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Gepubliceerd in: Netherlands Heart Journal 9/2014

Open Access 01-09-2014 | Original Article

Perioperative cardiovascular complications versus perioperative bleeding in consecutive patients with known cardiac disease undergoing non-cardiac surgery. Focus on antithrombotic medication. The PRAGUE-14 registry

Auteurs: P. Widimský, Z. Moťovská, L. Havlůj, M. Ondráková, R. Bartoška, L. Bittner, L. Dušek, V. Džupa, J. Knot, M. Krbec, L. Mencl, J. Pachl, R. Grill, P. Haninec, P. Waldauf, R. Gürlich

Gepubliceerd in: Netherlands Heart Journal | Uitgave 9/2014

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Abstract

Background

Interruption of antithrombotic treatment before surgery may prevent bleeding, but at the price of increasing cardiovascular complications. This prospective study analysed the impact of antithrombotic therapy interruption on outcomes in non-selected surgical patients with known cardiovascular disease (CVD).

Methods

All 1200 consecutive patients (age 74.2 ± 10.2 years) undergoing major non-cardiac surgery (37.4 % acute, 61.4 % elective) during a period of 2.5 years while having at least one CVD were enrolled. Details on medication, bleeding, cardiovascular complications and cause of death were registered.

Results

In-hospital mortality was 3.9 % (versus 0.9 % mortality among 17,740 patients without CVD). Cardiovascular complications occurred in 91 (7.6 %) patients (with 37.4 % case fatality). Perioperative bleeding occurred in 160 (13.3 %) patients and was fatal in 2 (1.2 % case fatality). Multivariate analysis revealed age, preoperative anaemia, history of chronic heart failure, acute surgery and general anaesthesia predictive of cardiovascular complications. For bleeding complications multivariate analysis found warfarin use in the last 3 days, history of hypertension and general anaesthesia as independent predictive factors. Aspirin interruption before surgery was not predictive for either cardiovascular or for bleeding complications.

Conclusions

Perioperative cardiovascular complications in these high-risk elderly all-comer surgical patients with known cardiovascular disease are relatively rare, but once they occur, the case fatality is high. Perioperative bleeding complications are more frequent, but their case fatality is extremely low. Patterns of interruption of chronic aspirin therapy before major non-cardiac surgery are not predictive for perioperative complications (neither cardiovascular, nor bleeding). Simple baseline clinical factors are better predictors of outcomes than antithrombotic drug interruption patterns.

Background

Interruption of antithrombotic therapy may be detrimental in some patients. Meta-analysis of six studies on aspirin adherence revealed that aspirin non-adherence/withdrawal was associated with a threefold higher risk of major adverse cardiac events [1]. Non-cardiac surgery is frequently accompanied by interruption of antithrombotic therapy and thus increases the risk of stent thrombosis, myocardial ischaemia/infarction, and death, especially soon after stent placement. The risk of surgical haemorrhage is increased 20 % by aspirin or clopidogrel alone and 50 % by dual antiplatelet therapy. Therefore, some authors recommend to continue antiplatelet therapy throughout the perioperative period except when the risk of bleeding outweighs the risk of acute stent thrombosis, while others suggest 5–10 days interruption prior to surgery [2].
In moderate to high risk patients receiving acetylsalicylic acid (ASA) and requiring non-cardiac surgery, the American College of Clinical Pharmacy (ACCP) recommends ASA to be continued around the time of surgery. Perioperative antithrombotic management should be based on individual risk assessment for thrombotic versus bleeding risk [3]. In patients with semi-urgent surgery, the decision to prematurely stop antiplatelet agents has to be taken after multidisciplinary consultation, evaluating the individual thrombotic and bleeding risk. Urgently needed surgery has to take place under full antiplatelet therapy despite the increased bleeding risk. A multidisciplinary approach for optimal antithrombotic and haemostatic patient management is mandatory in this situation [4]. Multiple studies have reported an independent association between postoperative myocardial ischaemia and major adverse cardiac events (MACE) and mortality, in both the short and the long term [5].
Surgeons usually recommend to stop all antithrombotic medication 1 week before surgery to prevent perioperative bleeding. Such a strategy may increase the risk of perioperative cardiovascular (frequently thrombotic / ischaemic) complications. This study was designed to collect data from all consecutive (non-selected) patients with known cardiovascular disease undergoing acute or elective major non-cardiac surgery in order to analyse the bleeding / thrombotic risk balance with focus on antithrombotic therapy.

