiplatelet agents is evolving. In patients on ASA for AF or for primary prevention of MI and stroke, the drug can be stopped 7—10 days before operation without major consequences.
Despite that, there was no increase in mortality. In patients undergoing cardiac surgery , preoperative ASA administration increases postoperative bleeding and red blood cell requirements with no effect on mortality, re-exploration rate, and perioperative MI.
In conclusion, with the exception of high-risk bleeding procedures intracranial and medullary canal surgery, posterior chamber of the eye surgery, and transurethral prostate resection , ASA continuation perioperatively is not associated with significant bleeding events or with increased mortality. Algorithm for perioperative management of antiplatelet therapy.
Adapted from Di Minno and colleagues, 99 with permission. As with ASA, when the ADP receptor inhibitors are recommended for treatment of AF or primary prevention of cardiac or cerebrovascular events, these agents can be stopped before operation without major consequences.
Several aspects need to be considered in patients with stents undergoing surgery: the appropriate time frame after stent placement before surgery can be safely performed, the potential consequences of stopping DAPT, the urgency of the intervention, and the bleeding risk associated with the intervention. Many studies have revealed that premature discontinuation of DAPT before the recommended interval necessary for complete endothelialization of the stent can lead to fatal consequences.
The perioperative period is marked by a prothrombotic state due to increased levels of circulating fibrinogen and C-reactive protein. While there is no controversy regarding the minimum duration of DAPT after balloon angioplasty only 2 weeks and after BMS placement 4—6 weeks , the optimal duration after DES placement is uncertian.
A prospective trial involving DES patients receiving either 6 or 12 months of DAPT showed that the risk of target vessel failure at 12 months is similar. In a randomized study of patients, 3 months of DAPT were non-inferior compared with the standard 12 months therapy in the occurrence of the primary endpoint at 1 yr cardiovascular death, MI, ST, target vessel revascularization, or bleeding.
While the above data were obtained outside the peri-procedural area, similar outcomes have also been recorded perioperatively. As a result, it is still unclear what is the optimal duration of DAPT and timing of surgery. The key to these questions is the individual risk for delayed stent endothelialization.
However, in high-risk patients, it might be prudent to wait 12 months after DES implantation before proceeding with elective procedures. In patients with coronary stents, in addition to the risk of MACE, the clinician needs to take into account the bleeding risk incurred in the perioperative period. Prior data had reported increased hematomata associated with carotid endarterectomy.
The average transfusion requirement was — ml in all groups. Patients undergoing thoracic surgery do not seem to experience increased bleeding while on clopidogrel, but the incidence of perioperative MI is significantly higher among patients with stents discontinuing DAPT in the perioperative period.
Patients on DAPT undergoing orthopaedic surgery especially patients undergoing hip and knee replacement have an increase in bleeding complications and increased risk of transfusion in the operating theatre or in the first 24 h after operation. Urological surgery, with the exception of transurethral resection of prostate, can be safely performed while on DAPT. In patients undergoing intra-abdominal surgery, data suggest that these operations can be safely performed while continuing DAPT. The study concluded that clopidogrel cannot be stopped in those patients with a recently implanted DES.
As noted above, all available evidence to date addresses patients undergoing non-cardiac procedures while on DAPT with ASA and clopidogrel.
Perioperative data for patients on prasugrel and ticagrelor are lacking, probably due to their recent availability on the market.
On the other hand, for patients on DAPT undergoing cardiac surgery , available evidence suggests that increased bleeding occurs if the ADP inhibitor is continued before operation. Therefore, current guidelines recommend stopping the ADP receptor inhibitor 5 days prior for clopidogrel and ticagrelor and 7 days prior for prasugrel.
While it is advisable to wait at least 4—6 weeks after BMS placement and 6—12 months after DES placement, the urgency of certain procedures sometimes takes priority. In emergent procedures, there is not sufficient time to discontinue DAPT.
Platelet transfusion can be given to counteract the effect of the antiplatelet agents. Despite the theoretical efficacy of such a measure, newer evidence from the trauma literature suggests that platelet transfusions reverse the effect of ASA on thrombocytes but not that of clopidogrel. ASA has a short half-life and therefore has a low likelihood of affecting the transfused platelets even if the drug was ingested within an hour of the surgical procedure.
On the other hand, clopidogrel has a half-life of 7—9 h so if the transfusion is administered within that time frame, the new platelets will be affected by the available circulating drug. Moreover, platelet transfusions can put the patient at risk for ST.
Therefore, the clinician should perform a risk—benefit analysis before making this decision. In patients at low risk of cardiovascular complications undergoing surgeries of low or intermediate bleeding risk urgent or elective , ASA should be continued while discontinuing the ADP inhibitor.
