Indications for dual antiplatelet therapy with aspirin and clopidogrel: evidence-based recommendations for use.

OBJECTIVE: To review the literature assessing dual antiplatelet therapy with aspirin and clopidogrel and subsequently provide evidence-based recommendations for appropriate indications and length of therapy. DATA SOURCES: An English-language MEDLINE search (1950-December 2007) was conducted using the search terms antiplatelet, aspirin, thienopyridine, and clopidogrel to identify articles assessing dual antiplatelet therapy. Evaluation of references from identified trials for possible inclusion was also conducted. STUDY SELECTION AND DATA EXTRACTION: All studies that assessed treatment with the combination of aspirin and clopidogrel for any indication were included. DATA SYNTHESIS: Aspirin and clopidogrel have complementary mechanisms of action to inhibit platelet function. Indications that have been studied include coronary artery disease (CAD), atherosclerotic ischemic stroke, and atrial fibrillation. This combination has been beneficial in patients with acute coronary syndrome (ACS) with or without percutaneous coronary intervention (PCI), and in PCI patients without an acute event. There is a small but significant risk for increased bleeding with dual antiplatelet therapy for these indications. When used in patients with a history of atherosclerotic ischemic stroke or for prevention of cardioembolic stroke in patients with atrial fibrillation, this combination has been shown to increase bleeding, providing no clinical benefit, and to increase outcomes including stroke, myocardial infarction, and death, respectively. CONCLUSIONS: There is evidence to support use of aspirin in combination with clopidogrel for patients presenting with all ACS types, as well as for patients presenting with PCI for any indication. The treatment duration varies, but patients who have received stenting should receive at least 1 year of combination therapy. There is no evidence to support this combination for primary prevention of CAD or atherosclerotic ischemic events, secondary prevention of stable CAD, or prevention of cardioembolic stroke in patients with atrial fibrillation. The possible benefits of dual antiplatelet therapy also must be weighed against the risk of bleeding.

Effects of cerivastatin withdrawal on statin persistence.

BACKGROUND: Medication-taking behavior is influenced by many factors, as described by the Health Belief Model. Information on withdrawals of drugs from the market may be an example of negative external stimuli that might influence patients' decisions to persist with long-term drug therapy. OBJECTIVE: To evaluate the association between the withdrawal of cerivastatin from the market and persistence in taking all other statins in patients who recently experienced acute coronary syndrome (ACS). METHODS: Patients from a large ACS registry who responded to questions about medication use during a postdischarge telephone survey between November 2000 and February 2002 were categorized into 3 groups: pre- (November 1, 2000-April 30, 2001), peri- (May 1, 2001-August 31, 2001), and post- (September 1, 2001-February 28, 2002) cerivastatin withdrawal periods. Patients were considered persistent if, at the time of the survey, they continued to take study medication that had been prescribed at discharge. Persistence with angiotensin-converting enzyme inhibitors, aspirin, and beta-blockers was also assessed to determine whether changes in statin persistence were unique to the class or related to other medication issues that affected all classes. The Kruskal-Wallis test, with post hoc Mann-Whitney U test, was used to analyze the differences in persistence between the groups. All comparisons were considered statistically significant at p less than 0.05. RESULTS: There were no significant differences in patient characteristics between study groups. Persistence with statins decreased during the periwithdrawal period (88.4% pre vs 76.7% peri) and rebounded in the postwithdrawal period (90.8%; p = 0.007). There were no significant differences in persistence with the other drug classes. CONCLUSIONS: The temporary decline in statin persistence appeared to be associated with the withdrawal of cerivastatin, while persistence with the other study medications remained constant. Clinicians need to understand the potential effect of factors such as media attention surrounding a drug's withdrawal on patients' medication-taking behavior.

Practical application of nonrandomized research to patient care: a case study of nesiritide.

Prospective, randomized clinical trials are the gold standard for establishing cause-and-effect relationships between therapeutic interventions and specific outcomes. Unfortunately, these types of studies are not always available to evaluate important clinical end points such as mortality. Meta-analyses and observational studies are often used in an attempt to fill the gap in the literature when no prospective, randomized trials exist to answer a research question. A rapid increase in the number of published meta-analyses and observational studies has occurred in recent years. In the absence of prospective, randomized studies, it is essential for the clinician to understand the important issues involved in interpreting these other types of studies. When evaluating a meta-analysis, the clinician should assess for several different forms of bias, clinical heterogeneity, and use of appropriate methodology. When evaluating an observational study, sources of bias and confounding should be identified. If the potential for confounding is present, the methods used to minimize the impact of confounders should be evaluated for appropriateness. Mortality associated with nesiritide in the treatment of acute decompensated heart failure is a contemporary example of the use of nonrandomized research to address a research question that is unanswered by prospective, randomized studies. We review the details of a recent meta-analysis and observational evaluation of mortality associated with nesiritide and discuss the issues that are important in critical evaluation of nonrandomized study designs.