Therapeutic drug monitoring of mexiletine at a large academic medical center.

INTRODUCTION: The therapeutic trough range for mexiletine (0.8-2 mcg/mL) was largely established in the setting of arrhythmia prophylaxis following myocardial infarction. OBJECTIVE: Describe the usage patterns of serum mexiletine concentrations and the impact of these concentrations on mexiletine dosing in modern practice for ventricular arrhythmia treatment. METHODS: A single-center, retrospective analysis was conducted using the electronic medical record to identify serum mexiletine concentrations drawn between December 2004 and December 2014. The primary endpoint was the incidence of mexiletine concentrations drawn as troughs. Secondary outcomes included the incidence of mexiletine concentrations that prompted a dose change, association between adverse events and elevated concentrations, and association between baseline characteristics and mexiletine concentrations. RESULTS: A total of 237 individual concentrations were included for analysis with 109 (46.0%) drawn appropriately as trough concentrations. Only 31 (13.1%) of the 237 concentrations drawn prompted a dose change. Mexiletine was primarily used for the treatment of ventricular arrhythmias (96.2%), and 108 (45.6%) concentrations were drawn in an effort to assess efficacy. The median concentration was statistically different between patients with and without an adverse event (0.8 vs 0.7 mcg/mL, respectively; p = 0.017), but may not represent a clinical significance. Patients with hepatic dysfunction had higher median concentrations compared to those without hepatic dysfunction (1.30 vs 1.07 mcg/mL; p = 0.01). CONCLUSION: Mexiletine concentrations are often drawn at inappropriate times and seldom influence a dose change. This study suggests that routine monitoring of mexiletine concentrations may not be necessary; however, therapeutic drug monitoring may be considered in patients with hepatic dysfunction or to confirm mexiletine absorption in patients where this represents a concern.

Safety of nonsteroidal antiinflammatory drugs in patients with cardiovascular disease.

Nonsteroidal antiinflammatory drugs (NSAIDs) are used in the management of a variety of conditions, but their prevalence is likely underreported as a result of widespread availability and the perception that nonprescription therapies are unnecessary to report during medication history taking. However, NSAIDs are associated with a number of adverse effects, especially in patients with cardiovascular disease (CVD). Patients with CVD and comorbidities for which NSAIDs may provide symptomatic relief (e.g., osteoarthritis, rheumatoid arthritis) tend to be older, which places them at greater risk of harm. For these reasons, the use of NSAIDs in patients with CVD is a significant public health concern. An understanding of the risks associated with NSAIDs is critical for clinicians across practice settings. In this review, we detail the safety of NSAIDs in patients with CVD, provide recommendations on their use in specific disease states, and discuss therapeutic alternatives.

The effect of cardiovascular credentialed pharmacists on process measures and outcomes in myocardial infarction and heart failure.

OBJECTIVE: The purpose of this study was to determine if institutions with inpatient cardiovascular credentialed pharmacists exhibit improved quality measures for acute myocardial infarction (AMI) and heart failure (HF) care compared with institutions without inpatient cardiovascular credentialed pharmacists. METHODS: We conducted a multicenter, retrospective, cross-sectional, matched case-control study. Hospitals with at least one Added Qualification in Cardiology (AQCV) inpatient pharmacist were included in the case group. Each case group hospital was matched to hospitals without an AQCV pharmacist by region, number of cardiovascular discharges, and teaching hospital designation in a 1:3 ratio (case:control). The 34 AQCV hospitals were matched to 102 non-AQCV hospitals. The proportions of discharges meeting HF and AMI process of care measures and 30-day outcomes (readmission and mortality) for each hospital were determined from public data and compared between the case and control groups. RESULTS: Hospitals with AQCV pharmacists performed better on process of care measures than hospitals without AQCV pharmacists (odds ratio 1.41, 95% confidence interval 1.25-1.58, p<0.0001, p<0.001 for heterogeneity), which was mainly driven by the aspirin on discharge for AMI and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker on discharge for HF measures. No differences were observed between the groups for either readmission or mortality at 30 days. CONCLUSIONS: Hospitals that used inpatient AQCV pharmacists performed better on process of care measures than hospitals that do not use inpatient AQCV pharmacists. However, improvements in process of care performance measures observed in AQCV hospitals did not translate into improved 30-day clinical outcomes.

Evaluation of proprotein convertase subtilisin/kexin type 9: focus on potential clinical and therapeutic implications for low-density lipoprotein cholesterol lowering.

Reduction in low-density lipoprotein cholesterol (LDL-C) is associated with a decrease in coronary heart disease (CHD). Statins are currently the most effective medications for LDL-C lowering; however, there continues to be a residual risk for cardiovascular events. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease that promotes LDL receptor degradation, leading to an increase in LDL-C blood levels. Patients with PCSK9 gain-of-function mutations can have up to a 20-fold increase in associated CHD compared with patients without these mutations. Conversely, patients with PCSK9 loss-of-function mutations can have up to an 88% reduction in CHD without any deficits in neurologic or physiologic functions. PCSK9 can be modulated by current antihyperlipidemic therapies. In particular, statins lead to an increase in PCSK9, which may attenuate their full lipid-lowering effects. These attributes have made PCSK9 inhibition a desirable target for future drug therapies. Current investigational modalities inhibiting PCSK9 will also be discussed.