• Top POEMs of 2018

    American Family Physician's annual collection of the top 20 research studies for primary care addresses a variety of topics with the potential to change practice. A group of primary care clinicians with expertise in evidence-based practice rated these studies highly based on their clinical relevance, validity, and reported outcomes. Known as POEMs, for patient-oriented evidence that matters, the studies are organized by topic and summarized with a clinical question, bottom-line answer, and brief discussion.

    See related AFP article, "Top 20 Research Studies of 2018 for Primary Care Physicians."

    Top POEMs Collection

    Hypertension

    Ambulatory Blood Pressure Important for Decision-Making About Treatment

    Clinical question
    What is a better predictor of mortality: ambulatory or office-based measurement of blood pressure?

    Bottom line
    This study supports the guidelines recommending that treatment decisions be based on ambulatory blood pressure (BP) measurements rather than in-office BP results. The difference between the 2 measurements in this cohort was 19/11 mm Hg, which is enough to change the decision to prescribe a medication at all, or to add a second or third medication. (LOE = 2b)

    Reference
    Banegas JR, Ruilope LM, de la Sierra A, et al. Relationship between clinic and ambulatory blood-pressure measurements and mortality. N Engl J Med 2018;378:1509-1520.

    Study design: Cohort (prospective)

    Funding source: Government

    Setting: Population-based

    Synopsis
    How we measure things matters: For example, nonfasting lipid levels are a better predictor of mortality than fasting lipid levels. Recent guidelines for hypertension, including from the U.S. Preventive Services Task Force, have emphasized the need to confirm elevated BPs in most patients using some form of ambulatory BP monitoring. This study used data from a large Spanish hypertension registry to look at the association between clinic BPs, ambulatory blood BPs, and mortality. The registry includes adults with an indication for ambulatory BP monitoring, such as suspected white coat hypertension, borderline or labile hypertension, or hypertension refractory to treatment. The registry supplies data on clinic BPs, measured by automated devices after 5 minutes of seated rest, and 24-hour ambulatory BP measurements. These data were linked to national vital statistics databases to determine cardiovascular and all-cause mortality. The analysis was adjusted for comorbidities, age, sex, tobacco use, and body mass index. The mean age of patients was 58 years, 58% were male, and only 11% had a diagnosis of cardiovascular disease. During a median 4.7 year follow-up, there were a total of 3808 deaths including 1295 cardiovascular deaths. The mean ambulatory BP was 129/76, compared with 148/87 in the clinic. Recall, the clinic BPs were measured by an automated device after 5 minutes of rest, yet they were still far higher than the ambulatory measurements. In the fully adjusted model that adjusted for clinic BPs, the hazard ratio for all-cause mortality was 1.58 (95% CI 1.56 - 1.60) for the ambulatory systolic BP versus 1.02 (1.00 - 1.04) for the clinic systolic BP adjusted for ambulatory BP. A similar pattern was seen for diastolic BPs. The inflection point for an increase in both cardiovascular and all-cause mortality is at a systolic BP of 140 to 160. Mortality was not increased in patients with controlled hypertension, but was increased in those with both white-coat and masked (normal in clinic, abnormal at home) hypertension.

    Mark H. Ebell, MD, MS
    Professor
    University of Georgia
    Athens, GA

    A Single Blood Pressure Measurement Is Often Falsely Elevated

    Clinical question
    Is a single office blood pressure measurement reliable to assess hypertension?

    Bottom line
    Don't rely on a single blood pressure measurement. The first blood pressure reading taken during an office visit will be substantially different than subsequent readings in almost half of typical patients, and if relied upon will result in 1 in 8 patients being falsely labeled as hypertensive. (LOE = 1b)

    Reference
    Burkhard T, Mayr M, Winterhalder C, Leonardi L, Eckstein J, Vischer AS. Reliability of single office blood pressure measurements. Heart 2018;104(14):1173-1179.

    Study design: Cross-sectional

    Funding source: Self-funded or unfunded

    Setting: Outpatient (primary care)

    Synopsis
    The authors enrolled 1000 consecutive patients who presented for internal medicine, obstetric, or gynecologic care, though only 802 patients completed the study. Each patient, after 5 minutes of rest, had 4 consecutive blood pressure measurements, 2 minutes apart, by 1 of 13 trained physicians. The first systolic blood pressure was more than 10 mm Hg higher than the mean of subsequent measurements in 23.9% of patients; in total, 45.9% of patients had a systolic difference of more than 5 mm Hg. Similarly, diastolic blood pressures were more than 10 mm Hg different in 4.4% of patients; in total, 21.6% of patients had a difference of more than 5 mm Hg. More important, hypertension would have been diagnosed in error in 1 in 8 patients (12%) if only the first measurement had been obtained, and 2% of patients would have had their hypertension undiagnosed by the single measurement.

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    Alex Shreiber, PharmD

    Second Blood Pressure Reading Drops 8 mm Hg from Initial High Reading

    Clinical question
    In patients with high blood pressure, does a second reading show lower results?

    Bottom line
    If you're not rechecking high blood pressures, you should. In fact, set your electronic health record to remind you to do it. In this large study, when reminded, clinicians rechecked elevated blood pressures 83% of the time, finding a median drop in blood pressure of 8 mm Hg during the same visit. That drop is equivalent to a typical reduction in blood pressure with pharmacologic treatment over time, and resulted in one-third fewer patients being labeled with high blood pressure at that visit. (LOE = 2b)

    Reference
    Einstadter D, Bolen SD, Misak JE, Bar-Shain DS, Cebul RD. Association of repeated measurements with blood pressure control in primary care. JAMA Intern Med 2018 doi:10.1001/jamainternmed.2018.0315. [Epub ahead of print]

    Study design: Cohort (prospective)

    Funding source: Government

    Setting: Outpatient (primary care)

    Synopsis
    This study was conducted in primary care offices of a large US health system. The electronic health record was set to remind clinicians to recheck the blood pressure of a patient when a value greater than 140/90 mm Hg was documented. The reminder worked: Clinicians rechecked high blood pressures 83% of the time. The authors then evaluated the effect of this simple intervention on 38,260 patients, average age 61 years, 39% of whom had a high initial reading. With repeated measurement, the median drop in blood pressure was 8 mm Hg (interquartile range 2 mm Hg - 17 mm Hg) and 36% of patients no longer had a blood pressure of 140/90 mm Hg or higher.

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    Systolic Blood Pressure at Least 140 mm Hg Best Place to Begin Treatment

    Clinical question
    At what systolic blood pressure should we begin treatment for the most benefit?

