Beta-Blocker Use in Situations Other than Just Post-MI
Source: Bangalore S, et al. JAMA 2012; 308:1340-1349.
Current standard-of-care management of post-myocardial infarction (MI) patients includes long-term use of a beta-blocker, unless otherwise contraindicated. The length of the leash on this concept is not long, however, as prospective data confirming benefits of beta-blockers post-MI are limited to just a few years. Since clinicians have not been given concrete advice about when to stop beta-blockers, most patients are kept on beta-blockers indefinitely. Perhaps our indecisiveness is bolstered by anxieties related to the potential consequences of beta-blocker withdrawal in persons with known coronary artery disease (CAD).
In the absence of data from a randomized, prospective, long-term trial, observational data may provide some clues about the relative benefit (or lack thereof) of beta-blockers in at-risk populations. To that end, Bangalore et al report on the outcomes of three different at-risk populations from a CAD registry: post-MI patients (n = 14,043), CAD patients without history of MI (n = 12,012), and patients with CAD risk factors but no known CAD (n = 18,653). Study subjects were enrolled in 2003-2004, and followed for approximately 4 years.
Beta-blocker use was not associated with improved outcomes in any of the three subgroups, even the one group we take for granted that there will be beneficial effects: the post-MI group. In the 1990s, the term "cardioprotective" was sometimes used in reference to beta-blockers. Although this may be true for the few short years immediately after an MI where older clinical trials have found a benefit, whether such benefits persist, or extend to other at-risk groups, remains to be determined.
Long-Term Sexual and Psychological Adverse Effects of Finasteride
Source: Irwig MS. J Clin Psychiatry 2012;73:1220-1223.
Cutaneous dihydrotestosterone is etiologically involved in the development of male pattern baldness. Since finasteride blocks the conversion from testosterone to dihydrotestosterone, it is commonly used to treat the disorder. Systemic alpha-reductase inhibitors like finasteride are occasionally associated with sexual side effects, but only recently has there been the suggestion that finasteride-associated sexual side effects might persist beyond the time treatment is administered. Additionally, recent FDA labeling changes have added depression as a recognized adverse effect of finasteride treatment. Although mechanisms to explain persistent adverse sexual effects are unclear, some animal data suggest persistent diminution in penile relaxation and contraction subsequent to finasteride.
From a population of young men (mean age 31 years) with male pattern baldness (n = 91), Irwig compared men who reported sexual dysfunction for at least 3 months after finasteride cessation to men with male pattern baldness who had not used finasteride. Outcomes of interest were depression scores and suicidal thoughts.
Depression, depressive symptoms, and suicidal thoughts were all substantially more common in the former finasteride users than controls. For example, 75% of former users had a Beck Depression Inventory Score of at least 14 (confirming depression) as opposed to 10% of controls. It is important that clinicians recognize the potential for enduring adverse sexual and psychological symptoms associated with finasteride.
Novel CV Risk Markers: How Much Cluck for the Buck?
Source: The Emerging Risk Factors Collaboration. N Engl J Med 2012;367:14: 1310-1320.
The C-reactive Protein (CRP) debate has no end in sight. While traditional risk stratification tools like the Framingham Risk Score remain well established to distinguish high- and low-risk groups, the intermediate-risk group is the population in which further refinement in risk score might be helpful. Tools like CRP and fibrinogen, when applied to persons of intermediate Framingham risk, might help identify a subgroup that merits consideration for interventions like statins.
The Emerging Risk Factors Collaboration analyzed data from prospective cohort studies (n = 246,669) that included persons free of CV disease at baseline in whom CRP, fibrinogen, and components of Framingham risk score were available. Among persons with an intermediate Framingham risk score (10-20% risk of CV event over the next 10 years), the addition of either CRP or fibrinogen to risk assessment would result in reclassification of approximately 5% from intermediate to high risk. Such risk status elevation would justify statin treatment. According to current outcomes data, statin intervention in this population would prevent one CV event for every 440 intermediate-risk persons screened. Results were similar for fibrinogen.
The results obtained are "modeled" results rather than actual outcomes. CRP and fibrinogen testing are readily available. Yet, the number needed to test for avoidance of one CV event — more than 400 — is substantial. The authors do not offer an opinion on the propriety of such an investigation as CRP or fibrinogen; rather, they simply provide a metric to help quantify how much cluck for the buck one might anticipate.