Methods and patients

The study protocol was approved by the Ethics Committee of the University Hospital Kralovske Vinohrady and by the Czech Ministry of Health (IGA). The study is registered on www.​ClinicalTrials.​gov under the identifier NCT01897220.
All departments performing major non-cardiac surgery in a large tertiary university hospital participated: general surgery (43.3 % patients), trauma and orthopaedic surgery (39.9 %), urology (10.5 %), neurosurgery (5.5 %) and anaesthesiology (0.8 %). The study was designed and coordinated by the department of cardiology in the same hospital. All 1200 consecutive patients undergoing non-cardiac surgery during the study period, while having known cardiovascular disease, were enrolled (6.3 % of 18,951 patients undergoing non-cardiac surgery during the study period 2011–2013).
The cardiovascular diagnoses at baseline (which formed the only entry criteria for the study) were coronary artery disease (n = 820), atrial fibrillation (n = 369), valvular disease (n = 176), prior stroke (n = 127), presence of a prosthetic valve (n = 72), congestive heart failure (n = 48), prior venous thromboembolism (n = 40) and cardiomyopathy (n = 23). Patients could have more than one (e.g. coronary artery disease and atrial fibrillation).
Acute (urgent or emergent, i.e. done during an acute unscheduled hospital admission) surgery was performed in 37.4 % of patients, elective (planned) surgery in the remaining 61.4 %, while in 1.2 % this was unspecified. General anaesthesia was used in 64.4 %, another type of anaesthesia (epidural, subarachnoid) in 35.6 %.
The decision to stop antithrombotic medication preoperatively was left to the discretion of attending physicians (usually a cardiologist or internist in collaboration with the anaesthesiologist or surgeon). No specific recommendations were prescribed by the study protocol.
The following data were recorded during the hospital stay: ECG, medication (prior, during and after surgery), blood counts, INR, creatinine, type of surgery, type of anaesthesia, perioperative bleeding, perioperative cardiovascular complications (myocardial infarction, clinically manifest pulmonary embolism or deep venous thrombosis, acute limb ischaemia, acute stroke, new onset or recurrent heart failure) and the cause of death. Perioperative bleeding was classified as (A) fatal, (B) postoperative serious bleeding requiring surgical revision, (C) postoperative serious bleeding requiring transfusions but not revision, (D) intraoperative serious bleeding complicating the procedure and (E) intraoperative bleeding greater than usual prolonging the procedure. This classification has significant similarities (Table 1) with the classification of the International Society on Thrombosis and Haemostasis (ISTH) [6]. We decided on a simple original classification of bleeding, also in the light of certain criticism of the ISTH classification [7].
Table 1
Perioperative bleeding complications
Type of bleeding (PRAGUE-14 classification)
Number of patients
Type of bleeding (ISTH classification)
Number of patients
Fatal (type A)
2
Fatal (class 1)
2
Postoperative serious requiring surgical revision (type B)
16
Surgical requiring second intervention (class 4)
16
Postoperative serious requiring transfusions but not revision (type C)
25
Large surgical without second intervention (class 5)
35
Intraoperative serious complicating surgery (type D)
13
Intraoperative greater than usual, prolonging surgery (type E)
103
  
  
Extrasurgical leading to transfusions (class 3)
2
  
Bleeding in critical area or organ (class 2)
1

Statistical analyses

Electronic case report forms were prepared with software Oracle XE 10 G, data mining was done with Rapidminer 5.3, and data were exported to Microsoft Excel 2010. Statistical analyses were performed using Statistica 8 Statsoft, SPSS 20.0.1 (IBM Corporation, 2011) and RStudio 0.96.331 (R Core Team, 2012).
Standard descriptive statistics were applied in the analysis; categorical variables were described using absolute and relative frequencies, continuous variables using mean and standard deviation. Statistical significance of association between categorised parameters was assessed using Fisher’s exact test for both 2 × 2 and r × c contingency tables; for categorical variables Pearson’s parametric coefficient of correlation was used to assess the relationship among continuous parameters [8]. Non-parametric Mann–Whitney was applied to test differences in continuous variables among groups of patients. We employed logistic regression models to assess the association between potential predictors and selected binary coded endpoints (perioperative ischaemia, perioperative bleeding and hospital mortality). Both univariate and multivariate regression models were applied, resulting in age-adjusted and multivariate-adjusted estimates of odds ratio with corresponding 95 % confidence limits. All factors reaching p value <0.1 in the univariate models and their properly coded interaction terms (if significant) entered the multivariate models as initial pool of independent variables. A stepwise backward procedure was applied to filter the final set of mutually independent predictors providing the best model. The models used maximum likelihood estimation directly comparing the likelihood L0 for the null model where all slope parameters are zero, with the likelihood L1 of the fitted model. Significance of regression coefficients was tested with the help of the Wald statistic, which is based on the asymptotic normality property of maximum likelihood estimates (tested against Chi-square distribution). All statistical tests were two-sided, and a value α <0.05 was considered to be a threshold for statistical significance in all the comparisons made.

