Does preoperative dual antiplatelet therapy affect bleeding and mortality after total arch repair for acute type A dissection?

Abstract

OBJECTIVES

Data are scarce and mixed regarding the impact of preoperative dual antiplatelet therapy (DAPT) on the surgical outcomes of acute type A aortic dissection (ATAAD). We seek to evaluate the impact of DAPT on bleeding-related events and early- and mid-term mortality after total arch replacement and frozen elephant trunk in such patients.

METHODS

This study comprised 48 ATAAD patients on preoperative DAPT and 418 without DAPT (the whole series, i.e. unmatched cohort), from which 45 matched pairs were selected by propensity score (matched cohort). Bleeding-related events (reoperation for bleeding, bleeding of ≥1500 ml within the first 12 h postoperatively or transfusion of ≥10 units of red blood cell or use of recombinant activated factor VII), operative mortality and mid-term survival were compared in the unmatched and matched cohorts. The impact of preoperative DAPT was evaluated with multivariable analysis.

RESULTS

In the unmatched cohort, bleeding of ≥1500 ml/12 h postoperatively was more common in the DAPT group (18.8% vs 8.4%, P = 0.020); operative mortality was 9.7%, which did not differ with DAPT (12.5% vs 9.3%, P = 0.48). Nor did bleeding-related events (54.2% vs 43.5%, P = 0.16) differ significantly between 2 groups. In the matched cohort, neither were drainage of ≥1500 ml/12 h (20% vs 6.7%, P = 0.063) and bleeding-related events (53.3% vs 42.2%, P = 0.30), nor operative mortality (13.8 vs 8.9%, P = 0.50) and mid-term survival (79.3% vs 76.4%, P = 0.93) significantly different between 2 groups. DAPT was not identified as a predictor for operative mortality [odd ratio (OR) 0.97, 95% confidence interval (CI) 0.31–3.08; P = 0.96; adjusted OR 1.28, 95% CI 0.22–7.20; P = 0.78] and bleeding-related events (OR 1.50, 95% CI 0.76–2.95; P = 0.24; adjusted OR 2.03, 95% CI 0.80–3.66; P = 0.14).

CONCLUSIONS

In patients with ATAAD undergoing total arch replacement and frozen elephant trunk, although preoperative DAPT led to more postoperative bleeding, it did not increase bleeding-related events nor operative mortality nor mid-term death. The results of this study imply that for patients with ATAAD, emergency surgical repair, even if as extensive as total arch repair, should not be contraindicated or delayed simply because of ongoing DAPT.

Acute type A aortic dissection (ATAAD) is a highly lethal catastrophe with a mortality rate of 1–2% per hour in untreated patients [1], which requires early diagnosis and emergency surgery to prevent aortic rupture [2, 3].

INTRODUCTION

Acute type A aortic dissection (ATAAD) is a highly lethal catastrophe with a mortality rate of 1–2% per hour in untreated patients [1], which requires early diagnosis and emergency surgery to prevent aortic rupture [2, 3]. Because acute severe chest or back pain is the most common symptom, sometimes patients with ATAAD are misdiagnosed with acute coronary syndrome (ACS) and receive dual antiplatelet therapy (DAPT) in some cases. Consequently, life-threatening bleeding might be encountered in those ATAAD patients if surgical aortic repair is performed under deep hypothermic circulatory arrest [4, 5], especially with ongoing inhibition of platelet function [6, 7]. Therefore, discontinuation of antiplatelet agents before elective cardiac surgery is recommended [8]. However, up to date, no data are available concerning the impact of preoperative DAPT on the early- and mid-term outcomes of ATAAD patients undergoing total arch replacement and frozen elephant trunk (TAR + FET) implantation. The purpose of this study was to assess the impact of preoperative DAPT on bleeding-related complications, transfusion, early mortality and mid-term survival after TAR + FET in patients with ATAAD.

PATIENTS AND METHODS

Ethical statement

The Ethics Committee of Beijing Anzhen Hospital of Capital Medical University approved the submission and publication of this work and waived the need for informed patient consent (No. 2020023X).

