Digest 79 – August Updates: Oral Meds for Cholesterol, Aspirin Monotherapy for VTE prophylaxis, and Mortality with Alcohol Consumption

August 28, 2026 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this issue we discuss everything from Oral Meds for Cholesterol, Aspirin Monotherapy for VTE prophylaxis, and Mortality with Alcohol Consumption, and much more. Effortlessly absorb important medical news, with our monthly newsletter featuring easily digestible analysis of the latest practice-changing articles, and of course…bad puns. 

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Issue 79

08/28/2026

Appetizers (to whet your appetite) 

Palate Cleanser (aka the melon part of the meal) 

The Main Course

A Digestif or two

Appetizers

Brought to you hot off the stove, from a variety of specialties. Delivered in super tasty, bite-sized morsels.  

Jennifer Desalvo MD, Joshua Gilman MD, Laura Glick MD

• LDL-C, meet your match: promising results with oral PCSK9 inhibition. JACC recently published a randomized, phase 3 clinical trial (CORALreef AddOn) evaluating the efficacy and safety of the oral PCSK9 inhibitor Enlicitide in statin-treated adults with LDL>55 mg/dL and ASCVD or LDL>70 at intermediate-to-high cardiovascular risk. Patients were randomized 2:1:1:2 to Enlicitide 20 mg, bempedoic acid 180 mg, ezetimibe 10 mg, or bempedoic acid 180 mg plus ezetimibe 10 mg once daily for 56 days. The primary outcome–mean percentage change in LDL-C from baseline to end of study–was −64.6% (95% CI: −68.3% to −60.9%) with Enlicitide, which was superior to all other groups (P < 0.001). Secondary outcomes of improvement in ApoB and non-HDL-C were also achieved with Enlicitide (P < 0.001). Adverse events and subsequent rate of discontinuation were similar across all treatment groups. This oral PCSK9 inhibitor has again demonstrated its utility as an effective lipid lowering therapy in patients treated with statins. (JD)
• An aspirin a day keeps the VTE away? Rethinking postoperative thromboprophylaxis. NEJM recently published a noninferiority, randomized controlled trial (EPCAT III) assessing the effectiveness of aspirin monotherapy compared to a DOAC followed by aspirin in preventing venous thromboembolism (VTE) after hip and knee arthroplasty. Participants were randomized to aspirin 81 mg daily or rivaroxaban 10 mg daily for 5 days followed by aspirin 81 mg daily for 9 additional days after knee arthroplasty (30 additional days after hip arthroplasty). Aspirin-only therapy was noninferior to treatment with rivaroxaban followed by aspirin, with similar rates of symptomatic VTE (risk difference 0.02%, 95% CI –0.34 to 0.39; P<0.001 for noninferiority) with similar rates of bleeding. Given the event rates in this trial were lower than other previous trials assessing the use of aspirin monotherapy, further research may be needed prior to a paradigm shift in post-operative thromboprophylaxis. (JD) 
• Less is Better. The Alcohol Intake and Health Study, just published in J Stud. Alcohol Drugs, reviewed over 7,200 articles to estimate lifetime alcohol-attributable mortality and morbidity risk based on average weekly consumption in the United States population. The results showed no protective effect of drinking (even at low levels), with increased morbidity and mortality starting at low levels of use. Men consuming more than 6.5 drinks per week and women consuming more than 7.0 drinks per week had a lifetime alcohol-attributable mortality risk exceeding 1 in 1,000. This risk reached approximately 1 in 25 (4%) for men consuming over 14 drinks per week. Researchers found that drinking patterns mattered independent of the total volume. Greater consumption was also associated with an increased risk of breast cancer and cardiovascular disease.  (LG) 
• Can we stop the GDMT already?? JAMA Network Open recently published the DEFINITION-AF pilot trial, an open-label, single-center, parallel group, randomized study addressing whether guideline directed medication therapy (GDMT) can be safely stopped in patients with presumed atrial fibrillation (AF)-mediated heart failure with improved ejection fraction (HFimpEF) after successful AF ablation. 50 patients were randomized 3 months post-ablation to either stepwise GDMT withdrawal or continuation. The primary endpoint was HF deterioration, defined as worsening clinical HF, reduction in EF by >10% to less than 55%, elevated NT-proBNP, or increase in LV chamber size on imaging. At 6 month follow up, the primary endpoint occurred in 0% of the continuation patients compared to 13% (3 pts) in the withdrawal group (p=0.11). Recovery in parameters occurred after GDMT reinitiation. Arrhythmia recurrence was similar between the groups, and there were more drug-related adverse reactions in the continuation arm (20.8% vs 0%, p=0.05). Larger studies will be needed to validate this approach. (JG)
• Should we counsel more caution around e-cigarette use? Nature Medicine recently published a large, retrospective cohort study out of South Korea examining whether using electronic cigarettes (e-cigarettes) after quitting combustible cigarettes attenuates the lung cancer prevention benefit of complete smoking cessation. Over 4.5 million adults with a history of cigarette use enrolled in the Korean National Health Screening Program in 2018 were followed until 2023. Participants were categorized based on both cigarette and e-cigarette smoking status. Compared with complete smoking cessation, former smokers who used e-cigarettes daily had a higher risk of lung cancer incidence (adjusted HR 1.56, 95% CI 1.24-1.97) and lung cancer-specific death (adjusted HR 2.00, 95% CI 1.28-3.15). Additionally, there was no significant difference in lung cancer incidence or lung cancer-specific death between active smokers and former smokers with current e-cigarette use. These associations held across both short and long-term quitters and were most pronounced in the higher-risk subgroup of patients (age 50-80 with ≥20 pack year history). As an observational study with e-cigarette use defined only at baseline, causality cannot be established, but these findings reinforce recommendations around cessation of both cigarettes and e-cigarettes. (JG) 

