Monday, November 23, 2015

Which patients should SPRINT to a systolic goal of 120?

- Jennifer Middleton, MD, MPH

Two weeks ago, I wrote about the controversy surrounding the early closure of SPRINT. That same day, the SPRINT research group published the results of their study; for SPRINT participants, a systolic blood pressure (SBP) goal of 120, compared to 140, resulted in lower risk of several cardiovascular events including mortality, but we should proceed with caution before applying these findings to our patients.

SPRINT was a randomized controlled trial that enrolled over 9000 community-dwelling participants across 102 clinical sites in the United States. Participants had to be at least 50 years old, have a SBP between 130 and 180, and had to have "an increased risk of cardiovascular events," which the research group defined as prior cardiovascular disease (CVD) excluding stroke, chronic kidney disease (CKD), a 10-year Framingham risk score of at least 15%, or age of at least 75 years. Participants were excluded if they had diabetes or a history of a stroke. The research group provided a suggested protocol for antihypertensive medications. Participants in the intensive group had a mean SBP of 121.4 mmHg, and participants in the control group had a mean SBP of 136.2 mmHg.

The researchers' primary outcome was a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, or death from CVD, and the rate of the composite outcome was lower in the intensive group (hazard ratio 0.75 [0.64-0.89]). The number needed to treat to prevent a primary outcome event was 61. The intensive treatment group also had a higher likelihood of worsening renal function, and since the study was stopped early, it's impossible to know how likely it is that those renal effects would be irreversible. Other adverse events more common in the intensive treatment group: hypotension, syncope, and electrolyte abnormalities.

The study population may not be generalizable to your practice; it's important to note that these findings should not be extrapolated to suggest that all of our adult patients should aim for SBPs below 120. Certainly, that may be a reasonable goal for patients over the age of 50 with "an increased risk of cardiovascular events," but I suspect that many of our patients over the age of fifty with hypertension (and without diabetes) do not have those risk factors. Those patients who do meet the study parameters should still engage in patient-centered decision making regarding the risks of intensive treatment.

Dr. Lin commented on other challenges of applying this study to our patients; office blood pressure measurements, for example, are rarely done with the level of precision they were measured with in SPRINT. Aggressively adjusting medication doses based on what may be inaccurate office BP readings could potentially cause patients significant harm. Most of the time, the JNC 8 guidelines are likely to be more applicable to the patients in our offices than SPRINT's narrowly defined parameters.

Has SPRINT changed how you treat hypertension?

Tuesday, November 17, 2015

Two perspectives on the PSA screening pendulum

- Kenny Lin, MD, MPH

Two research studies published today in JAMA presented compelling evidence that the 2012 U.S. Preventive Services Task Force recommendation statement that discouraged prostate specific antigen (PSA)-based screening for prostate cancer has had a significant impact on clinical practice. In one study, researchers from the American Cancer Society used data from the Surveillance, Epidemiology, and End Results registries to document an 18% relative decrease (from 37.8% to 30.8%) from 2010 to 2013 in the percentage of men age 50 years and older who reported PSA screening in the previous 12 months. In another study, a separate team of investigators found a similar decline in the prevalence of PSA screening reported in the National Health Interview Survey in men age 50 to 74 years.

For me, and for other proponents of the view that PSA screening is not effective in reducing mortality from prostate cancer and instead leads to substantial psychological and physical harms, this reversal in practice is good news. In an editorial published in the October 15th issue of American Family Physician, Dr. Vinay Prasad argued that family physicians who reduce or discontinue their use of the PSA test for screening are on solid ground:

When it comes to PSA screening, the pendulum has swung. Not only has our understanding of the benefits and harms shifted, as reflected by a continual change in guidelines away from testing, but the burden to justify screening has also swung. For decades, critics of PSA testing have shown the many unintended repercussions of the test, cautioning that our initial widespread adoption was not justified. Moving forward, it must be the proponents of screening who shoulder the burden of proof. Their task will be to show in a future randomized study whether any PSA screening algorithm can improve survival or quality of life compared with what is now the standard of care—no routine screening. Before primary care physicians consider reintroducing the PSA test, they must have proof that it improves outcomes.

In another editorial that accompanied the JAMA studies, Dr. David Penson also described the shift in practice as a "pendulum," but took the position that until a better screening test is developed, "the PSA test can be deployed more effectively (or strategically), maximizing benefit while minimizing harm." If PSA screening does in fact save some lives, Dr. Penson argued, then extending screening intervals and focusing on men who are more likely to develop "high-risk" prostate cancer could be a better approach than not screening at all:

Certainly, physicians have been overly aggressive in their approach to prostate cancer screening and treatment during the past 2 decades, but the pendulum may be swinging back the other way. It is time to accept that prostate cancer screening is not an “all-or-none” proposition and to accelerate development of personalized screening strategies that are tailored to a man’s individual risk and preferences. By doing this, it should be possible to reach some consensus around this vexing problem and ultimately help men by stopping the swinging pendulum somewhere in the middle.

Where is your practice on the pendulum of PSA screening?

Monday, November 9, 2015

Should we SPRINT to lower blood pressure goals?

