Each year family physicians are inundated with an extensive array of newly published medical articles. Identifying the most relevant, as well as reading and analyzing articles, is a complex and time-consuming task and can be overwhelming. This publication presents a compilation of the 10 medical studies of 2023 most likely to impact primary care practice, along with evidence for 2 noteworthy “up and coming” medications. These selections aim to address the diverse needs of comprehensive family physicians.

The PEER (Patients, Experience, Evidence, Research) team systematically identified clinical studies relevant to primary care by searching the tables of contents of influential medical journals (eg, New England Journal of Medicine, the Lancet, and BMJ). Additionally, we used EvidenceAlerts,1 ACCESSSS,2 and the American College of Physicians Journal Club3 to find high-quality articles. Our team of primary care professionals independently ranked the identified articles. All presented study results are statistically significant unless otherwise stated.

How does prescribing a high-dose statin compare to a “treat-to-target” strategy in patients with coronary artery disease?

Bottom line: Empirically prescribing a high-intensity statin has similar effects on cardiovascular outcomes and mortality and may be simpler than a “treat-to-target” strategy.4

Methods: In an open-label randomized controlled trial (RCT) in South Korea, 4400 patients with coronary artery disease (mean age 65, mean low-density lipoprotein cholesterol [LDL-C] level of 2.2 mmol/L, 25% taking high-intensity statins) were randomized to statins titrated to a target LDL-C level of 1.3 to 1.8 mmol/L or to empiric high-intensity statins (atorvastatin 40 mg or rosuvastatin 20 mg daily).

Results: Patients in both groups achieved an average LDL-C level of about 1.8 mmol/L. At 3 years, cardiovascular events (8.1% vs 8.7%) and all-cause death (2.5% in both groups) were not statistically different. Patients in the treat-to-target group were less likely to receive a high-intensity statin (56% vs 89%), but more likely to receive ezetimibe (20% vs 11%) compared with the high-intensity group.

Can semaglutide reduce cardiovascular events in obese adults without diabetes?

Bottom line: In adults with obesity and known cardiovascular disease (CVD), cardiovascular events occurred in 6.5% of patients taking semaglutide compared with 8.0% taking placebo (number needed to treat [NNT] of 67).5 More patients stopped treatment owing to adverse events with semaglutide (17%) compared with placebo (8%).

Methods: In an industry-funded, double-blind trial of 17,604 adults with known CVD and without diabetes (mean age 62, mean body mass index of 33 kg/m2), participants were randomized to semaglutide (target dose 2.4 mg subcutaneously per week) or placebo.

Results: After 40 months, cardiovascular events (death from cardiovascular cause, nonfatal myocardial infarction, or stroke) occurred in 6.5% of participants taking semaglutide versus 8.0% with placebo. There was no difference in mortality. Body weight decreased by 9% in the semaglutide group versus 1% in the placebo group. More patients taking semaglutide withdrew owing to adverse events compared with placebo (17% vs 8%); these were mainly gastrointestinal.

Among older adults, does respiratory syncytial virus (RSV) vaccination prevent respiratory illness?

Bottom line: At 6.7 months, RSV vaccination prevented 1 case of RSV-related lower respiratory tract disease for every 379 medically stable patients older than 60 years compared with placebo.6 The study was conducted during the COVID-19 pandemic, potentially lowering baseline RSV incidence. There was no increase in serious adverse events, but fatigue, injection site pain, and myalgia were more common with vaccination.

Methods: The study was an industry-funded trial of 24,966 adults aged 60 or older (mean age 70, 39% with stable conditions increasing risk of severe RSV) randomized to single-dose adjuvanted RSV prefusion F protein vaccine or placebo. The trial was planned for 3 years, but results were presented after the first RSV season.

Results: Cases of RSV-related lower respiratory tract disease occurred in 0.06% of patients receiving the vaccine compared with 0.3% receiving placebo (number needed to vaccinate of 379). Severe RSV disease (>2 clinical signs or investigator-assessed) occurred in 0.008% of those receiving the vaccine versus 0.14% with placebo (number needed to vaccinate of 758). The most common adverse events were pain at the injection site (61% vs 9% with placebo), fatigue (34% vs 16%), and myalgia (29% vs 8%). There was no difference in serious adverse events. Patients who were immunocompromised, had unstable comorbidities, or resided in long-term care were generally not included.

