Three-Year Outcomes of Bariatric Surgery in Patients With Obesity and Hypertension: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 173, No 9

Background: Midterm effects of bariatric surgery on patients with obesity and hypertension remain uncertain. Objective: To determine the 3-year effects of Roux-en-Y gastric bypass (RYGB) on blood pressure (BP) compared with medical therapy (MT) alone. Design: Randomized clinical trial. (ClinicalTrials.gov: NCT01784848) Setting: Investigator-initiated study at Heart Hospital (HCor), São Paulo, Brazil. Participants: Patients with hypertension receiving at least 2 medications at maximum doses or more than 2 medications at moderate doses and with a body mass index (BMI) between 30.0 and 39.9 kg/m2 were randomly assigned (1:1 ratio). Intervention: RYGB plus MT or MT alone. Measurements: The primary outcome was at least a 30% reduction in total number of antihypertensive medications while maintaining BP less than 140/90 mm Hg. Key secondary outcomes were number of antihypertensive medications, hypertension remission, and BP control according to current guidelines (<130/80 mm Hg). Results: Among 100 patients (76% female; mean BMI, 36.9 kg/m2 [SD, 2.7]), 88% from the RYGB group and 80% from the MT group completed follow-up. At 3 years, the primary outcome occurred in 73% of patients from the RYGB group compared with 11% of patients from the MT group (relative risk, 6.52 [95% CI, 2.50 to 17.03]; P < 0.001). Of the randomly assigned participants, 35% and 31% from the RYGB group and 2% and 0% from the MT group achieved BP less than 140/90 mm Hg and less than 130/80 mm Hg without medications, respectively. Median (interquartile range) number of medications in the RYGB and MT groups at 3 years was 1 (0 to 2) and 3 (2.8 to 4), respectively (P < 0.001). Total weight loss was 27.8% and −0.1% in the RYGB and MT groups, respectively. In the RYGB group, 13 patients developed hypovitaminosis B12 and 2 patients required reoperation. Limitation: Single-center, nonblinded trial. Conclusion: RYGB is an effective strategy for midterm BP control and hypertension remission, with fewer medications required in patients with hypertension and obesity. Primary Funding Source: Ethicon, represented in Brazil by Johnson & Johnson do Brasil.

The American College of Physicians' Endorsement of Single-Payer Reform: A Sea Change for the Medical Profession

Policy Recommendations to Promote Prescription Drug Competition: A Position Paper From the American College of Physicians

The prescription drug market in the United States relies on competition to keep prices reasonable. Although many policies have been implemented to spur competition and decrease costs for patients, these policies may be outdated and should be redesigned and updated to achieve success in the current prescription drug market. In this paper, the American College of Physicians (ACP) proposes that new policies should be implemented to prevent market manipulation, help lower-cost alternatives make it to the market faster, and ensure a robust and competitive market for generic and biosimilar drugs. The ACP believes these changes will have a meaningful effect on patients without shifting costs to other areas of the health care system.

Dual Versus Triple Therapy for Atrial Fibrillation After Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 172, No 7

Background: The safety and effectiveness of dual therapy (direct oral anticoagulant [DOAC] plus P2Y12 inhibitor) versus triple therapy (vitamin K antagonist plus aspirin and P2Y12 inhibitor) in patients with nonvalvular atrial fibrillation (AF) after percutaneous coronary intervention (PCI) is unclear. Purpose: To examine the effects of dual versus triple therapy on bleeding and ischemic outcomes in adults with AF after PCI. Data Sources: Searches of PubMed, EMBASE, and the Cochrane Library (inception to 31 December 2019) and ClinicalTrials.gov (7 January 2020) without language restrictions; journal Web sites; and reference lists. Study Selection: Randomized controlled trials that compared the effects of dual versus triple therapy on bleeding, mortality, and ischemic events in adults with AF after PCI. Data Extraction: Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. Data Synthesis: Four trials encompassing 7953 patients were selected. At the median follow-up of 1 year, high-certainty evidence showed that dual therapy was associated with reduced risk for major bleeding compared with triple therapy (risk difference [RD], −0.013 [95% CI, −0.025 to −0.002]). Low-certainty evidence showed inconclusive effects of dual versus triple therapy on risks for all-cause mortality (RD, 0.004 [CI, −0.010 to 0.017]), cardiovascular mortality (RD, 0.001 [CI, −0.011 to 0.013]), myocardial infarction (RD, 0.003 [CI, −0.010 to 0.017]), stent thrombosis (RD, 0.003 [CI, −0.005 to 0.010]), and stroke (RD, −0.003 [CI, −0.010 to 0.005]). The upper bounds of the CIs for these effects were compatible with possible increased risks with dual therapy. Limitation: Heterogeneity of study designs, dosages of DOACs, and types of P2Y12 inhibitors. Conclusion: In adults with AF after PCI, dual therapy reduces risk for bleeding compared with triple therapy, whereas its effects on risks for death and ischemic end points are still unclear. Primary Funding Source: None.

Biomarkers to Personalize Preoperative Cardiovascular Risk Stratification: Ready for Prime Time?