    Bottom line
    Beginning antihypertensive treatment when the systolic blood pressure (SBP) is greater than 140 mm Hg delays death and prevents major cardiovascular events in some people without pre-existing heart disease; in patients with existing heart disease it prevents further events, but does not extend life. These results may appear to conflict with those from SPRINT trial, which found benefit with lowering SBP to below 120 mm Hg. However, the SPRINT investigators measured blood pressure using automated devices which give readings 10 mm Hg to 20 mm Hg lower than typical office measurements. So, the goal of less than 120 mm Hg in the SPRINT study is likely to be very similar to the goal of less than 140 mm Hg in this study. (LOE = 1a)

    Reference
    Brunstrom M, Carlberg B. Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels. A systematic review and meta-analysis. JAMA Intern Med 2018;178(1):28-36.

    Study design: Meta-analysis (randomized controlled trials)

    Funding source: Foundation

    Setting: Various (meta-analysis)

    Synopsis
    The authors followed PRISMA guidelines to search 3 databases, including Cochrane CENTRAL, as well as reference lists of identified studies to identify all randomized trials with at least 1000 patient-years of follow-up that compared drug treatment with placebo or compared blood pressure targets against one another. Two researchers independently extracted the data and assessed the quality of the research (more than two-thirds of the studies had a low risk of bias). They identified 74 studies enrolling 306,273 patients (60.1% men, average age 63.6 years). In patients without pre-existing heart disease (ie, primary prevention), lowering SBP that was initially greater than 140 mm Hg decreased the risk of death (relative risk [RR] = .93, 95% CI -.88 to 1.0 if SBP > 160 mm Hg; RR = 0.87, .75 to 1.00 if SBP 140 - 159 mm Hg) and major cardiovascular events (RR = .78, .7 to .87 if > 160 mm Hg; RR = .88, .8 - .96 if 140 - 159 mm Hg). Treating SBP that was initially less than 140 mm Hg did not affect morbidity or mortality. In patients with previous coronary heart disease and a mean SBP of 138 mm Hg, treatment reduced the risk for further major cardiovascular events (RR = .9; .84 to .97), but did not extend life. There was a high degree of heterogeneity among these trial results, reducing our confidence in the results. There was some evidence of publication bias in studies that evaluated the effect on major cardiovascular events, meaning that studies failing to show a difference in outcomes were not published.

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    Lower Systolic BP During Antihypertensive Treatment Associated with More Deaths In the Elderly

    Clinical question
    Is lower systolic blood pressure associated with better outcomes in elderly patients who take antihypertension medications?

    Bottom line
    In this small cohort study of patients older than 85 years, lower systolic blood pressure during treatment with antihypertensive medications is associated with higher death rates and greater cognitive decline. (LOE = 1b-)

    Reference
    Streit S, Poortvliet RKE, Gussekloo J. Lower blood pressure during antihypertensive treatment is associated with higher all-cause mortality and accelerated cognitive decline in the oldest-old data from the Leiden 85-plus Study. Age Ageing 2018;47(4):545-550.

    Study design: Cohort (prospective)

    Funding source: Government

    Setting: Population-based

    Synopsis
    Are you tired of all the ping-ponging, guideline-based blood pressure targets? Unfortunately, this study won't improve your fatigue. These researchers assembled a cohort of 570 residents of Leiden in the Netherlands who turned 85 years of age between 1997 and 1999. They excluded people who died within 3 months of enrollment and those who had no blood pressure measurement at baseline. At baseline, and periodically over the course of 5 years of follow up, the researchers collected all kinds of information: sociodemographics, medical diagnoses, medications, mental status, grip strength (as a proxy for frailty), blood pressure, and so forth. They assessed the main outcome—death from any cause—by using municipal records. Slightly fewer than half of the residents (44%) took antihypertensive medications at baseline; these patients were more likely to have other cardiovascular disorders than those not taking antihypertensive medications (62% vs 36%). During the 5 years of follow-up, 263 (46%) participants died. For those taking antihypertensive medications, all-cause mortality was significantly higher with decreasing systolic blood pressure (hazard ratio 1.29 per 10 mmHg lower systolic blood pressure; 95% CI 1.15 - 1.46). For the residents who were not taking antihypertensive medications, there was no significant correlation between systolic blood pressure and all-cause mortality. Additionally, the patients taking antihypertensives had more rapid cognitive decline with lower systolic blood pressure. Although many explanations for the differences in treatment thresholds are given by the various guidelines, one is how we value clinical trial versus observational data: The guidelines that promulgate lower blood pressure targets are more likely to value observational data. The data from this study are subject to many of the biases inherent in cohort studies, but they should moderate the enthusiasm for lower blood pressure targets.

    Henry C. Barry, MD, MS
    Professor
    Michigan State University
    East Lansing, MI

    Infection

    Short Courses of Antibiotics As Effective As Longer Courses for Outpatient Infections

    Clinical question
    Are short courses of antibiotics as effective as longer courses for common outpatient infections?

    Bottom line
    Just about every time someone asks "Can I get away with a shorter course of antibiotics," the answer is "Yes, you can." Shorter courses reduce cost, and may reduce the likelihood of adverse events. (LOE = 1a)

    Reference
    Dawson-Hahn EE, Mickan S, Onakpoya I, et al. Short-course versus long-course oral antibiotic treatment for infections treated in outpatient settings: a review of systematic reviews. Fam Pract 2017;34(5):511-519.

    Study design: Meta-analysis (randomized controlled trials)

    Funding source: Government

    Setting: Various (meta-analysis)

    Synopsis
    This is a relatively new kind of study: a systematic review of systematic reviews, also called a systematic overview. The authors searched 5 databases and identified 9 systematic reviews that compared the duration of antibiotic therapies for a common outpatient infection. The reviews included between 2 studies and 17 studies, with a total of between 395 and 5763 patients. The best studied conditions were urinary tract infection (UTI), sinusitis, and community-acquired pneumonia (CAP). The authors found that, in children, 5 to 7 days was as good as 10 days for strep pharyngitis; 3 days was as good as 5 days for CAP; more than 2 days was as good as 7 or more days for otitis media, and 2 to 4 days was as good as 7 to 14 days for UTI. In adults, 3 to 7 days was as good as 6 to 10 days for acute bacterial sinusitis, 3 days was as good as 5 or more days for uncomplicated UTI in nonpregnant women, and 7 to 14 days was as good as 14 to 42 days for acute pyelonephritis. The authors also found that 7 or fewer days was as good as more than 7 days for CAP, and 3 to 6 days was as effective as 7 to 14 days for UTI in older women. There was some evidence that shorter courses resulted in fewer adverse events when treating acute otitis media in children and acute sinusitis in adults.

