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Madri: Among low-risk patients with acute MI who underwent early complete revascularisation and received one month of dual antiplatelet therapy (DAPT), P2Y12 inhibitor monotherapy was noninferior to continued DAPT for adverse cardiovascular and cerebrovascular events, while reducing bleeding risk.
These late-breaking findings were presented in a Hot Line session today at ESC Congress 2025 and simultaneously published in New England Journal of Medicine.
Current ESC Guidelines recommend 12 months of DAPT − aspirin plus a potent P2Y12 inhibitor − after percutaneous coronary intervention (PCI) for MI.2 Principal Investigator of the TARGET-FIRST trial, Professor Giuseppe Tarantini from the University of Padua, Italy, explained: “No randomised trials have previously assessed early aspirin discontinuation in acute MI patients who achieve early, complete revascularisation with modern stents. In such cases, bleeding risk may outweigh residual ischaemic risk, making antiplatelet therapy de-escalation attractive.”
In this open-label randomised controlled trial conducted at 40 European centres, eligible adults with an ST-segment elevation MI (STEMI) or non-STEMI underwent complete revascularisation within seven days using a contemporary drug-eluting stent and completed one month of DAPT without adverse events.
They were randomised 1:1 to continue DAPT or switch to P2Y12 inhibitor monotherapy for 11 months. The primary endpoint was a composite of all-cause death, MI, stent thrombosis, stroke or Bleeding Academic Research Consortium (BARC) type 3/5 bleeding at 11 months. Noninferiority was defined as an absolute difference ≤1.25 percentage points in the upper bound of the two-sided 95% CI.
The mean age of the 1,942 randomised patients was 61 years and 21.6% were women.
The primary endpoint occurred in 2.10% of the P2Y12 inhibitor monotherapy group and 2.18% of the continued DAPT group (difference –0.09 percentage points; 95% CI –1.39 to 1.20; p=0.021 for noninferiority). MI occurred in 0.7% vs. 1.1%, definite/probable stent thrombosis in 0.1% vs. 0.0% and ischaemic stroke in 0.3% vs. 0.2%, respectively. BARC type 3/5 bleeding occurred in 0.7% in each group.
The main secondary endpoint (BARC type 2/3/5 bleeding) was significantly lower with P2Y12 inhibitor monotherapy (2.65% vs. 5.57%; hazard ratio [HR] 0.46; 95% CI 0.29 to 0.75; p=0.002).
The patient-oriented composite outcome (all-cause death, MI, stent thrombosis, stroke, repeat ischaemia-driven revascularisation or BARC type 2/3/5 bleeding) occurred in 4.5% in the monotherapy group and 7.2% in the DAPT group (HR 0.61; 95% CI 0.42 to 0.89). Therapy adherence at 11 months was high in both groups (86.9% with monotherapy and 88.6% with DAPT).
Professor Tarantini concluded: “In low-risk acute MI patients with early complete revascularisation and no complications after one month of DAPT, switching to P2Y12 inhibitor monotherapy-maintained protection from ischaemic events and reduced bleeding. These results reflect the benefits of modern stents, high procedural success and optimal medical therapy, making early aspirin discontinuation feasible in this selected population.”
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People with learning disabilities progress faster to severe type 2 diabetes and are at greater risk of dying from their condition than people without these disabilities, suggests research published in the open access journal BMJ Open Diabetes Research & Control.
This is despite having better overall blood glucose control and similar risks of vascular complications, the findings indicate.
Around 1.5 million people (950,000 adults) in the UK have a learning disability, which includes conditions such as Down syndrome and cerebral palsy, note the researchers.
Type 2 diabetes in those with learning disabilities can be challenging as it requires a substantial amount of monitoring and management, which they may not always be able to do, potentially compromising their blood glucose control, explain the researchers.
But there’s been no large study on the potential impact of learning disabilities on the outcomes of type 2 diabetes, including blood glucose control, progression to microvascular and macrovascular complications, initiation of insulin therapy (proxy for severe disease), and risk of death, they add.
