Top POEMs of 2016 Consistent with the Principles of the Choosing Wisely Campaign: Additional Top POEMs

Top 20 POEMs of 2016 Consistent with the Principles of the Choosing Wisely Campaign

Low HbA1C, BP, and Cholesterol in Elderly Patients with DMT2 Associated with High Mortality

Clinical question
Is there an association between mortality and glycemic control, blood pressure levels, and cholesterol levels in patients with type 2 diabetes who are older than 80 years?

Bottom line
Although subject to many of the limitations of cohort studies, the data from this study are consistent with those from many other studies that suggest that elderly patients are worse off with low glycosylated hemoglobin (HbA1C), low blood pressure, and low cholesterol levels. (LOE = 1b)(www.essentialevidenceplus.com)

Reference
Hamada S, Gulliford MC. Mortality in individuals aged 80 and older with type 2 diabetes mellitus in relation to glycosylated hemoglobin, blood pressure, and total cholesterol. J Am Geriatr Soc 2016;64(7):1425-1431.

Study design: Cohort (prospective)

Funding source: Government

Setting: Population-based

Synopsis
These authors evaluated a population-based primary care database in the United Kingdom to identify nearly 26,000 patients older than 80 years with type 2 diabetes. The database includes data on physical examinations, test results, diagnoses, and medications. The researchers mined this database for all they could: clinical data, comorbidities, number of office visits, classes of prescribed medication, smoking status, and so forth. Approximately half the cohort were women, one third had co-existing cardiac disease, and about half had diabetes for at least 10 years. Approximately 10% of the patients were older than 90 years. There was a median of 2 years of follow-up, during which about 4500 patients died (17%, 105 per 1000 person-years). The authors estimated the mortality, adjusting for a variety of factors, including age, sex, and duration of diabetes. Similar to other studies, the relationship between mortality and glycemic control as measured by HbA1C and blood pressure levels follows a U-shaped pattern, with the nadir for HbA1C between 7% and 7.5% (53 - 57 mmol/mol) and for blood pressure between 150/90 mmHg and 155/95 mmHg. For each of these, the mortality progressively worsened with lower and higher HbA1C or blood pressure levels. The relationship between total cholesterol and mortality was more curvilinear, with the highest mortality associated with the lowest cholesterol levels and an asymptotic decrease as cholesterol levels increase.

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

Normotensive Patients at Intermediate Risk of CV Disease Do Not Benefit from ARB + HCTZ (HOPE-3)

Clinical question
In patients with an intermediate risk for cardiovascular disease, does blood pressure lowering (regardless of initial blood pressure) improve clinical outcomes?

Bottom line
This large trial provides important guidance for primary care physicians and their patients. For patients at intermediate risk of cardiovascular (CV) disease who have a systolic blood pressure lower than 143 mm Hg, there is no benefit to prescribing candesartan plus hydrochlorothiazide. For those with elevated blood pressure, there is a small benefit in terms of the composite outcome (number needed to treat [NNT] = 59 over 5.6 years to prevent one CV death, nonfatal MI, or nonfatal stroke) but no mortality benefit. The recent SPRINT trial found a benefit, but in a much higher risk group. This study supports current recommendations for limiting use of antihypertensives in low-risk and intermediate-risk patients to those with a systolic blood pressure higher than 140 mm Hg. (LOE = 1b)(www.essentialevidenceplus.com)

Reference
Lonn EM, Bosch J, Lopez-Jaramillo P, et al, for the HOPE-3 Investigators. Blood-pressure lowering in intermediate risk persons without cardiovascular disease. N Engl J Med 2016;374(21):2009-2020.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry + govt

Allocation: Concealed

Setting: Outpatient (any)

