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Top POEMs of 2018 Consistent with the Principles of the Choosing Wisely Campaign: Additional Top POEMs

Top 20 POEMs of 2018 Consistent with the Principles of the Choosing Wisely Campaign

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)(www.essentialevidenceplus.com)(www.essentialevidenceplus.com)

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)(www.essentialevidenceplus.com)(www.essentialevidenceplus.com)

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)(www.essentialevidenceplus.com)(www.essentialevidenceplus.com)

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-)(www.essentialevidenceplus.com)(www.essentialevidenceplus.com)

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

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)(www.essentialevidenceplus.com)(www.essentialevidenceplus.com)

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-)(www.essentialevidenceplus.com)(www.essentialevidenceplus.com)

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

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

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

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).

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