Macrovascular complications refer to stroke, coronary heart disease, heart failure, peripheral vascular disease, or amputation more than 6 months after diagnosis of type 2 diabetes. Microvascular complications refer to diabetic nephropathy, retinopathy, or neuropathy.
In a bid to plug this knowledge gap, the researchers extracted anonymised medical records for 352,215 adults newly diagnosed with type 2 diabetes in primary care between January 2004 and January 2021 from the UK Clinical Practice Research Datalink (CPRD) GOLD.
Of these, 280,300 met the eligibility criteria for inclusion in the study, 2074 of whom had a learning disability when they were diagnosed.
They tended to be younger (average age 51 vs 64) and have a shorter monitoring period. And they included higher proportions of men, people of White ethnicity, people living with severe obesity and in areas of greatest deprivation than those without learning disabilities.
They were also more likely to be taking medication for diabetes and high blood pressure and to have more complications related to diabetes at the time of their diagnosis.
Even after adjusting for these potentially influential risk factors they were 19% less likely to have poor blood glucose control than those without learning disabilities 5 years after diagnosis.
But they were 20% more likely to progress faster to severe disease and the need for insulin therapy than those who didn’t have learning disabilities.
And they were around twice as likely to die from any cause and specifically from diabetes despite having similar risks of vascular complications as those who didn’t have learning disabilities.
This is an observational study, and as such, can’t establish cause and effect, and the researchers acknowledge that large numbers of values for the outcome variables for blood glucose control were missing among those with learning disabilities. Complication rates may therefore have either been underdiagnosed or under-recorded, they suggest.
“Our finding of higher rates of insulin initiation in those with learning disabilities warrants further investigation into whether this is due to poorer glycemic control at presentation (and therefore faster advancing type 2 diabetes) or due to having a greater degree of clinical surveillance,” say the researchers.
“Future research into the mechanisms behind this could help reduce health disparities for people with [type 2 diabetes] and learning disabilities,” they add.
Reference:
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Taking low-dose colchicine daily may slow the progression of a common acquired gene mutation found in the blood of older adults that can lead to certain blood cancers and increased risk of cardiovascular disease, according to a subanalysis of the LoDoCo2 trial published in JACC, the flagship journal of the American College of Cardiology, and simultaneously presented at ESC Congress 2025.
Clonal hematopoiesis (CH) is an acquired mutation in blood stem cells that is linked to risk of developing leukemia and other blood cancers. It is also associated with a more than 1.5-fold increased risk of cardiovascular disease, including coronary heart disease, heart failure and arrhythmias. The most common driver genes that can lead to CH are DNMT3A, TET2 and ASXL1, which represent about 80% of CH cases. Research has shown that over 10% of people 70 years old and older carry one or more of these mutations and the risk increases with age.
In this study, researchers looked at a subset of participants in the LoDoCo2 Trial, which previously found that 0.5 mg daily of colchicine reduced the risk of cardiovascular disease by 31% in people with chronic coronary disease, to determine if colchicine also modified CH growth in the same individuals. Colchicine is a medication commonly used to treat gout and other inflammatory conditions.
Participants provided four blood samples: at the beginning of the study, after 30 days, one-year post randomization and at the end of the study. Their blood DNA was sequenced to detect and quantify CH mutations and analyze changes over time. Also, two blood biomarkers of inflammation were measured at the first three timepoints.
Those randomized to colchicine had a non-significant 6.3% annual increase in the number of overall mutated CH cells compared to a significant 14.9% increase in those taking placebo. Colchicine was associated with significantly attenuated clonal growth in TET2 CH, specifically, with a 9.1% annual increase in TET2 clone size in the colchicine group, compared with a 29.6% increase in the placebo group.
“These findings are striking in part because larger CH clones have been more strongly linked to both cardiovascular disease and cancer, and TET2 CH in particular has been consistently associated with increased cardiovascular risk,” said Michael Honigberg, MD, MPP, FACC, cardiologist at Massachusetts General Hospital and the study’s senior author. “Our study suggests that individuals with CH, especially TET2-mutated CH, may derive particular benefit from colchicine, including for cardiovascular risk reduction.”