Association Between Treatment With Apixaban, Dabigatran, Rivaroxaban, or Warfarin and Risk for Osteoporotic Fractures Among Patients With Atrial Fibrillation: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 173, No 1

Background: It is unclear whether anticoagulant type is associated with the risk for osteoporotic fracture, a deleterious complication of anticoagulants among patients with atrial fibrillation (AF). Objective: To compare the risk for osteoporotic fracture between anticoagulants. Design: Population-based cohort study. Setting: Territory-wide electronic health record database of the Hong Kong Hospital Authority. Participants: Patients newly diagnosed with AF between 2010 and 2017 who received a new prescription for warfarin or a direct oral anticoagulant (DOAC) (apixaban, dabigatran, or rivaroxaban). Follow-up ended on 31 December 2018. Measurements: Osteoporotic hip and vertebral fractures in anticoagulant users were compared using propensity score–weighted cumulative incidence differences (CIDs). Results: There were 23 515 patients identified (3241 apixaban users, 6867 dabigatran users, 3866 rivaroxaban users, and 9541 warfarin users). Overall mean age was 74.4 years (SD, 10.8), ranging from 73.1 years (warfarin) to 77.9 years (apixaban). Over a median follow-up of 423 days, 401 fractures were identified (crude event number [weighted rate per 100 patient-years]: apixaban, 53 [0.82]; dabigatran, 95 [0.76]; rivaroxaban, 57 [0.67]; and warfarin, 196 [1.11]). After 24-month follow-up, DOAC use was associated with a lower risk for fracture than warfarin use (apixaban CID, −0.88% [95% CI, −1.66% to −0.21%]; dabigatran CID, −0.81% [CI, −1.34% to −0.23%]; and rivaroxaban CID, −1.13% [CI, −1.67% to −0.53%]). No differences were seen in all head-to-head comparisons between DOACs at 24 months (apixaban vs. dabigatran CID, −0.06% [CI, −0.69% to 0.49%]; rivaroxaban vs. dabigatran CID, −0.32% [CI, −0.84% to 0.18%]; and rivaroxaban vs. apixaban CID, −0.25% [CI, −0.86% to 0.40%]). Limitation: Residual confounding is possible. Conclusion: Among patients with AF, DOAC use may result in a lower risk for osteoporotic fracture compared with warfarin use. Fracture risk does not seem to be altered by the choice of DOAC. These findings may help inform the benefit–risk assessment when choosing between anticoagulants. Primary Funding Source: The University of Hong Kong and University College London Strategic Partnership Fund.

Management of Acute Pain From Non–Low Back, Musculoskeletal Injuries: A Systematic Review and Network Meta-analysis of Randomized Trials: Annals of Internal Medicine: Vol 173, No 9

Background: Patients and clinicians can choose from several treatment options to address acute pain from non–low back, musculoskeletal injuries. Purpose: To assess the comparative effectiveness of outpatient treatments for acute pain from non–low back, musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs). Data Sources: MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020. Study Selection: Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks' duration from non–low back, musculoskeletal injuries. Data Extraction: Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Data Synthesis: The 207 eligible studies included 32 959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence). Limitations: Only English-language studies were included. The number of head-to-head comparisons was limited. Conclusion: Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit–harm ratio for patients with acute pain from non–low back, musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms. Primary Funding Source: National Safety Council. (PROSPERO: CRD42018094412)

The Patient in Front of You

Residual Shunt After Patent Foramen Ovale Closure and Long-Term Stroke Recurrence: A Prospective Cohort Study: Annals of Internal Medicine: Vol 172, No 11

Background: Residual shunt is observed in up to 25% of patients after patent foramen ovale (PFO) closure, but its long-term influence on stroke recurrence currently is unknown. Objective: To investigate the association of residual shunt after PFO closure with the incidence of recurrent stroke and transient ischemic attack (TIA). Design: Prospective cohort study comparing stroke or TIA recurrence in patients with and without residual shunt after PFO closure. Setting: Single hospital center. Participants: 1078 consecutive patients (mean age, 49.3 years) with PFO-attributable cryptogenic stroke who were undergoing percutaneous PFO closure were followed for up to 11 years. Measurements: Residual shunt was evaluated by transthoracic echocardiography with saline contrast. Primary outcome was a composite of the first recurrent ischemic stroke or TIA after PFO closure. Results: Compared with complete closure, the presence of residual shunt after PFO closure was associated with an increased incidence of recurrent stroke or TIA: 2.32 versus 0.75 events per 100 patient-years (hazard ratio [HR], 3.05 [95% CI, 1.65 to 5.62]; P < 0.001). This result remained robust after adjustment for important covariates, namely age; study period; device; presence of atrial septal aneurysm, hypertension, hyperlipidemia, diabetes, hypercoagulability, or hypermobile septum; and medication use (HR, 3.01 [CI, 1.59 to 5.69]; P < 0.001). Further stratification based on shunt size revealed that moderate or large residual shunts were associated with a higher risk for stroke or TIA recurrence (HR, 4.50 [CI, 2.20 to 9.20]; P < 0.001); the result for small residual shunts was indeterminate (HR, 2.02 [CI, 0.87 to 4.69]; P = 0.102). Limitation: Nonrandomized study with potential unmeasured confounding. Conclusion: Among patients undergoing PFO closure to prevent future stroke, the presence of residual shunt, particularly a moderate or large residual shunt, was associated with an increased risk for stroke or TIA recurrence. Primary Funding Source: National Institutes of Health.

Annals Clinical Decision Making: Translating Population Evidence to Individual Patients