Patients

This study included 466 consecutive patients with ATAAD who underwent emergency TAR + FET from December 2015 to December 2017 at Beijing Anzhen Hospital, which is the largest aortic centre in China, with a radius of referring hospitals over 650 km. The patients were divided into groups with preoperative DAPT (n = 48) and without DAPT (n = 418). Preoperative DAPT refers to medication with aspirin and clopidogrel (n = 45) or aspirin and ticagrelor (n = 3) (Fig. 1). Routinely, a loading dose of aspirin (300 mg) and clopidogrel (300 mg) or ticagrelor (180 mg) was given to ATAAD patients who were misdiagnosed as ACS, followed by a daily dose of 100, 75 and 180 mg, respectively. Patients taking warfarin for anticoagulation were excluded from this study. None of the 48 patients in DAPT group were on chronic antiplatelet therapy before symptom onset.

Figure 1:

Diagram displaying patient inclusion and the cohort of study. DAPT: dual antiplatelet therapy; FET: frozen elephant trunk; TAAD: type A aortic dissection; TAR: total arch replacement.

Surgical techniques

At our centre, TAR + FET is indicated in patients with ATAAD for any of the following conditions: (i) entry tear in the arch or descending aorta; (ii) aneurysm or dilation of the arch or descending aorta; (iii) dilation, dissection or anomaly of the brachiocephalic arteries [9]; and (iv) concomitant Marfan syndrome [10]. For DeBakey type II dissections, or type A aortic dissections with dilated ascending aorta or proximal arch, we would perform a limited repair (Bentall, ascending or hemiarch).

Our surgical techniques have been described in detail previously [11]. Briefly, cardiopulmonary bypass (CPB) was set up via cannulation of the femoral artery and right atrium, and right axillary artery cannulation is used for CPB and unilateral selective antegrade cerebral perfusion under moderate hypothermic circulatory arrest at a target nasopharyngeal temperature of 25°C. The procedure involves deployment of an FET, Cronus^® (MicroPort Medical, Shanghai, China) in the descending aorta (above T6 in most cases), followed by TAR with a four-branched vascular graft (Maquet Cardiovascular, Rastatt, Germany). In selected patients, the arch was reconstructed using a modified en bloc technique [12, 13], which involves reimplantation of the innominate artery and the left carotid artery as a patch and transposition of left subclavian artery to the left carotid artery. To minimize the time of cerebral, myocardial and spinal cord ischaemia, distal reperfusion is initiated once the distal anastomosis is completed, and the left carotid artery is reconstructed first (after which rewarming is started and the brain is perfused bilaterally), followed by the ascending aorta (to resume myocardial perfusion), then the left subclavian artery, and finally, the innominate artery. To improve haemostasis, we routinely reapproximate the residual aortic wall to create a Cabrol shunt from the perigraft space to the right atrium and use fibrinogen and prothrombin complex in all patients. Recombinant activated factor VII (rFVIIa) is used in case of intractable bleeding during surgery.

End points, definitions and follow-up

The primary outcome was bleeding-related events, a composite end point including one or more of the following: reoperation for bleeding, chest tube drainage of ≥1500 ml within the first 12 h postoperatively, transfusion of ≥10 units of red blood cell [14] or use of rFVIIa [15]. The secondary end point was operative mortality and mid-term mortality. Operative mortality was defined as all-cause death occurring within 30 days of surgery or before final discharge from the primary hospitalization (including transfers to other facilities). Cardiac tamponade was defined as a pericardial haemorrhage with circulatory compromise. Blood transfusion was indicated if the haemoglobin level was <7 g/dl in stable patients and <9 g/dl in patients with ongoing bleeding. Platelet transfusion was indicated in patients with low platelet count (<50 000/μl). Plasma was transfused in patients with ongoing bleeding and signs of impaired coagulation on thromboelastometry. Operative survivors were followed up by reviewing medical records and imaging data, and contacting patients and referring physicians for survival status and details of adverse events.

Statistical analysis

Statistical analysis was performed using SPSS 18.0 (SPSS, Chicago, IL, USA). Continuous variables were presented as mean and standard deviation (SD) or median with interquartile range and compared using Student’s t-test or Mann–Whitney U-test. Categorical variables were expressed as numbers and percentages, and compared with χ² test or Fisher’s exact test.