In a second study published in JACC and being presented at ESC Conference 2025, researchers looked at whether CH’s relevance to cardiovascular disease risk decreased as women got older. Older adults have the highest risk of cardiovascular disease, and some previous studies have failed to demonstrate an association between CH and CVD after age 70.
Researchers in this study looked at over 6,600 women in the Women’s Health Initiative Long Life Study who had a median age of 80. They found that several CH subtypes (TET2, ASXL1, and JAK2) were associated with incident CVD, suggesting that CH remains associated with cardiovascular health into later life.
“Clonal hematopoiesis is emerging as a key link between aging, cardiovascular disease and cancer,” said Harlan Krumholz, MD, FACC, JACC Editor-in-Chief and Harold H. Hines Jr Professor of Medicine, Yale University School of Medicine. “This study advances our understanding of how inflammation and genetic changes in blood cells may shape cardiovascular risk, pointing to new opportunities for prevention and treatment.”
Reference:
Common inflammation drug may slow blood mutation, related CVD risk, Meeting: ESC Congress 2025.
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A new study published in the journal of Diabetologia showed that the intensity of menopausal symptoms is associated with moderate to severe abnormalities in glucose control, which are reported by almost two-thirds of postmenopausal women with type 1 diabetes.
The amount of insulin needed by women with type 1 diabetes varies throughout pregnancy and the menstrual cycle. Whether women with type 1 diabetes notice changes in glucose control during and after the menopausal transition has not yet been investigated. Thus, this study evaluated the relationships between glucose regulation and type 1 diabetes.
To find out if women with type 1 diabetes think that their glucose management has changed since their last menstrual cycle, this study performed a cross-sectional survey. In the Netherlands, adverts for the online surveys were placed in hospitals and on websites for individuals with type 1 diabetes. Type 1 diabetic postmenopausal women (≥1 year of amenorrhea) between the ages of 45 and 65 were included.
The study excluded participants who had been diagnosed with postmenopausal diabetes, premenopausal hysterectomy, or primary amenorrhea. Using a 5-point Likert scale, the main result measured how much individuals thought their glucose control had changed after their last menstrual cycle. The Greene climacteric scale (GCS) was used to measure the severity of menopausal symptoms.
A total of 159 ladies in all filled out the relevant questions. The average age of the participants was 54.9 years, their average duration of diabetes was 30.3 years, and their average age at menopause was 50.1 years.
In all, moderate to severe postmenopausal alterations in glucose control were reported by 67.4% of respondents. 41.9% reported higher glucose levels, 19.6% reported lower levels, and 38.5% reported no change. 55.0% of respondents said glucose fluctuations were more common, while 18.1% said they were less often.
While 38.5% of women reported more hypoglycemic incidents and 28.0% fewer, 61.6% of women reported an increase in hyperglycemic events. The severity of menopausal symptoms was higher after menopause than before (mean GCS 18.8 vs. 11.7; p<0.001).
The likelihood of experiencing glycemic alterations was positively correlated with the intensity of symptoms (adjusted OR 1.04; p=0.014). Furthermore, 57.2% reported having poor sleep quality (PSQI >5), although this did not correlate with perceived increases in blood sugar levels (adjusted OR 1.10; p=0.731).
Overall, because women going through the menopausal transition may encounter changes in glucose metabolism that may effect their treatment goals, the results illuminate the need of medical providers being aware of these changes while treating women with type 1 diabetes.
Source:
Speksnijder, E. M., Simsek, S., Bisschop, P. H., Stenvers, D. J., Siegelaar, S. E., & MenoPause Consortium. (2025). Perceived blood glucose regulation after menopause: a cross-sectional survey in women with type 1 diabetes in the Netherlands. Diabetologia. https://doi.org/10.1007/s00125-025-06518-z
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A new HIV antiretroviral shows promise as a long-acting, oral prophylactic agent, according to a new study by Izzat Raheem, Tracy Diamond and colleagues from Merck & Co., Inc., Rahway, NJ, USA, published August 26th in the open-access journal PLOS Biology.
