The addition of clopidogrel to aspirin has been shown to result in significant clinical benefit to patients after a recent acute coronary syndrome and is also an important component of the pharmacologic management of patients receiving coronary stents.1–4 Prasugrel is a newer, more potent P2Y12 platelet inhibitor than is clopidogrel, and it, too, may offer superior clinical outcomes to the patient with acute coronary syndrome, albeit at the cost of a greater incidence of bleeding-related complications.5 Numerous studies have demonstrated that clopidogrel is associated with a higher rate of significant perioperative bleeding in patients undergoing coronary artery bypass procedures6,7 and that completing the surgery off-pump does not necessarily reduce this risk,8,9 although this latter finding has been disputed by some.10 In their recent update on clinical guidelines for blood conservation in cardiac surgery, The Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists propose a class I recommendation to discontinue thienopyridine antiplatelet agents (clopidogrel and prasugrel) before surgical myocardial revascularization (either on-pump or off-pump) at least 3 days before surgery.11 The Canadian Cardiovascular Society also recommends stopping clopidogrel 3 to 5 days before planned coronary surgery as long as the patient would not be exposed to a higher risk for an ischemic event by doing so.12 Most of the published data in this regard pertain to coronary surgery performed via sternotomy, irrespective of whether it is done off-pump or on-pump.
However, for more than a decade now, we have preferentially used an off-pump minimally invasive nonsternotomy approach for isolated surgical revascularization of the left anterior descending (LAD) coronary artery. In recent years, our preferred strategy has been to harvest the left internal mammary artery (LIMA) using robotic-assisted techniques and then to either complete the operation endoscopically inside the closed chest or, more commonly, fashion a direct LIMA to LAD anastomosis via a left minithoracotomy. A significant proportion of patients referred for these procedures receive both aspirin and a thienopyridine agent preoperatively, but few data are available regarding the safety of combination antiplatelet therapy in nonsternotomy robotic-assisted coronary bypass. We sought to determine whether there is an increased incidence of bleeding and transfusion in those patients who undergo robotic-assisted minimal-access coronary surgery while still maintained on both aspirin and either clopidogrel or prasugrel.
Between January 2010 and November 2011, a total of 110 consecutive patients underwent robotic-assisted off-pump coronary surgery at our institution. Those patients who had robotic-assisted minimally invasive direct coronary artery bypass (MIDCAB) had the LIMA harvested using the robot, followed by a direct hand-sewn coronary anastomosis to the LAD via a left minithoracotomy. A smaller group of patients underwent total endoscopic coronary artery bypass (TECAB), in which the entire operation was performed using the robot system inside the closed chest. All cases were completed on the beating heart, without the use of extracorporeal circulatory support.
For the purposes of analysis, all patients were separated into two groups on the basis of preoperative antiplatelet therapy. Group 1 consists of those patients who were maintained on aspirin alone as their sole preoperative antiplatelet agent, although a few patients are also included in whom all antiplatelet medications were discontinued before surgery. Group 2 comprises patients who were continued on dual antiplatelet agents (aspirin and either clopidogrel or prasugrel) up to and including the time of surgery.
After selective lung isolation, the da Vinci Intuitive robot system (Intuitive Surgical Inc, Sunnyvale, CA USA) is docked to the operating table. Three ports are introduced into the left pleural cavity under vision, usually in the second, fourth, and sixth interspaces. The LIMA is harvested as a skeletonized vessel using robotic-assisted techniques, after division of the endothoracic fascia, facilitated by carbon dioxide insufflation of the pleural cavity. After the LIMA has been completely mobilized from the chest wall, the patient is heparinized to achieve an activated clotting time longer than 300 seconds, and the conduit is divided distally.
For a MIDCAB procedure, a left anterior muscle-sparing minithoracotomy is performed by extending the middle (robot camera) port incision, with access to the pericardium usually optimal through the fourth intercostal space. Rib trauma is minimized as much as possible, facilitated by the use of an Alexis soft tissue wound protector (Applied Medical, Rancho Santa Margarita, CA USA). The anastomosis to the LAD coronary artery is then undertaken under direct vision, using standard off-pump coronary grafting techniques. A compression or suction myocardial stabilization system is used, according to the preference of the surgeon. An intracoronary shunt is used for all cases, and a humidified carbon dioxide blower system is used to improve visualization at the operative field.