To minimize potential biases due to the disproportionate group sizes, patient heterogenicity and variance in DAPT regimen in the comparison of outcomes between 2 groups, patients with and without preoperative DAPT were matched on an identical propensity score using a greedy algorithm in a higher-digit priority order, namely, a five-digit to a four-, three-, two- or one-digit match. If 2 or more control patients were matched to 1 DAPT patient, patients without preoperative DAPT would be selected randomly. Eventually, 45 matched pairs of patients were obtained. Variables that differed between 2 groups with a P-value of <0.1 were included in the propensity score model, including age, hypertension, time from onset, cardiac troponin I and myoglobin (as markers of coronary ischaemia), and international normalized ratio.

Clinically relevant variables whose univariate association with mortality and bleeding-related events had a P-value of <0.2 were entered into multivariable logistic regression models, including DAPT, age (years), left ventricular ejection fraction (%), moderate-to-severe aortic insufficiency, platelet count (10⁴/μl) and lactic acid (mmol/l), coronary artery bypass grafting (CABG) and CPB time (min). Survival was estimated using Kaplan–Meier method and compared with log-rank test. A two-sided P-value of <0.05 was considered statistically significant.

RESULTS

Baseline characteristics

The mean age was 48.1 years (SD 10.8; range 24–71) and 363 were male (77.9%). Hypertension was seen in 75.8% of patients (353/466). Tamponade occurred in 109 patients (23.4%), moderate-to-severe aortic regurgitation in 164 (36.8%) and malperfusion of the lower extremity in 30 (6.4%) in the entire series. The mean time from last dose of DAPT to surgery was 26.3 h (SD 10 h). In the whole series, compared to those without DAPT, patients who received preoperative DAPT were older (52 vs 48 years, P = 0.012) and more likely to be hypertensive (87.5% vs 74.4%, P = 0.045) and had significantly higher levels of preoperative cardiac troponin I (0.66 vs 0.50 μg/l, P = 0.007), myoglobin (64.8 vs 34.5 μg/l, P = 0.028) and international normalized ratio (1.35 vs 1.10, P = 0.042).

In the matched cohort, patients with and without DAPT showed no significant difference in all baseline characteristics (Table 1).

Table 1:

Baseline patient characteristics

Variables	Whole series (n = 466)	Unmatched cohort				Matched cohort
		Preoperative DAPT		P-value	SMD	Preoperative DAPT		P-value	SMD
		No (n = 418)	Yes (n = 48)			No (n = 45)	Yes (n = 45)
Age (years), mean ± SD	48.1 ± 10.8	47.6 ± 10.8	52.1 ± 9.8	0.012	0.43	51.0 ± 10.6	51.6 ± 9.7	0.81	0.05
Body mass index (kg/m2), mean ± SD	26.4 ± 4.5	26.2 ± 3.9	27.5 ± 8.0	0.47	0.21	27.1 ± 4.1	27.7 ± 8.2	0.57	0.08
Female gender, n (%)	103 (22.1)	92 (22.0)	11 (22.9)	0.88	0.02	7 (15.6)	9 (20)	0.58	0.12
Time from onset to surgery (h), mean ± SD	46.3 ± 59.1	45.2 ± 58.4	55.5 ± 64.7	0.076	0.17	46.7 ± 63.7	56.3 ± 66.6	0.22	0.15
Time from last dose of DAPT to surgery (h), mean ± SD	NA	NA	26.3 ± 16.0	NA	NA		26.0 ± 16.2	NA	NA
Hypertension, n (%)	353 (75.8)	311 (74.4)	42 (87.5)	0.045	0.34	42 (93.3)	39 (86.7)	0.49	0.22
Diabetes, n (%)	23 (4.9)	19 (4.6)	4 (8.3)	0.28	0.15	3 (6.7)	4 (8.9)	0.70	0.08
COPD, n (%)	4 (0.9)	4 (1.0)	0 (0.0)	1.00	0.14	0 (0)	0 (0)	1.00	0
Lower limb malperfusion, n (%)	30 (6.4)	28 (6.7)	2 (4.2)	0.76	0.11	5 (11.1)	2 (4.4)	0.43	0.25
Moderate-to-severe AI,a  n (%)	164 (36.8)	144 (36.2)	20 (41.7)	0.46	0.11	12 (27.9)	20 (44.4)	0.11	0.35
Cardiac tamponade, n (%)	109 (23.4)	99 (23.7)	10 (22.2)	0.83	0.04	10 (22.2)	10 (22.2)	0.86	0.04
Coronary ischaemia, n (%)	40 (8.6)	32 (7.6)	8 (16.7)	0.035	0.11	4 (8.9)	8 (17.8)	0.22	0.26
LVEF (%), mean ± SD	61.3 ± 5.3	61.3 ± 5.4	61.3 ± 4.8	0.99	0.001	61.1 ± 5.2	61.3 ± 5.0	0.89	0.03
LVEDD (mm), mean ± SD	50.0 ± 6.8	49.9 ± 6.9	50.2 ± 6.1	0.76	0.04	51.1 ± 5.8	50.3 ± 6.3	0.66	0.13
Creatinine (μmol/l), mean ± SD	94.4 ± 61.4	93.2 ± 58.8	104.2 ± 80.4	0.25	0.16	117.9 ± 120.6	105.7 ± 82.8	0.90	0.12
Cardiac troponin I (μg/l), mean ± SD	0.52 ± 4.2	0.50 ± 4.3	0.66 ± 1.78	0.007	0.05	0.29 ± 0.88	0.69 ± 1.82	0.070	0.28
Myoglobin (μg/l), median (IQR)	35.7 (21.9–85.3)	34.5 (21.9–82.0)	64.8 (23.9–117.2)	0.028	0.14	39 (26.8–73.0)	63.5 (24.5–123)	0.28	0.06
International normalized ratio, mean ± SD	1.12 ± 0.50	1.10 ± 0.14	1.35 ± 1.50	0.042	0.23	1.10 ± 0.12	1.12 ± 0.10	0.31	0.22
Haemoglobin (g/dl), mean ± SD	13.6 ± 1.8	13.6 ± 1.8	13.7 ± 1.6	0.90	0.07	13.7 ± 1.9	13.8 ± 1.6	0.85	0.05
Platelet (104/μl), mean ± SD	17.6 ± 6.4	17.7 ± 6.6	17.5 ± 4.7	0.81	0.02	16.9 ± 9.3	17.4 ± 4.8	0.14	0.07