HIV pre-exposure prophylaxis (PrEP) is a key part of reducing the number of new HIV infections. The most common oral PrEP therapies, consisting of once-daily pills, are highly effective at protecting people from acquiring HIV, but they only work if taken properly. Currently, the only long-acting PrEP therapies require injection by a healthcare provider, which isn’t always feasible for people. Long-acting, oral PrEP therapies could facilitate adherence, provide greater privacy and discretion, reduce concerns about stigma, and improve accessibility for more people to initiate and continue on PrEP, ultimately helping to stem the tide of the nearly 1.3 million new HIV infections globally per year.
Researchers from Merck engaged in a lead optimization campaign to develop a novel nucleoside reverse transcriptase translocation inhibitor (NRTTI). NRTTIs are a new class of anti-HIV drugs that have shown potential for long-acting prophylaxis. They inhibit viral replication by more than one mechanism, including blocking translocation of reverse transcriptase on the growing viral DNA chain.
Using a known NRTTI, islatravir, as a starting point, researchers used several medicinal chemistry strategies to modify the structure and optimize it using both in vitro and in vivo assays. The lead compound, dubbed MK-8527, showed robust antiviral activity in vitro, and pharmacokinetics in animal studies demonstrated that it may be suitable as a long-acting oral therapy. Studies in humans are underway to assess the safety and tolerability of MK-8527 as a once-monthly oral pill in volunteers at low likelihood of HIV exposure, and at least one completed clinical study shows promising results.
Reference:
Izzat T. Raheem ,Vinay Girijavallabhan,Kerry L. Fillgrove,Shih Lin Goh,Carolyn Bahnck-Teets,Qian Huang,Fangbiao Li,Bang-Lin Wan,Gregory T. O’Donnell,Jonathan B. Patteson,Maria E. Cilento,Amrith Bennet, MK-8527 is a novel inhibitor of HIV-1 reverse transcriptase translocation with potential for extended-duration dosing, PLOS Biology, https://doi.org/10.1371/journal.pbio.3003308.
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A father’s exposure to passive smoking as a child may impair the lifelong lung function of his children, putting them at risk of COPD-a risk that is heightened further if they are childhood passive smokers themselves-finds research published online in the respiratory journal Thorax.
The findings highlight the intergenerational harms of smoking, say the researchers, who urge fathers to intercept this harmful legacy by avoiding smoking around their children.
Chronic obstructive pulmonary disease, more usually known by its acronym of COPD, includes chronic bronchitis and emphysema. Now the third leading cause of death around the world, COPD kills around 3 million people every year, say the researchers.
Several factors throughout the lifespan may increase the risk of poor lung function and subsequent COPD, and attention is now beginning to focus on the potential role of intergenerational factors, they explain.
While previously published research showed that passive smoking during a father’s childhood may be linked to a heightened risk of asthma in his children by the time they are 7, it’s not clear if compromised lung function may extend into middle age and beyond, they add.
To explore this further, the researchers drew on 8022 child participants in the Tasmanian Longitudinal Health Study (TAHS), all of whom had tests to assess their lung function (spirometry).
Their parents completed an initial comprehensive survey on their and their children’s respiratory health. Further check-ups ensued when those children were 13, 18, 43, 50 and 53. These included spirometry to assess 2 measures of lung function (FEV1 and FVC) as well as questionnaires on demographics and respiratory symptoms/disease.
Of the 7243 parents who were alive and could be traced in 2010, 5111 were re-surveyed about whether either of their own parents had smoked when they were under the age of 5 and/or up to when they were 15.
Among the 5097 respondents with complete data, 2096 were fathers. The final analysis included 890 father-child pairs with data on the father’s passive smoke exposure before puberty and lung function data for their children up to the age of 53.
More than two thirds of the fathers (nearly 69%) and more than half of their children (56.5%) had been exposed to passive smoking during their childhoods.
Around half of the children (49%) had a history of active smoking by middle age, and just over 5% of them had developed COPD by this time point, as assessed by spirometry.