- Jennifer Middleton, MD, MPH

Just as we were all adjusting to JNC 8's blood pressure goal recommendations this past December (140/90 for most and 150/90 for adults over 60 without co-morbidities), in September the National Institutes of Health (NIH) issued a press release stating that they were halting SPRINT early due to preliminary findings that the benefits of a systolic blood pressure goal of 120 reduced the risk of cardiovascular events and mortality compared to a systolic blood pressure goal of 140.

SPRINT, the Systolic Blood Pressure Intervention Trial, aimed to prospectively enroll and then follow over 9000 patients during a four- to six-year time period to definitely answer that age-old blood pressure treatment question - how low should we go? Participants were at least 50 years of age, had a systolic blood pressure of at least 130, and had at least one additional risk factor for cardiovascular disease (chronic kidney disease, a Framingham score of at least 15%, and/or age of at least 75 years) but no prior history of cardiovascular disease. Patients with diabetes were excluded. The primary outcomes of interest were incidence of myocardial infarction (MI), acute coronary syndrome (ACS), stroke, heart failure, or cardiovascular death; they examined several other secondary outcome measures as well, including all-cause mortality and worsening chronic kidney disease.

Prior studies examining this question found no benefit for keeping systolic blood pressure under 120 but possible harm from doing so; Dr. Lin has reviewed this evidence base twice on the AFP Community Blog, in 2013 and again earlier this year. (There's also an AFP By Topic on Hypertension if you'd like to read more.) So, if the SPRINT findings are legitimate, significant changes may be quickly coming about blood pressure treatment recommendations, including the possible early retirement of JNC 8. The stakes are high.

Stopping a study early isn't necessarily a bad thing. If it's clear, for example, that one arm of the trial is causing harm, then researchers are ethically obligated to stop the study. Similarly, it can be questionable to continue a study when it's clear one treatment is far superior to the other. But stopping studies early also has risks; for example, a smaller number of participants, and/or a decreased amount of time following them, can skew results to look more impressive than they might otherwise have been.

The NIH has faced significant backlash on social media, but for more than just stopping the study early:

From Health News Review:
The big announcement about these “landmark” results doesn’t actually include any “results” from the SPRINT study. You can search the news release high and low but you’ll find nary a single statistic from the study or a number related to what the researchers found.
From The Incidental Economist:
[T]his is basically the release of conclusions without methods or even results. It hasn’t been peer reviewed. I don’t know the details....Those who conducted and funded the study can’t be the ones to judge its merit. 

From Scientific American:
Doctors and reporters only had the slick NIH press release, which glistened with words such as “landmark” and “life-changing” and provided hype but little substance. It did not emphasize that the findings may only apply to a limited segment of the population...and it did not mention potential risks associated with taking multiple blood pressure drugs...
From the PLOS blog:
If the primary outcome turns out to be rock solid and confirmed in the future, other aspects of the study...are vulnerable to the shorter intervention period. That includes knowledge about longer term and less common adverse events, and the impact on subgroups of sicker people.

When it comes to data release of clinical trial results, the NIH should set the standards. It shouldn’t be moving the bar. In this case, one could imagine some overly pushy drug company using this data release to justify releasing more data on its own product. That leads us even further into a world where science is conducted by press release. That shouldn’t be an outcome anyone wants.
Your patients may already be reading and asking about SPRINT; how are you responding? What do you want to see from SPRINT before considering a change in how you manage patients with high blood pressure?

SPRINT was just published today, and no doubt there will be a lot of discussion in the coming weeks dissecting its findings. Watch for more on this topic from the AFP Community Blog, too!

Monday, November 2, 2015

If CBT came in a pill, how much would it cost?

- Kenny Lin, MD, MPH

Family physicians commonly treat patients with depression, anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), sleep disorders, and other psychiatric conditions. Although some patients respond to medication, prescribing has significant downsides. Antidepressants can increase suicide risk, and a study that once declared medications to be superior to behavioral therapy for ADHD is now receiving a second look. In contrast, an article by Drs. Scott Coffey, Anne Banducci, and Christine Vinci in the November 1st issue of American Family Physician reported that cognitive behavior therapy (CBT) effectively relieves symptoms of all of these conditions, plus those from post-traumatic stress disorder, autism, obsessive-compulsive and tic disorders, personality disorders, and eating disorders. The article answered several common questions about CBT, including how it works:

The aim of CBT is to help patients adopt more adaptive patterns of thinking and behavior to improve function and quality of life. Treatment goals are selected collaboratively with patients to determine whether progress is being made. CBT involves three core strategies applied alone or in combination, depending on the patients' needs: (1) identifying and challenging problematic thoughts and beliefs, with the goal of helping patients develop more realistic and adaptive thoughts and beliefs, (2) scheduling pleasant activities to increase environmental reinforcement, and (3) extended exposure to unpleasant thoughts, situations, or physiologic sensations to decrease avoidance and arousal associated with anxiety-eliciting stimuli.

Finding a qualified therapist many be a challenge in some communities, and CBT usually doesn't come cheaply. However, CBT for most conditions is time-limited: one session per week for 8 to 12 weeks. At $150 to 200 per session, the typical cost for a treatment course would be between $1200 and $2400.