Is chlorthalidone better than hydrochlorothiazide for cardiovascular risk reduction?

Bottom line: Chlorthalidone does not have a lower occurrence of major cardiovascular events or death compared with hydrochlorothiazide.7

Methods: In an open-label RCT 13,523 veterans (mean age 72, 11% with past CVD) already taking hydrochlorothiazide (25 to 50 mg daily) were randomized to receive chlorthalidone 12.5 to 25 mg or continue hydrochlorothiazide.

Results: At a median 2.4 years, cardiovascular events (10.4% vs 10.0%) and all-cause death (6.6% in both groups) were not statistically different between chlorthalidone and hydrochlorothiazide.

Does amitriptyline improve symptoms of irritable bowel syndrome (IBS)?

Bottom line: Low-dose amitriptyline (10 to 30 mg at bedtime) improves IBS symptoms for patients who have not improved adequately with first-line treatments.8

Methods: An RCT of 463 patients with IBS for whom first-line therapies failed (100% trying dietary changes and 78% trying antispasmodics) randomized patients to amitriptyline (10 mg at bedtime, titrated over 3 weeks to a maximum of 30 mg) or placebo. Both groups also received dietary advice. At baseline, the mean IBS Severity Scoring System score was about 273 (range 0 to 500), indicating moderate to severe symptoms.

Results: At 6 months, amitriptyline was superior to placebo, with approximately 60% of patients having symptom relief versus 45% of those taking placebo (NNT=7). Additionally, more patients taking amitriptyline had adequate symptom relief for 50% of the weeks versus placebo (41% vs 30%, NNT=10). More patients found amitriptyline acceptable to take and wanted to continue taking it (58% vs 47% taking placebo, NNT=10). Dry mouth, drowsiness, and blurred vision were more common with amitriptyline.

Are opioids effective for acute neck or low back pain?

Bottom line: Opioids were not superior to placebo in managing acute neck or low back pain at 6 weeks.9

Methods: A triple-blind, non–industry-funded RCT (346 participants, mean age 45, mean pain score 5.7 on a 0- to 10-point scale) compared oxycodone-naloxone with placebo in adults who had acute neck or low back pain. Modified-release oxycodone-naloxone tablets were titrated up to 10 mg twice daily. Treatment was stopped when pain improved (score of 0 or 1 for 3 consecutive days) or after 6 weeks.

Results: At 6 weeks, there was no significant difference in pain intensity between groups (oxycodone 2.8 vs placebo 2.3), and pain was worse with opioids at 1 year (oxycodone 2.4 vs placebo 1.8). In outcomes like functioning, quality of life, health care use, absenteeism, and others, results were the same or worse (for 1 physical function and quality-of-life measure) in the opioid group. Adverse events were no different; however, more participants were at risk of opioid misuse (current Opioid Misuse Measure Scale score ≥9) at 1 year with oxycodone (20% vs 10% placebo, number needed to harm of 10).

Can patients with low-risk penicillin allergies receive oral challenges safely?

Bottom line: For patients with low-risk penicillin allergy, oral challenge with 250 to 500 mg of amoxicillin is similarly as safe as standard-of-care penicillin skin testing.10

Methods: The Penicillin Allergy Decision Rule (PENFAST) is a clinical decision tool that enables point-of-care risk assessment of penicillin allergy for adults. In an open-label RCT of 382 adults with a PENFAST score less than 3, most patients had PENFAST scores of 1 or less (96%), with mostly remote (>15 years) mild reactions to penicillin requiring no treatment. Patients with anaphylaxis history (with any drug) or with non-immunoglobulin E–mediated reactions were excluded. Patients were randomized to oral challenge (mostly 250 to 500 mg of amoxicillin) or intradermal testing followed by amoxicillin challenge if skin test results were negative. Patients were observed for 60 minutes.

Results: In each group, 1 patient had a positive oral challenge result (both mild skin reactions) within 1 hour of ingestion, which was resolved with a single dose of antihistamine. Delayed immune-mediated reactions occurred in 5% of participants in both groups (9 vs 6 cases [control] needed antihistamines, but no hospitalizations or emergency department visits were needed). The penicillin allergy label was removed for more than 98% of patients in both groups.