Palate Cleanser

The melon part. To get rid of the taste of those pesky apps.  And to fill your brain with some fun facts.

The Prescription We Never Write: Take a Sabbatical. Yale professor Dr. Laurie Santos explores “The life changing power of a sabbatical”in her most recent podcast episode on The Happiness Lab, in which she meets with DJ DiDonna, author of Big Time Off: The Transformative Power of Sabbaticals and How to Take One (before it takes you). They explore the meaning of a sabbatical as an intentional extended leave from your routine job for a period of time measured in months, which is already available at some companies and in other countries. This allows people to create space to actively rest, rediscover their creativity, and expand their identities beyond their job. They also offer advice to help plan your sabbatical within your workplace and day to day responsibilities to recover from burnout and the perception of judgment from others for taking time for yourself. Perhaps in healthcare, we don’t need another resilience module or wellness lecture; we may simply need permission to stop and accept that the hospital, clinic, and pager will survive in our absence. 

– Jennifer DeSalvo MD

The Main Course

Alexander Chaitoff MD, MPH 

Are ACOs being gamed?
While we’re usually focused on the evidence that can help clinicians provide high-value care, we all work within complex systems with often unknown, powerful, incentive structures. So we thought we’d take the time this month to dive into one in particular.  You’ve probably heard the term “accountable care organization,” or ACO, but you’re in good company if you’re not quite sure what it is. Envisioned as a way to rein in healthcare costs without compromising quality, ACOs are groups of clinicians, practices, and hospitals that collectively take responsibility for the cost and quality of care delivered to a defined cohort of Medicare patients usually identified by where they get their primary care. If costs are kept lower and quality higher than agreed-upon benchmarks, these groups can receive some of the difference as bonus payments.