    Mark H. Ebell, MD, MS
    Professor
    University of Georgia
    Athens, GA

    Nothing Works for Cough Associated with the Common Cold

    Clinical question
    Which treatments are safe and effective for cough associated with the common cold?

    Bottom line
    Suck it up: you have a cold, it'll get better. That seems to be the bottom line from this expert panel report, which found little evidence of benefit for most commonly used medications for the self-limited condition of the common cold. Ultimately, physicians must often act in the absence of good evidence, and it is reasonable to recommend safe options for the treatment of cough even if the optimal evidence is not available. These treatments include honey, dextromethorphan, and possibly zinc for patients with cough. (LOE = 1a-)

    Reference
    Malesker MA, Callahan-Lyon P, Ireland B, Irwin RS, CHEST Expert Cough Panel. Pharmacologic and nonpharmacologic treatment for acute cough associated with the common cold: CHEST Expert Panel Report. Chest 2017;152(5):1021-1037.

    Study design: Systematic review

    Funding source: Other

    Setting: Other

    Synopsis
    Although billed as an "expert panel report," this was really a hybrid of a systematic review, an "umbrella review" of published systematic reviews, and a guideline. The authors did a careful literature search, identifying randomized controlled trials (RCTs), as well as previous systematic reviews, and updated the searches of the published systematic reviews. They included any randomized trial of any treatment for acute cough in patients with an upper respiratory tract infection or the common cold. Although the authors said they looked for studies of herbal supplements, and included a few of them, the Cochrane Review of pelargonium sidioides was not included.The studies were assessed for quality using the Cochrane Risk of Bias tool for RCTs and a similar tool for systematic reviews, and excluded any studies at high risk of bias. The expert panel reviewed the evidence, then made 4 key recommendations. They concluded that there was insufficient evidence to make a recommendation for acetylcysteine or carbocysteine, and they recommend against the use of over-the-counter cold medications available in the United States to treat cough. They also recommend against the use of nonsteroidal anti-inflammatory drugs, given their lack of proven efficacy and, of course, their potential harms. Honey gets some love: The authors conclude that for children older than 1 year and adolescents with cough, honey is probably better than placebo or diphenhydramine, but not any better than dextromethorphan (…which they just told us not to use). Zinc had mixed evidence, and some of the benefit was attributed to underlying zinc deficiency in some countries, as well as the difficulty in masking patients to the treatment. In the end, the panel did not recommend the use of zinc. They also found no good evidence supporting or refuting the benefits of over-the-counter antitussives, expectorants, mucolytics, antihistamines, or combinations of any of them. Finally, the panel recommends against using codeine-containing medications in children.

    Mark H. Ebell, MD, MS
    Professor
    University of Georgia
    Athens, GA

    Subacute Cough Treatments: Limited Data, Unclear Benefits

    Clinical question

    Which treatments for subacute cough are effective?

    Bottom line
    The available evidence for treating patients with subacute cough is limited and fails to demonstrate meaningful improvements. (LOE = 1a-)

    Reference
    Speich B, Thomer A, Aghlmandi S, Ewald H, Zeller A, Hemkens LG. Treatments for subacute cough in primary care: systematic review and meta-analyses of randomised clinical trials. Br J Gen Pract 2018;68(675):e694-e702.

    Study design: Systematic review

    Funding source: Foundation

    Setting: Outpatient (any)

    Synopsis

    Subacute cough—defined as cough that lasts no more than 8 weeks, is not accompanied by radiographic evidence of pneumonia, and resolves on its own—is fairly common, especially following respiratory infections. These authors systematically searched PubMed and the Cochrane Central Register of Clinical Trials to identify randomized trials published in English that evaluated various treatments in patients at least 16 years old with subacute cough. The studies could have included drug and nondrug treatments, but excluded Chinese or Asian herbal remedies. They also hand-searched reference lists of included studies, relevant systematic reviews, and clinical practice guidelines. Two authors independently assessed the inclusion of studies and the risk of bias for each study. They used a third author to resolve disagreements. They were able to find only 6 trials with between 30 and 276 patients (median = 96). The studies included montelukast, inhaled albuterol (also called salbutamol) plus ipratropium, gelatin, inhaled corticosteroids (fluticasone propionate, budesonide), and opioids. Five of the studies compared treatment with placebo, one with usual care. Overall, the reporting of the studies made assessing their risk of bias difficult. The studies used a variety of cough severity scores. Although the authors identified statistically significant improvement of cough scores with some interventions, none were clinically important. Additionally, some interventions provided short-term improvement but none were sustained beyond 2 weeks. Five studies reported on adverse effects of treatment, which were mostly mild and ranged from 0% to 40% for active treatment and 0% to 27% for placebo or usual care.

    Henry C. Barry, MD, MS
    Professor
    Michigan State University
    East Lansing, MI

    Five-Day Nitrofurantoin Superior to Single-Dose Fosfomycin for Women with Uncomplicated UTI

    Clinical question
    Is a 5-day course of nitrofurantoin as effective as single-dose fosfomycin in the treatment of women with uncomplicated lower urinary tract infection?

    Bottom line
    A 5-day course of nitrofurantoin is significantly more likely than single-dose fosfomycin to achieve both clinical and microbiologic resolution of uncomplicated lower urinary tract infections (UTIs) in otherwise healthy adult women. (LOE = 1b-)

    Reference
    Huttner A, Kowalczyk A, Turjeman A, et al. Effect of 5-day nitrofurantoin vs single-dose fosfomycin on clinical resolution of uncomplicated lower urinary tract infection in women. A randomized clinical trial. JAMA 2018;319(17):1781-1789.

    Study design: Randomized controlled trial (single-blinded)

    Funding source: Government

    Allocation: Concealed

    Setting: Outpatient (primary care)

    Synopsis
    These investigators identified women,18 years and older, who presented with at least 1 symptom of acute lower UTI, including dysuria, urgency, frequency, or suprapubic tenderness, and a urine dipstick result positive for either nitrites or leukocyte esterase. Exclusion criteria included pregnancy, lactation, suspected upper UTI, antibiotic treatment for a UTI in the previous 4 weeks, indwelling urinary catheter, or immunosuppression. The patients randomly received (concealed allocation assignment) either oral nitrofurantoin, 100 mg 3 times daily for 5 days, or a single 3-g dose of oral fosfomycin. Although patients were directly aware of treatment group assignment (open-label), individuals masked to treatment group assignment assessed all outcomes, including the primary outcome of clinical resolution of all symptoms and signs of UTI without prior failure. Complete follow-up occurred for 92% of patients at 28 days. Using both intention-to-treat and per-protocol analyses, significantly more patients in the nitrofurantoin group achieved clinical resolution than in the fosfomycin group (70% vs 58%; number needed to treat = 8.1; 95% CI 4.8 - 25.9). Similarly, microbiologic resolution based on a negative urine culture occurred significantly more often in patients treated with nitrofurantoin. No significant group differences occurred in the development of pyelonephritis or urosepsis. Adverse events were mild and occurred similarly in both treatment groups.