Results

Patient characteristics

The patients’ baseline characteristics are shown in Table 2. The baseline chronic antithrombotic medication included ASA (53.2 %), warfarin ± ASA (24.6 %), ASA + clopidogrel (3.7 %), clopidogrel alone (1.7 %), dabigatran (0.3 %) and no antithrombotic agents (16.5 %). Other chronic medication included beta-blockers (61.4 %), angiotensin-converting enzyme inhibitors (54.1 %), statins (29.8 %), diuretics (40.2 %), calcium channel blockers (19 %) and nitrates (8.1 %).
Table 2
Baseline characteristics of study patients per complication type
Parameter
Uncomplicated patients
Patients with cardiovascular complications
Patients with bleeding complications
Patients with both types of complications
N =
973
67
136
24
Mean age
73.9 ± 10.2
78.9 ± 11.5
73.4 ± 8.8
77.5 ± 9.8
Female sex
434 (44.6 %)
31 (46.3 %)
52 (38.2 %)
10 (41.7 %)
Mean body weight
79.1 ± 16.2
76.7 ± 19.9
79.2 ± 14.0
74.0 ± 15.4
Diabetes mellitus
291 (29.9 %)
24 (35.8 %)
46 (33.8 %)
10 (41.7 %)
Hypertension
758 (77.9 %)
48 (71.6 %)
111 (81.6 %)
17 (70.8 %)
Chronic kidney disease
110 (11.3 %)
5 (7.5 %)
17 (12.5 %)
3 (12.5 %)
Chronic liver disease
44 (4.5 %)
2 (3.0 %)
5 (3.7 %)
3 (12.5 %)
Chronic pulmonary disease
121 (12.4 %)
13 (19.4 %)
15 (11.0 %)
6 (25.0 %)
Current tumour
152 (15.6 %)
11 (16.4 %)
20 (14.7 %)
4 (16.7 %)
Current haematological disease
30 (3.1 %)
1 (1.5 %)
6 (4.4 %)
1 (4.2 %)
Presence of vascular (coronary or peripheral) stent
195 (20.0 %)
12 (17.9 %)
36 (26.5 %)
9 (37.5 %)
History of any previous bleeding requiring treatment
9 (0.8 %)
1 (1.2 %)
0 (0 %)
0 (0 %)

Perioperative complications

Perioperative cardiovascular complications occurred in 91 (7.6 %) patients: acute or worsening heart failure (n = 46), acute myocardial infarction (n = 24), venous thromboembolism (n = 15), acute limb ischaemia (n = 11) and acute stroke (n = 3). Multivariate analysis revealed the following independent risk factors for perioperative cardiovascular complications: age, acute surgery (versus elective), preoperative anaemia, history of previous PCI, history of chronic heart failure, general anaesthesia (versus other types of anaesthesia). For details see Table 3.
Table 3
Univariate (age-adjusted) and multivariate-adjusted estimates of odds ratios of predictors associated with perioperative cardiovascular complications as risk end-point
Predictors (Risk and reference categories)
 
Univariate age-adjusted model
Multivariate model
OR
95 % IC
p*
OR
95 % IC
p*
Baseline characteristics
 Age (continuous)
Adjusting factor
1.05
1.03–1.08
<0.001
1.04
1.02–1.08
<0.001
 Haemoglobin: below normal
Reference: norm
2.26
1.45–3.52
<0.001
1.91
1.21–3.03
0.005
 Platelets: above norm
Reference: norm
2.55
1.19–5.47
0.016
   
 Creatinine: above norm
Reference: norm
1.81
1.16–2.82
0.009
   
 Prior PCI: yes
Reference: no
2.25
1.35–3.78
0.002
1.91
1.09–3.34
0.023
 Chronic heart failure: yes
Reference: no
3.12
1.48–6.57
0.003
2.80
1.26–6.22
0.011
 Hypertension: yes
Reference: no
0.61
0.37–0.99
0.043
   
 Current smoking: yes
Reference: no
2.05
1.03–4.11
0.042
   
Treatment
 ASA interrupted ≤ 7 days
Reference: > 7 days or no ASA
1.32
0.85–2.06
n.s.
   
Reference: > 7 days
1.87
0.84–4.13
n.s.
   
 ASA interrupted ≤ 3 days
Reference: > 3 days or no ASA
1.71
1.04–2.78
0.031
   
Reference: > 3 days
1.68
0.79–3.62
n.s.
   
 Clopidogrel/Ticlopidin interrupted ≤ 3 days
Reference: > 3 days
1.49
0.29–7.54
n.s.
   
 Warfarin interrupted ≤ 3 days
Reference: > 3 days or no Warfarin
2.61
1.16–5.86
0.020
   
Reference: > 3 days
2.94
0.93–9.23
n.s.
   