If the same patient population is undergoing surgeries of high bleeding risk, then both the ADP inhibitor and ASA should be discontinued Fig. In patients at high risk of cardiovascular complications undergoing elective surgeries, the procedure should be postponed until the required period of DAPT has been fulfilled.
In urgent cases that cannot be postponed until the recommended period of DAPT has been completed, different therapeutic strategies have been proposed. If the bleeding risk is low, the surgical procedure can be performed while the patient continues DAPT.
When patients at high risk of cardiovascular events undergo procedures with a high risk of bleeding, DAPT needs to be discontinued. Consideration should be given to replacing DAPT with a short-acting agent whose effect on platelet function rapidly dissipates upon discontinuation, known as bridging therapy Fig.
Bridging therapy with unfractionated or low molecular weight heparin, similar to what is recommended for patients on warfarin, has been considered. However, heparin has relatively minor effects on platelets, and thus does not prevent a thrombotic event. The bridging protocols require discontinuing clopidogrel 5 days before the surgical procedure. Patients are started on an i. Tirofiban is stopped 3—6 h and eptifibatide 4—12 h before the planned procedure. Another drug that appears useful as a bridging agent is cangrelor, studied in a prospective, randomized, double-blind, placebo-controlled, multicentre BRIDGE trial.
These patients did not demonstrate an increased rate of major bleeding before CABG surgery, but exhibited more minor postoperative bleeding episodes. Cangrelor is not yet FDA approved. Eptifibatide was associated with a similar risk as placebo, even when surgery was performed within 2 h of drug cessation. Limited data available for tirofiban show that bleeding is not increased compared with ASA or heparin. Intraoperatively, antiplatelet agents represent a particular challenge for the anaesthesiologist when regional anaesthetic techniques are considered see Banzon and colleagues, this issue.
Antiplatelet agents represent a quintessential therapy in preventing and treating cardiovascular events. Currently, with an increasing patient population requiring antiplatelet therapy in conjunction with an increase in the number of interventional procedures, the anaesthesia community is frequently faced with the need to manage various antiplatelet regimens perioperatively.
In general, antiplatelet agents used for primary prevention or for AF can be safely discontinued before surgery. On the other hand, recent data suggest that, with few exceptions, proceeding with surgery on DAPT is a relatively safe alternative.
In situations of life-threatening bleeding, anaesthesiologists can consider platelet transfusions. The more challenging cases are those patients at high risk of cardiovascular events who are undergoing procedures with a high risk of bleeding, and thus are required to completely stop their antiplatelet medications. In these situations, the perioperative team can consider using bridging therapies. Each patient has to be stratified according to individual thrombotic and surgical bleeding risk.
The perioperative team should all participate in the decision-making process by performing a thorough risk—benefit analysis of stopping or continuing each type of antiplatelet agent.
Google Scholar. We are writing to express grave concern about the recent article by Oprea and Popescu. Our paper 2 listed as their reference , is the largest series to date and shows that neither aspirin, clopidogrel nor warfarin increase the rate of haemorrhage in patients undergoing 25 guage vitreoretinal surgery under retrobulbar block. These results have been confirmed in a prospective study by Ryan et al.
Vitreoretinal surgery is synonomous with posterior chamber surgery. We believe the inclusion of posterior chamber eye surgery as high risk is perhaps a continuation of Chassot's original table published in 4 in which the authors postulated, based on no studies, that surgery of closed spaces, such as posterior chamber eye surgery, would be high risk for bleeding complications.
Other authors, again with no substantiating studies, have continued to include posterior chamber eye surgery as high risk in their algorithms for perioperative antiplatelet management. Our primary concern in having posterior chamber surgery continue to be listed as somehow high risk is that our cardiology colleagues charged with preparing and approving their recent DES stent patients will and have recommend ed these patients to prematurely discontinue their DAPT having been misled that vitreoretinal aka posterior segment surgery, is high risk for surgical haemorrhage.
Premature discontinuation of DAPT is well known to be associated with in-stent thrombosis and acute coronary syndrome. Indeed, a few years ago we had a patient who had discontinued his DAPT himself believing that he would need to do so prior to surgery. He arrived in cardiogenic shock for his eye surgery. We thank the authors for this contribution to the literature on perioperative management of antiplatelet medications and allowing us to unequivocally state that antiplatelet therapy in the setting of posterior segment vitreoretinal surgery is low risk with regards to haemorrhagic complications.
We recommend that these patients continue them without cessation due to the life threatening events associated with premature discontinuation of their antiplatelet medications. This has been our evidenced-based practice for years in our high volume retinal surgery practice at our eye hospital.
