Latest news with #2025ScientificSessions
Medscape
05-05-2025
- Health
- Medscape
Single Antiplatelet After TAVR Lowers Risk
Patients who received a single antiplatelet drug therapy— usually aspirin — after transcatheter aortic valve replacement (TAVR) had about half the risk of dying in the subsequent 6 months compared with patients who received dual antiplatelet drug therapy. The findings were similar in men and women and in patients with and without coronary artery disease. Francesco Pelliccia, MD, PhD 'This is one of the first demonstrations in real-world data that single antiplatelet therapy is not only associated with a lower risk of bleeding but also lower mortality,' said lead author Francesco Pelliccia, MD, PhD, a cardiologist at Sapienza University in Rome, Italy. Mortality rates for those who received dual antiplatelet therapy increased steadily during the 6 months after the procedure, he reported at the Society for Cardiovascular Angiography and Interventions (SCAI) 2025 Scientific Sessions in Washington, DC. Ischemic and major bleeding events were dramatically reduced in those receiving a single drug, according to a real-world study of 5514 patients undergoing TAVR at 20 centers. The centers participate in the Transfusion Requirements in Transcatheter Aortic Valve Implantation (TRITAVI) registry. In the 6 months after the procedure, 2.4% of the 3197 patients who received a single antiplatelet drug died of any cause, as did 5.4% of 2317 patients who received two antiplatelet drugs (hazard ratio [HR], 1.65). Dual therapy was associated with a higher risk for death in both men (HR, 2.08) and women (HR, 1.53). Risk for death was also higher in patients with coronary artery disease (HR, 1.83) and without coronary artery disease (HR, 1.52). All results were statistically significant. Balancing Risks and Benefits The popularity of TAVR, which was introduced in 2002, has grown to the point that, in 2019, it surpassed the use of surgical aortic valve replacement. But the procedure is associated with an increased risk for both thrombosis and bleeding. Antiplatelet therapy with aspirin and clopidogrel helps prevent thrombosis but can increase the risk of bleeding. This has led to a debate about the best balance for antiplatelet therapy after TAVR with either single therapy — usually with aspirin — or dual therapy with both aspirin and clopidogrel. A series of studies have addressed this problem. Dual therapy did not show any benefits over single therapy in terms of major adverse cardiac and cerebrovascular events in a 2011 small randomized study. A 2014 small randomized study also showed no benefit for morbidity or mortality from dual therapy. A larger 2017 randomized trial showed that single therapy reduced the risk for major or life-threatening events but did not increase the risk for myocardial infarction or stroke. Bleeding and bleeding plus thromboembolic events were significantly lower with aspirin than with aspirin plus clopidogrel after a year's follow-up in the 2020 POPular TAVI trial. Findings from three of these trials were pooled in a 2018 meta-analysis, which showed that dual therapy increased the risk for major adverse events after TAVR and did not prevent ischemic events any more than single therapy. Based on this evidence, many centers changed their practice. And current European guidelines recommend a single antiplatelet drug for patients undergoing TAVR who do not have additional indications for oral anticoagulation therapy. By the Numbers Randomized trials are generally considered the best evidence for medical questions such as this one. 'But randomized trials often do not reflect real-world reality. We have to look at what really happens,' Pelliccia said. Retrospective data from registries can also provide large numbers of patients; in this case, TRITAVI provided data on thousands of patients rather than the hundreds examined in combined randomized trials. 'The results, for the first time, provide clinicians more information on how to treat their patients who are at high risk for bleeding and provide evidence that single antiplatelet therapy should be considered the standard of care in all patients undergoing TAVR,' Pelliccia said.
Yahoo
30-03-2025
- Health
- Yahoo
Lilly's lepodisiran reduced levels of genetically inherited heart disease risk factor, lipoprotein(a), by nearly 94% from baseline at the highest tested dose in adults with elevated levels
In Phase 2 ALPACA results, lepodisiran significantly reduced levels of genetically inherited cardiovascular risk factor, with some patients sustaining reductions for nearly 1.5 years These data were presented at the American College of Cardiology 2025 Scientific Sessions and simultaneously published in the New England Journal of Medicine (NEJM) INDIANAPOLIS, March 30, 2025 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced positive Phase 2 results for lepodisiran, an investigational small interfering RNA (siRNA) therapy designed to lower the production of lipoprotein(a) [Lp(a)], a genetically inherited risk factor for heart disease. In the Phase 2 ALPACA study, lepodisiran significantly reduced Lp(a) levels by an average of 93.9% over the 60 to 180-day period after treatment with the highest tested dose (400 mg), meeting the primary endpoint.i Participants who received the 16 mg and 96 mg lepodisiran doses experienced a 40.8% reduction and a 75.2% reduction in Lp(a) levels over the same time period, respectively.i Lepodisiran also met additional secondary endpoints, showing reductions in Lp(a) levels following one or two administrations of each of the three tested doses across all timepoints assessed throughout the nearly 18-month-long Lepodisiran was administered twice at each dose (16 mg, 96 mg, or 400 mg), once at baseline and at day 180, with a separate group receiving 400 mg at baseline and placebo at day 