Synopsis
This is part of a large Canadian-led international trial that simultaneously evaluted the effect of blood pressure lowering and cholesterol lowering in patients at intermediate risk for CV disease, but who had no known CV disease at trial entry. The trial was co-sponsored by Astra-Zeneca, but their role was limited to providing the trial drug and having one member on a 24-person steering committee. The researchers enrolled men older than 55 years and women older than 65 years with at least one risk factor, and women older than 60 years with 2 risk factors; approximately half the patients were Asian. Patients with and without hypertension were included. On average the patients were at intermediate risk, defined as a 10-year risk of a CV event of approximately 10%. A total of 14,682 patients entered a run-in phase to assess for compliance and adverse drug effects, and 12,705 completed the run-in and were randomized to receive either candesartan 16 mg plus hydrochlorothiazide 12.5 mg or placebo. The groups were balanced at the start of the study, analysis was by intention to treat, and the study was powered to detect a 22% relative reduction in the "coprimary outcomes." (I know, I know, "primary" means 1 outcome, not 2.) The average age of participants was 66 years, 46% were women, and 22% were already taking an antihypertensive medication other than one of the study drugs. Patients were followed up for a median of 5.6 years. The mean blood pressure at the start of the trial was 138/82 mm Hg, and the active treatment group had their blood pressure lowered by 6 mm Hg more than the placebo group (10.0 vs 4.0 mm Hg). As noted above, the authors looked at coprimary composite outcomes: (1) CV death, nonfatal myocardial infarction, and nonfatal stroke; and (2) those outcomes plus resuscitated cardiac arrest, heart failure, and need for revascularization. At the end of the trial, there was no significant difference between groups in these 2 outcomes (4.1% vs 4.4% and 4.9% vs 5.2%, respectively), as well as no difference in the rates of death from CV causes (2.4% vs 2.7%) and all-cause mortality (5.4% vs 5.5%). The researchers had prespecified an analysis stratified by the initial blood pressure. For patients with an initial blood pressure higher than 143.5 mm Hg (the upper tertile) there was a significant reduction in the likelihood of both coprimary outcomes: For the composite of nonfatal myocardial infarction, nonfatal stroke, and CV death, it was 4.8% vs 6.5% (hazard ratio = 0.73, 95% CI 0.56 - 0.94; NNT = 59 over 5.6 years to prevent one event).

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

Hypertensive Urgency Not Really an Urgent Problem

Clinical question
How urgently should we aim to control hypertensive urgency?

Bottom line
It seems that rapid treatment of patients with hypertensive urgency is both unsuccessful and unnecessary. In this study of almost 60,000 patients, 80% did not have controlled blood pressure (< 140/< 90 mm Hg) after 1 month of treatment, including patients who were hospitalized. On the other hand, the risk of a major cardiovascular event was also low: 1 in 1000 over the next 7 days. (LOE = 2b)(www.essentialevidenceplus.com)

Reference
Patel KK, Young L, Howell EH, et al. Characteristics and outcomes of patients presenting with hypertensive urgency in the office setting. JAMA Intern Med 2016;176(7):981-988.

Study design: Cohort (retrospective)

Funding source: Self-funded or unfunded

Setting: Outpatient (any)

Synopsis
These authors identified all patients in a single healthcare system (N = 58,535) who presented to an office or emergency department with a blood pressure of at least 180 mm Hg systolic and/or 110 mm Hg diastolic. Most of the patients in the analysis just met these minimums; only 10.2% had a systolic pressure of 200 mm Hg or higher and 5.7% had a diastolic pressure of 120 mm Hg or higher. The mean age of the patients was 63.1 years, 57.7% were women, and 76% were white. A small proportion (0.7%) were hospitalized for blood pressure management; however, half of these patients had pressures of at least 200 mm Hg systolic or at least 120 mm Hg diastolic. Regardless of treatment or place of treatment, both the likelihood of blood pressure control and the likelihood of adverse effects were low. At 1 month, less than 15% of patients had controlled blood pressure; at 6 months, less than 40% had controlled blood pressure. Even so, the likelihood of a major adverse cardiovascular event was low in the next 7 days (0.1%), at 8 to 30 days (0.2%), or within 6 months (0.9%). Hospitalization was not associated with a decrease in the risk of adverse outcomes.

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

BP Lowering and Statins Not Synergistic for CV Risk Reduction (HOPE-3)

Clinical question
In persons at intermediate risk for a cardiovascular event, does medication to reduce blood pressure and cholesterol reduce the likelihood of cardiovascular events?

Bottom line
This large and well-executed trial confirms that treating elevated blood pressure reduces the likelihood of cardiovascular (CV) events and that statins provide a consistent relative reduction in risk, regardless of the baseline risk. But the absolute risk reduction is lower and the number needed to treat (NNT) is higher when the person starts at a lower baseline risk. Statins at a dose similar to that given in this study reduce the likelihood of a CV event by approximately 25%. So, if you are starting at a 10-year risk of 20%, that gets you down to 15%, for an NNT of 20. Pretty good. If your 10-year risk is 10%, as in this population, it reduces your likelihood to 7.5%, for an NNT of 40. If your 10-year risk is only 5%, it takes you down to 3.75%, for an NNT of 80. These numbers should be the basis of our discussions with patients about statins. (LOE = 1b)(www.essentialevidenceplus.com)

