Monday, March 23, 2015

Stop beta-blockers 30 days after acute MI?

- Jennifer Middleton, MD, MPH

Although prescribing a beta-blocker for patients with acute myocardial infarction (AMI) has been dogma for decades, a recent meta-analysis raises serious questions about the benefit - and harms - of continued use afterwards. The March 15 AFP reviews this study that found the benefits of beta-blockade may be limited to 30 days after AMI, and the harms may be greater than previously realized.

The authors of this large meta-analysis identified 60 studies that met their inclusion criteria (randomized controlled trials examining beta-blocker use in patients with AMI); they divided studies into pre-reperfusion-era ("early," before stents, thrombolytics, etc) and reperfusion-era ("modern era"). They found that, while in the early studies, beta-blockers conferred significant survival benefit (incident rate ratio [IRR] 0.86; 95% confidence interval [CI], 0.79-0.94), in the modern era they did not (IRR 0.98; 95% CI, 0.92-1.05). In the modern era, beta-blockers did reduce angina and reinfarction rates, but only in the first 30 days, and they increased the rates of heart failure and cardiogenic shock. The authors hypothesized that reperfusion technologies are so effective nowadays that any added benefit from beta-blockers is minimal.

COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) was by far the largest study in the modern era group; published in 2005, it had 45,000+ participants and found that metoprolol did not reduce the risk of death, reinfarction, or cardiac arrest even in the first few days after AMI. The COMMIT authors did not seem to seek to change practice widely, however, stating only that "it might generally be prudent to consider starting β-blocker therapy in hospital only when the haemodynamic condition after MI has stabilised."

Beta-blocker use following AMI is a Joint Commission Core Measure, and hospitals receive performance incentives for demonstrating that patients admitted with AMI are discharged with a beta-blocker. The American College of Cardiology and the American Heart Association's (ACC/AHA) 2013 Guideline for the Management of ST-Elevation Myocardial Infarction also recommends beta-blocker use after AMI. (The AFP By Topic on Coronary Artery Disease/Coronary Heart Disease includes many additional resources if you'd like to read more.)

The COMMIT trial sought to explore appropriate beta-blocker use immediately after AMI; the Joint Commission and ACC/AHA, similarly, describe recommended practice immediately after AMI. While this new meta-analysis potentially raises questions about beta-blocker use immediately after AMI, the bigger issue is what happens 30 days after AMI, when the risk of harm and lack of benefit are clear. The greatest challenge for family physicians managing patients following up after an AMI admission may be the decision to stop a beta-blocker. Discontinuing therapies may be difficult for physicians; many physicians continue clopidogrel (Plavix) past its recommended 12 months following drug-eluting stent placement, and many patients with asthma remain on controller treatment regimens past the 3 month time when physicians and patients should investigate stepping down that regimen. Inertia can be difficult to overcome, especially when other colleagues and specialities follow other practices. 

Will this meta-analysis change how you care for patients when they follow-up after AMI?

Monday, March 16, 2015

Advise patients to steer clear of these six orthopedic procedures

- Kenny Lin, MD, MPH

After the American Academy of Orthopaedic Surgeons (AAOS) released its Choosing Wisely list, it was criticized for selecting items that are uncommonly used or have little effect on the income of its members. In an editorial in the New England Journal of Medicine, Dr. Nancy Morden and colleagues pointed out that the five services listed by this specialty group were particularly "low impact":

The American Academy of Orthopaedic Surgeons named use of an over-the-counter supplement [glucosamine and chondroitin] as one of the top practices to question. It similarly listed two small durable-medical-equipment items and a rare, minor procedure (needle lavage for osteoarthritis of the knee). Strikingly, no major procedures — the source of orthopedic surgeons' revenue — appear on the list, though documented wide variation in elective knee replacement and arthroscopy among Medicare beneficiaries suggests that some surgeries might have been appropriate for inclusion.

At the Lown Institute's recent "Road to Right Care" conference, a group of orthopedic surgeons identified five other low-value surgical procedures that, in contrast to the AAOS list, are frequently performed at great expense in the U.S. but provide little or no benefit to patients.

1) Vertebroplasty for spinal compression fractures - in two randomized controlled trials comparing vertebroplasty to a sham procedure, there were no differences in pain or quality of life between the intervention and control groups. Risks of vertebroplasty include causing compression fractures in adjacent vertebrae, dural tears, osteomyelitis, cement migration, and radiculopathies requiring subsequent surgery.