In comparison, a one-month supply of the newer antidepressants levomilnacipran, vortioxetine, and vilazodone (which are labeled only for treatment of major depressive disorder in adults, and are often prescribed indefinitely) cost $286, $254, and $149, respectively, at the time each drug was reviewed in AFP's STEPS (Safety, Tolerability, Effectiveness, Price, and Simplicity) department. So a newer antidepressant could cost as much or more than a course of CBT in as little as 4 to 8 months.

If CBT could somehow be packaged into a pill and patented, though, it would likely cost a lot more, given its versatility and enormous potential market share. It might become the next big blockbuster drug, like newer antiviral treatments for hepatitis C that cost between $84,000 and $156,000 for a 12-week course of treatment, or $1000 or more for a single pill. Or, since CBT has been around since the 1960s, perhaps a better benchmark would be the infamous recent example of the 62 year-old drug pyrimethamine (Daraprim), whose manufacturer raised the per-tablet price from $13.50 to $750, literally overnight.

Monday, October 26, 2015

Thickened feeds may help infant GERD but may also cause excess weight gain

- Jennifer Middleton, MD, MPH

Thickening infant feeds with rice cereal is not a new practice; my mother has told me more than once that doing so "cured" my belly woes as an infant, and she frequently recommends the same to new mothers whose babies are struggling with frequent spit-ups and fussiness. As discussed in an article in the current issue of AFP, thickening feeds is one of many remedies often tried for symptomatic gastroesophageal reflux disease (GERD) in infants prior to treating with medication, but this common remedy can be associated with excess weight gain.

This finding comes from a 2008 systematic review, cited by the AFP authorsThe included studies also demonstrated mixed results regarding the efficacy of thickening feeds, and the systematic review authors, citing a 2002 guideline, assert that "thickening agents and infant diets containing thickening agents should be used only for selected infants with failure to thrive caused by excessive nutrient losses associated with regurgitation and used only in conjunction with appropriate medical treatment and supervision."

Although the connection between excess weight gain from thickening agents in formula and weight later in life has not been studied, another 2008 systematic review did find that overweight children tend to remain overweight into adulthood. This study, recently featured in the Journal of Family Practice, included 13 studies dating back to 2001 deemed to be of high quality and looking at children's weights as far back as 1 year of age; one study also included birth weights in its cohort. Although there was significant variability in study findings, in general, children with BMIs greater than the 85th percentile were at least twice as likely to be overweight as adults. It's perhaps not an impossible stretch that minimizing infants' excess calories may benefit them later in life, especially since even what our mothers ate while pregnant can affect our risk for obesity. 

There are several other conservative measures to recommend first for infants with GERD. If you'd like to read more, there's also an AFP article from 2009 on infant formula as well as an AFP by Topic on nutrition.

Monday, October 19, 2015

RightCare Action Week and Choosing un-Wisely

- Kenny Lin, MD, MPH

This week, American Family Physician is joining clinicians, patients and organizations all over the country in supporting the Lown Institute's RightCare Action Week (#RCAW), which aims to re-focus the U.S. health system on care that is "effective, affordable, needed and wanted by well-informed patients, and especially, free of clinical decisions that are made with financial or business considerations." This goal is more far-reaching than the three year-old Choosing Wisely campaign objective of encouraging conversations between physicians and patients about potentially unnecessary care. As Dr. Jennifer Middleton mentioned in last week's post, AFP has developed several resources to help family physicians implement Choosing Wisely in their practices. On the patient side, Consumer Reports has worked with more than 20 physician groups to create and distribute educational content about specific items in the campaign.

Are these efforts to reduce unnecessary care making a measurable difference? JAMA Internal Medicine recently published a study of national insurance claims data by Dr. Alan Rosenberg and colleagues that analyzed trends among seven of the earliest Choosing Wisely "don't do" recommendations from 2010 through 2013. Although there were statistically significant declines in CT and MRI for uncomplicated headaches and cardiac testing in patients without heart conditions, use of two other inappropriate services increased (NSAID prescriptions in patients with hypertension, heart failure, or chronic kidney disease; and primary HPV testing in women younger than age 30). Since the study didn't include data from 2014 or 2015, the results could either mean that the campaign isn't working or that it was just too early to tell.

Family physicians and patients should keep in mind that even care that is recommended by evidence-based guidelines and incentivized by pay-for-performance programs can be harmful if provided to patients without regard to their individual circumstances. In an Annals of Internal Medicine essay titled "The Tyranny of Guidelines," Dr. George Sarosi described the six-year saga of Mr. O, an independent octogenarian with mild hypertension and diabetes who suffered a hip fracture and subsequent stroke as the unfortunate end result of a "relentless downhill medical care spiral fueled by interventions ... to tightly control both the blood sugar and the blood pressure."

The pitfall in this case wasn't the guidelines themselves as much as the one-size-fits-all way they were applied by "the system" to the patient. Dr. Sarosi concluded, "We need a system that rewards the physician who understands the limitations of guidelines." Indeed, a Right Care system would reward physicians who prevent patients from receiving too much medicine.