Annals of Long Term Care

This article is part I of a two-part series update on pharmacotherapy, and it focuses on cardiology, neurology, and psychiatry. Part II, which will be published in a subsequent issue of the Journal, will focus on infectious disease, positive Beers criteria, and pharmacist interventions.

Introduction

This article is intended to provide a review of recently published literature of relevance to the care of older adults. It focuses on studies that involve pharmacotherapeutic interventions, including both risks and benefits. It is important for clinicians to decide independently how the results of these investigations should be applied to individual patients; clinicians are encouraged to refer to the original articles to assist with making decisions and applying the results to patient care.

Cardiology

Aspirin/Dipyridamole versus Clopidogrel for Recurrent Stroke

Stroke is the leading cause of disability in adults, and approximately 1 in 5 nursing home residents have had a stroke. Aspirin reduces the risk of recurrent ischemic stroke by slightly more than 20% relative to placebo. The European Stroke Prevention Study 2 (ESPS-2)1 and the European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT)2 demonstrated a significant 21% relative risk reduction in recurrent ischemic stroke with the use of aspirin and extended-release dipyridamole as compared to aspirin alone. Studies with clopidogrel indicate a small relative risk reduction in recurrent stroke as compared to aspirin, particularly when including only patients with stroke as the qualifying event from the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial.3 Indirect comparisons suggest that the combination of aspirin/dipyridamole is better than clopidogrel for secondary stroke prevention.4 The Prevention Regimen For Effectively Avoiding Second Strokes (PRoFESS) study5 was the first to directly compare aspirin plus extended-release dipyridamole to clopidogrel for secondary (noncardioembolic) stroke prevention. The study was originally designed to look at the combination of aspirin/dipyridamole versus the combination of clopidogrel/aspirin, but with the findings of excess bleeding with this combination in the Management of ATherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischemic Attacks or Ischemic Stroke (MATCH) study,6 the clopidogrel/aspirin arm was changed to clopidogrel alone. The study enrolled more than 20,000 patients age 50 years and older (mean age, 66 yr) with ischemic stroke within 120 days. Patients were randomized to treatment with either aspirin 25 mg plus extended-release dipyridamole 200 mg twice daily or clopidogrel 75 mg once daily. The primary outcome of the study was recurrent stroke of any kind.

After a mean follow-up of 2.5 years, recurrent stroke of any kind occurred in 9.0% of the patients receiving aspirin/dipyridamole and 8.8% receiving clopidogrel (hazard ratio [HR] = 1.01; 95% confidence interval [CI], 0.92-1.11). The combined outcome of stroke, myocardial infarction (MI), or vascular death (secondary outcome) occurred in 13.1% of patients in each group. Major hemorrhagic events occurred more frequently in the aspirin/dipyridamole group, 4.1% as compared to 3.6% with clopidogrel (HR = 1.15; 95% CI, 1.00-1.32). Intracranial hemorrhage also occurred more frequently in the aspirin/dipyridamole group as compared to the clopidogrel group (1.4% vs 1.0%; HR = 1.42; 95% CI, 1.11-1.83). The combined risk of recurrent stroke or major hemorrhagic event was similar between the two treatments, 11.7% with aspirin/dipyridamole and 11.4% with clopidogrel (HR = 1.03; 95% CI, 0.95-1.11).

The PRoFESS study was designed to initially test for noninferiority of combined aspirin/dipyridamole as compared with clopidogrel. If this condition was satisfied, then the superiority of aspirin/dipyridamole as compared with clopidogrel could be tested.