AI: aortic insufficiency; COPD: chronic obstructive pulmonary disease; DAPT: dual antiplatelet therapy; LVEF: left ventricular ejection fraction; LVEDD: left ventricular end diastolic diameter; IQR: interquartile range; SD: standard deviation; SMD: standardized mean difference.

^aBased on echocardiographic data.

Operative data

The times of CPB, cross-clamp and circulatory arrest did not differ significantly in patients with and without preoperative DAPT (214 vs 213 min, P = 0.79; 117 vs 119 min, P = 0.54; and 22.5 vs 23.2 min, P = 0.50) in the whole series. Neither did these differ significantly in the matched cohort (Table 2).

Table 2:

Operative data, bleeding-related events and operative mortality

Variables	Whole series (n = 466)	Unmatched cohort			Matched cohort
		Preoperative DAPT		P-value	Preoperative DAPT		P-value
		No (n = 418)	Yes (n = 48)		No (n = 45)	Yes (n = 45)
Operative data
CPB time (min), mean ± SD	213.6 ± 53.4	213.5 ± 53.8	214.1 ± 58.5	0.79	219.6 ± 50.7	214.2 ± 59.8	0.34
Cross-clamp time (min), mean ± SD	118.6 ± 35.4	118.8 ± 35.5	116.7 ± 34.7	0.54	116.3 ± 37.5	115.9 ± 35.6	0.85
Circulatory arrest time (min), mean ± SD	23.1 ± 9.0	23.2 ± 9.0	22.5 ± 8.7	0.50	24.3 ± 12.0	22.7 ± 8.9	0.40
Operation time (min), median (IQR)	480 (420–540)	480 (420–540)	480 (420–525)	0.66	480 (420–590)	480 (420–510)	0.50
CABG, n (%)	28 (6.0)	24 (5.7)	4 (8.3)	0.48	4 (8.9)	4 (8.9)	1.00
Valve/root replacement, n (%)	199 (42.7)	182 (43.5)	17 (35.4)	0.28	13 (28.9)	17 (37.8)	0.37
Early outcomes
Operative mortality, n (%)	45 (9.7)	39 (9.3)	6 (12.5)	0.48	4 (8.9)	6 (13.3)	0.50
Bleeding-related events, n (%)	208 (44.6)	182 (43.5)	26 (54.2)	0.16	19 (42.2)	24 (53.3)	0.30
Reoperation for bleeding, n (%)	42 (9.0)	39 (9.3)	3 (6.3)	0.60	2 (4.4)	3 (6.7)	0.64
Postoperative bleeding
Within 12 h (ml), median (IQR)	500 (300–900)	500 (300–860)	600 (300–1200)	0.31	500 (300–750)	650 (300–1200)	0.36
≥1500 ml/12 h, n (%)	44 (9.4)	35 (8.4)	9 (18.8)	0.020	3 (6.7)	9 (20.0)	0.063
Blood transfusion
RBC (unit), median (IQR)	8 (4–14)	8 (4–14)	9 (5–15)	0.29	8 (4–14)	8 (4–16)	0.54
RBC ≥10 units, n (%)	195 (41.8)	171 (40.9)	24 (50)	0.23	18 (40.0)	22 (48.9)	0.40
Plasma (unit), median (IQR)	400 (0–800)	400 (0–800)	500 (0–900)	0.53	400 (0–800)	600 (0–800)	0.73
Platelets (unit), median (IQR)	0 (0–2)	0 (0–2)	0 (0–2)	0.73	1 (0–2)	0 (0–2)	0.15
Use of rFVIIa, n (%)	30 (6.4)	26 (6.2)	4 (8.3)	0.54	3 (6.7)	4 (8.9)	0.70

