Secondary prevention in concurrent coronary artery, cerebrovascular, and chronic kidney disease: focus on pharmacological therapy.

Patients with coronary artery disease (CAD) commonly have varying degrees of coexisting cerebrovascular disease (CVD) and chronic kidney disease (CKD), and proper management is complicated partly because of a lack of unifying guidelines. The aim of this article is to review the current literature and propose the optimal treatment regimen in patients with all three disease states. Angiotensin-converting enzyme inhibitors (ACE-I) should be universally administered. High-dose statin therapy to reach a target low-density lipoprotein (LDL) of 70-100 mg/dL is advocated, although patients with a history of cerebral bleeding must be carefully monitored for possible recurrence. Beta-blockers are appropriate after a recent coronary event, and amlodipine or thiazide diuretics should be used after a recent stroke (within 6 months). Patients with a history of stroke (with or without coexisting CAD and CKD) should receive aspirin (75-150 mg/day) indefinitely. Clopidogrel or aspirin plus extended-release dipyridamole (ER-DP) may be prescribed in patients allergic or resistant to aspirin. If stroke is attributable to cardiogenic embolism, anticoagulation is indicated. In patients with acute coronary syndromes (ACS) (excluding ST-elevated myocardial infarct) who undergo percutaneous coronary intervention (PCI), aspirin plus clopidogrel is indicated for secondary prevention for up to 12 months. There are no data supporting the use of aspirin plus clopidogrel in patients with CKD who develop ACS. Aspirin plus clopidogrel is contraindicated for stroke prevention.

Combination antiplatelet therapy for secondary stroke prevention: enhanced efficacy or double trouble?

The evaluation of antithrombotic agents for secondary stroke prevention has focused on stroke reduction. The aim of this analysis was to focus specifically on the increase in bleeding risk. The annualized rates of total and major bleeding events in secondary stroke prevention trials of antithrombotics were assessed and cross compared. A Medline search for major randomized clinical studies with a follow-up duration of > or =1 year identified 13 studies. Pooled data sets were used to compare mean bleeding rates for aspirin (< or =325 mg/day), clopidogrel, anticoagulants (warfarin and other vitamin K antagonists), aspirin plus clopidogrel, and aspirin plus extended-release dipyridamole (ER-DP). Total bleeding occurred at mean rates of 4.8% with aspirin (< or =325 mg/day) alone, 2.9% with clopidogrel alone, 3.6% with aspirin plus ER-DP, 10.1% with aspirin plus clopidogrel, and 16.8% with anticoagulation. Major bleeding occurred at mean rates of 1% with aspirin (< or =325 mg/day) alone, 0.85% with clopidogrel, 0.93% with aspirin plus ER-DP, 1.7% with aspirin plus clopidogrel, and 2.5% with anticoagulation. In conclusion, the combination of aspirin and clopidogrel is associated with significantly greater bleeding than either aspirin (< or =325 mg/day) or clopidogrel alone. Aspirin plus ER-DP has a greater bleeding rate than clopidogrel but a lower rate than aspirin (< or =325 mg/day) alone.

New developments in anticoagulation for atrial fibrillation.

The incidence of stroke in patients with atrial fibrillation (AF) is five times greater than that in age-matched controls. Warfarin reduces this incidence by two thirds and is the most effective agent for this indication. However, despite its efficacy, warfarin management is tedious and is useful only in a subsegment of the population who needs anticoagulation and has no contraindications. Many agents are poised to replace warfarin as an effective anticoagulant for stroke prevention in AF. The direct thrombin inhibitor dabigatran is furthest along in clinical development, followed by the factor Xa inhibitors rivaroxaban and apixaban. All these agents seem effective, and none appears mechanistically superior over another. Dabigatran's advantage is that it was tested in two dosages in a phase 3 evaluation based on earlier phase 2 studies in patients with AF, whereas dosage data for the other agents were extrapolated from phase 2 programs for venous thromboembolism prevention. The vitamin K antagonist ATI-5923 offers clinical benefits similar to warfarin's, but with no or fewer drug-drug interactions, potentially greater time in therapeutic range, and probably less need for dose adjustment and laboratory monitoring. It challenges the newer mechanistic agents in efficacy and raises the bar for comparison in future head-to-head trials. Further analysis and clinical trial testing are still needed to determine whether one or all of these agents are effective anticoagulants for stroke prevention in patients with AF.