180. The effect of additional doses of lepodisiran remains undetermined. "Nearly a quarter of the world's population has elevated levels of Lp(a), putting them at a significantly higher risk of cardiovascular events such as heart attacks and strokes. Unfortunately, there are no approved cholesterol-lowering therapies specifically for this genetic risk factor, and lifestyle changes like diet and exercise do not provide meaningful reductions," said Steven Nissen, M.D., chief academic officer of the Heart, Vascular & Thoracic Institute at the Cleveland Clinic. "These significant and sustained Lp(a) reductions are encouraging and suggest that siRNA approaches like lepodisiran could potentially offer durable benefits with long-term dosing." About 20% of Americans have high levels of Lp(a), which increases their risk of cardiovascular disease.1,2 Elevated Lp(a) levels can double or even triple the risk of a heart attack and are associated with other cardiovascular issues such as stroke and heart valve narrowing (aortic valve stenosis).3,4,5 Lepodisiran is an investigational siRNA therapy designed to reduce levels of Lp(a) by inhibiting the production of apolipoprotein(a) (apo[a]), a key component of Lp(a). "Reducing the inherited cardiovascular risk for patients with high Lp(a) has long been a critically unmet need. These results offer hope for a long-term, durable treatment option," said Ruth Gimeno, group vice president, diabetes, obesity and cardiometabolic research at Lilly. "These data underscore Lilly's commitment to advancing genetic medicine to address one of the world's most pressing healthcare challenges. We will continue to evaluate the potential benefits of lepodisiran in the ongoing Phase 3 cardiovascular outcomes trial." Results from additional secondary endpoints showed: Participants who received 400 mg of lepodisiran at both baseline and day 180 experienced a 94.8% reduction in average Lp(a) levels over the day 30 to 360 period, which remained 91.0% below baseline at day 360 (~1 year) and 74.2% below baseline at day 540 (~1.5 years).ii Lepodisiran also reduced apolipoprotein B (apoB) levels, a separate cholesterol biomarker. The highest dose (400 mg) of lepodisiran showed 14.1% and 13.7% ApoB reductions from baseline at day 60 and 180, respectively. A second 400 mg lepodisiran dose at day 180 sustained these apoB reductions through day Treatment-emergent adverse events (TEAEs) related to the study drug occurred in 1% (1/69) of the placebo group, 3% (1/36) of the 16 mg group, 12% (9/74) of the 96 mg group and 14% (20/141) of the pooled 400 mg group. There were no serious adverse events related to lepodisiran treatment. A single death occurred in the 16 mg dose group due to complications of chronic coronary disease. One participant in the placebo group was withdrawn from the study drug due to a TEAE; however, no participants receiving lepodisiran experienced a TEAE leading to withdrawal from treatment or the study. The ACCLAIM-Lp(a) Phase 3 clinical development program, investigating the effect of lepodisiran on the reduction of cardiovascular events in adults with elevated Lp(a), is currently enrolling. About ALPACAALPACA was a randomized, double-blind, placebo-controlled Phase 2 study designed to investigate the efficacy and safety of lepodisiran in adults with elevated Lp(a). A total of 320 participants were randomized to receive either placebo or one of three doses of lepodisiran (16 mg, 96 mg, or 400 mg) both at baseline and day 180. An additional group received 400 mg of lepodisiran at baseline and placebo at day 180. Results from the two groups receiving 400 mg of lepodisiran were pooled for the primary analysis. The primary endpoint was placebo-adjusted, time-averaged percent change in Lp(a) serum concentration from day 60 to 180. About LillyLilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit and or follow us on Facebook, Instagram, and LinkedIn. P-LLY Trademarks and Trade Names All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are references in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company's or their rights thereto. We do not intend the use or display of other companies' trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies. i Placebo-adjusted values based on the treatment-regimen Placebo-adjusted values based on the efficacy estimand, which represents efficacy prior to discontinuation of study drug or initiation of medications known to affect lipoprotein(a). Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about lepodisiran as a potential treatment for people with high risk for cardiovascular events and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study results to date, that lepodisiran will prove to be a safe and effective treatment for the reduction of cardiovascular events associated with a reduction in Lp(a), that lepodisiran will receive regulatory approval, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. References Family Heart Foundation. Lipoprotein(a) - Family Heart Foundation. Last accessed Feb. 20, 2025. Family Heart Foundation. Diagnosing High Lipoprotein(a) - Family Heart Foundation. Last accessed Feb. 20, 2025. Harvard Medical School. Heart Health: The Latest on Lipoprotein(a), an Inherited Cause of Early Heart Disease. Last accessed Feb. 20, 2025. NIH National Heart, Lung, and Blood Institute. Research Feature – Lipoprotein(a): What to know about elevated levels. Access here: https:// Last accessed Feb. 20, 2025. Khan, M. I., et al. Role of Lipoprotein (A) in aortic valve stenosis: Novel disease mechanisms and emerging pharmacotherapeutic approaches. IJC Heart & Vasculature 2024;55, 101543. Refer to: Stefanie Prodouz; 317-287-9899 (Media)Michael Czapar; czapar_michael_c@ 317-617-0983 (Investors) View original content to download multimedia: SOURCE Eli Lilly and Company Sign in to access your portfolio
