The Clinical Chronicle

EDITION 6

Author

Vijay Sam Nethala
March 27, 2025

Welcome to the SIXTH Edition of The Clinical Chronicle!

From statins cutting liver cancer risk by 33% to the debate over heparin’s grip on PE treatment, we break down the latest practice changing studies. Alzheimer’s progression differs sharply by sex, with women showing faster tau buildup, while a pilot trial hints nitrates could dethrone calcium blockers post CABG.

With TB cases at a 12-year high, automated insulin tech reshaping diabetes care, and high-dose vitamin D slowing MS progression, this edition unpacks urgent public health shifts. From the FDA’s expanded approval of Guselkumab in Crohn’s to the butter vs. plant oils mortality debate, we decode the science shaping tomorrows practice.

Stay informed. Stay prepared.

Landmark Study Links Statin Use to 33% Lower Liver Cancer Risk & 22% Reduced Hepatic Decompensation.

Statins Show Promise in Combating Liver Disease Complications

A recent study of 16,501 chronic liver disease patients found statin use linked to a 33% lower risk of hepatocellular carcinoma (HCC) and a 22% reduced risk of hepatic decompensation over 10 years. Statin users had a 3.8% cumulative incidence of HCC compared to 8% in non-users, and a 10.6% risk of decompensation versus 19.5% in non-users. Lipophilic statins (e.g., atorvastatin, simvastatin) showed stronger protective effects, with prolonged use (≥600 cumulative doses) offering the greatest benefit.

Statin use was also tied to slower liver fibrosis progression. Among patients with intermediate fibrosis scores, 14.7% of statin users progressed to high-risk levels vs. 20% of non-users. Conversely, 31.8% of high-risk statin users regressed to intermediate fibrosis, compared to 18.8% of non-users. Researchers suggest statins may mitigate fibrosis, reducing HCC and decompensation risks.

While observational, the findings highlight statins potential as a low-cost preventive tool. Authors urge clinical trials to confirm causality, noting the need for large-scale studies to solidify statins role in liver disease management.

Source: JAMANETWORK

Why UFH Remains Overused for Acute PE?

Misconceptions and Institutional Habits Drive UFH Use Despite Guidelines

Source: JAMA

Despite guidelines recommending low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs) for most hospitalized patients with acute pulmonary embolism (PE), unfractionated heparin (UFH) continues to be commonly used. A study in JAMA Network Open reveals that misconceptions and institutional habits contribute to this trend.

From 2011 to 2020, the percentage of PE patients treated initially with UFH increased from 41.9% to 56.3%. Physicians expressed indifference toward anticoagulation choice, often believing it had little impact on outcomes. Misconceptions about UFH being stronger or safer, due to its quick-on, quick-off IV nature, were prevalent.

Institutional norms and training practices reinforced reliance on UFH, with many hospitalists avoiding transitions to LMWH or DOACs until discharge for convenience.

Experts highlight that LMWH is not contraindicated for catheter-directed interventions and can be partially reversed with protamine. Addressing these misconceptions through education, research, and policy changes is key to improving patient outcomes and aligning practice with evidence-based guidelines.

Source: JAMA

ASRAB-Pilot Trial: Rethinking Post-CABG Medications for Radial Artery Grafts

A Pilot Study Challenges Calcium Channel Blockers. Are Nitrates a better alternative?

This Chinese trial suggests that Nicorandil and Isosorbide Mononitrate may outperform the commonly used calcium channel blocker (diltiazem), in preventing spasm-induced radial artery (RA) graft failure following coronary artery bypass grafting (CABG).

The ASRAB trial, conducted between 2020 and 2022, randomized 150 CABG patients to receive either nicorandil (15 mg daily), isosorbide mononitrate (50 mg daily), or diltiazem (180 mg daily) for 24 weeks post-surgery. Coronary CT angiography at one week post-CABG showed RA graft failure rates of 18.2% (isosorbide mononitrate) and 19.4% (nicorandil) compared to 25% (diltiazem). At 24 weeks, failure rates remained lower with isosorbide mononitrate (12.5%) and nicorandil (16.1%) compared to diltiazem (27.8%).

Traditionally, RA grafts have been underutilized in CABG, despite strong guideline recommendations favoring their use over saphenous vein grafts, due to their higher long-term patency. One major concern has been postoperative spasm, which has led to the widespread use of calcium channel blockers, despite limited supporting evidence. The ASRAB trial supports the greater vasodilatory effect of nitric oxide donors such as nitrates and nicorandil, which may explain their lower failure rates.