CPB: cardiopulmonary bypass; CABG: coronary artery bypass grafting; DAPT: dual antiplatelet therapy; IQR: interquartile range; RBC: red blood cell; rFVIIa: recombinant activated factor VII; SD: standard deviation.

Bleeding-related events

In the whole series, drainage of ≥1500 ml within the first 12 h postoperatively was more common in the DAPT group (18.8% vs 8.4%, P = 0.020). Reoperation for bleeding (6.3% vs 9.3%, P = 0.60) and postoperative blood loss within the first 12 h (600 vs 500 ml, P = 0.31) did not differ between 2 groups. Neither did the amount of transfused red blood cells (9 vs 8 units, P = 0.29), fresh frozen plasma (500 vs 400 ml, P = 0.53) and platelets (0 vs 0 units, P = 0.73), nor the use of rFVIIa (8.3% vs 6.2%, P = 0.54) and the incidence of bleeding-related events (54.2% vs 43.5%, P = 0.16) differ significantly between patients with and without DAPT.

In the match cohort, however, the difference in bleeding of ≥1500 ml within the first 12 h did not reach statistical significance (20.0% vs 6.7%, P = 0.063). As shown in Table 2, the 2 groups did not differ either in reoperation for bleeding (6.7% vs 4.4%, P = 0.64) and blood loss within the first postoperative 12 h (650 vs 500 ml P = 0.36), or the amount of transfused red blood cells (8 vs 8 units, P = 0.54), fresh frozen plasma (600 vs 400 ml, P = 0.73) and platelets (0 vs 1 units, P = 0.15) and the use of rFVIIa (8.9% vs 6.7% P = 0.70), or the incidence of bleeding-related events (53.3% vs 42.2%, P = 0.30).

Operative mortality

Operative mortality was 9.7% (45/466) in the whole series, which, although higher in the DAPT group, did not reach statistical significance in both the unmatched (12.5% vs 9.3%, P = 0.48) and matched cohorts (13.3% vs 8.9%, P = 0.50).

Operative mortality was significantly higher in patients with bleeding-related events (15.8%, 33 of 208 vs 4.7%, 12 of 258; P < 0.001) in the unmatched cohort, which, however, did not differ significantly in the matched cohort (16.3%, 7 of 43 vs 6.4%, 3 of 47; P = 0.18).

Mid-term survival

In the matched cohort, clinical follow-up was complete in 97.5% (38/39 and 40/41 in operative survivors with and without DAPT, P = 0.98), with a median duration of 39.6 months (interquartile range 30.2–50.0). Survival in patients with and without DAPT was 82.2% [95% confidence interval (CI) 67.6–90.7%] and 82.2% (95% CI 67.6–90.7%) at 1 year, 79.3% (95% CI 63.8–88.7%) and 80.0% (95% CI 65.1–89.1%) at 3 years and 79.3% (95% CI 63.8–88.7%) and 76.4% (95% CI 60.0–86.7%) at 5 years, respectively (Fig. 2). No significant difference in survival was found between patients with and without DAPT (P = 0.93).