Practically, patients in ACOs remain on Traditional Medicare, and Medicare continues paying for each patient’s visits, tests, and hospitalizations. However, in the background, Medicare also compares the total annual spending and quality of care for each ACO’s patients with risk-adjusted benchmarks. To achieve their cost and quality goals, clinicians in an ACO might integrate workflows or hire staff to reduce costly care. For example, a health system might hire a nurse to make post-discharge phone calls to prevent avoidable readmissions, allowing the ACO to capture some of the savings Medicare would have otherwise had to spend on the hospitalization.

Making generalizations about whether ACOs have been successful is difficult because they come in many shapes and sizes. However, it is fair to say they have not had a consistently positive impact.  2018 data suggested ACOs may or may not generate cost savings depending on which types of practices are included in them. Many factors may explain why this incentive structure hasn’t been transformative. Maybe more important to patients, ACOs may also not lead to any improvements in quality.  Unlike Health Maintenance Organizations (HMOs), which restrict patients from using costly services, ACOs are not insurance plans, and patients can see whichever providers they want (including ones not in the ACO) and use as much care as they want.  Furthermore, evidence suggests many clinicians aren’t aware of their membership in an ACO and don’t know the ACO’s objective (e.g. your average clinician working for a large healthcare system).

ACOs are increasingly national
You might imagine an ACO is a local network of providers (e.g. primary care doctor, cardiologist, and nurse in the same hospital system) all working to keep a patient healthy and out of the hospital. However, third-party firms known as conveners are increasingly assembling otherwise independent practices, sometimes in different states, into a single ACO. Conveners are companies that supply the capital, data analytics, administrative infrastructure, and financial-risk management that smaller practices need to participate in Medicare’s program, typically in exchange for a portion of any shared-savings payments they receive for beating benchmarks.

Why bundle practices across different states? Because Medicare compares an ACO’s risk-adjusted patient spending against the local averages. If an ACO’s attributed patients cost less than their regional peers, the ACO can pocket a shared-savings bonus. This setup can give conveners an incentive: identify clinicians whose patient panels already cost less than their surrounding county averages, regardless of where those clinicians actually practice, and recruit them to join their ACO.

The rise of geographically distributed ACOs
Despite the original intention behind ACOs, a recent paper in Health Affairs highlights the rise of convener-assembled, geographically-distributed clinician groups. In the paper, the authors analyzed national Medicare Shared Savings Program data from 2012–21, covering 845 ACOs, and manually identified those managed by conveners. They mapped clinicians’ practice locations, classified ACOs by geographic dispersion, and compared their shared-savings payments and quality performance. The proportion of beneficiaries in convener-led ACOs grew from 11% to 23%, while the proportion in geographically dispersed convener ACOs rose from 13% to 42%. Dispersed convener ACOs earned the highest adjusted bonuses, $171 per beneficiary annually, compared with $95 for local convener ACOs, but did not demonstrate better quality care. Of course, this study was observational, so it could not determine whether these geographically dispersed ACOs lowered spending through better care or earned more mostly by strategically recruiting clinicians already caring for low-cost patients – but the latter needs to be considered.

The findings hint at a potential mismatch between the original vision of an ACO model and its evolving reality. A program designed to foster local clinical integration increasingly includes far-flung collections of clinicians who may share a financial contract without sharing patients or coordinating care. The authors argue that Medicare should consider stronger standards for clinical integration and geographic coherence for its shared savings programs. While not the primary driver of rising healthcare costs–and while it won’t change how you treat patients–this study reminds us of the incredibly complex web of perverse incentives most frontline clinicians never see.

Read the Health Affairs study HERE!

Digestifs

Before you go….
we’ve got a few nibbles!

Consolidate your learning with a Quiz!  

This week on The Curbsiders: Episode #537 with Dr. Joel Topf will teach you all the tricks of how to manage potassium–the lows and the highs! 

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The Curbsiders Digest

Issue 79
Editor in Chief: Nora Taranto MD
Banner: Kate Grant  MBChB, DipGUMed

Jennifer DeSalvo, Joshua Gilman, Laura Glick, Alyssa Mancini, and Nora Taranto report no disclosures.

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