    David C. Slawson, MD
    Professor and Vice Chair of Family Medicine for Education and Scholarship
    Atrium Health
    Professor of Family Medicine, UNC Chapel Hill
    Charlotte, NC

    Increased Water Intake Decreases UTI Recurrence in Women

    Clinical question
    Does increased water intake decrease urinary tract infection recurrence in women?

    Bottom line
    Drinking an additional 1.5 liters per day of water halved the recurrence of urinary tract infection (UTI) in women with a history of at least 3 episodes per year. (LOE = 1b-)

    Reference
    Hooton TM, Vecchio M, Iroz A, et al. Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections. JAMA Intern Med 2018;178(11):1509-1515.

    Study design:Randomized controlled trial (nonblinded)

    Funding source: Industry

    Allocation: Concealed

    Setting: Outpatient (any)

    Synopsis
    These researchers enrolled 140 premenopausal women with 3 or more documented episodes of lower UTI but not pyelonephritis in the previous year. In this unblinded study (What is a suitable placebo for water?), the women were randomized, using concealed allocation, to continue their normal levels of water intake or to drink an additional 1.5 liters (3 bottles) of Evian-branded water daily for 12 months, which participants, on average, were able to maintain. Women in the extra water group had approximately half as many infections as the usual intake group, an average 1.7 documented UTIs over the year as compared with an average 3.2 infections in the usual intake group (P < .001). All that extra water resulted in an additional 2 more trips to the bathroom every day, on average, than the usual intake group.

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    Alex Schreiber, PhamD

    Pain Management

    Nonopiods Equivalent to Opioids for Severe Chronic Back, Hip, or Knee Pain with Fewer Adverse Outcomes

    Clinical question
    Are opioid medications preferable for improving pain-related function in adults with severe chronic back, hip, or knee pain?

    Bottom line
    Nonopioid medications were at least as effective as opioid medications for improving pain-related function over 12 months in adults with severe chronic back pain or knee or hip osteoarthritis pain. The evidence that opioids are NOT superior to nonopioid medications for both chronic and acute pain continues to mount. The tough job will be getting patients and their clinicians to believe the evidence. (LOE = 1b)

    Reference
    Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain. The SPACE randomized clinical trial. JAMA 2018;319(9):872-882.

    Study design: Randomized controlled trial (double-blinded)

    Funding source: Government

    Allocation: Concealed

    Setting: Outpatient (primary care)

    Synopsis
    For decades both patients and clinicians have believed/assumed that opioids are superior for reducing pain and improving function in patients with severe chronic pain. These investigators identified adults with chronic back pain or hip or knee osteoarthritis pain that rated at least moderately severe on a standard pain rating scale and persisted every day for at least 6 months. Patients with severe depression or posttraumatic stress disorder symptoms were NOT excluded. Study participants (N = 240) randomly received assignment (concealed allocation) to either an opioid or nonopioid pain management group. Patients in the opioid group started taking immediate release (IR) oral opioids with escalation to sustained-released (SA) oral opioids and finally to transdermal fentanyl, if needed. Titration continued to a maximum daily dose of 100 morphine-equivalent milligrams. Patients in the nonopioid medication group started with acetaminophen and nonsteroidal anti-inflammatory drugs, with step-up as needed to adjuvant oral medications (eg, amitriptyline, gabapentin) and topical analgesics (eg, capsaicin, lidocaine), and finally to pregabalin, duloxetine, and/or tramadol, if needed. Medication adherence was monitored by urine drug testing and with regular checking of a state prescription monitoring program. Individuals who assessed outcomes remained masked to treatment group assignment. Follow-up rates ranged from 90% to 98% of patients at 12 months. Mean age was 58.3 years (range = 21 – 80 years) and 13% were women. Using intention-to-treat analyses, there was no significant group difference in pain-related function over 12 months based on standard rating scales. Overall, pain intensity was significantly better in the nonopioid group over 12 months. Drop-outs due to adverse medication-related symptoms were significantly higher in the opioid group than in the nonopioid group (19% vs 8%, respectively). No deaths or diversions were detected in either group. Tramadol was dispensed to 11% of patients in the nonopioid group over the 12 months of follow-up.

    David C. Slawson, MD
    Professor and Vice Chair of Family Medicine for Education and Scholarship
    Atrium Health
    Professor of Family Medicine, UNC Chapel Hill
    Charlotte, NC

    Ibuprofen + Acetaminophen Equals Opioid + Acetaminophen for Acute Severe Extremity Pain

    Clinical question
    What oral analgesic combinations are effective for reducing the pain of an acute extremity injury in adults in the emergency department?

    Bottom line
    In adults presenting to the emergency department with acute extremity pain severe enough to warrant radiologic investigation, ibuprofen plus acetaminophen was equally effective in reducing pain intensity at 2 hours compared with 3 different opioid and acetaminophen combination analgesics. In a similar study (Friedman BW, et al. JAMA 2015;314(15):1572-80), naproxen alone was as effective as naproxen plus oxycodone/acetaminophen or naproxen plus cyclobenzaprine for reducing pain from acute musculoskeletal low back pain. It's time we stopped believing that opioids are superior to nonsteroidal anti-inflammatory drugs for acute pain control. We'd save a lot of lives. (LOE = 1b)

    Reference
    Chang AK, Bijur PE, Esses D, Barnaby DP, Baer J. Effect of a single dose of oral opioid and nonopioid analgesics on acute extremity pain in the emergency department. A randomized clinical trial. JAMA 2017;318(17):1661-1667.

