Platelet inhibition and secondary prevention in cardiac surgery patients
Abstract
ABSTRACT
Background and objective
Coronary artery bypass grafting (CABG) is the most common cardiac surgery
procedure. Dual antiplatelet therapy (DAPT) reduces the risk for ischaemic
events in patients with acute coronary syndrome (ACS) but increases the
bleeding risk, both for spontaneous bleedings and procedure-related
bleedings for the subset of ACS patients undergoing urgent CABG. Statins,
beta-blockers, and renin-angiotensin-system (RAS) inhibitors are commonly
prescribed after CABG but the scientific evidence for their use after CABG
is scarce. The objective of this thesis is to investigate how different aspects
of pharmacotherapy are associated with short- and long-term risk for adverse
events after CABG.
Methods
Study I: Platelet function before and after cardiac surgery was analysed using
impedance aggregometry in patients treated with acetylsalicylic acid and the
P2Y12-inhibitor ticagrelor. Associations between pre- and postoperative
platelet function and risk for severe postoperative bleeding were investigated.
Study II-IV: Individual patient data from the Swedish Cardiac Surgery
Registry, the National Patient Register, the Swedish Prescribed Drug
Register, LISA register and the Cause of Death Register was merged to obtain
data on procedural aspects, baseline comorbidities, adverse events and
mortality after CABG. Study II investigated associations between use of
statins, beta-blockers, RAS-inhibitors and platelet inhibitors and mortality
risk. Study III investigated if the combination of ASA and ticagrelor was
associated with improved clinical outcome compared to ASA monotherapy
in patients with acute coronary syndrome undergoing CABG. Study IV
investigated the associations between post-discharge major bleeding and
myocardial infarction respectively with subsequent mortality risk.
Results
Study I: Postoperative platelet aggregation induced by adenosin diphosphate
(ADP) had an area under curve (AUC) of 0.75 (95% CI 0.62-0.87) in
predicting severe bleeding. The corresponding value for preoperative testing
was AUC of 0.77 (95% CI 0.65-0.89).
Study II: Utilization of secondary prevention medication was high early after
CABG but decreased significantly over time. Ongoing use of statins, RAS
inhibitors and platelet inhibitors were associated with reduced mortality risk
after CABG. Use of beta-blockers was not associated with lower mortality
risk.
Study III: The combination of acetylsalicylic acid (ASA) and ticagrelor was
not associated with lower risk for ischaemic events but increased the bleeding
risk compared with ASA monotherapy.
Study IV: Post-discharge major bleeding was associated with increased
mortality risk, comparable to the increase in mortality risk associated with
post-discharge myocardial infarction.
Conclusions
Adding a postoperative test of platelet aggregation did not improve accuracy
in predicting severe bleeding. Improving long-term utilization of statins, RAS
inhibitors and platelet inhibitors poses an opportunity to improve long-term
survival after CABG. Prospective, randomized controlled trials are warranted
to establish the clinical outcome of DAPT with ticagrelor after CABG in ACS
patients, especially considering the increased mortality risk associated with
post-discharge major bleeding events.
Parts of work
Björklund E, Hansson EC, Romlin BS, Jeppsson A, Malm CJ. Postoperative platelet function is associated with severe bleeding in ticagrelor-treated patients. Interact Cardiovasc Thorac Surg. 2019 May 1;28(5):709-715, https://doi.org/10.1093/icvts/ivy336 Björklund E, Nielsen SJ, Hansson EC, Karlsson M, Wallinder A, Martinsson A, Tygesen H, Romlin BS, Malm CJ, Pivodic A, Jeppsson A. Secondary prevention medications after coronary artery bypass grafting and long-term survival: a population-based longitudinal study from the SWEDEHEART registry. Eur Heart J. 2020 May 1;41(17):1653-1661, https://doi.org/10.1093/eurheartj/ehz714 Björklund E, Malm CJ, Nielsen SJ, Hansson EC, Tygesen H, Romlin BS, Martinsson A, Omerovic E, Pivodic A, Jeppsson A. Comparison of midterm outcomes associated with aspirin and ticagrelor vs aspirin monotherapy after coronary artery bypass grafting for acute coronary syndrome. JAMA Netw Open. 2021 Aug 2;4(8):e2122597, https://doi.org/10.1001/jamanetworkopen.2021.22597 Björklund E, Enström P, Nielsen SJ, Tygesen H, Martinsson A, Hansson EC, Lindgren M, Malm CJ, Pivodic A, Jeppson A. Post-discharge major bleeding, myocardial infarction and mortality risk after coronary artery bypass grafting. Submitted
Degree
Doctor of Philosophy (Medicine)
University
University of Gothenburg. Sahlgrenska Academy
Institution
Institute of Medicine. Department of Molecular and Clinical Medicine
Disputation
Fredagen den 1 december 2023, kl. 9.00, Katastrofrummet, Thoraxklinikens administration, Sahlgrenska Universitetssjukhuset, Blå stråket 5, Göteborg
Date of defence
2023-12-01
Date
2023-11-06Author
Björklund, Erik
Keywords
coronary artery bypass grafting
secondary prevention
bleeding complications
impedance aggregometry
Publication type
Doctoral thesis
ISBN
978-91-8069-405-6 (PRINT)
978-91-8069-406-3 (PDF)
Language
eng