Surgery characteristics
 Type of operation: acute
Reference: elective
3.94
2.38–6.54
<0.001
4.00
2.41–6.66
<0.001
 General anaesthesia: yes
Reference: no
1.99
1.22–3.28
0.006
2.22
1.31–3.78
0.003
 Blood loss greater than usual: yes
Reference: no
2.08
1.21–3.59
0.008
   
p* Wald’s test
Perioperative bleeding occurred in 160 patients (13.3 %), 24 of them also had a cardiovascular complication. Bleeding complications are shown in Table 1. Mean perioperative blood loss was 149 ± 375 ml (median 0, IQR 0–200). Red blood cell transfusions were used in 12.5 %, frozen plasma in 5 % patients, thrombocytes in 0.2 %. Multivariate analysis found three independent predictors for bleeding complications: warfarin use in the last 3 days, history of hypertension, and general anaesthesia. Surprisingly, the length of aspirin interruption before surgery was not predictive for either cardiovascular or for bleeding complications (Table 4).
Table 4
Univariate (age-adjusted) and multivariate-adjusted estimates of odds ratios of potential predictors associated with perioperative bleeding as risk end-point
Predictors (risk and reference categories)
 
Univariate model
Multivariate model
OR
95 % IC
p*
OR
95 % IC
p*
History
 Hypertension: yes
Reference: no
1.54
0.99–2.41
0.045
1.61
1.03–2.53
0.037
Predictors (risk and reference categories)
 
Univariate age-adjusted model
Multivariate model
OR
95 % IC
p*
OR
95 % IC
p*
Antithrombotic treatment
 ASA therapy in the last 30 days: yes
Reference: no
0.72
0.52–1.03
n.s.
   
 Number of days before surgery when ASA was interrupted: continuous
0.99
0.96–1.02
n.s.
   
  Only for acute operation
1.01
0.92–1.10
n.s.
   
  Only for elective operation
0.99
0.94–1.03
n.s.
   
 ASA 7 days: interrupted ≤7 days
Reference: >7 days or ASA not applied
0.74
0.51–1.07
n.s.
   
Reference: >7 days
0.97
0.57–1.62
n.s.
   
 ASA 3 days: interrupted ≤3 days
Reference: >3 days or ASA not applied
0.81
0.51–1.27
n.s.
   
Reference: >3 days
1.05
0.60–1.85
n.s.
   
 Number of days before surgery when Clopidogrel/Ticlopidin was interrupted: continuous
0.88
0.72–1.08
n.s.
   
 Warfarin therapy in the last 30 days: yes
Reference: no
1.56
1.09–2.24
0.017
   
 Number of days before surgery when warfarin was interrupted: continuous
0.97
0.92–1.02
n.s.
   
  Only for acute operation
0.89
0.77–1.04
n.s.
   
  Only for elective operation
0.99
0.94–1.06
n.s.
   
 Warfarin 3 days: interrupted ≤3 days
Reference: >3 days or Warfarin not applied
3.12
1.62–6.01
0.002
3.11
1.61–6.02
0.001
Reference: >3 days
1.67
0.62–4.50
n.s.
   
 Last INR: continuous
 
1.11
0.81–1.50
n.s.
   
 Last INR >1.2
INR ≤1.2
0.89
0.47–1.69
n.s.
   
Surgery characteristics
 Type of operation: acute
Reference: elective
1.27
0.91–1.78
n.s.
   
 General anaesthesia: yes
Reference: no
1.47
1.02–2.11
0.037
1.47
1.01–2.14
0.040
*Wald’s test

In-hospital mortality

Forty-seven patients died during the hospital stay (in-hospital mortality 3.9 %). This is 4.3-times higher than the 0.9 % mortality among the remaining 17,740 patients without heart disease who underwent major surgery during the study period. The cause of death was heart failure in 20 patients, pulmonary embolism in 7, myocardial infarction in 3, sudden death in 2, acute stroke in 2, and bleeding caused death in 2 patients. Another cause of death was found in 7 patients. Thirty-four of the 91 patients with perioperative cardiovascular complications died (case fatality of cardiac patients with perioperative cardiovascular complications 37.4 %). Multivariate analysis revealed the following predictors of in-hospital mortality: age, preoperative anaemia, history of chronic heart failure, acute surgery and general anaesthesia (Table 5).
Table 5
Univariate (age-adjusted) and multivariate-adjusted estimates of odds ratios of potential predictors associated with hospital mortality as risk endpoint
Predictors (Risk and reference categories)
 
Univariate age-adjusted model
Multivariate model
OR
95 % IC
p*
OR
95 % IC
p*
Basic characteristics
 Age (continuous)
Adjusting factor
1.05
1.03–1.08
<0.001
1.05
1.02–1.09
0.004
 Haemoglobin: under norm
Reference: norm
2.89
1.57–5.33
0.001
2.57
1.36–4.87
0.004
 Chronic heart failure: yes
Reference: no
4.22
1.76–10.10
0.001
4.25
1.69–10.68
0.002
 Type of surgery: acute
Reference: elective
2.81
1.44–5.50
0.003
3.00
1.53–5.88
0.001
 General anaesthesia: yes
Reference: no
3.61
1.68–7.74
0.001
4.14
1.85–9.24
0.001
*Wald’s test

Antithrombotic medication

Antithrombotic medication was stopped at a median of 7 (aspirin, IQR 2–10), 4 (thienopyridine, IQR 1–8) and 8 (warfarin, IQR 5–10) days prior to surgery. Perioperative preventive low-dose anticoagulation (most frequently enoxaparin) was used in 94.8 % of patients.

