With any luck, we will also find time for another listening party, where the rotation is likely to include this, this, this, this and this. And what about you? Summer is rapidly nearing an end, but there is still time to enjoy the great outdoors. Remember, beaches, lakes, and hiking trails are beckoning. This may also be an opportunity to sample new eateries or catch up on your reading, or perhaps, simply plan the rest of your life. Well, whatever you do, have a grand time. But be safe. Enjoy, and see you on Tuesday, since this is a holiday weekend on this side of the pond. …

Novo Nordisk’s obesity drug Wegovy cut the risk of severe complications in patients with a common form of heart failure, according to a new analysis that could boost the company’s efforts to expand the label for the blockbuster treatment, STAT writes. Researchers combined data on nearly 4,000 patients across four trials who had heart failure with reduced ejection fraction (or HFpEF) and found that 5.4% of those treated with Wegovy experienced cardiovascular-related death or heart failure events, compared with 7.5% of those who received placebo. This translated to a 31% risk reduction. On heart failure events, defined as hospitalizations or urgent care visits, Wegovy cut the risk by 41%. On cardiovascular-related deaths, it reduced the rate by 18%, but this result was not statistically significant.

Meanwhile, Wegovy demonstrated still another benefit to patients in a study that found, compared to placebo, the medicine cut the chances of dying from Covid-19 by roughly a third, STAT notes. Given that obesity is a major risk factor for severe Covid outcomes, it perhaps seems obvious that a medicine that helps people lose weight also helps protect them from the worst tolls of a SARS-CoV-2 infection. But researchers say it might not be as straightforward as that. “All of that just means somebody is in a better state when they get hit by a medical disaster like a severe Covid infection,” said Benjamin Scirica, a cardiovascular medicine specialist at Brigham and Women’s Hospital in Boston, who presented the data Friday at the European Society of Cardiology’s annual meeting in London.

Continue to STAT+ to read the full story…

Apolipoprotein(a) (apo(a)) is covalently bonded to apoB100 within a modified low-density lipoprotein (LDL) particle to form lipoprotein(a) (Lp(a)). A substantial amount of data points to Lp(a) as a causative factor in the processes that encourage calcific aortic valve disease and atherogenesis. Based on Mendelian randomization studies, a significant decrease in Lp(a) could be necessary in order to provide a significant therapeutic effect.

Olpasiran is a small interfering RNA (siRNA) molecule linked to N-acetylgalactosamine (GalNAc) that obstructs the expression of the LPA gene by causing the messenger RNA encoding apo(a) to break down, thereby stopping the hepatocyte from assembling the Lp(a) particle. Olpasiran is a small interfering RNA (siRNA) that inhibits the translation of apolipoprotein(a) mRNA, hence blocking the formation of lipoprotein(a) (Lp(a)). This research by Michelle O'Donoghue and colleagues evaluated both the longer-term safety and the timing of Lp(a) returning to baseline following olpasiran withdrawal.

In the phase 2 dose-finding trial OCEAN(a)-DOSE (Olpasiran Trials of Cardiovascular Events And LipoproteiN[a] Reduction–DOSE Finding Study), a total of 281 participants with atherosclerotic cardiovascular disease and Lp(a) >150 nmol/L were enrolled to receive one of four active doses of olpasiran versus placebo (10 mg, 75 mg, 225 mg Q12W, or an exploratory dose of 225 mg Q24W administered subcutaneously). Week 36 was the last dosage of olpasiran, and after week 48, there was a minimum 24-week prolonged off-treatment follow-up period.

276 individuals (98.2%) of the total study population started the post-treatment follow-up phase. The mean duration of the trial encompassed both treatment and non-treatment periods, was 86 weeks (Q1-Q3: 79-99 weeks). At 60, 72, 84, and 96 weeks, the off-treatment placebo-adjusted mean percent decrease from baseline in Lp(a) for the 75 mg Q12W dosage were −76.2%, −53.0%, −44.0%, and −27.9%, respectively (all P < 0.001).

For the 225 mg Q12W dosage, the corresponding off-treatment decreases in Lp(a) were −84.4%, −61.6%, −52.2%, and −36.4% (all P < 0.001). In the follow-up phase of the extension, no additional safety issues were found. Overall, the RNA interference of Olpasiran causes a significant decrease in Lp(a), with long-term pharmacodynamic effects that last for many months after therapy is stopped.

Source:

O’Donoghue, M. L., Rosenson, R. S., López, J. A. G., Lepor, N. E., Baum, S. J., Stout, E., Gaudet, D., Knusel, B., Kuder, J. F., Murphy, S. A., Wang, H., Wu, Y., Shah, T., Wang, J., Wilmanski, T., Sohn, W., Kassahun, H., & Sabatine, M. S. (2024). The Off-Treatment Effects of Olpasiran on Lipoprotein(a) Lowering. In Journal of the American College of Cardiology (Vol. 84, Issue 9, pp. 790–797). Elsevier BV. https://doi.org/10.1016/j.jacc.2024.05.058

View the full post Ministry of Health statement on infant deaths at The General Hospital on NOW Grenada.