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Antiplatelet therapy with oral P2Y₁₂-receptor inhibitors (clopidogrel, prasugrel, and ticagrelor) is widely used in patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. However, patients often need to switch between these drugs for a variety of clinical reasons. In this Review, Rollini et al. summarize the practical considerations when switching therapies, including discussion of the new intravenous P2Y₁₂-receptor inhibitor cangrelor.

In this Review, Galli and colleagues discuss the mechanisms and associated biomarkers of traditional and emerging factors responsible for the residual risk of recurrent adverse cardiovascular events in patients with coronary artery disease, with a focus on new pathophysiological insights and the therapeutic implications.

Proton-pump inhibitors (PPIs) can alter the pharmacodynamic profile of clopidogrel and reduce its platelet-inhibitory effects. Ho and colleagues have reported that concurrent use of PPIs and clopidogrel leads to in an increase in adverse cardiovascular outcomes. In this article we discuss the clinical implications of the interaction between these two drugs.

Dual antiplatelet therapy (DAPT) with aspirin and the P2Y purinoceptor 12 (P2Y₁₂)-receptor inhibitor clopidogrel has been considered the gold standard of care in patients with acute coronary syndrome (ACS). The FDA approval of the novel P2Y₁₂-receptor antagonists prasugrel and ticagrelor, which are faster-acting and more potent than clopidogrel, in the past 5 years have improved clinical outcomes in patients with ACS. Even with these newer compounds, many patients continue to experience adverse ischaemic events. This Review will provide an overview of the antiplatelet agents currently used to treat patients with ACS. Furthermore, emerging antiplatelet therapies, including intravenous P2Y₁₂antagonists, oral PAR-1 antagonists and thromboxane-receptor inhibitors will be discussed.

Atherothrombosis underlies numerous manifestations of cardiovascular disease, including coronary artery disease (CAD) and cerebrovascular disease (CVD). Treatment of patients with concomitant CAD and CVD is complex, owing to their increased risk of both ischaemia and bleeding. Capodanno et al. review the use of antithrombotic drugs for the secondary prevention of atherothrombotic events in patients with concomitant CAD and CVD, particularly those with a history of noncardioembolic stroke or transient ischaemic attack.

Antithrombotic therapy, including antiplatelet and anticoagulant agents, is the cornerstone of pharmacological treatment to optimize clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). In this Review, Franchi et al. provide an overview of currently available antithrombotic therapies used in these patients, results from pivotal clinical trials and their implications for guidelines, as well as recommendations for clinical practice.

Patients with coronary artery disease (CAD) are at high risk of perioperative cardiovascular complications related to non-cardiac surgery. In this Review, Mehran and colleagues summarize trial data and guideline recommendations on preoperative risk stratification and periprocedural management of patients with CAD undergoing non-cardiac surgery.

Many patients with cardiovascular disease have a residual risk of ischaemic events despite receiving antiplatelet therapy. In this Review, Angiolillo and colleagues discuss the pharmacological rationale and clinical development of dual-pathway inhibition strategies for the prevention of atherothrombotic events in patients with cardiovascular disease.

In this Review, Angiolillo and colleagues discuss the latest evidence and updates on bleeding avoidance strategies in patients undergoing percutaneous coronary intervention, including risk stratification, timing of revascularization, pretreatment with antiplatelet agents, selection of vascular access, choice of coronary stents and antithrombotic treatment regimens.

Inhibition of factor XI has emerged as a promising strategy to mitigate bleeding while potentially preserving antithrombotic efficacy. In this Review, the authors comprehensively discuss the rationale, pharmacology, evidence and future directions for factor XI inhibitors across various clinical settings.

Coronary microvascular obstruction and dysfunction (CMVO) is common in patients with ST-segment elevation myocardial infarction (STEMI) despite prompt reperfusion. In this Review, the authors discuss the mechanisms of CMVO as well as strategies to reduce its incidence and improve prognosis.

The evolution of stent design has reduced the incidence of stent thrombosis, meaning that the duration of dual antiplatelet therapy after percutaneous coronary intervention (PCI) might be shortened. In this Review, the authors describe the current evidence base and ongoing clinical trials into the use of P2Y₁₂ inhibitor monotherapy after PCI.

In this Review, a panel of leading experts in antithrombotic pharmacotherapy discuss the principles guiding the role of acetylsalicylic acid (aspirin)-free strategies in the prevention and management of cardiovascular disease, along with their implications for clinical trial design and development.

In this Review, the authors address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities, who often have an increased risk of gastrointestinal bleeding. Approaches include tailoring of antithrombotic regimens and gastrointestinal-protection strategies.