After adjusting for potentially influential factors, including the father’s lifetime history of asthma/wheeze and his age, his passive smoke exposure as a child was associated with 56% higher odds of below average FEV1, but not FVC, across the lifespan of his children.
Similarly, fathers’ childhood passive smoke exposure was also associated with a doubling in the odds of an early low-rapid decline in FEV1/FVC in their children. This was statistically significant even after adjusting for potentially influential factors.
And paternal exposure to passive smoking as a child was also associated with a doubling in the risk of COPD by the age of 53 in his children, although this was no longer statistically significant after adjusting for potentially influential factors.
But children whose fathers had been exposed to passive smoking as a child were twice as likely to have below average FEV1 if they, too, had been exposed to passive smoking during their childhood.
The observed associations were only partly mediated through smoking and respiratory illnesses in fathers and their children (each contributing less than 15%).
This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. And the researchers acknowledge that TAHS lacks data on paternal lung function and genetics, preventing assessment of familial aggregation as a potential mechanism.
And their children’s childhood passive smoke exposure was defined as at least one parent smoking 6 days a week, which might have misclassified moderate/light smokers as non-smokers, they add.
But the period before puberty is especially critical for boys, when exposure to harmful substances may change gene expression and modify repair mechanisms, which may then become heritable, say the researchers by way of an explanation for their findings.
“Our findings are novel as this is the first study to investigate and provide evidence for an adverse association of paternal prepubertal passive smoke exposure, rather than just active smoking, on impaired lung function of offspring by middle age,” they write.
“This is of importance from a public health perspective, as passive smoke exposure affects about 63% of adolescents, which is significantly higher than the approximately 7% affected by active smoking.”
They conclude: “These findings suggest that smoking may adversely affect lung function not only in smokers but also in their children and grandchildren…Fathers exposed to tobacco smoke during prepuberty may still reduce risk for future generations by avoiding smoking around their children.”
Reference:
https://thorax.bmj.com/lookup/doi/10.1136/thorax-2024-222482
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New Delhi: With an aim to ease the processes for preclinical and analytical drug testing, the Ministry of Health and Family Welfare has released draft rules to amend the New Drugs and Clinical Trials Rules, 2019, proposing the approval timelines for the Central Licensing Authority to grant permissions under Rules 53 and 60 will be reduced from ninety working days to forty-five working days.
Under the proposed amended Rule 52(1) of the New Drugs and Clinical Trials Rules, 2019, no person will be allowed to manufacture a new drug or an investigational new drug for the purpose of conducting a clinical trial, a bioavailability or bioequivalence study, or for examination, testing, and analysis, without first obtaining permission from the Central Licensing Authority, or through a notification as provided under the proviso to sub-rule (2) of Rule 52, as applicable.
A new provision has been added after sub-rule (2) of Rule 52 of the New Drugs and Clinical Trials Rules, 2019, which allows the manufacture of a new drug or investigational new drug for analytical and preclinical testing on the basis of an online notification, rather than waiting for prior approval. However, this relaxation will not apply to certain sensitive categories, namely sex hormones, cytotoxic drugs, beta-lactam antibiotics, biologics containing live microorganisms, and narcotic or psychotropic substances.
This came as a draft of certain rules further to amend the New Drugs and Clinical Trials Rules, 2019, which the Central Government proposes to make, in exercise of the powers conferred by sub-section (1) of section 12 and sub-section (1) of section 33 of the Drugs and Cosmetics Act, 1940 (23 of 1940), after consultation with the Drugs Technical Advisory Board is hereby published for information of all persons likely to be affected thereby, and notice is hereby given that the said draft rules shall be taken into consideration on or after the expiry of a period of thirty days from the date on which the copies of the Gazette of India containing these draft rules are made available to the public.
The draft amendment to Rule 53 of the New Drugs and Clinical Trials Rules, 2019, proposes to expedite approvals by reducing the time limit for the Central Licensing Authority to process applications. The existing period of ninety working days under sub-rule (1) and clause (ii) of sub-rule (3) will be cut down to forty-five working days, effectively halving the approval timeline for new drug and clinical trial applications.