    Study design:Randomized controlled trial (double-blinded)

    Funding source: Government

    Allocation:Concealed

    Setting:Emergency department

    Synopsis
    Opioid use for just 3 days can significantly increase the risk of opioid dependence. These investigators identified adults, aged 21 to 64 years, presenting to the emergency department for acute extremity pain, defined as pain originating distal to and including the shoulder joint in the upper extremities and distal to and including the hip joint in the lower extremities. Eligible patients (N = 411) included those with an injury severe enough to require radiologic imaging according to the judgment of the attending physician. After baseline pain measurement, patients randomly received (concealed allocation assignment) identical capsules containing either ibuprofen 400 mg plus acetaminophen 1000 mg; oxycodone 5 mg plus acetaminophen 325 mg; hydrocodone 5 mg plus acetaminophen 300 mg; or codeine 30 mg plus acetaminophen 300 mg. Patients masked to their treatment group assignment self-assessed pain intensity using a verbal numerical rating scale from 0 (no pain) to 10 (worse pain imaginable). The minimum clinically important difference was predefined as a mean pain scale score of 1.3. Complete follow-up occurred for 100% of patients at 2 hours. Using intention-to-treat analysis, pain intensity significantly declined by 3.5 to 4.4 points at 2 hours compared with baseline in all treatment groups, but was not significantly different among the 4 groups. Pain intensity was also similarly reduced in all treatment groups at 1 hour and there were no group differences in the use of rescue analgesia. Even with post hoc analysis, no statistical difference was present for those with 10/10 pain (severe) and those with acute fractures.

    David C. Slawson, MD
    Professor and Vice Chair of Family Medicine for Education and Scholarship
    Atrium Health
    Professor of Family Medicine, UNC Chapel Hill
    Charlotte, NC

    Gabapentin and Pregabalin Not Effective for Low Back Pain with or Without Radiculopathy

    Clinical question
    Are anticonvulsants an effective treatment for low back pain?

    Bottom line
    The use of anticonvulsants like gabapentin for painful conditions has increased greatly in recent years. This review finds good evidence that these drugs are not an effective treatment for low back pain with or without radiculopathy, and are associated with an increased risk for adverse events. (LOE = 1a)

    Reference
    Enke O, New HA, New CH, et al. Anticonvulsants in the treatment of low back pain and lumbar radicular pain: a systematic review and meta-analysis. CMAJ 2018;190(26):E786-E793.

    Study design:Meta-analysis (randomized controlled trials)

    Funding source:Self-funded or unfunded

    Setting: Various (meta-analysis)

    Synopsis
    Particularly in this era of heightened awareness of the potential harms of opioids, anticonvulsants are often prescribed for the treatment of painful conditions. Although there is evidence of their effectiveness primarily for peripheral and diabetic neuropathy, they are increasingly prescribed for other conditions, including low back pain. This systematic review included a comprehensive search of the literature and the authors identified 9 randomized trials (3 of which were crossover studies) that compared topiramate, pregabalin, or gabapentin with placebo in patients with low back pain with or without radiculopathy. They excluded studies of pregnant women; pre-operative patients; and patients with mixed conditions, such as neck and back pain. The trials were assessed for risk of bias, and only 1 was at high risk. The studies used a range of pain scales, so the standardized mean difference in pain scores between treatment and placebo groups was the primary outcome. The 9 studies reported a total of 14 comparisons, with only 2 showing a statistically significant benefit. One was a small study of high-dose gabapentin (3600 mg/day) in 43 patients with lumbar radicular pain, and the other was a study of 96 patients with low back pain who were given 300 mg topiramate 300 each day. The other topiramate study found no benefit, as did none of the other studies of pregabalin or gabapentin. Where results could be pooled, there was essentially no difference between groups. Where results could be pooled, there was essentially no difference between groups. There was no difference in serious adverse events: 4 in the pregabalin group, 6 in the placebo group (though these were reported in only 2 studies with a total of 423 patients). Any adverse events, however, were significantly more common with active treatment (relative risk 1.4; 95% CI 1.2 - 1.7).

    Mark H. Ebell, MD, MS
    Professor
    University of Georgia
    Athens, GA

    Behavioral Medicine

    Physical Activity Associated with Reduced Incidence of Depression

    Clinical question

    Is physical activity at baseline associated with a reduced risk of subsequent incident depression?

    Bottom line
    This was a large meta-analysis of prospective cohort studies of individuals of all ages without depression at baseline. All of the studies included at least one year of follow-up. People with high physical activity (> 150 minutes per week of at least moderate-intensity activity) were less likely to have subsequent incident depression than those who had low levels of physical activity. Given the large size of the population, the prospective nature of the studies, and the consistency across age groups, the suggestion that exercise is a preventive factor for new onset depression is relatively strong. This is further evidence that exercise is medicine. (LOE = 2a)

    Reference
    Schuch FB, Vancampfort D, Firth J, et al. Physical activity and incident depression: a meta-analysis of prospective cohort studies. Am J Psychiatry 2018;175(7):631-648.

    Study design:Meta-analysis (other)

    Funding source:Unknown/not stated

    Setting:Various (meta-analysis)

    Synopsis
    For this meta-analysis of prospective cohort studies the authors included 49 studies without overlapping populations. The studies included a total of 266,939 individuals who were followed up for more than 1.8 million person-years. Men and women were nearly equally represented (47% and 53%, respectively). Studies were included if: the participants were free of depression or threshold depressive symptoms as measured by any of several tools; physical activity was measured (generally with a self-report questionnaire); the study was a prospective cohort design with at least one year of follow-up (average 7.4 years); and the study evaluated incident depression as an outcome (various methods). Higher physical activity was considered to be more than 150 minutes per week of at least moderate-intensity activity, such as brisk walking. People with higher levels of physical activity were less likely to have incident depression (adjusted odds ratio 0.83; 95% CI 0.79 - 0.88; P < .001). Several potential confounders (including age, sex, body mass index, smoking, and baseline [subthreshold] depressive symptoms) were considered and did not significantly change the results. Subgroup analyses by age group (< 18 years, 18 – 65 years, > 65 years) showed no significant differences from the baseline analysis.

    Linda Speer, MD
    Professor and Chair, Department of Family Medicine
    University of Toledo
    Toledo, OH

    OneThird of Patients with Anxiety Disorder Will Relapse When SSRI/SNRI Treatment Stops

    Clinical question
    How common is relapse in patients with anxiety disorder following the discontinuation of treatment with an antidepressant?

    Bottom line
    Discontinuing the antidepressant treatment of patients with anxiety disorders will cause a relapse in almost one third of them. Unfortunately, 1 in 6 patients previously treated successfully will also relapse despite continued treatment. (LOE = 1a-)

    Reference
    Batelaan NM, Bosman RC, Muntingh A, Scholten WD, Huijbregts KM, van Balkom AJLM. Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials. BMJ 2017 Sep 13;358:j3927.