Figure 2:

Survival stratified by preoperative DAPT. DAPT: dual antiplatelet therapy.

Multivariable analysis of operative mortality and bleeding-related events

In multivariable analysis, DAPT was not identified as a risk factor for operative mortality [odd ratio (OR) 0.97, 95% CI 0.31–3.08; P = 0.96 before matching; adjusted OR 1.28, 95% CI 0.22–7.20; P = 0.78], neither was DAPT predictive of bleeding-related events (unadjusted OR 1.50, 95% CI 0.76–2.95; P = 0.24; adjusted OR 2.03, 95% CI 0.80–3.66; P = 0.14) (Table 3 and Supplementary Material, Tables S1 and S2).

Table 3:

Impact of preoperative DAPT on bleeding and operative mortality

End point/risk factor	Odds ratio	95% confidence interval	P-value
Bleeding-related events
Unmatched cohort	1.50	0.76–2.95	0.24
Matched cohort	2.03	0.80–3.66	0.14
Operative mortality
Unmatched cohort	0.97	0.31–3.08	0.96
Matched cohort	1.28	0.22–7.20	0.78

DAPT: dual antiplatelet therapy.

DISCUSSION

The present study shows that although preoperative DAPT in patients with ATAAD undergoing TAR + FET increases bleeding within the first 12 h after surgery, the incidences of bleeding-related outcomes (transfusion, re-exploration and early mortality) were not significantly different compared to patients without preoperative DAPT, nor was DAPT associated with significantly decreased survival in the medium term.

ATAAD patients who are misdiagnosed as ACS are often given DAPT [16]. Operation in ATAAD patients with preoperative DAPT is challenging due to the increased risk of perioperative bleeding. In our centre, an aggressive approach using TAR + FET has been the standard operation to repair ATAAD involving the arch or descending aorta, given the strikingly young average age and longer life expectancy of our patients [17]. The technical complexity of the surgery increases the difficulty in haemostasis [18]. Radical aortic surgery, together with deep hypothermia [4, 5] may further exacerbate the pre-existing coagulation disorders secondary to acute dissection [18–20]. Moreover, the use of preoperative platelet inhibition [6, 7] increases the risk of haemorrhage postoperatively. Hence, the 2011 ACC/AHA Guidelines for CABG gave a class I recommendation for discontinuation of clopidogrel and ticagrelor for at least 24 h, and a class IIb recommendation for discontinuation for <5 days before urgent CABG [8].

Due to the increased bleeding risk, it may be reasonable to postpone immediate surgery in ATAAD patients with preoperative DAPT. However, acute type A dissection is an absolute indication for immediate surgery, and the surgeon does not really have a choice to postpone emergency repair for patients with ongoing DAPT. Paradoxically, the mortality of ATAAD is rapidly increasing over time especially in the acute phase if left untreated. Surgeons are sometimes confronted with a dilemma of deciding the best timing of surgery in such patients. Up to date, the impact of preoperative DAPT on early- and mid-term outcomes of ATAAD patients undergoing extensive repair using TAR + FET has not been investigated. Most previous studies in ATAAD patients were focused on aortic root surgery with or without hemiarch repair, with only ∼5% receiving TAR + FET [21], and reported either higher mortality or increased bleeding and transfusion requirement [21–23]. In contrast, the present study shows that preoperative DAPT did not significantly increase bleeding-related events, neither did it confer excessive risk of operative and mid-term mortality. These results suggest that the risks of excessive bleeding and increased mortality associated with DAPT may have been overestimated previously. Given the extensive nature of total arch repair with an FET, the results of the present study imply that it is inappropriate to delay or cancel emergent surgery simply because a patient with ATAAD was given DAPT preoperatively. Such clinical scenarios may include ATAADs that were erroneously diagnosed as ACS, iatrogenic aortic dissections occurring in catheter-based intervention with upstream treatment of DAPT, etc.