Aspirin interruption

Among the patients with perioperative cardiovascular complications, aspirin was stopped a median of 2.5 days (IQR 0 – 6) before surgery (Table 6) while in patients without cardiovascular complications aspirin was stopped a median of 7 days (IQR 2 – 10) before surgery (p < 0.001). Among patients with perioperative bleeding, aspirin was stopped a median of 7 days (IQR 2 – 12) before surgery while in patients without bleeding aspirin was stopped a median of 7 days (IQR 2 – 10) before surgery (n.s.). Surprisingly, the median time of preoperative aspirin interruption was 7 days (IQR 2–12) among patients with bleeding complications versus 2.5 days (IQR 0–6) in those with cardiovascular complications (p = 0.001).
Table 6
Length of antithrombotic drugs interruption in subgroups per complication type
 
How many days before surgery the drug was interrupted in subgroups per complication types
 
N=
Mean
SD
Median
Percentile 25
Percentile 75
Min
Max
ASA
No complications
563
7.6
7.9
7
2
10
0
90
CV complications
38
4.1
4.8
2.5
0
6
0
18
Bleeding
67
10.3
13.8
7
2
12
0
90
Both types of complications
10
4.4
6.6
1
0
6
0
20
Clopidogrel
No complications
44
6.1
6.1
5
1
8
0
24
CV complications
6
6.5
7.9
3
0
15
0
18
Bleeding
11
3.5
4.3
1
0
7
0
12
Both types of complications
1
11
 
11
11
11
11
11
Warfarin
No complications
191
9.4
7.9
8
5
11
0
60
CV complications
16
8.4
7.3
7.5
2.5
10
0
23
Bleeding
40
9
10.1
7
3
9.5
0
46
Both types of complications
5
5
6
3
1
6
0
15

Warfarin interruption

There was no significant difference (p = 0.80) in the median length of warfarin interruption between patients with perioperative bleeding (7 days, IQR 3 – 9.5) versus patients with perioperative cardiovascular complications (7.5 days, IQR 2.5-10). However, warfarin interruption ≤3 days before surgery was an independent predictor of bleeding complications.

Discussion

The initial idea of our study was to see the results of this registry and then (if there proved to be some trend for less cardiovascular events in patients with continuing ASA treatment) consider a randomised study comparing the two strategies (a one-week ASA interruption vs. no interruption at all). As no trends were observed, we decided not to initiate a randomised study. In our current view (knowing the registry results) such a study would most likely be futile.
The independent predictors of in-hospital mortality (age, preoperative anaemia, history of chronic heart failure, acute surgery and general anaesthesia) are one of the important findings of this study. The relative importance of bleeding events versus cardiovascular events is reflected in the fact that the number of deaths related to cardiovascular complications was 34 vs. only 2 deaths related to bleeding. Perioperative cardiovascular complications are usually more serious and more difficult to treat than most bleeding complications [9, 10].
One study detected perioperative myocardial ischaemia in 40.5 % of patients. However, major adverse cardiac events occurred in only 8 % [11]. A large study in patients with atherosclerosis or at risk for it undergoing non-cardiac surgery found myocardial infarction in 5 % and troponin release in 8 % of patients [12]. In general surgical patients with documented coronary artery disease or at high risk for it, Filipovic et al. found troponin elevation in 16 % and myocardial ischaemia on continuous ECG in 46 % of patients [13].
The role and timing of interruption of antiplatelet agents before non-cardiac surgery has been studied by several authors. The STRATAGEM study randomised 291 patients undergoing elective non-cardiac surgery to either aspirin or placebo starting 10 days before surgery. The study did not find a significant difference in the number of major complications between the aspirin vs. placebo groups [14]. Aspirin increased the rate of bleeding complications in a meta-analysis by factor 1.5; however it did not lead to more severe bleeding complications with the exception of intracranial surgery and transurethral prostatectomy [15]. A single-centre study analysed 516 ASA-treated patients undergoing elective non-cardiac surgery: 289 patients had antiplatelet therapy stopped in the perioperative period. The decision to cease antiplatelet therapy, which occurred commonly, did not appear to be guided by perioperative cardiac risk stratification [16]. A Swedish study concluded that in high-risk patients undergoing non-cardiac surgery, perioperative aspirin reduced the risk of major adverse cardiac events without increasing bleeding complications [17].
The role of clopidogrel was investigated by Burdess et al.: in patients with critical limb ischaemia, perioperative dual antiplatelet therapy reduces biomarkers of atherothrombosis without causing unacceptable bleeding [18].
Our study seems to confirm that previous PCI with coronary stent implantation is an independent risk factor for perioperative complications. Savonitto et al. [19] and Motovska [20] recommend stratifying the risk of surgical bleeding and cardiac ischaemic events in order to manage perioperative antiplatelet therapy whenever surgery cannot be postponed.
The situation is even more difficult when patients are treated with long-term oral anticoagulation. The analysis of 1024 patients with warfarin therapy interruption before minor surgery found 7 post-procedure thromboembolic events and 23 clinically significant bleedings [21]. Another study on 556 patients with mechanical prosthetic valves evaluated the risk of thrombotic and bleeding complications when warfarin was stopped 4–5 days prior to a surgical procedure and re-started after the procedure as soon as haemostasis was assured. The 3-month incidence of thromboembolism was 0.9 %. None of those few cases were fatal. The cumulative incidence of major bleeding was 3.6 % and was fatal in 0.2 % [22]. Douketis et al. analysed 650 consecutive patients with a mechanical heart valve, chronic atrial fibrillation, or embolic stroke who required interruption of warfarin therapy because of an invasive procedure. Warfarin was stopped 5 or 6 days before the procedure, and patients received subcutaneous dalteparin starting 3 days before the procedure. Two patients died due to thromboembolism, 2 patients suffered non-fatal thromboembolic complications, there were 6 major bleeding episodes and 32 patients had episodes of increased wound-related blood loss [23].
The POISE-2 study (www.​clinicaltrials.​gov, identifier NCT01082874) is a large trial investigating the effectiveness of aspirin and clonidine versus placebo (factorial 2 × 2 design) in 10,000 patients with coronary artery disease undergoing non-cardiac surgery. The aim is to provide data to guide the decision-making on aspirin in the perioperative setting. The hope is that in the future perioperative antiplatelet therapy will be based on clinical evidence rather than on consensus.

