Continuous Improvement of Antiplatelet Therapy in Cardiovascular Disease

Besides lifestyle and lipid management, antiplatelet strategies are cornerstones in the secondary prevention of cardiovascular disease. The major drawback of antiplatelet agents is the occurrence of bleeding, which may vary from nuisance hemorrhages to fatal bleeding. Impressive improvements have been made in the past decade to lower the risk of bleeding and maintaining the anti-ischemic efficacy. These steps forward consist not only in the use of one antiplatelet alone, but also in the combination of several agents as well as other effective medications in secondary prevention like lipid-lowering drugs. Greater pathophysiological insights, as well as appreciating ethnic differences in thrombosis and bleeding have also gained much interest.[1]

In this special theme issue of Thrombosis and Haemostasis, four papers are published on some recent developments of antiplatelet therapy in cardiovascular disease alone, and its role in combination with the strongest lipid-lowering strategy today.

It is well known that in cardiovascular disease, aspirin and statins have synergistic effects both clinically and in laboratory observations. Schrör et al summarize the evidence,[2] but also studied the data on the novel player in lipid-lowering strategies proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and their interaction with platelets. And the focus in their work is on the crosstalk of platelets, PCSK9, endothelial cells, and macrophages. Although PCSK9 inhibition is extremely effective in lipid lowering and secondary prevention of cardiovascular disease,[3] [4] the question remains whether the described interactions with platelet and vessel wall will translate in further reduction of clinical events.

As said, major bleeding is the most severe and sometimes life-threatening complication of antiplatelet agents often resulting in therapy interruption, identification of the bleeding source, and its repair. Remaining question when to restart antiplatelet therapy is extensively addressed by Geisler et al.[5] Not only the current major bleeding definitions are reviewed, but also the balance of the risk of bleeding versus the ischemic risk is discussed by the authors. They elegantly address the different risk scores to define bleeding risk and tradeoff between bleeding and ischemic risk in patients treated with antiplatelet agents. And they also present a suggested algorithm for interruption and resumption of antiplatelet or anticoagulation according to bleeding severity type.

In patients with ST-elevation myocardial infarction (STEMI) thrombus load in the culprit lesion need immediate and strong platelet inhibition. Even the strongest oral antiplatelet agents take several hours to exhibits their inhibitory effects, and therefore parental antiplatelet drugs are necessary in this condition, such as platelet glycoprotein IIb/IIIa receptor blockers. But these agents are associated with excess major bleeding partly due to thrombocytopenia. Rikken et al[6] summarize the available and future parenteral antiplatelet medications and put their potential role for STEMI into perspective.

Finally, an option of diminishing bleeding risk with antiplatelet therapy is dropping one agent in case of dual-antiplatelet therapy (DAPT) in patients who had undergone percutaneous coronary intervention (PCI). The current default is to stop after a certain time the P2Y12 receptor antagonist and continue with aspirin monotherapy, which usually results in a decrease in bleeding. Alternatively, aspirin may be dropped from DAPT, whereas at the cessation of DAPT P2Y12 blocker monotherapy is maintained. Results from recent trials suggest that the latter option reduces bleeding even more than aspirin monotherapy after PCI without increasing ischemic events.[7] Verheugt et al present the current evidence of P2Y12 blocker monotherapy after PCI including currently running trials in this field.[8]

Publication History

Received: 05 November 2022

Accepted: 07 November 2022

Article published online:
05 January 2023

• References

• 1 Kim HK, Tantry US, Smith Jr SC. et al. The East Asian paradox: an updated position statement on the challenges to the current antithrombotic strategy in patients with cardiovascular disease. Thromb Haemost 2021; 121 (04) 422-432
• 2 Schrör K, Verheugt FWA, Trenk D. Drug-drug interaction between antiplatelet therapy and lipid lowering agents (statins and PCSK9 inhibitors). Thromb Haemost 2023; 123, In press
• 3 Sabatine MS, Giugliano RP, Keech AC. et al; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376 (18) 1713-1722
• 4 Schwartz GG, Steg PG, Szarek M. et al; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018; 379 (22) 2097-2107
• 5 Geisler T, Poli S, Huber K. et al. Resumption of antiplatelet therapy after major bleeding. Thromb Haemost 2022; 123, In press
• 6 Rikken SAOF, Storey RF, Andreotti F, Clemmensen P, Ten Berg JM. Parenteral antiplatelet drugs in ST-elevation myocardial infarction: current status and future directions. Thromb Haemost 2022; 123, In press
• 7 O'Donoghue ML, Murphy SA, Sabatine MS. The safety and efficacy of aspirin discontinuation on a background of a P2Y₁₂ inhibitor in patients after percutaneous coronary intervention: a systematic review and meta-analysis. Circulation 2020; 142 (06) 538-545
• 8 Verheugt FWA, Huber K, Clemmensen P, Collet JP, Cuisset T, Andreotti F. Platelet P2Y12 inhibitor monotherapy after percutaneous coronary intervention: an emerging option of antiplatelet therapy de-escalation. Thromb Haemost 2023; 123, In press