Reference
Yusuf S, Lonn E, Pais P, et al, for the HOPE-3 Investigators. Blood-pressure and cholesterol lowering in persons without cardiovascular disease. N Engl J Med 2016;374(21):2032-2043.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry + govt

Allocation: Concealed

Setting: Outpatient (any)

Synopsis
This is part of a large clinical trial that evaluted the simultaneous effect of blood pressure lowering and cholesterol lowering in patients at intermediate risk for CV disease. The researchers enrolled men older than 55 years and women older than 65 years with at least one CV risk factor, and women older than 60 years with 2 risk factors. The patients had an average 10-year risk of having a CV event of 10%, which the authors categorized as intermediate risk. Astra-Zeneca provided the medications and had one member on a 24-person steering committee. After a run-in period to identify compliant patients without adverse events (something that creates a bias in favor of the drug) patients were randomized into 1 of 4 groups: candesartan- hydrochlorothiazide (HCTZ) plus rosuvastatin, candesartan-HCTZ plus placebo, rosuvastatin plus placebo, or placebo plus placebo. Two other articles compared the effects of candesartan-HCTZ versus placebo and rosuvastatin versus placebo; this one only compares the patients who received both drugs (n = 3180) with those who received only placebos (n = 3168). The previous trials found small benefits to rosuvastatin (NNT = 91 to prevent one CV event over 5.6 years) and a similar benefit to giving the blood pressure medicines to patients with a systolic blood pressure higher than 143 mm Hg (but not to those with normal blood pressure). As with the other 2 reports, patients in this trial had a mean age of 67 years, 46% were women, groups were balanced at the start of the study, and analysis was by intention to treat. The primary outcome was a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke: Patients who received candesartan-HCTZ plus rosuvastatin had a somewhat lower likelihood of this outcome, but the likelihood was similar to that in the rosuvastatin study (3.6% vs 5.0%; P = .005; NNT = 67 over 5.6 years). As with the individual drug comparison studies, there was no change in CV deaths or all-cause mortality. Prespecified subgroup analyses by sex, age, race, or ethnicity did not reveal any heterogeneity of benefit.

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

Blood Pressure Goal of 140-150 mmHg Best for Patients with Diabetes

Clinical question
What is the appropriate antihypertensive treatment goal for patients with diabetes?

Bottom line
Although most recent practice guidelines have relaxed the blood pressure goals for patients with diabetes, there are a still a few holdouts that suggest aggressive treatment. This analysis shows that the sweet spot for hypertension control in patients with diabetes is between 140 mmHg and 150 mmHg; higher or lower sustained blood pressures increase mortality, the so-called J-curve. (LOE = 1a)(www.essentialevidenceplus.com)

Reference
Brunstrom M, Carlberg B. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses. BMJ 2016;352:i717.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Various (meta-analysis)

Synopsis
These researchers searched 4 databases, including the Cochrane CENTRAL library, identifying 49 studies enrolling 73,738 participants with (mostly type 2) diabetes who were treated for hypertension. Two authors independently selected articles for inclusion and extracted data. Heterogeneity and publication bias were assessed but not reported. Most studies were at low risk of bias. The studies evaluated the effect of hypertension treatment on mortality and cardiovascular events but were not specifically designed to compare benefit across different target systolic blood pressures. So, the authors got creative and looked at mortality rates based on both baseline (before treatment) and attained (after treatment) systolic blood pressure. In patients with a baseline blood pressure greater than 140 mm Hg or greater than 150 mmHg treatment decreased all-cause mortality on average, though not by much (relative risk [RR] 0.88; 95% CI 0.78 - 0.98 and RR 0.89; 0.88 - 0.99). However, cardiovascular mortality, myocardial infarction risk, and development of end-stage renal disease were decreased by 15% to 25%. If baseline blood pressure, however, was less than 140 mmHg, further treatment did not decrease all-cause mortality and significantly increased the risk of cardiovascular mortality (RR 1.15; 1.00 - 1.32). These results are somewhat at variance with a meta-analysis published last year that found a reduced risk of stroke and albuminuria with treatment (JAMA 2015;313:603-615).

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

Delayed Rx for Respiratory Infections Produces Similar Results and Satisfaction as Immediate Treatment

Clinical question
In patients with respiratory tract infections (bronchitis, sinusitis, pharyngitis), is a delayed prescription strategy as effective as immediate treatment and as accepted by patients?