Our study limitations

This study was designed to include all-comers with various cardiovascular diseases undergoing major surgery with no exclusion criteria. Over one-third of the patients were admitted (and operated) acutely without sufficient time to withdraw the antithrombotic medication. Some of our findings may be influenced by this fact. The all-comers design is a strength of this study (giving a real-life picture) but simultaneously a weakness (causing heterogenicity of patients, their medications and surgical procedures). This study has no power to assess dual antiplatelet therapy in this setting or to produce any recommendations regarding patients with coronary stents or with prosthetic valves due to the relatively low number of these patients within the studied population.
As the study aim was to describe the real-life situation in nonselected consecutive patients, we did not prescribe any prospective criteria for when to stop the antithrombotic therapy. The number of patients on warfarin was 296 and thus the study was not powered to analyse this group. Very few patients were on the newer antithrombotic agents (dabigatran). The relatively low number of patients with perioperative complications is clinically encouraging, but statistically is certainly a limitation for the interpretation of the study results.
Another serious limitation for the interpretation of our study results is the fact that most patients received low-dose perioperative anticoagulation to prevent venous thromboembolism. This might further complicate the interpretation of our data.

Conclusions

Perioperative cardiovascular complications in these high-risk elderly all-comer surgical patients with known cardiovascular disease are relatively rare, but once they occur, the case fatality is high. Perioperative bleeding complications are more frequent, but their case fatality is extremely low. Patterns of interruption of chronic aspirin therapy before major non-cardiac surgery are not predictive for perioperative complications (neither cardiovascular, nor bleeding). Simple baseline clinical factors are better predictors of outcomes than antithrombotic drug interruption patterns.

Acknowledgments

The study was supported by a research grant of the Czech Ministry of Health IGA no. NT 11506-6/2010. The authors acknowledge the work of many physicians and nurses from the participating departments.

Conflict of interests

None declared by any of the authors.
Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
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Netherlands Heart Journal

Het Netherlands Heart Journal wordt uitgegeven in samenwerking met de Nederlandse Vereniging voor Cardiologie en de Nederlandse Hartstichting. Het tijdschrift is Engelstalig en wordt gratis beschikbaa ...

