Volume 8 Issue 10, October 2011

According to a meta-analysis of five clinical trials, high-dose statin therapy is associated with increased risk of new-onset diabetes mellitus. When treating patients with excessive levels of non-HDL cholesterols despite moderate-dose statin therapy, should we prescribe a strategy known to be efficacious, but associated with safety concerns, or should we prescribe combination therapy that has no proven effects on outcomes?

The appropriateness of percutaneous coronary intervention in the US has been examined from a large database of more than 500,000 procedures. The findings are surprising and, given their potential to be applied to quality-improvement initiatives, peer-review, and possibly reimbursement decisions, the proper interpretation of these results is essential.

In this state-of-the-art Review, Drs Yousuf and Bhatt appraise landmark trials of various existing, new, and investigational antiplatelet agents. They also discuss the optimal dosing and timing of antiplatelet medications in relation to percutaneous and surgical intervention, and the challenges associated with high platelet reactivity in patients receiving dual antiplatelet therapy.

Evidence is increasing that genetic variation between patients underlies the considerable variability in their response to antiplatelet agents, and, therefore, in clinical outcomes. Drs Ahmad, Voora, and Becker review the genetic loci that seem to have a role in determining platelet response; genes that are involved in the absorption, metabolic activation, and biological activity of aspirin and clopidogrel. Finally, they discuss, in the context of ongoing clinical trials, the merits and potential dangers of using commercial genetic testing and pharmacogenetics to personalize antiplatelet therapy to individual patients.

Dual and triple antiplatelet therapies prevent ischemic events in high-risk patients with coronary artery disease or during percutaneous coronary interventions, but can cause bleeding complications. In this Review, Dr. Tantry and Dr. Gurbel discuss the utility of platelet function assays for the assessment of ischemic and bleeding risk to personalize antithrombotic combination therapies.

Drs Arnold, Cohen, and Magnuson review the published cost-effectiveness analyses of oral antiplatelet therapies for various clinical settings. This information is of increasing importance, given the enormous health-care expenditure worldwide, the advent of novel oral antiplatelet drugs, and the availability in many countries of generic clopidogrel, which is cheaper than the branded version and likely to improve its cost-effectiveness compared with alternative medications.

Antiplatelet agents effectively reduce the incidence of ischemic events associated with plaque rupture but can cause adverse effects, most notably hemorrhage. Drs Kalyanasundaram and Lincoff address key adverse effects that are associated with antiplatelet agents and discuss potential interactions between these drugs and other medications.

Patients with atrial fibrillation are at substantial risk of thromboembolism and acute ischemic stroke. Professor Gregory Lip gives his perspective on the role of using the antiplatelet agent aspirin for stroke prevention in these patients, compared with warfarin and novel anticoagulant drugs, supported by data from randomized, clinical trials and guideline recommendations.

Platelets have a central role in thrombosis, including in the pathogenesis of coronary artery disease and acute coronary syndromes. Therapies that target the platelet are, therefore, a vital component of our armamentarium against ischemic cardiovascular events. Antiplatelet therapy is a fast-moving area of research that is of interest not only to cardiologists, but also to general internists, surgeons, medical geneticists, as well as policy and decision makers. This focus issue features five Review articles and a Perspectives opinion piece, written by leading experts, which cover the current major themes in the field.