Antidepressants and Auto Accidents
Source: Orriols L, et al. J Clin Psychiatry 2012;73:1088-1094.
Driving simulation tests performed with healthy, non-depressed volunteers indicate varying degrees of deleterious effect on driving skills with tricyclics (TCA) and mirtazapine, but less so with selective serotonin reuptake inhibitors (SSRIs) and venlafaxine. In direct contrast, but perhaps more pertinent to clinical medicine, trials of driving performance in depressed patients on antidepressants suggest better driving skills on SSRIs or mirtazapine than TCAs or venlafaxine. To gain more insight into the effects of antidepressant treatments on auto crashes, Orriols et al reviewed the database of accidents accrued by the French police force from 2005-2008 (n = 210,818).
Being on an antidepressant increased the odds ratio of being the at-fault driver by 34% compared with persons not on antidepressants. The immediate time period around initiation or change of treatment was particularly high risk. Subgroup analysis found the greatest risk among persons receiving serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine) and the least risk among TCA recipients (e.g., amitriptyline). Even though driving simulation tests suggest that depressed patients who are being treated perform better than untreated patients, clinicians must still exercise vigilance and should consider informing patients — especially upon initiation of or change in treatment — about driving risks.
A Different Kind of Fish Story
Source: Rizos EC, et al. JAMA 2012;308: 1024-1033.
The idea that omega-3 polyunsatu-rated fatty acids — a.k.a. fish oil — are beneficial stems from some positive randomized clinical trials. But the word "some" is limiting in the previous sentence, since some other trials do not report benefit. Rizos et al performed a systematic review and meta-analysis based on 28 studies (n = 68,680) in which adults were treated with omega-3 fatty acids for primary or secondary prevention of cardiovascular disease.
Studies were reported between 1999-2010, and averaged 2 years of follow-up, although some data went as long as 6.2 years. The majority of trials were secondary prevention trials, which — because they represent a higher risk group — might be anticipated to more readily demonstrate risk reduction.
Contrary to popular opinion, this meta-analysis was unable to confirm any positive effects of omega-3 fatty acids, whether the metric was all-cause mortality, cardiac death, sudden death, MI, or stroke. Most of the trials used combinations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), leaving open the possibility that an EPA or DHA individually might have produced different results. The authors conclude that their data support neither the routine inclusion of omega-3 fatty acids in clinical practice nor guideline recommendations that advocate their use.
Risk of Cancer in RA Patients Treated with Disease-Modifying Drugs
Source: Lopez-Olivo MA, et al. JAMA 2012;308:898-908.
In the early years of treatment experience with biologic response modifiers (BRMs) for rheumatoid arthritis (RA), concern was raised that the immune-modulating effects responsible for dramatic symptomatic improvement might also lead to increased risk for cancer. Indeed, based on excess cases of lymphoma reported in the Adverse Event Reporting System database among children and adolescents treated with BRMs, the FDA recommended a warning label for all TNF-inhibitors. Should we be worried about cancer risk in patients treated with BRMs?
Lopez-Olivo et al performed a data analysis on randomized, controlled trials (n = 63 trials) of BRM treatment in RA patients in which a BRM was compared with placebo or another traditional therapy such as methotrexate (n = 29,423). A wide variety of BRMs was included in the analysis (e.g., abatacept, adalimumab, anakinra).
This dataset was restricted to trials with at least 6 months' duration. No signal for increased risk of cancer was discerned. Although a trend for increased risk of lymphoma was found, the numbers did not achieve statistical significance. It is not possible to determine whether longer-term outcomes in relation to BRMs will be impacted by cancer risk, since this dataset is comprised of studies of 3 years' duration or less. Additionally, whether RA patients who have already suffered a cancer are at greater risk of recurrence subsequent to BRM treatment is unknown. The dramatic RA disease remission we have come to commonly see thanks to treatment with BRMs appears to be safe from an increased risk for cancer.
Beta-Blocker Use in Situations Other than Just Post-MI; Long-Term Sexual and Psychological Adverse Effects of Finasteride; Novel CV Risk Markers: How Much Cluck for the Buck?; Antidepressants and Auto Accidents; A Different Kind of Fish Story; Risk of Cancer in RA Patients Treated with Disease-Modifying DrugsYou have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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