2) Rotator cuff repair for non-traumatic tears in older adults - A randomized trial comparing physical therapy, physical therapy plus acromioplasty, and physical therapy plus acromioplasty and rotator cuff repair found no differences between the control and surgery groups after one year. About 600,000 Americans undergo rotator cuff surgery every year.

3) Clavicle fracture plating in adolescents - In adolescents with clavicle fractures that were displaced and shortened, there were no differences between nonoperative management (a sling for the affected arm) and surgery in appearance, range of motion, or participation in sports activity two years after the injury. However, 1 in 4 adolescents who underwent surgery required re-operation for surgical complications.

4) Anterior cruciate ligament (ACL) reconstruction - In young, active adults with acute ACL tears, a randomized trial comparing early (within 10 weeks of the injury) ACL reconstructive surgery plus physical rehabilitation to rehabilitation plus optional delayed reconstruction up to 2 years after the injury found similar outcomes between the groups. 61 percent of the optional reconstruction group did not require surgery. More than 100,000 ACL reconstructions are performed in the U.S. each year.

5) Partial medial meniscectomy for adults with knee osteoarthritis and no mechanical symptoms - A randomized trial found no benefit of partial meniscectomy compared to sham surgery in adults with degenerative meniscal tears and no osteoarthritis. A systematic review of 7 trials came to the same conclusion. In adults with osteoarthritis, surgery plus physical therapy was not more effective than physical therapy alone. Arthroscopic partial meniscectomy is the most commonly performed orthopedic procedure in the U.S., with 700,000 operations annually.

Finally, a randomized trial just published in JAMA suggested that another procedure whose use is increasing worldwide provides no benefits.

6) Surgery for adults with displaced proximal humerus fractures - Patients who underwent fracture fixation or humeral head replacement within 3 weeks of sustaining a displaced fracture of the proximal humerus had no better outcomes than patients assigned to nonoperative management (sling immobilization) after 2 years.

What accounts for the continued popularity of ineffective orthopedic procedures? Excessive magnetic resonance imaging (MRI) plays a role; immediate MRI is rarely indicated for common musculoskeletal conditions, and may often provide deceptive or confusing results, such as identifying meniscal tears that are unlikely to be the cause of patients' chronic knee pain. Primary care clinicians' lack of comfort with the orthopedic examination may lead to unnecessary referrals. Patients who perceive surgery to be a "quick fix" may not have the patience to stick with physical therapy and rehabilitation. And there is the inescapable reality that, necessary or not, these procedures pay well.

Monday, March 9, 2015

Helping patients with neuropathic pain

- Jennifer Middleton, MD, MPH

Neuropathic pain can be difficult to treat, and a 2014 Cochrane systematic review brings the efficacy of one treatment option into question. The March 1 issue of AFP includes a "Cochrane for Clinicians" about this review that showed minimal benefit to patients with neuropathic pain from controlled-release oxycodone (Oxycontin or "oxycodone CR").

The Cochrane authors sought to include randomized controlled trials (RCTs) of oxycodone CR for any type of neuropathic pain and/or fibromyalgia. They found only three studies that met these criteria; the studies included patients with diabetic neuropathy and postherpetic neuralgia, but none investigated fibromyalgia. Each study compared oxycodone CR with a placebo (1 used benztropine as its placebo). The Cochrane authors concluded that:
No convincing, unbiased evidence suggests that oxycodone (as oxycodone CR) is of value in treating people with painful diabetic neuropathy or postherpetic neuralgia.
A meta-analysis published in The Lancet Neurology earlier this year studied this question more broadly; they sought to include all treatments for all types of neuropathic pain. The authors categorized "strong opiates" as "a weak recommendation for use and [proposed them] as third-line" treatment behind first-line options of tricyclic antidepressants (TCAs), serotonin-noradrenaline reuptake inhibitors (SNRIs), pregabalin, and gabapentin and second-line options of tramadol and topical capsaicin patches.

Although both of these reviews come to different conclusions, it is possible that both are accurate within their self-defined parameters. Perhaps other opiates are more effective for neuropathic pain than oxycodone CR, or perhaps opiates, in general, are more effective for other types of neuropathic pain besides diabetic neuropathy and postherpetic neuralgia. Both systematic reviews agree in placing the utility of opiates for neuropathic pain below that of other medication classes. Both reviews noted the high incidence of unpleasant side effects with opiate use.