Literatuur
1.
go back to reference Biondi-Zoccai G, Lotrionte M, Agostoni P, et al. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50 279 patients at risk for coronary artery disease. Eur Heart J. 2006;27:2667–74.PubMedCrossRef Biondi-Zoccai G, Lotrionte M, Agostoni P, et al. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50 279 patients at risk for coronary artery disease. Eur Heart J. 2006;27:2667–74.PubMedCrossRef
2.
go back to reference Vetter TR, Boudreaux AM, Papapietro SE, et al. The perioperative management of patients with coronary artery stents: surveying the clinical stakeholders and arriving at a consensus regarding optimal care. Am J Surg. 2012;204:453–61.PubMedCrossRef Vetter TR, Boudreaux AM, Papapietro SE, et al. The perioperative management of patients with coronary artery stents: surveying the clinical stakeholders and arriving at a consensus regarding optimal care. Am J Surg. 2012;204:453–61.PubMedCrossRef
3.
go back to reference Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(Suppl):e326S–50.PubMedPubMedCentral Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(Suppl):e326S–50.PubMedPubMedCentral
4.
go back to reference Korte W, Cattaneo M, Chassot PG, et al. Peri-operative management of antiplatelet therapy in patients with coronary artery disease Joint position paper by members of the working group on Perioperative Haemostasis of the Society on Thrombosis and Haemostasis Research (GTH), the working group on Perioperative Coagulation of the Austrian Society for Anesthesiology, Resuscitation and Intensive Care (ÖGARI) and the Working Group Thrombosis of the European Society for Cardiology (ESC). Thromb Haemost. 2011;105:743–9.PubMedCrossRef Korte W, Cattaneo M, Chassot PG, et al. Peri-operative management of antiplatelet therapy in patients with coronary artery disease Joint position paper by members of the working group on Perioperative Haemostasis of the Society on Thrombosis and Haemostasis Research (GTH), the working group on Perioperative Coagulation of the Austrian Society for Anesthesiology, Resuscitation and Intensive Care (ÖGARI) and the Working Group Thrombosis of the European Society for Cardiology (ESC). Thromb Haemost. 2011;105:743–9.PubMedCrossRef
5.
go back to reference Landesberg G, Luria MH, Cotev S, et al. Importance of long-duration postoperative ST-segment depression in cardiac morbidity after vascular surgery. Lancet. 1993;341:715–9.PubMedCrossRef Landesberg G, Luria MH, Cotev S, et al. Importance of long-duration postoperative ST-segment depression in cardiac morbidity after vascular surgery. Lancet. 1993;341:715–9.PubMedCrossRef
6.
go back to reference Schulman S, Angerås U, Bergqvist D, et al. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost. 2010;8:202–4.PubMedCrossRef Schulman S, Angerås U, Bergqvist D, et al. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost. 2010;8:202–4.PubMedCrossRef
7.
go back to reference Rosencher N, Zufferey P, Samama CM. Definition of major bleeding in surgery: an anesthesiologist’s point of view: a rebuttal. J Thromb Haemost. 2010;8:1442–3.PubMedCrossRef Rosencher N, Zufferey P, Samama CM. Definition of major bleeding in surgery: an anesthesiologist’s point of view: a rebuttal. J Thromb Haemost. 2010;8:1442–3.PubMedCrossRef
8.
go back to reference Pagano M, Halvorsen KT. An algorithm for finding the exact significance levels of r × c contingency tables. J Am Stat Assoc. 1981;76:931–4. Pagano M, Halvorsen KT. An algorithm for finding the exact significance levels of r × c contingency tables. J Am Stat Assoc. 1981;76:931–4.
9.
go back to reference Mehta RH, Sheng S, O’Brien SM, et al. Reoperation for bleeding in patients undergoing coronary artery bypass surgery: incidence, risk factors, time trends, and outcomes. Circ Cardiovasc Qual Outcomes. 2009;2:583–90.PubMedCrossRef Mehta RH, Sheng S, O’Brien SM, et al. Reoperation for bleeding in patients undergoing coronary artery bypass surgery: incidence, risk factors, time trends, and outcomes. Circ Cardiovasc Qual Outcomes. 2009;2:583–90.PubMedCrossRef
10.
go back to reference Koch CG, Li L, Sessler DI, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008;358:1229–39.PubMedCrossRef Koch CG, Li L, Sessler DI, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008;358:1229–39.PubMedCrossRef
11.
go back to reference Lurati Buse G, Schumacher P, Seeberger E, et al. Randomized comparison of sevoflurane versus propofol to reduce perioperative myocardial ischemia in patients undergoing noncardiac surgery. Circulation. 2012;126:2696–704.PubMedCrossRef Lurati Buse G, Schumacher P, Seeberger E, et al. Randomized comparison of sevoflurane versus propofol to reduce perioperative myocardial ischemia in patients undergoing noncardiac surgery. Circulation. 2012;126:2696–704.PubMedCrossRef
12.
go back to reference Devereaux PJ, Xavier D, Pogue J, et al. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011;154:523–8.PubMedCrossRef Devereaux PJ, Xavier D, Pogue J, et al. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011;154:523–8.PubMedCrossRef
13.
