Clinical Briefs in Primary Care
September 1, 2013
Clinical Briefs in Primary Care
Evidence-based updates in primary care medicine By Louis Kuritzky, MD
Supplement to Clinical Cardiology Alert, Clinical Oncology Alert, Critical Care Alert, Hospital Medicine Alert, Infectious Disease Alert, Neurology Alert, OB/GYN Clinical Alert, Primary Care Reports.
Once-daily Tadalafil for ED: Efficacy and Safety
Source: Seftel AD, et al. Int J Impot Res 2013;25:91-98.
The utilization of pde5 inhibition (PDE5-i) for restoration of sexual function in men suffering erectile dysfunction (ED) is well established, beginning with the introduction of sildenafil (Viagra) in 1998. In the earliest years of PDE5-i treatment, regimens were typically targeted to PRN use. Almost a decade later, consideration of lower-dose, daily use of tadalafil became popular.
In this retrospective analysis, Seftel et al report on the safety and efficacy of once-daily tadalafil (TAD-QD) in doses ranging from 2.5-10.0 mg/day. The rationale for their study was to specifically define whether age impacts the efficacy of TAD-QD, since older men (age > 50 years, by their definition) might be more refractory to PDE5-i than younger men (age < 50 years). Additionally, they wished to examine the tolerability profile of TAD-QD in men with mild-moderate ED, who comprise the largest segment of men taking PDE5-i. The dataset used in this analysis included 522 men, predominantly Caucasian (> 75%), most of whom had long-standing ED and about half of whom had comorbidities of hypertension and/or diabetes.
TAD-QD more than doubled the rates of successful intercourse (from 33.4% pretreatment to 76.8% on treatment), with no discernible difference in younger men vs older men. TAD-QD was also well tolerated, with the most common adverse events — headache, dyspepsia, and myalgias — consistent with what has been seen in prior literature.
The authors conclude that TAD-QD provides substantial improvements in ED, independent of age, in men with mild-moderate ED, and is well tolerated.
Psychological Disorders: How to Give Patients What They Want and What They Need
Source: McHugh RK, et al. J Clin Psych 2013;74:595-602.
Commonplace psychiatric disorders such as anxiety, depression, posttraumatic stress disorder, and obsessive compulsive disorder respond to pharmacotherapy, psychotherapy, and their combination. The National Comorbidity Survey Replication data have indicated that persons with psychiatric disorders often do not use mental health services because of perceived barriers to access (e.g., cost, logistics). Identification of patient preferences for treatment is of value not only for patient satisfaction, but also because clinical outcomes are better among patients who receive their treatment of choice. Additionally, patients who are concordant with the therapeutic choice have been reported to be more adherent with therapy.
Data from 34 clinical trials (total patient n = 90,071) were assessed by meta-analysis. Overall, patients expressed a preference for psychological treatment over pharmacotherapy by 3:1. This preference was consistent irrespective of the underlying psychiatric disorder studied, including depression, anxiety, and hypochondriasis. The availability of additional alternatives (e.g., combination treatment, watchful waiting, no treatment) did not affect the balance of patient preferences.
At the current time, treatment of patients with mild-moderate psychiatric disorders with pharmacotherapy vs psychotherapy is at equipoise. Hence, identification of patient preference — in situations where outcomes are similar between choices — is a sensible direction to take. This large literature base suggests that as many as 75% of patients with commonplace psychiatric issues prefer psychological treatment to pharmacotherapy. Although pharmacotherapy is often a more expedient path for primary care clinicians, the importance of addressing patient preference is well highlighted by this study.
Reducing Stroke Risk After TIA or Minor Ischemic Stroke
Source: Wang Y, et al. N Engl J Med 2013;369:11-19.
The very large clopidogrel for high Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) clinical trial concluded that dual antiplatelet therapy in stable ambulatory vasculopathic patients who are distant — at least 1 year post-MI, post-stroke — from their vascular event does not meaningfully reduce risk over monotherapy, and is associated with increased risk of bleeding. As convincing as this dataset is, it only addresses populations who are distant from their vascular event, rather than subjects who are in the higher risk period immediately following an acute event.
The Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial enrolled — within 24 hours of onset — Chinese subjects (n = 5170) who had sustained a minor ischemic stroke or transient ischemic attack (TIA). Subjects were randomized to treatment (double-blind) with low-dose aspirin (75 mg/d-300 mg/d) plus clopidogrel (300 mg on day 1, then 75 mg/d [CLO + ASA]) or low-dose aspirin plus placebo (ASA). The primary outcome was incidence of stroke (ischemic or hemorrhagic) over 90 days of follow-up.
CLO + ASA was associated with a 32% reduction in risk for stroke compared to aspirin alone. Risk for central nervous system hemorrhage was no different in the CLO + ASA group than ASA alone. In the immediate post-TIA/minor stroke period (up to 90 days), dual antiplatelet treatment meaningfully reduced risk without increasing bleeding.
Long-term Mortality Among Adults with Asthma
Source: Ali Z, et al. Chest 2013;143: 1649-1655.
In the united states, approximately 5000 persons die each year from asthma. Counterintuitively, deaths in asthma are equally distributed among patients identified as mild, moderate, and severe. Studies of patients with near-fatal asthma have found a decreased sensitivity to hypoxia, hypercapnea, and resistance loading, suggesting that persons destined to succumb to asthma may not fully appreciate the severity of their symptoms, placing them at risk for unrecognized deterioration.
The long-term picture of causes of death in asthmatic adults was the subject of this report by Ali et al. The authors drew on a population of asthmatics enrolled from 1974-1990 in Denmark at their first visit for asthma to the Copenhagen Frederiksbergy Hospital Allergy and Chest Clinic, having been referred there by their general practitioners in the community. More than 75% of the enrollees were younger than 50 years of age at the time of enrollment.
Compared with age- and sex-matched control subjects, all-cause mortality in asthmatic subjects was essentially doubled over 25 years of follow-up. The excess risk for death was primarily due to obstructive airways disease, but was unrelated to smoking status (hence deaths were predominantly not related to chronic obstructive pulmonary disease). Degree of peripheral blood eosinophilia correlated with mortality, intimating that unmitigated atopy in asthmatics may contribute to adverse outcomes.
Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes
Source: The Look AHEAD Research Group. N Engl J Med 2013;369:145-154.
Type 2 diabetes (dm2) is characterized by increased risk for cardiovascular (CV) events, which are not only more frequent but also more severe than similar events in non-diabetics. Most DM2 patients in America are overweight or obese. Weight loss and exercise have been shown to improve glucose control, lipids, blood pressure, and progression from pre-diabetes to diabetes, but no large clinical trials have confirmed risk reduction for CV events attributable to lifestyle intervention.
The Look AHEAD trial randomized overweight or obese DM2 patients (n = 5145) to intensive lifestyle or control (the control group still received education and support in reference to care of their DM2). The goal of intensive lifestyle was to reduce weight by at least 7% and participate in at least 175 minutes/week of moderate-intensity physical activity.
The trial was originally intended to go on for 13.5 years, but was stopped early (at 9.6 years) because futility analysis demonstrated no likely possible benefit of the intensive intervention for CV events compared to controls, despite greater weight loss and improved glycemic control attained in the intensive lifestyle group.
Intensive lifestyle intervention in DM2 improves glycemic indices and body mass index, but does not appear to improve CV risk.
New Hope for Hepatitis C Patients
Source: Jacobson IM, et al. N Engl J Med 2013;368:1867-1877.
The centers for disease control and Prevention has recently advocated routine screening for hepatitis C (HEP-C) among all adults born from 1945-1965. These recommendations stem from the observation of the ever-growing burden of persons with HEP-C and its consequences who do not necessarily endorse traditionally recognized risk factors for HEP-C such as intravenous drug use, tattoos, etc. Early identification allows for potential cure of HEP-C, since as many as 80% of previously untreated individuals can achieve sustained virologic response with "standard" antiviral regimens (e.g., ribaviron plus interferon).
This does, however, leave a substantial minority of HEP-C patients (those who fail treatment, who are intolerant of treatment, or who have contraindications to it) at risk. Fortunately sofosbuvir, a new polymerase inhibitor, has demonstrated high efficacy in both untreated HEP-C and treatment failures.
Sofosbuvir was studied in two populations of HEP-C genotype 2 or 3: persons with contraindications to interferon and cases that had not responded to interferon therapy. Sustained virologic response was seen in 78% of subjects with interferon contraindications, and (at 16 weeks) 73% of interferon failures. Sofosbuvir was generally well tolerated, with a discontinuation rate of 1-2%.
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