I suspect that many family physicians, though, could relate stories of patients who have benefited from oxycodone CR or other opiates for intractable neuropathic pain. These two new pieces of evidence still allow for individual physician judgment and specific patient needs; "EBM [evidence-based medicine] integrates clinical experience and patient values with the best available research information." Most patients with neuropathic pain should start with one of the first- or second-line options above, but for some patients those options may not suffice. Oxycodone and other opiates for neuropathic pain remain an option for treating patients whose symptoms have inadequately responded to other modalities, but family physicians should remain cautious with their use given the risk of adverse events.

You can read more about treating neuropathy in the AFP By Topics on Pain: Chronic and Diabetes: Type 2.

How do you care for patients with neuropathic pain? Will these systematic reviews change your management?

Tuesday, March 3, 2015

ACC/AHA and Framingham calculators overestimate cardiovascular risk

- Kenny Lin, MD, MPH

After more than a decade of titrating medications to low density lipoprotein cholesterol targets, family physicians who have transitioned to the 2013 American College of Cardiology / American Heart Association cholesterol treatment guideline now base treatment decisions on a patient's estimated 10-year risk for a cardiovascular event. Although it endorsed the ACC/AHA guideline last year, the American Academy of Family Physicians expressed concern that the guideline's new risk calculator had not been validated in contemporary U.S. populations and could potentially overestimate risk compared to the venerable Framingham calculator.

An analysis published in the Annals of Internal Medicine compared predicted risk scores from the ACC/AHA calculator and four other cardiovascular risk calculators (three derived from the Framingham Heart study) to actual cardiovascular events observed in the Multi-Ethnic Study of Atherosclerosis (MESA), a diverse cohort of adults recruited from six U.S. communities in 2000 to 2002 and followed for ten years. The authors found that both the ACC/AHA and Framingham-derived risk calculators overestimated cardiovascular risk by 37 to 154 percent in men and 8 to 67 percent in women. The Reynolds Risk Score, which includes a measurement of high-sensitivity C-reactive protein, was the most accurate at predicting cardiovascular risk in the MESA cohort, underestimating events by 3 percent overall.

A previous AFP editorial criticized the ACC/AHA guideline for recommending a statin for primary prevention in patients with 7.5 percent 10-year cardiovascular risk, noting that personal estimates of potential benefits of statin therapy relied on a calculator with a "nontrivial margin of error." Nontrivial, indeed. The Annals analysis found that men in the MESA cohort with a calculated ACC/AHA risk score of 7.5 to 10 percent had an actual event rate of only 3 percent; and just over 5 percent of women with a similar risk score experienced cardiovascular events.

Although statins appear to reduce the risk of future cardiovascular events by the same relative proportions in high-risk and low-risk populations, lower-risk patients will experience lower absolute benefits that may not be outweighed by the inconvenience, expense, and potential side effects of therapy. Compounding this problem, a recent systematic review found that most patients already overestimate treatment benefits and underestimate harms. This new analysis won't lead me to abandon cardiovascular risk calculators, but going forward (or until better ones are developed) I plan to acknowledge their lack of precision in discussions with patients, especially those on the lower end of the range of risk where statins are recommended.

Monday, February 23, 2015

Depression treatment: the evidence base from a primary care perspective

- Jennifer Middleton, MD, MPH

Most patients with depression receive treatment solely from a primary care physician. Family physicians have had to largely rely on studies and guidelines from psychiatric settings to make decisions about depression treatment, but a new systematic review, published in this month's Annals of Family Medicine, looks at this issue solely from a primary care perspective.

Linde et al performed a systematic review of treatments for depression, both both psychological and pharmacological, with one main stipulation - the participants "had to be recruited from a primary care setting." For clarity's sake, the authors divided their massive systematic review into 2 articles, one focusing on psychological treatments and one focusing on pharmacologic treatments.

In Effectiveness of Psychological Treatments for Depressive Disorders in Primary Care: Systematic Review and Meta-Analysis, the authors identified 30 studies that met inclusion criteria. There were several types of therapies in these studies: Cognitive Behavioral Therapy (CBT), "problem-solving" therapy, and/or "other face-to-face psychosocial therapies." The authors further grouped these studies by time spent between patient and therapist: face-to-face (at least 6 sessions), guided self-help (fewer than 6 face-to-face sessions), and no/minimal contact (less than 90 minutes of total face-to-face time). A handful of studies also investigated telephone counseling with either CBT or problem-solving therapy.