Notably, the study also reported hypotension as a common side effect, affecting 22% (nicorandil), 20% (isosorbide mononitrate), and 32.6% (diltiazem), with renin-angiotensin-aldosterone system inhibitors needing withdrawal in 46.0%, 36.0%, and 53.1% of cases, respectively.

While the findings provide valuable insight, the study had limitations, including a highly selective patient population, a lack of a no-treatment control group, and being underpowered for clinical outcomes. However, it raises important questions about optimizing pharmacological management to improve RA graft patency and enhance long-term CABG outcomes.

GRAVITI-TRIAL

The FDA has expanded the approval of Guselkumab (Tremfya) for the treatment of moderately to severely active Crohn's disease. This dual-acting monoclonal antibody, an IL-23 inhibitor, is now available in both subcutaneous and intravenous induction forms.

This approval is supported by data from the phase III GRAVITI trial and the GALAXI program, involving over 1,300 patients who had failed prior therapies. Guselkumab therapy resulted in significantly higher clinical remission (47-56% vs. 15-22% with placebo, P<0.001) and endoscopic response (34-36% vs. 9-13%, P<0.001) at 12 weeks. At 48 weeks, guselkumab continued to show superior results compared to placebo, with clinical remission rates of 59-65% vs. 17%, and endoscopic remission of 31-40% vs. 6%.

When compared head-to-head with Ustekinumab (Stelara), another IL-23/IL-12 blocker, Guselkumab demonstrated superior endoscopic response. Common adverse events (≥3%) included respiratory tract infections, abdominal pain, headache, and fatigue. Warnings include potential hypersensitivity reactions, infections, and a contraindication for live vaccines.

In addition to Crohn’s disease, Guselkumab is also approved for plaque psoriasis and psoriatic arthritis, as well as UC, which it was approved for in 2024. Prior to starting treatment, patients should have liver enzyme and bilirubin levels checked, and receive any necessary vaccinations.

Over 10,300 cases reported in 2024, marking an 8% increase from the previous year

UNSPLASH

TBcases in the U.S. surged to their highest levels in more than 12 years. Last year, more than 10,300 cases were reported, an 8% increase from 2023, according to the CDC’s preliminary data. This marks the highest number of cases since 2011, with cases rising across all age groups. Alarmingly, 34 states experienced an increase in TB infections.

The rise in TB cases is primarily linked to international travel and migration, with the majority of U.S. cases diagnosed in individuals born outside the country. Additional factors such as other immune-compromising conditions have also contributed to the resurgence, causing latent TB infections to become active.

Recent outbreaks in various states, including a significant surge in Kansas City (148% increase), have driven these trends. States like Alaska and Hawaii continue to report the highest TB case rates.

Source: CDC

NEJM

Over a 13-week period, participants using an AID system experienced a 0.6 % greater reduction in HbA1c compared to the control group. The AID group saw their HbA1c drop from 8.2% to 7.3%, while controls only dropped from 8.1% to 7.7%.

In addition to better glycemic control, those using AID systems spent 3.4 more hours per day in the target glucose range (70-180 mg/dL), increasing their time from 48% to 64%. This improvement was notably higher compared to the control group, which saw little change.

The AID system used in the trial, consisting of the Tandem t:slim X2 insulin pump with Control-IQ+ technology and the Dexcom G6 continuous glucose monitor (CGM), was shown to benefit a variety of subgroups, including those using GLP-1 receptor agonists and SGLT2 inhibitors. AID use led to a substantial reduction in insulin dose, with participants using 87 units per day at 13 weeks, compared to 95 units per day at baseline.

The trial also revealed that even patients with a baseline HbA1c above 9% experienced significant improvements, with the AID group reducing HbA1c by 1.0 percentage point more than controls.

While the study found a modest weight gain in AID users (+2.4 kg vs 0.9 kg in controls), hypoglycemia rates remained low, and no new safety concerns arose for type 2 diabetes patients using AID.

This trial is the most rigorous evaluation of AID technology for type 2 diabetes patients and reinforces its potential to improve glycemic control and quality of life.

Source: NEJM

A retrospective study from Nagoya University Hospital raised concerns about the safety of discontinuing oral anticoagulants (OACs) after atrial fibrillation (Afib) catheter ablation. The study, following patients for a mean of 4.8 years, found that stopping OACs led to a higher thromboembolic risk: 0.86 events per 100 person-years compared to 0.37 in those continuing OACs. However, the discontinuation group experienced fewer bleeding events (0.10 vs 0.65 per 100 person-years).

