Evolving Approaches to Antithrombotics in Stroke Prevention and Treatment

Vijayakumar Javalkar, MD, MCh; Okkes Kuybu, MD; Abdallah Amireh, MD; Roger E. Kelley, MD


South Med J. 2020;113(11):585-592. 

In This Article

Abstract and Introduction


The optimization of antithrombotic therapy for acute stroke treatment and secondary prevention is an evolving process based on an increasing array of studies that provide an evidence-based approach. Options have increased dramatically with the release of the non–vitamin K oral anticoagulants and with the results of recent randomized clinical trials designed to assess potential benefits versus risks for patients in an individualized fashion. Recent studies have provided important information to guide choice and dosing of antiplatelet agents as well as the length of treatment. Anticoagulant use is particularly pertinent for stroke prevention in patients at higher risk of atrial fibrillation and may have a place in certain other stroke mechanisms. One important focus of study is the potential benefit of combined antiplatelet and anticoagulant therapy. Options for our patients, when the initial choice of therapy does not demonstrate benefit or is not well tolerated, clearly, are valuable. For example, short-term dual antiplatelet therapy for minor stroke and transient ischemic attack is being adopted, but with the recognition that longer-term combined therapy is not worth the increased risk of bleeding. Alternative antiplatelet choices, such as cilostazol and possibly ticagrelor, may be of benefit for refractory patients and this could affect the decision-making process. This review represents an effort to incorporate the information from more recent stroke prevention and treatment studies with information gleaned from prior studies.


Antithrombotic therapy typically is subcategorized to antiplatelet therapy and anticoagulant therapy. Antiplatelet agents include aspirin, clopidogrel, dipyridamole, ticagrelor, prasugrel, and cilostazol. Aspirin, as a monotherapy for the prevention of recurrent nonembolic stroke, is well established. In selected cases, aspirin for primary prevention of stroke is justified, as summarized in Table 1.[1,2] There have been a number of studies addressing secondary ischemic stroke prevention with the antiplatelet agents aspirin, dipyridamole, and clopidogrel either alone or in combination. The results have been somewhat contradictory, based upon clinical trials and meta-analyses. Table 2 [2–4] attempts to summarize the pertinent information provided by these previous studies. Anticoagulants include warfarin and non–vitamin K oral anticoagulants (NOACs) for prevention of stroke in higher risk patients with nonvalvular atrial fibrillation (NVAF). In previous trials, warfarin showed no benefit over aspirin in secondary stroke prevention for patients with nonembolic stroke, those with at least 50% symptomatic intracranial atherosclerosis, or those with significantly reduced cardiac ejection fraction.[5–7]

Following atherosclerotic plaque rupture, platelets play an important role in the formation of occlusive thrombus by platelet activation and aggregation.[8] The relative contribution of various platelet activation pathways (ie, adenosine diphosphate platelet, thromboxane A2 platelet, thrombin platelet, coagulation, and phosphodiesterase activity) to the development of thrombus formation in the individual patient is unknown.[9]

More recent studies, guided by information provided from earlier studies, have provided important information regarding preferable antiplatelet dosing and length of treatment. The choice of an antithrombotic agent for stroke treatment and prevention should be based on a mechanistic approach toward the ischemic threat. For example, anticoagulant therapy tends to be most applicable for a cardiogenic source of cerebral embolus, hypercoagulable condition, or cerebral venous sinus thrombosis. Small- or large-vessel thrombotic risk is more effectively managed with antiplatelet therapy; however, a combination of therapies may be in order in certain conditions. This review focuses on how to effectively navigate an evidence-based approach to optimize stroke preventive care for our patients.

We conducted a cumulative review by researching the available English-language studies. The literature review was performed using PubMed. Randomized trials and their subgroup analyses, relevant society guidelines, and meta-analyses were included. When faced with the lack of availability of controlled comparisons, we included relevant descriptive studies. The studies reviewed were published from 1996 to 2019. The mechanism of action of the antiplatelet agents and NOACs, as well as suggested dosing, are summarized in Table 3.