The draft amendment to Rule 59 of the New Drugs and Clinical Trials Rules, 2019 introduces a proviso allowing manufacturers to produce a new drug or investigational new drug for analytical and preclinical testing on the basis of an online notification instead of prior approval. However, this relaxation will not apply to specific high-risk categories such as sex hormones, cytotoxic medicines, beta-lactam antibiotics, biologics containing live microorganisms, and narcotic or psychotropic substances.
The draft amendment to Rule 60 of the New Drugs and Clinical Trials Rules, 2019 proposes to cut down the approval timelines for permissions granted by the Central Licensing Authority.
Rule 60 of the New Drugs and Clinical Trials Rules, 2019 deals with the grant of permission to manufacture unapproved active pharmaceutical ingredients for the development of pharmaceutical formulations for tests or analysis or clinical trials or bioavailability and bioequivalence studies.
At present, the authority has up to ninety working days to approve or reject applications for manufacturing or importing new drugs and investigational new drugs. The draft amendment reduces this timeframe to forty-five working days, thereby halving the approval period and allowing faster initiation of clinical trials, bioavailability and bioequivalence studies, and related drug development activities in the country.
As per the proposed amendment,
“1. (i) These rules may be called the New Drugs and Clinical Trials (… Amendment) Rules, 2025.(ii) These rules shall come into force from the date as specified by the Government at the time of final publication of the rules in the Official Gazette.2. In the New Drugs and Clinical Trials Rules, 2019, the sub-rule (1) of rule 52 shall be substituted, namely:―“(1) No person shall manufacture a new drug or an investigational new drug to conduct a clinical trial or bioavailability or bioequivalence study or for examination, test and analysis without obtaining permission or the notification as referred to in the provision to sub-rule (2) of rule 52 to the Central Licensing Authority, as the case may be, to manufacture such new drug or investigational new drug.”3. In the New Drugs and Clinical Trials Rules, 2019, after the sub-rule (2) of rule 52, the following proviso shall be inserted, namely: ―“Provided that in case of manufacture of new drug or Investigational new drug for Analytical and preclinical testing (excluding the new drug and Investigational new drug of category of sex hormones, cytotoxic, beta lactum, Biologics with live microorganism and narcotics & psychotropic drugs) an online application shall be submitted as notification and applicant can manufacture such drugs based on the notification.”4. In the New Drugs and Clinical Trials Rules, 2019, in rule 53: ―(a) under the sub-rule (1), the words “ninety working days” shall be substituted with the words “forty-five working days” wherever occurs.(b) under the clause (ii) of sub-rule (3), the words “ninety working days” shall be substituted with the words “forty-five working days”.5. In the New Drugs and Clinical Trials Rules, 2019, after the sub-rule (1) of rule 59, the following proviso shall be inserted, namely: ―“Provided that in case of manufacture of new drug or Investigational new drug for Analytical and preclinical testing (excluding the new drug and Investigational new drug of category of sex hormones, cytotoxic, beta lactum, Biologics with live microorganism and narcotics & psychotropic drugs) an online application shall be submitted as notification and applicant can manufacture such drugs based on the notification.”6. In the New Drugs and Clinical Trials Rules, 2019, in rule 60: ―(a) under the clause (i) of sub-rule (1), the words “ninety working days” shall be substituted with the words “forty-five working days”.(b) under the clause (ii) of sub-rule (1), the words “ninety working days” shall be substituted with the words“forty-five working days”.(c) under the clause (ii) of sub-rule (2), the words “ninety working days” shall be substituted with the words“forty-five working days”.”
Further, the gazette notification stated that objections and suggestions that may be received from any person within the period specified above will be considered by the Central Government.
“Objections and suggestions, if any, may be addressed to the Under Secretary (Drugs), Ministry of Health and Family Welfare, Government of India, Room No. 545, A Wing, Nirman Bhavan, New Delhi – 110011 or emailed at drugsdiv-mohfw@gov.in.”the notification added.
To view the official notice, click the link below:
https://medicaldialogues.in/pdf_upload/20250827gsr-588e-299522.pdf
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