Spironolactone for facial acne in women

Bottom line: At 24 weeks, oral spironolactone led to self-assessed acne improvement for about 80% of women compared with roughly 60% of those taking placebo.11

Methods: In a double-blind RCT, 410 adult women with facial acne (mean age 29, about 53% with moderate to severe acne) were randomized to spironolactone (50 mg daily for 6 weeks, then 100 mg daily) or placebo.

Results: After 6 months, 82% of spironolactone participants reported overall improvement versus 63% of those taking placebo (NNT=6). Investigator’s global assessment noted improvement in 19% of participants taking spironolactone versus 6% taking placebo (NNT=8) at 12 weeks, but this outcome was not measured at 24 weeks. Headache occurred in approximately 20% of participants taking spironolactone compared with 12% taking placebo.

In older adults, can frailty be reversed with an educational intervention incorporating exercise and protein?

Bottom line: Recommending resistance exercises, walking, and regular protein intake can reduce and reverse frailty progression.12

Methods: An open-label RCT (N=168, mean age 77) conducted in primary care randomized people aged 65 or older with Clinical Frailty Scale13 scores of 5 or less (mildly frail or less frail) to an educational intervention or usual care for the span of 3 months. The intervention included a home exercise regimen (10 strength exercises 4 or more days per week and walking 30 to 45 minutes 3 to 4 times per week14) and dietary protein guidance (1.2 g/kg body weight daily). Education was provided by family physicians using pamphlets and demonstrations (≤5 minutes overall). The primary outcome was the number of participants considered frail on the SHARE (Survey of Health, Ageing and Retirement in Europe) Frailty Instrument.15

Results: At 3 months, 6% were considered frail in the intervention group versus 18% in the usual care group (NNT=9). Good adherence was reported in 92% of participants in the intervention group, and 66% thought the intervention was “easy or very easy” to undertake.

Chronic disease management in Alberta

Bottom line: Family physicians play an important role in chronic disease management by providing the majority of care for patients with hypertension, diabetes, asthma, and chronic obstructive pulmonary disease.16

Methods: In a population-based retrospective cohort study of 970,783 adult Albertans, administrative data were used to determine which providers were providing longitudinal care (≥2 visits to the same provider over 5 years) for 7 specified chronic diseases.

Results: Family physicians were the sole providers for most patients with hypertension (86%), diabetes (71%), asthma (66%), and chronic obstructive pulmonary disease (60%). Other specialists were more often the sole providers for ischemic heart disease (49%), heart failure (36%), and chronic kidney disease (42%), although family physicians were involved in their care (either comanaged with another specialist or as sole provider) in 51%, 64%, and 58% of patients, respectively. It should be noted that some authors of this study are co-authors of this paper.

Does retatrutide help with weight loss?

Bottom line: Retatrutide reduces weight by about 7% to 22% more than placebo in patients with obesity.17

Methods: A double-blind, phase 2, industry-funded RCT compared retatrutide (1, 4, 8, or 12 mg subcutaneously weekly) with placebo in 338 adults with obesity and without diabetes (mean baseline weight of 108 kg).

Results: At 48 weeks, the mean reductions in weight for 1, 4, 8, and 12 mg of retatrutide were 9%, 17%, 23%, and 24%, respectively (2% for placebo). The proportions of patients who lost 10% or more of their body weight were 27%, 75%, 91%, and 93%, respectively (9% for placebo). Withdrawals owing to adverse effects were more common with retatrutide (16% for 12 mg of retatrutide vs 0% for placebo). Gastrointestinal effects occurred commonly (eg, nausea 45% for 12 mg of retatrutide vs 11% for placebo). Future studies are required to validate these findings.

How effective is fezolinetant for the treatment of vasomotor symptoms?

Bottom line: For women with hot flashes, 45% to 57% of participants taking fezolinetant will have a 50% or greater reduction in hot flashes versus 30% taking placebo over 12 weeks.18

Methods: The study was a double-blind RCT comparing fezolinetant (30 to 45 mg daily) with placebo in 527 women with menopause and 7 or more hot flashes per day (baseline of 10 to 11).

Results: At 12 weeks, fezolinetant reduced daily hot flashes to 4 to 5 versus 7 with placebo. More patients receiving fezolinetant had a 50% or greater reduction in moderate to severe hot flashes (45% to 57% vs 30% placebo, NNT=4 to 7). Quality of life was not meaningfully improved. No increase in adverse events was observed, which is consistent with findings of a 52-week safety RCT.19 A second RCT had similar results.20