Certain factors, such as asymptomatic Afib, left ventricular ejection fraction <60%, and left atrial diameter ≥45 mm, were linked to higher thromboembolic risks after stopping OACs. Conversely, OAC discontinuation was more favorable in patients with HAS-BLED scores ≥2, reducing bleeding risk without affecting survival.

The study suggests that OAC continuation is critical for high-risk patients, while those with a low-risk profile might safely discontinue. CHA2DS2-VASc scores should guide decisions, as clinical guidelines recommend continued OAC therapy for higher-risk individuals.

This research underscores the need for prospective randomized studies to determine the best approach for long-term anticoagulation in Afib patients after ablation. Until more data is available, careful consideration of the risks and benefitsof OAC discontinuation is essential.

Source: JAMA

D-Lay MS study demonstrated that high-dose vitamin D significantly reduced disease activity in early multiple sclerosis (MS) and clinically isolated syndrome (CIS). The trial followed 303 patients for 24 months, comparing those taking 100,000 IU of oral cholecalciferol every two weeks to a placebo group. The results were promising, showing that 60.3% of the vitamin D group experienced disease activity, compared to 74.1% of the placebo group (HR 0.66, 95% CI 0.50-0.87, P=0.004).

The median time to disease activity was significantly longer in the vitamin D group (432 days vs 224 days, P=0.003). MRI results also favored vitamin D supplementation with a reduction in MRI activity (HR 0.71, P=0.02), new lesions(HR 0.61, P=0.003), and contrast-enhancing lesions (HR 0.47, P=0.001).

These findings are important because vitamin D deficiency has been identified as a risk factor for MS, and this study is the first to provide real proof of vitamin D's efficacy in reducing disease activity in early MS and CIS. The effects of high-dose vitamin D were comparable to those of some disease-modifying drugs for MS, with excellent safety. With the increasing recognition of vitamin D's role in MS, this research offers a valuable step toward improving patient outcomes.

Source: JAMA

Substituting Butter with Plant-Based Oils Reduces Mortality Risk

JAMA

A large-scale study has found that higher butter intake is associated with increased mortality risk, while plant-based oils, such as olive, soybean, and canola oils, offer significant survival benefits. Over a follow-up of 33 years, those in the highest quartile for butter consumption had a 15% higher risk of death compared to those in the lowest quartile (HR 1.15, 95% CI 1.08-1.22). In contrast, higher intake of plant-based oils reduced mortality by 16% (HR 0.84, 95% CI 0.79-0.90), even when olive oil was excluded (HR 0.92, 95% CI 0.86-0.98).

Substituting just 10g of butter per day with plant-based oils was linked to a significant survival benefit (HR 0.83, 95% CI 0.79-0.86), especially for cancer-related deaths (HR 0.83, 95% CI 0.76-0.90). However, no significant effect was seen on cardiovascular disease mortality (HR 0.94, 95% CI 0.86-1.03). This study reinforces dietary guidelines from the American Heart Association and the Dietary Guidelines for Americans, which recommend replacing saturated fats like butter with healthier unsaturated fats to lower chronic disease risk.

Notably, affordable plant oils, such as canola and soybean oils, may offer an accessible alternative to more expensive options like olive oil, making it easier for people to adopt healthier dietary practices.

Source: JAMA

Faster tau accumulation may increase dementia risk

unsplash

A large meta-analysis of 6 longitudinal tau-PET studies reveals that women with high brain amyloid-beta (Aβ) accumulate tau at a significantly faster rate than men, particularly in brain regions most vulnerable to Alzheimer’s disease. Over an average of 2.8 years, women with high Aβ levels experienced accelerated tau buildup in the:

  • Inferior temporal region (β = -0.14, P=0.009)

  • Temporal fusiform region (β = -0.13, P=0.02)

  • Lateral occipital region (β = -0.15, P=0.009)

Among APOEε4 carriers, women also had faster tau accumulation in the inferior-temporal region (β = -0.10, P=0.01). These findings suggest that biological differences not just longevity contribute to women’s higher Alzheimer’s risk.

Tau accumulation is a critical step in Alzheimer’s progression, often preceding cognitive decline within a few years. Researchers emphasize the need for sex-specific considerations in the timing of anti-amyloid and anti-tau treatments, as well as further investigation into the roles of menopause, inflammation, and cardiovascular risk in disease progression.

This study, the largest longitudinal tau-PET meta-analysis to date, highlights the urgency of understanding when tau differences first emerge to better target preventive and therapeutic interventions.

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