Br J Anaesth ; Suppl 1: i Ophthalmology ; Clin Experiment Ophthalmol ; Br J Anaesth ; Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account.
Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Role of the activated platelet in coagulation. Specific drugs. Authors' contributions. Declaration of interest. Perioperative management of antiplatelet therapy.
Oprea , A. E-mail: adriana. Oxford Academic. Cite Cite A. Select Format Select format. Abstract Worldwide, cardiovascular events represent the major cause of morbidity and mortality. Open in new tab Download slide. Table 1 Major characteristics of traditional and newer antiplatelet medications. Mechanism of action. Loading dose.
Maintenance dose. Time to recover platelet function after drug withdrawal. Platelet inhibition. Administration route. Open in new tab. Table 2 Bleeding risk in non-cardiac surgery. Surgical haemorrhagic risk. Blood transfusion requirement. Type of surgery. Low Usually not required Peripheral, plastic, and general surgery biopsies Minor orthopaedic, otolaryngology, and general surgery Endoscopy Eye anterior chamber Dental extraction and surgery Intermediate Frequently required Visceral surgery Cardiovascular surgery Major orthopaedic surgery Otolaryngology Urological surgery Reconstructive surgery High Possible bleeding in a closed space Intracranial neurosurgery Spinal canal surgery Eye posterior chamber surgery.
Google Scholar Crossref. Search ADS. Antiplatelet drugs: a review of their pharmacology and management in the perioperative period. Autologous platelets as a source of proteins for healing and tissue regeneration. Google Scholar PubMed. Coagulation and platelet activation pathways. A review of the key components and the way in which these can be manipulated.
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Interruption of antiplatelet therapy is more hazardous in the perioperative period, which is characterized by increased platelet aggregability.
Stopping dual antiplatelet therapy to allow major surgery during the first six weeks after angioplasty and stenting bare-metal or drug-eluting leads to a cardiovascular mortality of up to 71 percent, whereas it is no more than 5 percent when the treatment is maintained perioperatively 25 — 28 Table 2 18 , 19 , 24 — Mortality is inversely related to the delay between revascularization and surgery.
Nonsurgical 18 , 19 , 24 , Perioperative 25 — Information from references 18 , 19 , and 24 through Although there is a lack of RCTs comparing the effects of withdrawing versus continuing antiplatelet agents in the perioperative period, it appears that the average relative increase in bleeding during noncardiac surgery is 20 percent with aspirin or clopidogrel alone. A meta-analysis including studies comparing surgical bleeding of patients operated on with or without aspirin reported no change in the mortality and complication rates.
In patients with stents who are on continuous dual antiplatelet therapy, the combined rate of perioperative MI and mortality is the same as in stable coronary artery disease 1 to 6 percent, depending on the type of surgery , whereas withdrawing antiplatelet therapy is associated with a five- to fold increase in the risk of MI 20 to 40 percent and mortality 20 to 85 percent , depending on the delay between revascularization and surgery.
Table 3 outlines perioperative management based on patients' cardiovascular and surgical bleeding risks. Elective surgery: according to risk balance Vital surgery: okay Maintain aspirin Maintain clopidogrel, if prescribed. Elective surgery: postponement Vital or urgent surgery: possible under aspirin and clopidogrel. Stop clopidogrel five days before surgery, if prescribed; restart within 24 hours after surgery.
These delays can be modified according to the amount of myocardium at risk, the instability of the coronary situation, or the risk of spontaneous hemorrhage.
The same recommendations apply to newer second-generation drug-eluting stenting. Perioperative antiplatelet therapy: the case for continuing therapy in patients at risk of myocardial infarction. Br J Anaesth. In the absence of clinical trials, the current recommendations from specialty society guidelines are based on observational data and attempt to provide the safest possible management given the high risk of premature discontinuation of antiplatelet agents.
Dual antiplatelet therapy is recommended during the two weeks after simple dilatation, six weeks after bare-metal stents, and at least 12 months after drug-eluting stents. Only vital surgery should be performed when the patients are still taking aspirin and clopidogrel; unless the hemorrhagic risk is excessive, dual antiplatelet therapy should not be interrupted before surgery. During the first six weeks after bare-metal stents or surgical revascularization, the operative risk is higher than without revascularization.
The full benefit of revascularization is manifested only after three months, when mortality becomes identical to the postoperative mortality of patients without coronary artery disease. Even if clopidogrel treatment must be interrupted in high-risk surgical situations, aspirin must be continued without interruption.
Already a member or subscriber? Log in. Interested in AAFP membership? Learn more. Reprints are not available from the authors. Coronary-artery revascularization before elective major vascular surgery.
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