β-Blockers (metoprolol, bisoprolol, and carvedilol) are a cornerstone of heart failure (HF) treatment. However, it is well recognized that responses to a β-blocker are variable among patients with HF. Numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to a β-blocker, including left ventricular ejection fraction improvement, survival, and hospitalization due to HF exacerbation. This review summarizes the pharmacogenetic data for β-blockers in patients with HF and discusses the potential implications of β-blocker pharmacogenetics for HF patients.

Pharmacogenomics aims to use molecular genetic markers to predict treatment outcome. Indeed within the past decade, there has been a rapid emergence of pharmacogenetic tests to aid clinicians to predict efficacy or toxicity for some drugs. Despite this major advance in therapeutic drug management there remain challenges to the appropriate use of pharmacogenetic tests. We discuss UGT1A1 pharmacogenetic testing to illustrate the knowledge gaps impeding widespread use of pharmacogenetic tests in the clinical setting.

β-Blockers are an important cardiovascular drug class, recommended as first-line treatment of numerous diseases such as heart failure, hypertension, and angina, as well as treatment after myocardial infarction. However, responses to a β-blocker are variable among patients. Results of numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to β-blockers. This review summarizes the pharmacogenetic data for β-blockers in patients with various diseases and discusses the potential implications of β-blocker pharmacogenetics in clinical practice.

Background

An altered diurnal blood pressure (BP) pattern has been linked to risk of developing heart failure (HF). We tested whether an altered diurnal BP pattern is associated with adverse outcomes (hospitalization due to HF exacerbation or death) in HF patients.

Methods and Results

One hundred eighteen HF patients were enrolled from a tertiary care HF clinic and followed for death or heart failure hospitalization for up to 4 years. 24-hour ambulatory BP was monitored. Forty patients (34%) had normal BP dipping pattern (night-day ambulatory BP ratio < 0.9), 44 (37%) had a non-dipping pattern (0.9 ≤ night-day ambulatory BP ratio < 1.0) and 34 (29%) had a reverse dipping BP pattern (night-day ambulatory BP ratio ≥ 1.0). A total of 39 patients had an adverse outcome. Adverse outcome rates were the lowest in dippers and the highest in reverse dippers (Log rank p=0.052). Predictors of adverse outcomes, selected based on log likelihood contrast, were NYHA functional class (Hazard ratio (HR) 1.96, 95% confidence interval (CI) 1.11-3.44), anemia (HR 2.50, 95% CI 1.23-5.08) and dipping status (HR 1.65, 95% CI 1.08-2.50).

Conclusions

In addition to other traditional predictors, blood pressure dipping status may be an important prognostic factor in HF.

Objectives

To establish and assess the effectiveness of a 10-week summer research program on increasing doctor of pharmacy (PharmD) students' interest in research, particularly as it related to future career choices.

Design

Survey instruments were sent to 25 participants who had completed the research program in the summer of 2004, 2005, or 2006 to assess their satisfaction with the program and its influence on their career choices after graduation.

Assessment

Respondents reported a high degree of satisfaction with the program, indicating that the program allowed them to determine their suitability for a career in research, and 55% reported their intention to pursue additional research training.

Conclusion

A brief introduction to the clinical research environment helped pharmacy students understand the clinical sciences and careers in research. The introduction increased the likelihood of students pursuing a research career path after obtaining their PharmD degree.