    Study design:Meta-analysis (randomized controlled trials)

    Funding source:Self-funded or unfunded

    Setting: Various (meta-analysis)

    Synopsis
    The authors searched 3 databases, including Cochrane CENTRAL, as well as clinical trial registries, to identify published and unpublished studies of patients with anxiety disorders (panic disorder, agoraphobia, social phobia, generalized anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, or a specific phobia) who responded to antidepressant treatment and were subsequently randomized to either continue antidepressant treatment or be switched to placebo. Two researchers independently selected research for inclusion, abstracted data, and evaluated study quality. The 28 included studies enrolled a total of 5233 patients, and followed them up for 8 weeks to 52 weeks. Relapse occurred in 36.4% of patients who were witched to placebo, but also in 16.4% of patients who continued treatment (odds ratio 3.11; 95% CI 2.48 - 3.89). There was no significant difference in relapse rates based on type of anxiety. The rate of relapse varied across the studies, likely due to the different durations of follow-up. All but 2 of the studies were sponsored by pharmaceutical companies and 6 were previously unpublished; additional unpublished studies were identified but data could not be obtained, increasing the risk of publication bias.

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    Nonbenzodiazepine Hypnotic Drugs Are Associated with Increased Fractures in Older Adults

    Clinical question
    Are zolpidem, zopiclone, eszopiclone and zaleplon—nonbenzodiazepine hypnotics that are also known as z-drugs—associated with harms in older adults?

    Bottom line
    Among 14 studies reporting on harms of taking so-called z-drugs, the data show an association with higher fracture and injury risk. (LOE = 2a-)

    Reference
    Treves N, Perlman A, Kolenberg Geron L, Asaly A, Matok I. Z-drugs and risk for falls and fractures in older adults: a systematic review and meta-analysis. Age Ageing 2018;47(2):201-208.

    Study design:Meta-analysis (other)

    Funding source:Self-funded or unfunded

    Setting:Various (meta-analysis)

    Synopsis
    These authors searched 2 databases and a clinical trials registry to identify studies of nonbenzodiazepine hypnotic drugs that included an assessment of fractures, falls, and injuries. These hypnotic drugs—zolpidem (Ambien), zopiclone (Zimovane, Imovane), eszopiclone (Lunesta), and zaleplon (Sonata, Starnoc, and Andante)—are sometimes called z-drugs. The authors also scanned the reference lists of retrieved studies. Their search included randomized trials, as well as observational studies. Two investigators independently determined study eligibility and resolved disagreements by discussion and consensus. Ultimately, they included 14 studies with more than 800,000 patients. All of the studies were observational: 10 studies (> 830,000 patients) reported on fractures, 3 studies (> 19,000 patients) reported on falls, and 2 studies (> 160,000) reported on injuries. Patients taking z-drugs were 1.6 times more likely to experience a fracture (95% CI 1.4 - 1.9), but these data demonstrated high levels of heterogeneity. Patients taking z-drugs were not at a statistically significant increased risk of falls, but these data, too, were quite heterogeneous. Finally, patients taking zolpidem (the only drug studied for differences in injury rates) were twice as likely as those not taking it to have injuries (odds ratio 2.05; 1.95 - 2.15) with no evidence for statistical heterogeneity. The results didn't vary when taking various subgroup analyses into account.

    Henry C. Barry, MD, MS
    Professor
    Michigan State University
    East Lansing, MI

    Screening and Prevention

    FIT More Acceptable with Better Detection Rate Than gFOBT for Colorectal Cancer Screening

    Clinical question
    Are the uptake and detection rates better for the fecal immunochemical test than for older guaiac-based screening tests for colorectal cancer?

    Bottom line
    The fecal immunochemical test (FIT) is more sensitive and specific than the older guaiac-based fecal occult blood tests (gFOBTs) when screening for colorectal cancer. We now know that it is also more acceptable to patients and increases uptake in a centrally administered screening program. Physicians should offer patients the option of FIT or colonoscopy, and should replace their stocks of gFOBTs with FITs in their office practice. (LOE = 1b)

    Reference
    Moss S, Mathews C, Day TJ, et al. Increased uptake and improved outcomes of bowel cancer screening with a faecal immunochemical test: results from a pilot study within the national screening programme in England. Gut 2017;66(9):1631-1644.

    Study design: Non-randomized controlled trial

    Funding source: Government

    Allocation: Concealed

    Setting: Population-based

    Synopsis
    Previous randomized trials have shown that screening for colorectal cancer, even using the older gFOBTs, reduces disease-specific mortality. The most recent modeling estimates put this benefit at 220 to 270 life-years saved per 1000 persons screened over their lifetime (https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/colorectal-cancer-screening2). The FIT is a newer test for occult blood in the stool that is specific to human blood, and only requires a single sample with no food restrictions prior to testing. But do these advantages translate into greater uptake by patients? In England, the standard of care has been to mail 3 gFOBT cards to all persons aged 60 years to 74 years every 2 years, and ask them to obtain 2 samples from each of 3 separate bowel movements. The current study gave every 28th person (in a region with 1.2 million screening candidates) the newer FIT; the other 27 people got the standard gFOBT. Although not randomized, the authors assure us that the order of persons on the screening list is not influenced by age, sex, socioeconomic status, or other demographic factors. They found that the uptake was significantly higher for the FIT than for gFOBTs (66.4% vs 59.3%; P < .001). Uptake increased for both men and women in all age groups and in all levels of socioeconomic status. The increase in uptake was somewhat greater in men than in women. And among previous nonresponders, the response rate approximately doubled. At lower cutoffs for hemoglobin, the number of colonoscopies required increased three- to fourfold, but the detection rate for cancers and advanced adenomas was also significantly higher. For example, using a cutoff of 40 mcg/g feces, 5.2% of persons had a positive FIT result compared with 1.7% using gFOBTs; the rates of cancer and advanced adenoma detection were 0.24% and 1.29% with the FIT, and only 0.12% and 0.35% with gFOBTs.

    Mark H. Ebell, MD, MS
    Professor
    University of Georgia
    Athens, GA

    Statins Ineffective for Primary Prevention in Patients 75 Years or Older Without Diabetes

    Clinical question
    In older people without a history of cardiovascular disease, is statin treatment associated with better outcomes

    Bottom line
    In this retrospective study, statin treatment in patients 75 years or older without pre-existing cardiovascular disease (CVD) did not change the likelihood of developing CVD or reduce any-cause mortality. However, patients aged 75 to 84 years with diabetes benefitted from treatment. (LOE = 2b)

    Reference
    Ramos R, Comas-Cufi M, Marti-Lluch R, et al. Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study. BMJ 2018;362:k3359.