In a TECAB operation, after LIMA harvesting is complete, a suction cardiac stabilizer is introduced into the field, and the LAD is controlled using proximal and distal silicone rubber vessel loops (Silastic; Dow Corning, Midland, MI USA). The LAD is opened using an endoscopic knife and is variably shunted. The LIMA to LAD anastomosis is performed using interrupted nitinol U-clips (Coalescent Surgical Inc, Sunnyvale, CA USA).
The heparin dose is usually completely reversed after completion of the graft. Graft flow and patency are assessed using a transit-time flow measurement system (Medistim VeriQ; Medistim USA Inc, Plymouth, MI USA) before wound closure. All patients are maintained on dual antiplatelet therapy postoperatively (aspirin and a thienopyridine agent), unless specifically contraindicated.
The patients were identified from our prospectively collected cardiac surgical registry, maintained in accordance with the New York State Cardiac Registry Reporting System guidelines. Approval for data review was obtained from our institutional review board.
Definitions of patient demographic characteristics, preoperative and intraoperative variables, and postoperative outcomes were obtained from the New York State Cardiac Surgery Reporting System and can be referenced online at the New York State Department of Health website at http://www.health.ny.gov/forms/cardiac_surgery. Data were analyzed using SPSS for Windows statistical software package, version 16.0 (SPSS Inc, Chicago, IL USA). Statistical significance was defined as P < 0.05.
During the study period, 110 patients underwent off-pump coronary surgery using a robotic-assisted nonsternotomy approach. Of this cohort, 53 patients (48.1%; group 1) were taking aspirin alone as their only preoperative antiplatelet agent, although a small number of patients within this group had all antiplatelet agents discontinued in the few days before surgery. The remaining 57 patients (group 2) were all continued on dual antiplatelet therapy to the time of surgery, namely, the combination of aspirin and a thienopyridine derivative (either clopidogrel or prasugrel).
The demographics of these patients are outlined in Table 1. Both patient groups were largely similar in risk profile. A similar proportion of patients in each group, just higher than 80%, had MIDCAB surgery, the remainder having a total endoscopic procedure, at the discretion of the operating surgeon. There were more female patients in group 1 (47.2% vs 17.5%, P = 0.001), and this group also tended to be slightly older (mean age, 68 vs 62 years; P = 0.011). As would be expected, significantly more patients in group 2 had a history of previous percutaneous coronary intervention (49.1% vs 18.9%, P = 0.001), the previous attempts at coronary revascularization providing the very reason for the continuation of dual antiplatelet therapy in these individuals.
As demonstrated in Table 2, the perioperative course of both groups of patients was similar and seemed to be unaffected by preoperative antiplatelet therapy. Operative times were comparable between the two patient cohorts, and, although the patients in group 2 seemed to have a slight tendency toward higher total chest tube output, this difference was not clinically or statistically significant. There were no differences in requirements for perioperative transfusion of blood products between the two patient groups.
In our series, the different regimens of preoperative antiplatelet therapy did not affect mortality or major morbidity (Table 3). Three patients (2.7%) in our entire cohort required surgical re-exploration for bleeding, one patient in group 1 (1.9%) and two patients in group 2 (3.5%). All three patients were found to have defined causes for continued hemorrhage, namely, actively bleeding vessels in the chest wall (two patients) and/or a persistently bleeding branch of the LIMA graft (one patient). No patient in either group sustained a perioperative myocardial infarction or stroke, and no patient developed a wound infection in the postoperative period.
The effect of antiplatelet therapy on perioperative bleeding in minimally invasive coronary surgery has not received much attention to date in the literature. Jegaden and associates13 describe their experience with 53 robotic-assisted MIDCAB procedures and 59 TECAB operations, both techniques performed off-pump. They reported a re-exploration rate for bleeding of 3.7% in the MIDCAB group and 8.5% in the TECAB group, but no comment is made regarding the preoperative antiplatelet medications that were used in these patients. Bonatti and colleagues14 had no re-explorations for bleeding in their early MIDCAB experience, but, again, no specifics regarding perioperative antiplatelet therapy are provided. Our re-exploration rate for bleeding was comparably low for both MIDCAB and TECAB procedures, irrespective of the antiplatelet agents used preoperatively. Importantly, all of our patients who required re-exploration for bleeding were found to have discrete bleeding vessels as the cause for the ongoing hemorrhage, and this would not have been any different had their antiplatelet medications been altered.
