Episode 394: 402. Cardiovascular Risk Factors, Zilebesiran, Shared Decision Making

https://www.nejm.org/doi/10.1056/NEJMoa2415879?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Key Findings:

1. Classic Risk Factors: The five risk factors examined were hypertension, hyperlipidemia, underweight and overweight or obesity, diabetes, and smoking. These factors are estimated to account for about 50% of the global burden of cardiovascular disease.
2. Lifetime Risk Estimates:
   • Among individuals free of these risk factors at age 50, the lifetime risk of cardiovascular disease was 13% for women and 21% for men.
   • For those with all five risk factors, the lifetime risk jumped to 24% for women and 38% for men.
3. Significance of Risk Factor Modification:
   • Adjusting certain risk factors during midlife, particularly managing hypertension and quitting smoking, led to the most significant gains in life expectancy free of disease.
   • For instance, controlling hypertension between ages 55 and 60 yielded the most additional life-years free of cardiovascular disease.
   • Quitting smoking during the same period was associated with the most additional life-years free of death from any cause.

https://jamanetwork.com/journals/jama/fullarticle/2834632

1. Study Design:
   • This was a phase 2, randomized, double-blinded trial with participants enrolled from 150 sites across 8 countries. The study spanned from January 2022 to June 2023, with analyses completed by March 2024.
   • Participants received indapamide, amlodipine, or olmesartan as background therapy. Those with a specified range of 24-hour mean ambulatory systolic blood pressure (SBP) were then randomized to receive either a single subcutaneous dose of 600 mg zilebesiran or placebo.
2. Efficacy Results:
   • At 3 months, zilebesiran significantly reduced the 24-hour mean ambulatory SBP compared to placebo across all cohorts:
     • Indapamide: -12.1 mmHg
     • Amlodipine: -9.7 mmHg
     • Olmesartan: -4.5 mmHg
   • Similar reductions were observed in office SBP measurements at 3 months.

https://pubmed.ncbi.nlm.nih.gov/40578930/

1. Primary Outcomes:
   • Discontinuation of Opioid Therapy: Patients in the greater SDM group were less likely to discontinue opioid therapy 3 months post-baseline compared to those in the lesser SDM group (Relative Risk: RR of 0.56).
   • Opioid Prescribing Frequency: Over a 12-month period, patients in the greater SDM group experienced more frequent opioid prescriptions (RR of 1.24).
2. Secondary Outcomes:
   • Physical Function: Interestingly, physical function was slightly worse in the greater SDM group, but this difference was not deemed clinically significant.
   • Back-related Disability: Both greater opioid use and SDM were associated with increased back-related disability and worse physical function, yet these findings were also not clinically significant.
   • No significant SDM x opioid therapy interaction effects were observed, indicating that more frequent opioid use coupled with SDM did not lead to better patient outcomes in pain, function, or health-related quality of life (HRQOL).