Bottom line
In almost 400 Spanish primary care patients with mild to moderate symptoms of respiratory infection of less than 1 week's duration, both a "take-and-hold" prescription and a "come back and pick up, if necessary" prescription produced a similar clinical response -- and similar patient satisfaction score -- as immediate antibiotic treatment, while decreasing overall antibiotic use. Other studies of this patient population have shown that patients prefer the security of a prescription, delayed or not, over withholding antibiotic treatment. The effect of legitimizing an illness by awarding a prescription should not be underestimated. (LOE = 1b)(www.essentialevidenceplus.com)

Reference
de la Poza Abad M, Mas Dalmau G, Moreno Bakedano M, et al, for the Delayed Antibiotic Prescription (DAP) Group. Prescription strategies in acute uncomplicated respiratory infections. A randomized clinical trial. JAMA Intern Med 2016;176(1):21-29.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (primary care)

Synopsis
These researchers evaluated 398 adults with acute, uncomplicated respiratory infections from 23 primary care centers in Spain. The patients had acute pharyngitis (46%), acute bronchitis (32%), rhinosinusitis (20%), or exacerbation of mild-to-moderate chronic obstructive pulmonary disease (2%). The physicians had "reasonable doubt as to whether to treat with an antibiotic." Patients were, on average, on the younger side (mid-40s), half were smokers or former smokers, almost no patients (< 2%) were febrile, and they reported mild to moderate symptoms for an average of 6 days. Patients were randomized, using concealed allocation, to 1 of 4 potential prescription strategies. One group was given an antibiotic to begin at once; 2 groups were given a delayed prescription, either a "take and hold prescription" or a "come back and pick up, if necessary prescription"; and the final group was not given any prescription. The average duration of symptoms was significantly longer in patients not given a prescription as compared with patients given an immediate antibiotic, with the duration in patients given delayed prescriptions somewhere in between but not significantly different from the immediate prescription. The duration of moderate or severe symptoms was lessened significantly with immediate treatment as compared with delayed prescriptions, but the average difference in duration was 0.5 day to 1.0 day. Patients in the delayed prescription groups experienced fewer days absent from work or unable to do their daily activities. Patient satisfaction was similar across all groups. Prescription use was decreased by two-thirds with the delayed prescription approaches.

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

Opioid Analgesia Hard to Tolerate and Not Effective for Chronic Low Back Pain

Clinical question
Is opioid analgesic treatment effective in patients with low back pain?

Bottom line
Effective pain control in patients with low back pain (LBP) is still elusive. Approximately half of all patients with LBP who take an opioid analgesic will stop treatment because of ineffectiveness or adverse effects. Patients staying the course will experience, on average, a small decrease in pain relative to patients who take placebo (similar to the benefit from nonsteroidal anti-inflammatory drugs) and will not have improved function. (LOE = 1a)(www.essentialevidenceplus.com)

Reference
Shaheed CA, Maher CG, Williams KA, Day R, McLachlan AJ. Efficacy, tolerability, and dose-dependent effects of opioid analgesics for low back pain a systematic review and meta-analysis. JAMA Intern Med. 2016;176(7):958-968.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Various (meta-analysis)

Synopsis
To identify randomized controlled trials that enrolled patients with nonspecific LBP, published in any language, and evaluated an opioid analgesic, these researchers searched 5 databases including Cochrane CENTRAL, as well as reference lists of identified studies. Two reviewers independently selected studies for inclusion and 2 reviewers independently extracted the data and evaluated study quality. They retrieved 20 studies with an enrollment of 7295 patients; all but one study enrolled patients with chronic LBP. The length of studies was 12 weeks or less. Most of the studies were of moderate to high quality. Based on 13 studies with moderate-quality evidence, opioids reduced pain in the short term, though the mean difference in pain scores was minimal (mean difference: 10.1 on a scale of 0 - 100). This effect size is similar to that for nonsteroidal anti-inflammatory drugs versus placebo for LBP in a prior Cochrane Review. Overall, opioid treatment did not produce clinically important pain relief compared with placebo (ie, a mean difference in pain scores of at least 20), even with doses as high as 240 mg morphine per day. Half of the studies had more than 50% of the enrolled patients drop out, either because of adverse effects or lack of effectiveness. The patients who dropped out were not considered in the estimates of treatment benefit, meaning that the actual overall likelihood of benefit is even smaller in clinical practice. Low-quality studies of disability did not show a reduction in disability using either the Oswestry Disability Index or the Roland Morris Disability Questionnaire. Study results were homogeneous, but there was some evidence of publication bias.

