Use of cilostazol for secondary stroke prevention: an old dog with new tricks?

OBJECTIVE: To evaluate the safety and efficacy of cilostazol for secondary prevention of non-cardioembolic ischemic stroke. DATA SOURCES: PubMed and MEDLINE searches were performed (January 1970-September 2011) using the key words cilostazol, antiplatelet, aspirin, acetylsalicylic acid, secondary stroke prevention, ischemic stroke, intracerebral hemorrhage, intracranial, cerebrovascular accident, and transient ischemic attack. Additionally, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles published in English and relevant primary literature evaluating the efficacy and safety of cilostazol in the secondary prevention of atherosclerotic ischemic stroke were included. DATA SYNTHESIS: Antiplatelet therapy plays a vital role in the multifaceted approach to secondary stroke prevention. Current American Heart Association/American Stroke Association clinical guidelines for secondary stroke prevention support the use of aspirin, clopidogrel, and combination aspirin/extended-release dipyridamole. The antiplatelet, antithrombotic, and vasodilatory effects of cilostazol make it a potential alternative agent for atherosclerotic stroke prevention. Recent literature has demonstrated superior efficacy of cilostazol 100 mg twice daily for secondary stroke prevention compared to placebo and aspirin. Three clinical trials were reviewed (1 placebo-controlled, 2 aspirin-controlled), all of which were conducted in Japan or China. Cilostazol reduced the primary outcome of recurrence of stroke, with significantly fewer major bleeding events when compared to aspirin. CONCLUSIONS: Available literature suggests that cilostazol may be safer and more effective than aspirin in the secondary prevention of stroke in Asian patients. Further large-scale studies in more heterogeneous study populations are warranted to determine whether cilostazol is a viable therapeutic option for patients with a history of non-cardioembolic ischemic stroke.

Aspirin dosing for the prevention and treatment of ischemic stroke: an indication-specific review of the literature.

OBJECTIVE: To evaluate the efficacy of aspirin for the treatment and prevention of ischemic stroke and identify the minimum dose proven to be effective for each indication. DATA SOURCES: PubMed and MEDLINE searches (up to January 2010) were performed to identify primary literature, using search terms including aspirin, stroke prevention, acute ischemic stroke, acetylsalicylic acid, atrial fibrillation, myocardial infarction, and carotid endarterectomy. Additionally, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles published in English were evaluated and relevant primary literature evaluating the efficacy of aspirin in the prevention of stroke was included in this review. DATA SYNTHESIS: Antiplatelet therapy is the benchmark for the prevention of ischemic stroke. Aspirin has been proven to prevent ischemic stroke in a variety of settings. Despite the frequency at which aspirin continues to be prescribed in patients at risk of ischemic stroke, there remains confusion in clinical practice as to what minimum dose is required in various at-risk patients. A thorough review of the primary literature suggests that low-dose (50-81 mg daily) aspirin is insufficient for some indications. Acute ischemic stroke treatment requires 160-325 mg, while atrial fibrillation and carotid arterial disease require daily doses of 325 and 81-325 mg, respectively. CONCLUSIONS: Available evidence suggests that aspirin dosing must be individualized according to indication. Recommendations provided by national guidelines at times recommend lower doses of aspirin than have been proven effective. Higher doses are indicated for stroke prevention in atrial fibrillation (325 mg) and acute ischemic stroke patients (160-325 mg). Aspirin has not yet been proven effective for primary prevention of strokes in men, and a minimum dose for these patients cannot be determined from the available data.

Weight-based argatroban dosing nomogram for treatment of heparin-induced thrombocytopenia.

BACKGROUND: Manufacturer recommendations for argatroban use in the setting of heparin-induced thrombocytopenia (HIT) state that the dosage should be titrated to a goal activated partial thromboplastin time (aPTT) of 1.5-3 times the baseline aPTT. The lack of a clear dosing strategy with argatroban may result in delayed stabilization of aPTT. There are no published nomograms to guide the dosing of argatroban. OBJECTIVE: To study the anticoagulant effect and incidence of bleeding and thrombotic events in patients receiving argatroban, with doses determined using a weight-based nomogram. METHODS: Patients with suspected or documented HIT at an 800-bed teaching community hospital were prospectively treated, in a nonrandomized, nonblinded manner, with argatroban; dosage adjustments were made according to 1 of 2 variations of a dosing nomogram: standard or hepatic/critically ill. The primary outcomes were time to aPTT stabilization and percentage of patients whose aPTTs were within the therapeutic range of 45-90 seconds at 6, 12, 24, 48, 72, and 96 hours. Secondary outcomes were the percentage of patients whose aPTTs were subtherapeutic, supratherapeutic, or above the therapeutic threshold of 45 seconds at each time interval; incidence of thrombotic events; number of dosage adjustments to achieve stabilization; and number of major bleeding events. RESULTS: Fifty-one patients were prospectively treated using the standard (n = 34) and hepatic/critically ill (n = 17) nomograms. Mean time to aPTT stabilization was 16.25 hours with the standard nomogram and 27.05 hours with the hepatic/critically ill nomogram. The percentages of patients with aPTTs within the therapeutic range at each time interval were 82.4%, 82.4%, 88.2%, 96.4%, 100%, and 100% with the standard nomogram and 58.8%, 82.4%, 76.5%, 93.3%, 100%, and 90.9% with the hepatic/critically ill nomogram. There were no thrombotic events after the initiation of argatroban. Three cases of major bleeding occurred. CONCLUSIONS: The nomogram is an effective dosing tool for achieving and maintaining therapeutic levels of anticoagulation.

Drug-eluting stents: a mechanical and pharmacologic approach to coronary artery disease.

Coronary artery disease is the largest killer of men and women in the United States and costs the health care system billions of dollars annually. Several advances in both mechanical and pharmacologic treatment of coronary artery disease have occurred in recent decades. Mechanically, percutaneous coronary intervention is commonly used to treat coronary atherosclerosis. This approach has dramatically reduced both morbidity and mortality for patients with different levels of severity of coronary artery disease. However, percutaneous coronary intervention is limited by restenosis, which is an increase in growth of the intimal layer of the vessel wall. Despite the introduction of intracoronary stents and the addition of systemic pharmacotherapy, restenosis still affects a significant number of patients. The new technology of drug-eluting stents combines mechanical and pharmacologic approaches to prevent restenosis. Various types of these stents exist in different stages of development; several have been shown to prevent or reduce intimal growth after stent deployment. An understanding of how this combined mechanical and pharmacologic approach reduces restenosis requires consideration of complex issues in pathophysiology and pharmacology.