Introduction
In 2007, the use of aprotinin was temporarily suspended following several publications
raising serious safety concerns.(1.2.3) However, Canadian and European Health Authorities
concluded that these studies suffered from major flaws and lifted the suspension in
2013.(4,5)
The reintroduction of aprotinin in 2016 was accompanied by a mandatory registry [Nordic
Aprotinin Patient Registry (NAPaR)] in order to monitor the pattern of use, the effect
of risk minimization measures, and overall safety.
Objective of this study was to analyse the use of aprotinin in Belgium.
Methods
NAPaR is a non-interventional Post-Authorisation Safety Study (PASS), endorsed by
the Pharmacovigilance Risk Assessment Committee of the European Medicine Agency.
Results
Between October 2018 and August 2020, six Belgian NAPaR centers included 694 patients
[median age 70 (range 13-90y); 62% male; median EuroSCORE II 4.6 (range 0.5-93.4)].
25% of the patients had an EuroSCOREII > 10.
57% of the patients were under an active antiplatelet therapy and 17% were treated
with novel oral anti-coagulants. Preoperative renal impairment was present in 2/3
of patients.
Only 4% of the patients received aprotinin on-label, i.e. for isolated coronary artery
bypass grafting (CABG) on cardiopulmonary bypass (CPB).
In 96% of the patients, aprotinin was used off-label, mainly for redo surgery (32%),
CABG + valve surgery (29%), aortic surgery (20%) and multiple valve surgery (17%).
One third of the procedures were urgent (23%) or emergent (9%). Median bypass time
was 128min (range 13-600min).
Median hospital stay was 11 days (range 3-151 days).
Main reported indications for the use of aprotinin were active dual antiplatelet therapy
(68% in iCABG), redo surgery (16%) and expected prolonged CPB time (55%).
In 83% of the cases, aprotinin was administered at the Half Hammersmith dose (1 Mio
KIU loading- and priming-dose + 250.000 KIU/h); most patients received the appropriate
test dose (98%), none developed anaphylactic reactions.
Median perioperative blood loss was 400ml (range 40 -10050 ml), 44% of the patients
had RBC transfusion and 6% underwent reoperation for bleeding or tamponade.
Overall mortality at discharge was 5%, i.e. within the range or lower than predicted
by the EuroSCORE II. 2% of the patients had a postoperative stroke. Postoperative
AKI as defined by a serum creatinine increase of 0,3mg/dL or more within 48 hours
after surgery was present in 13% of cases. Most of these patients (76%) suffered from
preoperative moderate or severe renal impairment including dialysis. Notably, in patients
with postoperative AKI median CPB time was significantly higher than in patients without
AKI: 172min (range 56-402) vs 125min (range 13-600min) (p<0,0001).
Discussion
In the Belgian centers, aprotinin was mainly used off-label and predominantly administered
to older patients with significant comorbidities undergoing high-risk procedures.
The observed safety outcomes are in line with published data within this high risk
patient population.
The data from the Belgian NAPaR suggest that aprotinin has an excellent safety profile
in adult cardiac surgery.
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© 2021 Published by Elsevier Inc.