In the present study, bleeding of ≥1500 ml within the first 12 postoperative hours was more common in the DAPT group, which did not reach statistical significance after propensity matching. This was most likely due to the small number of patients in the matched cohort. Our speculation is that the primary cause of bleeding in the immediate postoperative period is exudation of blood from the vascular graft and the surgical field, rather than from active bleeding. This can be ascribed in part to preoperative dual platelet inhibition, which leads to prolonged bleeding time. However, it remains unclear whether the differences in bleeding within the first 12 h between patients with and without DAPT are clinically relevant, as they were not associated with increased blood transfusion and incidence of re-exploration in patients with DAPT. The seemingly high rate of rethoracotomy (9%), routine use of Cabrol shunt and little transfusion of platelets and clotting factors in this series largely reflect our aggressive re-exploration strategy to minimize bleeding-related events in adaptation to a constant severe shortage of blood products in our work.

During ATAAD repair in patients with ongoing preoperative DAPT, a systemic blood conservation approach should be utilized to minimize blood loss and reduce blood transfusion. CPB with heparin-coated circuits [22] was proven to be blood-saving in CABG patients with preoperative DAPT. Thromboelastogram could serve as a precise tool to guide blood component transfusion perioperatively [23, 24]. Several reports have shown that platelet transfusion can be effective in counteracting DAPT in CABG patients [25, 26]. Furthermore, to shorten the CPB time and minimize the deleterious effect of deep hypothermic circulatory arrest on coagulation function, the surgical approach and extent of distal aortic repair should be tailored to the underlying aortopathy and surgeon experience. Finally, meticulosity should be exercised in haemostasis prior to chest closure to avoid active bleeding postoperatively.

Limitations

Although this study may be the first one to evaluate the impact of preoperative DAPT on the early and mid-term outcomes after TAR + FET in patients with ATAAD, it has several limitations that are inherent in a retrospective study based on a singer-centre experience, as have been described previously [17, 27]. Despite the use of propensity score matching and multivariable analysis, some other factors were not included in the matching and regression that may affect postoperative bleeding and mid-term survival. For example, preoperative malperfusion was not assessed with the Penn classification, which is another weakness of this study. Model fit was also affected by the small sample size and the limited number of events, particularly after propensity matching. Moreover, the possible variance in dosage and duration of dual antiplatelet regimen in different patients, together with the lack of preoperative test on platelet function, preclude the possibility of evaluating platelet inhibition rate and in-depth study of the impact of DAPT on postoperative bleeding.

CONCLUSION

In patients with ATAAD undergoing TAR + FET, although preoperative DAPT was associated with the higher risk of postoperative bleeding within the first 12 postoperative hours, it did not increase the incidence of re-exploration nor need for transfusion. Neither did preoperative DAPT significantly increase the operative and mid-term mortality in such patients. The results of this study imply that preoperative DAPT is not a contraindication for emergency operation in patients with ATAAD, and immediate surgical repair, even if as extensive as TAR + FET, should not be delayed simply because of ongoing DAPT.

SUPPLEMENTARY MATERIAL

Supplementary material is available at ICVTS online.

Funding

This work was supported in part by the Beijing Major Science and Technology Projects from the Beijing Municipal Science and Technology Commission [Z171100001017083, Z191100006619093 and Z191100006619094], the National Science and Technology Support Program [2015BAI12B03] and the National Natural Science Foundation of China [81970393].

Conflict of interest: none declared.

 

Author Contributions

Fu-Cheng Xiao: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Writing—original draft; Writing—review & editing. Wei-Guo Ma: Conceptualization; Formal analysis; Investigation; Methodology; Supervision; Visualization; Writing—original draft; Writing—review & editing. Yi-Pen Ge: Data curation; Formal analysis; Investigation; Methodology; Validation. Jun-Ming Zhu: Conceptualization; Data curation; Formal analysis; Funding acquisition; Investigation; Methodology; Project administration; Resources; Supervision; Writing—review & editing; Performing surgery. Li-Zhong Sun: Conceptualization; Funding acquisition; Project administration; Resources; Supervision; Validation.

Reviewer Information

Interactive CardioVascular and Thoracic Surgery thanks Dr Daniel-Sebastian Dohle and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.

ABBREVIATIONS

ACS

Acute coronary syndrome

ATAAD

Acute type A aortic dissection

CABG

Coronary artery bypass grafting

CI

Confidence interval

CPB

Cardiopulmonary bypass

DAPT

Dual antiplatelet therapy

FET

Frozen elephant trunk

OR

Odd ratio

rFVIIa

Recombinant activated factor VII

SD

Standard deviation

TAR

Total arch replacement