Medical Bulletin 12/November/2025

Low vitamin D levels have long been linked to adverse cardiovascular outcomes, but previous studies using standard supplementation doses failed to show measurable benefits. The Intermountain team aimed to test a more personalized strategy, adjusting supplementation based on blood levels rather than providing the same dose to all patients.

The TARGET-D trial enrolled 630 patients who had experienced a heart attack within one month of joining the study. Conducted from April 2017 to May 2023, with follow-up through March 2025, participants were randomly assigned to receive either no vitamin D management or active, targeted vitamin D3 treatment. The treatment group’s goal was to maintain blood vitamin D levels above 40 nanograms per milliliter (ng/mL). At enrollment, 85% of patients had levels below that threshold.

More than half of the patients in the treatment group required initial doses of 5,000 international units (IU) of vitamin D3—far higher than the typical 600–800 IU daily recommendation. Blood levels were checked regularly, and doses were adjusted until the target range was achieved.

Researchers tracked major adverse cardiac events (MACE), including heart attacks, strokes, heart failure hospitalizations, or deaths. Of the 630 participants, 107 experienced such events. While the overall MACE rates did not differ significantly between the two groups, the risk of a second heart attack was reduced by half among those receiving targeted vitamin D therapy.

Researchers plan to expand their work with a larger clinical trial to confirm these promising findings and explore whether targeted vitamin D management can also reduce other cardiovascular complications.

Reference: https://intermountainhealthcare.org/

New Smart Calculator Estimates How Well Blood Pressure Drugs Work: Lancet Study

A powerful new calculator predicts the blood pressure–lowering effects of hundreds of drugs, helping doctors tailor treatments more effectively. The findings were recently published in The Lancet, with researchers suggesting it could transform hypertension care worldwide. Developed using data from nearly 500 randomized clinical trials involving more than 100,000 participants, the tool enables physicians to estimate how much various medications can reduce a patient’s blood pressure with unprecedented precision.

Researchers at The George Institute for Global Health explained that the calculator allows clinicians to personalize therapy based on how much each patient needs to lower their blood pressure. The calculator works by analyzing average treatment effects across hundreds of studies and classifying therapies as low, moderate, or high intensity depending on their blood pressure (BP)–lowering impact—an approach similar to cholesterol management strategies. On average, a single blood pressure medication lowers systolic BP by only 8–9 mmHg, while many patients require drops of 15–30 mmHg to achieve target levels.

Anthony Rodgers, Senior Professorial Fellow at The George Institute, said the new tool challenges the traditional “start low, go slow, measure and judge” approach. “With this new method you specify how much you need to lower blood pressure, choose an ideal treatment plan to achieve that based on the evidence, and get the patient started on that ideally sooner rather than later.”

High blood pressure remains one of the world’s most serious health threats, affecting 1.3 billion people and causing roughly 10 million deaths annually. Researchers emphasized that even modest improvements in treatment precision could save millions of lives globally.

Reference: Nelson Wang, Abdul Salam, Rashmi Pant, Amit Kumar, Rupasvi Dhurjati, Faraidoon Haghdoost, Kota Vidyasagar, Prachi Kaistha, Hariprasad Esam, Sonali R Gnanenthiran, Raju Kanukula, Paul K Whelton, Brent Egan, Aletta E Schutte, Kazem Rahimi, Otavio Berwanger, Anthony Rodgers. Blood pressure-lowering efficacy of antihypertensive drugs and their combinations: a systematic review and meta-analysis of randomised, double-blind, placebo-controlled trials. The Lancet, 2025; 406 (10506): 915 DOI: 10.1016/S0140-6736(25)00991-2

Semaglutide and Tirzepatide Show Heart Benefits Beyond Weight Loss: Nature Medicine Study

A new database study has found that the injectable weight-loss drugs semaglutide and tirzepatide significantly reduce the risk of serious cardiovascular events in people with type 2 diabetes. The findings, published in Nature Medicine, show that these GLP-1-based therapies offer evident heart benefits beyond weight loss. Researchers from the Technical University of Munich (TUM) and Harvard Medical School compared the two drugs using large-scale insurance claims data from U.S. health insurers, revealing reductions in cardiovascular risk of up to 18 percent.

The study demonstrates that both semaglutide and tirzepatide provide cardioprotective effects in high-risk patients with type 2 diabetes. Compared with sitagliptin, a diabetes medication shown in earlier studies to lack cardiovascular benefits, semaglutide reduced the combined risk of stroke and heart attack by 18 percent. Tirzepatide, in comparison with dulaglutide—an older GLP-1 drug—lowered the risk of stroke, heart attack, or death by 13 percent.

The exact biological mechanisms behind these benefits remain unclear, but the results mark an important step toward understanding the broader effects of GLP-1 drugs. Since semaglutide and tirzepatide are relatively new therapies, direct comparative data on their cardiovascular effects have been limited.

"We hope our findings will provide clarity to physicians about how these new medications perform in clinical practice. Our transparent study design is also intended to support open scientific discussion about whether and how modern GLP-1 drugs should become part of the standard therapeutic repertoire in cardiovascular medicine,” said Dr. Nils Krüger, first author of the study and resident physician at the Department of Cardiovascular Diseases at the TUM University Hospital German Heart Center.

Reference: Krüger, N., Schneeweiss, S., Desai, R.J. Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice. Nat Med (2025). DOI: 10.1038/s41591-025-04102-x