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

Little Correlation Between Hip Pain and Radiographic Evidence of Osteoarthritis

Clinical question
Are pelvic x-rays useful for ruling in or ruling out osteoarthritis in patients with hip pain?

Bottom line
Do not rely on hip x-rays to rule in or rule out osteoarthritis in patients with hip pain. The correlation between radiographic indicators of hip arthritis and hip pain is very low. Hip pain is not present in many hips with radiographic evidence of osteoarthritis, and many people with painful hips, including older patients with groin or anterior pain and/or painful internal rotation, will not have indicators on x-ray. (LOE = 1b)(www.essentialevidenceplus.com)

Reference
Kim C, Nevitt MC, Niu J, et al. Association of hip pain with radiographic evidence of hip osteoarthritis: diagnostic test study. BMJ 2015;351:h5983.

Study design: Diagnostic test evaluation

Funding source: Industry + govt

Setting: Outpatient (any)

Synopsis
These authors used data from 2 different cohort studies conducted in the United States. The Framingham study imaged every ambulatory person 50 years or older in a single community, regardless of symptoms. Patients with hip pain were also examined for pain with internal rotation. The second study enrolled ambulatory patients, aged 45 years to 79 years, from 4 cities who had or were at risk of knee osteoarthritis; every patient underwent hip imaging as well. In other words, the participating patients had a wide range of symptoms and possible hip pathology. People with hip pain on most days were classified as having "frequent hip pain." In the Framingham study (n = 946), only 15.6% of patients with frequent hip pain had radiographic evidence of hip arthritis; conversely, only 20.7% of patients who met the criteria for hip osteoarthritis had frequent pain. In the second study group (n = 4366), only 9.1% of patients with frequent pain showed radiographic hip osteoarthritis, and 23.8% of those with radiographic hip osteoarthritis were frequently painful. In patients with hip pain localized to the groin (prevalence = 12.6% - 9.5%), the positive predictive value of the x-ray was only 6.0% to 7.1%. Results were similar with anterior thigh pain and/or painful internal rotation.

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

Parents Should Use an Oral Syringe to Measure and Administer Liquid Medicines

Clinical question
Do parents make more mistakes with certain dosing tools when measuring and administering medications?

Bottom line
In this experimental study - the study was performed in an office setting rather than at home - parents consistently made more dosing errors when using a medicine cup than when using an oral syringe to measure out liquid pediatric medicine. Some of these dosing errors were greater than twice the prescribed dose (5.8% more with the cup). Instruct parents to obtain an oral syringe when prescribing liquid medicine. Warn parents to stay away from tableware to measure medicines, since teaspoons vary quite a bit in their volume. Oh, and don't forget to use the term "milliliter" instead of "cc," since that is how oral syringes are marked. (LOE = 1b-)(www.essentialevidenceplus.com)

Reference
Yin HS, Parker RM, Sanders LM, et al. Liquid medication errors and dosing tools: a randomized controlled experiment. Pediatrics 2016;138(4):e20160357.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (primary care)

Synopsis
The researchers enrolled parents of children 8 years or younger visiting 1 of 3 outpatient pediatricians' offices. The 2110 parents were randomly assigned to 1 of 5 groups (using concealed allocation) and asked to interpret a standard prescription label expressing a dose of amoxicillin in terms of teaspoon (either abbreviated or spelled out) or milliliters (abbreviated as "mL"), or both. They were given 2 oral syringes of different sizes and markings, and a medicine cup with gradations on the size. All participants were asked to measure out 2.5 mL, 5 mL, and 7.5 mL using each instrument. Five groups were needed to randomize the order of measuring tool and the prescription labeling. A total of 84.4% of parents made one or more dosing errors, meaning they overdosed or underdosed by 20% or more, and 21.0% made a error of greater than twice the prescribed dose. Using the cup, 43% of parents made a dosing error in at least 1 of the 3 measurements as compared with 16% to 17% with the syringes (P < .001). More errors were made with cups than with either syringe size (odds ratio = 4.6; 95% CI 4.2 - 5.10). The number of errors was significantly higher when a cup was used instead of a syringe to measure either 2.5 mL or 5.0 mL doses. Errors were greater in parents with lower health literacy. Neither the parents nor the investigator were masked to group assignment, and this experimental study put parents on the spot to measure out the pink stuff in the office and not in the more natural setting of home.

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

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(www.essentialevidenceplus.com).

Advertisement