    Study design: Cohort (retrospective)

    Funding source: Government

    Setting: Population-based

    Synopsis
    This study enrolled 46,864 patients 75 years or older with no cardiovascular disease from a population database in Spain. The patients had an average age of 76 years (63% were women) and were followed up for an average of 5.6 years. Of these, 6550 patients began statin treatment in the 18 months before the start of the study. In participants without diabetes there was no difference in the onset of CVD (hazard ratio [HR] 0.94; 95% CI 0.86 - 1.04) or the rate of mortality due to any reason (HR 0.98; 0.91 - 1.05). In patients 85 years or older, there also was no reduction in the likelihood of CVD (HR 0.93; 0.82 - 1.06) or all-cause mortality (HR 0.97; 0.90 - 1.05), However, in patients with diabetes who were between the ages of 75 and 84 years, the likelihood of developing CVD was reduced (HR 0.76; 0.65 - 0.89). All-cause mortality was decreased over an average 5.6 years, with one additional person alive for every 16 persons treated with a statin (number needed to treat [NNT] = 15.63; 9.5 - 49.6). The difference was not significant for any patients 85 years or older.

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    Aspirin's Benefits and Harms Are Less Clear for Primary Prevention in Moderate-Risk Patients (ARRIVE)

    Clinical question
    Is low-dose aspirin effective for the primary prevention of cardiovascular disease in moderate-risk patients?

    Bottom line
    In this study, after 5 years of treatment, patients at moderate risk of heart disease who took low-dose aspirin did not show a decrease in coronary events and all-cause mortality, and had slightly more, albeit minor, gastrointestinal bleeding. If you are confused by all the aspirin-related folderol of late, join the club. Using aspirin for primary prevention of cardiovascular disease is not a one-size-fits-all proposition. We need to risk-stratify patients according to benefits and harms and engage in shared decision-making with each patient. (LOE = 1b)

    Reference
    Gaziano JM, Brotons C, Coppolecchia R, et al, for the ARRIVE Executive Committee. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet 2018;392(10152):1036-1046.

    Study design: Randomized controlled trial (double-blinded)

    Funding source: Industry

    Allocation:Concealed

    Setting: Outpatient (any)

    Synopsis
    Low-dose aspirin for secondary prevention and in the face of acute coronary events is pretty much a slam dunk. But despite of years of research, several meta-analyses, and numerous guidelines, its use for primary prevention still seems to rile people up. These researchers point out that most of the recommendations are largely for patients whose 10-year risk of a coronary event exceeds 20% and the role of aspirin in patients of intermediate risk is less clear. So, they conducted a double-blind randomized trial of 100 mg aspirin daily (n = 6270) or placebo (n = 6276) in patients at moderate risk of coronary artery disease. The study participants were men at least 55 years of age or women at least 60 years of age with a 10% to 20% 10-year risk based on age, sex, smoking status, blood pressure, lipid concentrations, and family history. They excluded patients with diabetes and those at high risk for bleeding complications. Using intention-to-treat analysis, after 5 years the rate of events (a composite of myocardial infarction, stroke, cardiovascular death, unstable angina, or transient ischemic attack) was similar between the treatment groups (4.3% vs 4.5%, respectively). The overall death rate was the same (2.6%) in each group. The aspirin-treated patients had more bleeding events (1% vs 0.5%), although very few had moderate or severe gastrointestinal bleeding. The graphs in the paper demonstrate nearly a linear relationship in outcomes over time, so the projected 10-year outcomes indicate that 9% of the placebo-treated patients would have had a coronary event. Recall last month another study that suggested aspirin's effect was potentially influenced by weight and sex (Rothwell et al. Lancet 2018;392(10145):387-399).

    Henry C. Barry, MD, MS
    Professor
    Michigan State University
    East Lansing, MI

    Exercise Alone and Various Combinations of Interventions Reduces the Risk of Injurious Falls in Older Adults

    Clinical question
    Are there specific interventions that are effective in reducing the risk of injurious falls in older adults?

    Bottom line
    Exercise alone; exercise combined with vision assessment/treatment; exercise combined with vision assessment/treatment and environmental assessment/modification; and clinic-level quality improvement strategies combined with multifactorial assessment/treatment and calcium and vitamin D supplementation are all effective interventions for reducing the risk of injurious falls in older adults. (LOE = 1a)

    Reference
    Tricco AC, Thomas SM, Veroniki AA, et al. Comparisons of interventions for preventing falls in older adults. A systematic review and meta-analysis. JAMA 2017;318(17):1687-1699.

    Study design: Meta-analysis (randomized controlled trials)

    Funding source: Foundation

    Setting: Various (meta-analysis)

    Synopsis
    These investigators thoroughly searched multiple databases including MEDLINE, EMBASE, the Cochrane Register, Ageline, and reference lists of relevant trials and reviews for randomized controlled trials that examined fall-prevention interventions for adults 65 years or older. Study authors were also contacted for unpublished studies or additional data. Two investigators independently reviewed all potential studies for inclusion criteria and methodologic quality using standard risk-of-bias scoring tools. Conflicts were resolved by consensus agreement with a third reviewer. The primary outcome of interest was the number of injurious falls and fall-related hospitalizations. A total of 283 randomized trials and 20 companion reports (N = 159,910 participants) met inclusion criteria. The overall risk of bias among the studies was moderate, with an unclear risk of bias for allocation concealment, contamination, and selective outcome reporting. A funnel plot analysis found no evidence of publication bias. Four interventions were significantly associated with a reduced risk of injurious falls compared with usual care: exercise alone; combined exercise and vision assessment and treatment; combined exercise, vision assessment and treatment, and environmental assessment and modification; and combined clinic-level quality improvement strategies, multifactorial assessment and treatment, calcium supplementation and vitamin D supplementation. Combined exercise and vision assessment and treatment was the most effective intervention. In a subgroup analysis, the best intervention for reducing the risk of hip fracture was combined osteoporosis treatment, calcium supplementation, and vitamin D supplementation.ealth status, but were divided as to whether life expectancy should be brought into the discussion.

    David C. Slawson, MD
    Professor and Vice Chair of Family Medicine for Education and Scholarship
    Atrium Health
    Professor of Family Medicine, UNC Chapel Hill
    Charlotte, NC

    Practice Guidelines

    Relaxed Hemoglobin A1c Goals for T2DM from the American College of Physicians

    Clinical question
    How tight should glycemic control be for adults with type 2 diabetes?