The authors found that all of these treatment modalities were more effective than usual care, though the effect size was greater for major depression diagnoses than for mild depression and/or dysthmia diagnoses. Interestingly, they also found that 6+ sessions of face-to-face counseling (regardless of the type of counseling) wasn't necessarily more effective than < 6 sessions and/or telephone counseling. For patients who find attending multiple counseling sessions burdensome, this meta-analysis shows that fewer sessions - or even telephone counseling - is just as effective.

In Effectiveness of Pharmacological Treatments for Depressive Disorders in Primary Care: Systematic Review and Meta-Analysis, the authors identified 66 studies that met inclusion criteria. Pharmacological treatments studied included multiple drug classes (TCAs, SSRIs, and several others). The authors found the most efficacy data for TCAs and SSRIs, though they found only "sparse" data on the "relative efficacy of anti-depressants" and could not make any determination regarding the superiority of any particular medications. They also found that TCAs are less acceptable to patients (higher rate of side effects leading to discontinuation) than SSRIs and the other newer classes of anti-depressants. The authors also commented that "there were no major differences in trials limited to patients with major depression and trials that included other depressive patients," which is helpful for family physicians who treat patients with less severe forms of depression.

Because this systematic review only included participants from a primary care setting, we can more comfortably generalize its findings to the patients we treat in our own offices. As family physicians, we need to be cautious about extrapolating too much from studies that focus on patients in a specialist's care population; by definition, these patients represent a narrower, often sicker population than the wider variety we see. This systematic review, sizable enough in scope to require 2 articles to fully describe its results, provides guidance for family physicians treating patients with mild to moderate depression as well as severe depression; it provides reassurance to patients unable to attend multiple psychotherapy sessions that even a few sessions can provide benefit. We need more studies like this one that report on participants from primary care settings.

There's an AFP By Topic on Depression and Bipolar Disorder if you'd like to read more; the collection contains articles about screening and diagnosis as well as treatment, and also has some helpful patient education materials.

Will this systematic review change the way you care for patients with depression?

Tuesday, February 17, 2015

Debating testosterone screening and therapy in older men

- Kenny Lin, MD, MPH

A good number of new patients to my practice are older men whose previous physicians have retired. More and more often, I've noticed while reviewing records from previous physicals that they have had their testosterone levels checked - usually without any documented rationale for doing so. In two Pro-Con editorials in the February 15th issue of American Family Physician, Drs. Joel Heidelbaugh and Adriane Fugh-Berman debate the merits and potential unintended consequences of screening for testosterone deficiency in older men. Dr. Heidelbaugh points out that observational studies have associated low serum testosterone levels with cardiovascular disease, cancer, impaired glucose tolerance, and metabolic syndrome. He further argues that symptoms of testosterone deficiency may be erroneously attributed to normal aging:

Although screening targets asymptomatic men, testosterone deficiency is unique because symptoms are not always well defined. This warrants casting a wider net to identify a treatable condition. Symptoms such as depression, fatigue, and inability to perform vigorous activity are related to low testosterone levels, whereas there is an inverse relationship between the number of sexual symptoms and testosterone levels.

On the other hand, Dr. Fugh-Berman raises concerns about overly aggressive marketing of testosterone supplements by pharmaceutical companies, such as online symptom surveys that seem designed to elicit "yes" answers from most older men.

These questions demonstrate how pharmaceutical companies use nonspecific symptoms to foster disease states and then convince physicians that these conditions are real. In this case, the disease state is marketed to consumers as Low T, and to physicians as late-onset hypogonadism.

Of observed associations between low testosterone levels and chronic diseases, Dr. Fugh-Berman counters that "association does not prove causation, and there is no reliable evidence that testosterone treatment improves any chronic disease."

Last September, an advisory committee to the U.S. Food and Drug Administration considered the potential cardiovascular risks for testosterone therapy and voted to exclude men with age-related testosterone declines from indications for testosterone use and to support performing additional studies to clarify cardiovascular harms. Whether clinical practice will evolve to reflect a similar level of caution is unclear. A 2013 analysis of a health insurance database showed that 25% of men prescribed a testosterone supplement never had a testosterone level checked, while other men with apparently normal levels nonetheless received therapy. At a minimum, family physicians who prescribe testosterone supplements should heed the Choosing Wisely recommendation to avoid these unsupported practices.