Although not widely commented upon in the cardiac surgical literature, the impact of antiplatelet agents on perioperative bleeding in robotic-assisted procedures has been examined in other fields of surgery. Binhas and colleagues15 compared 54 patients who underwent laparoscopic and robotic-assisted radical prostatectomy while on aspirin therapy, with 569 patients who had the same procedure without recently taking aspirin. No significant differences were found in median blood loss, transfusion requirements, operative times, or length of hospital stay. Nowfar and associates16 performed robotic-assisted radical prostatectomy on six patients who were still on aspirin at the time of operation because of previous coronary stent implantation. These patients were compared with 243 others who had the procedure on no antiplatelet agents at all. Although the number of patients continued on aspirin was small, no significant differences were noted in blood loss, need for transfusion, or changes in hematocrit. These results suggest that major surgical procedures using robotic-assisted techniques can be safely performed despite continued aspirin therapy, and our results support this assertion. Our data go somewhat further, however, and demonstrate that the addition of a thienopyridine derivative does not seem to adversely impact patient outcomes either. To the best of our knowledge, no other study has specifically addressed the impact of clopidogrel or prasugrel on bleeding in robotic-assisted surgery, cardiac or otherwise.
In their early experience with nonrobotic MIDCAB, Bonatti and colleagues14 reported an overall transfusion rate of 25%, which compared favorably with the 69.6% transfusion requirement in a contemporaneous cohort of patients who underwent traditional coronary artery bypass using cardiopulmonary bypass and cardioplegia. Our transfusion rates seem similar. In our entire series, 29.1% of the patients required a perioperative transfusion, and this was not significantly different between those patients on dual antiplatelet therapy (26.3%) as compared with those on aspirin alone or no antiplatelet agents (32.1%). Bonatti and colleagues17 also specifically analyzed their transfusion requirements in robotic TECAB operations, albeit performed on the arrested heart, and they, too, found no association between preoperative antiplatelet therapy and the need for perioperative transfusion of packed red blood cells. Interestingly, in addition, although age and female sex have both been associated with an increased risk for hemorrhagic complications after cardiac surgery,18 our patient groups, nevertheless, still incurred a similar transfusion burden, despite more patients in group 1 being older and more being women (Table 1).
We have found no significant increase in perioperative bleeding or transfusion requirements in the patients undergoing off-pump robotic-assisted minimally invasive single-vessel coronary surgery who were continued on combination antiplatelet therapy up to the time of operation. Although our study is limited somewhat by its retrospective design, our data support the safety of a nonsternotomy beating-heart approach in this population of patients, many of whom have had a recent acute coronary event or previous percutaneous attempts at revascularization. Although the individual surgeon may still elect to discontinue preoperative antiplatelet agents in the elective setting, we propose that it is not necessary to unduly delay robotic-assisted coronary surgery on the basis of preoperative antiplatelet therapy alone and that the operation can be safely undertaken without incurring a greater burden of bleeding or transfusion.
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This clinical series from Lenox Hill Hospital in New York examined the impact of dual antiplatelet therapy on bleeding and transfusion requirements in patients undergoing robotic-assisted minimally invasive coronary artery bypass grafting. This was a retrospective study which examined two groups of patients. Group 1 (n=53) received either aspirin alone, or no antiplatelet agents, and Group 2 (n=57) received aspirin plus clopidogrel or prasugrel. Peri-operative chest tube drainage was not significantly different between these two groups and transfusion requirements and other morbidities were also similar.
While these data strongly suggests the feasibility of performing off-pump robotic-assisted minimally invasive coronary artery bypass grafting on patients receiving dual antiplatelet therapy, this report has significant limitations. It is a relatively small, retrospective, non-randomized study that was not adequately powered to uncover differences in mortality and morbidity between these two approaches. Thus, the finding of no difference may represent a type 2 statistical error. Larger studies will need to be performed to fully define the safety of this approach. However, this study supports the idea that it may not be necessary to unduly delay robotic-assisted coronary surgery based on pre-operative anti-platelet therapy alone.