go back to reference Filipovic M, Jeger R, Probst C, et al. Heart rate variability and cardiac troponin I are incremental and independent predictors of one-year all-cause mortality after major noncardiac surgery in patients at risk of coronary artery disease. J Am Coll Cardiol. 2003;42:1767–76.PubMedCrossRef Filipovic M, Jeger R, Probst C, et al. Heart rate variability and cardiac troponin I are incremental and independent predictors of one-year all-cause mortality after major noncardiac surgery in patients at risk of coronary artery disease. J Am Coll Cardiol. 2003;42:1767–76.PubMedCrossRef
14.
go back to reference Mantz J, Samama CM, Tubach F, et al. Impact of preoperative maintenance or interruption of aspirin on thrombotic and bleeding events after elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled, STRATAGEM trial. Brit J Anaesth. 2011;107:899–910.PubMedCrossRef Mantz J, Samama CM, Tubach F, et al. Impact of preoperative maintenance or interruption of aspirin on thrombotic and bleeding events after elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled, STRATAGEM trial. Brit J Anaesth. 2011;107:899–910.PubMedCrossRef
15.
go back to reference Burger W, Chemnitius JM, Kneissl GD, et al. Low-dose aspirin for secondary cardiovascular prevention—cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation—review and meta-analysis. J Intern Med. 2005;257:399–414.PubMedCrossRef Burger W, Chemnitius JM, Kneissl GD, et al. Low-dose aspirin for secondary cardiovascular prevention—cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation—review and meta-analysis. J Intern Med. 2005;257:399–414.PubMedCrossRef
16.
go back to reference Alcock RF, Naoum C, Aliprandi-Costa B, et al. The peri-operative management of anti-platelet therapy in elective, non-cardiac surgery. Int J Card. 2013;167:374–7.CrossRef Alcock RF, Naoum C, Aliprandi-Costa B, et al. The peri-operative management of anti-platelet therapy in elective, non-cardiac surgery. Int J Card. 2013;167:374–7.CrossRef
17.
go back to reference Oscarsson A, Gupta A, Fredrikson M, et al. To continue or discontinue aspirin in the perioperative period: a randomized, controlled clinical trial. Brit J Anaesth. 2010;104:305–12.PubMedCrossRef Oscarsson A, Gupta A, Fredrikson M, et al. To continue or discontinue aspirin in the perioperative period: a randomized, controlled clinical trial. Brit J Anaesth. 2010;104:305–12.PubMedCrossRef
18.
go back to reference Burdess A, Nimmo AF, Garden OJ, et al. Randomized controlled trial of dual antiplatelet therapy in patients undergoing surgery for critical limb ischemia. Ann Surg. 2010;252:37–42.PubMedCrossRef Burdess A, Nimmo AF, Garden OJ, et al. Randomized controlled trial of dual antiplatelet therapy in patients undergoing surgery for critical limb ischemia. Ann Surg. 2010;252:37–42.PubMedCrossRef
19.
go back to reference Savonitto S, Caracciolo M, Cattaneo M, et al. Management of patients with recently implanted coronary stents on dual antiplatelet therapy who need to undergo major surgery. J Thromb Haemost. 2011;9:2133–42.PubMedCrossRef Savonitto S, Caracciolo M, Cattaneo M, et al. Management of patients with recently implanted coronary stents on dual antiplatelet therapy who need to undergo major surgery. J Thromb Haemost. 2011;9:2133–42.PubMedCrossRef
20.
go back to reference Motovska Z. Management of antiplatelet therapy in patients at risk for coronary stent thrombosis undergoing non-cardiac surgery. Drugs. 2011;71:1797–806.PubMedCrossRef Motovska Z. Management of antiplatelet therapy in patients at risk for coronary stent thrombosis undergoing non-cardiac surgery. Drugs. 2011;71:1797–806.PubMedCrossRef
21.
go back to reference Garcia DA, Regan S, Henault LE, et al. Risk of thromboembolism with short-term interruption of warfarin therapy. Arch Intern Med. 2008;168:63–9.PubMedCrossRef Garcia DA, Regan S, Henault LE, et al. Risk of thromboembolism with short-term interruption of warfarin therapy. Arch Intern Med. 2008;168:63–9.PubMedCrossRef
22.
go back to reference Daniels PR, McBane RD, Litin SC, et al. Peri-procedural anticoagulation management of mechanical prosthetic heart valve patients. Thromb Res. 2009;124:300–5.PubMedCrossRef Daniels PR, McBane RD, Litin SC, et al. Peri-procedural anticoagulation management of mechanical prosthetic heart valve patients. Thromb Res. 2009;124:300–5.PubMedCrossRef
23.
go back to reference Douketis JD, Johnson JA, Turpie AG. Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin. Assessment of a standardized periprocedural anticoagulation regimen. Arch Intern Med. 2004;164:1319–26.PubMedCrossRef Douketis JD, Johnson JA, Turpie AG. Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin. Assessment of a standardized periprocedural anticoagulation regimen. Arch Intern Med. 2004;164:1319–26.PubMedCrossRef
Metagegevens
Titel
Perioperative cardiovascular complications versus perioperative bleeding in consecutive patients with known cardiac disease undergoing non-cardiac surgery. Focus on antithrombotic medication. The PRAGUE-14 registry
Auteurs
P. Widimský
Z. Moťovská
L. Havlůj
M. Ondráková
R. Bartoška
L. Bittner
L. Dušek
V. Džupa
J. Knot
M. Krbec
L. Mencl
J. Pachl
R. Grill
P. Haninec
P. Waldauf
R. Gürlich
Publicatiedatum
01-09-2014
Uitgeverij
Bohn Stafleu van Loghum
Gepubliceerd in
Netherlands Heart Journal / Uitgave 9/2014
Print ISSN: 1568-5888
Elektronisch ISSN: 1876-6250
DOI
https://doi.org/10.1007/s12471-014-0575-3

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