    Bottom line
    The American College of Physicians suggests aiming for a hemoglobin A1c level between 7% and 8% for most adults with type 2 diabetes, but they add a caveat that the patient should be the one who makes that decision. The authors weakly recommend backing off treatment for patients with an A1c level of less than 6.5% (cue Moro reflex for those in the lower-is-better camp) and suggest forgoing A1c goals and treating to minimize symptoms in patients 80 years or older and those with a life expectancy of fewer than 10 years (cue spit take from same audience). (LOE = 5)

    Reference
    Qaseem A, Wilt TJ, Kansagara D, et al, for the Clinical Guidelines Committee of the American College of Physicians. Hemoglobin A1c targets for glycemic control with pharmacologic therapy for nonpregnant adults with type 2 diabetes mellitus: a guidance statement update from the American College of Physicians. Ann Intern Med 2018;168(8):569-576.

    Study design: Practice guideline

    Funding source: Self-funded or unfunded

    Setting: Various (guideline)

    Synopsis
    These authors followed good practices for developing guidelines. They focused on the benefits and harms of treatment and based their recommendations on outcomes from studies of outpatient adults with type 2 diabetes. They obtained the research after a systematic review of the available literature, graded the evidence, and included both a methodologist and a patient representative unencumbered by relationships with pharma. Voting members did not have financial conflicts of interest. As with recent changes to recommendations from the American Diabetes Association, they suggest basing glycemic goals on patient wishes, not hard-and-fast targets, following a discussion of benefits and harms. For most patients, an A1c level between 7% and 8% is suitable. In a direct smackdown to recommendations from US endocrinologist societies (Endocr Pract 2018;24(1):91-120), they suggest backing off treatment if a patient's A1c level is below 6.5%, to avoid hypoglycemic symptoms. With a nod toward other preventions aimed at baseline risk, they suggest tossing glycemic targets and treating to minimize symptoms related to hyperglycemia in patients 80 years or older or with other chronic diseases and/or a life expectancy of fewer than 10 years.

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    ACC/AHA Guidelines Take More Aggressive, Less Evidence-Based Approach to Hypertension Management

    Clinical question
    What changes to hypertension management are proposed by the 2017 guideline from the American College of Cardiology and the American Heart Association?

    Bottom line
    This guideline from the American College of Cardiology and the American Heart Association (ACC/AHA) labels all patients with a blood pressure greater than 130/80 as hypertensive, and methodologically takes a step back from the 2014 Joint National Committee 8 guidelines by focusing more on observational studies and disease-oriented outcomes to support their recommendations, and by extending the Systolic Blood Pressure Intervention Trial (SPRINT) findings to patients with diabetes, lower cardiovascular risk, and chronic kidney disease. The United States is in the midst of a "society war," pitting primary care professional societies against subspecialty societies regarding the definition of hypertension, when to begin treatment, and blood pressure treatment goals. In fact, this guideline was explicitly not endorsed by the American Academy of Family Physicians (AAFP). This conflict illustrates the problem with practice guidelines: Who is on the committee, how they assess the studies, and the types of outcomes they consider can result in different recommendations. If you choose to use a blood pressure target of 130/80 mmHg for your patients with diabetes, chronic kidney disease, or a greater than 10% 10-year risk of a cardiovascular event, it is critical that you measure blood pressure the same way that it was measured in the SPRINT trial (have the patient sit in a quiet room for 5 minutes before testing, then use the average of 3 mechanically measured blood pressures). (LOE = 5)

    Reference
    Whelton PK, Carey RM, Aronow AS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. J Am Coll Cardiol 2017; doi: 10.1016/j.jacc.2017.11.006 [Epub ahead of print].

    Study design: Practice guideline

    Funding source: Foundation

    Setting: Various (guideline)

    Synopsis
    The most recent US national hypertension guideline was originally developed by National Heart, Lung, and Blood Institute, and when it was proposed that its home move to the AHA/ACC, the members of the panel objected and published their "guideline formerly known as JNC 8" separately from either organization. That guideline endorsed a blood pressure target of 140/90 for most adults, with 150/90 acceptable for those older than 60 years. Similar targets have been endorsed by the AAFP and the American College of Physicians (ACP). The AHA/ACC have now released a new guideline in conjunction with a number of specialty societies, but notably without participation from the societies of physicians who take care of most hypertensive patients in the United States: the AAFP and ACP. The change that has received the most coverage is a target blood pressure of 130/80 for everyone, with drug therapy recommended for persons with known cardiovascular disease, diabetes, chronic kidney disease, or who have a 10-year risk of a cardiovascular event greater than 10%. This revised blood pressure target is based largely on the results of the recent, and controversial, SPRINT trial. This trial enrolled hypertensive patients without diabetes who had at least a 15% 10-year risk of cardiovascular event. However, evidence of similar benefit for patients with diabetes or those at lower risk is lacking or was not found in other trials. The guideline authors state that this new target would only lead to a relatively small increase in the percentage of persons requiring drug therapy compared with current goals, but it is not hard to imagine that it will become the new de facto standard for all patients, regardless of risk. The guideline recommends use of the pooled cohort equations to estimate risk, which are also used to guide decisions about statin and aspirin use. However, there is evidence that these equations somewhat overestimate risk, which could also lead to overtreatment. The SPRINT trial also measured blood pressure very differently than do most offices: patients sat alone in a quiet room for 5 minutes, and then the average of 3 measurements was used as the final reading. Sound like your office? A SPRINT blood pressure of 130/80 is probably closer to a typical office blood pressure of 140/90 or higher, again potentially leading to overtreatment. The actual absolute benefit of achieving a target of 120/80 instead of 140/90 (measured the SPRINT way) was modest, with an absolute reduction of 0.54% per year in cardiovascular events and 0.37% per year in all-cause mortality. And, of course, there were harms associated with a more aggressive blood pressure target, including higher risks of a greater than 30% reduction in glomerular filtration rate (0.86% per year), more episodes of hypotension, and the need to take one additional medication. The current guidelines extends the 130/80 target to patients with chronic kidney disease and diabetes, as well, despite inconsistent evidence of benefit from other trials such as ACCORD and HOPE-3 of more intensive blood pressure targets in these patients (see POEM 120502. There is a clear bias toward avoiding undertreatment, rather than avoiding the harms of overtreatment. The guideline also recommends chlorthalidone 12.5 mg to 25 mg over hydrochlorothiazide 25 mg to 50 mg as the diuretic of choice. These doses are higher than those currently used by many patients, and are based on the doses used in trials like ALLHAT; however, they also carry a higher risk of hypokalemia. Consistent with the US Preventive Services Task Force, the guidelines recommend out-of-office blood pressure measurements to guide care. An important question is whether physicians will actually use the pooled cohort equations, or whether they will take the simpler approach of just using a target of 130/80 for all adults, resulting in overtreatment.

    Mark H. Ebell, MD, MS
    Professor
    University of Gerogia
    Athens, GA

    Levels of Evidence definitions from Essential Evidence Plus

    POEMs are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com.