Episode Overview

Podcast: AACE Podcasts
Episode: 57 – 2025 AACE Dyslipidemia Guideline Overview
Date: February 5, 2025
Host: Dr. David Lieb
Guests: Dr. Shailesh Patel (Chair, Guideline), Dr. Kathleen (Kitty) Wein (Vice Chair, Guideline)
Theme:
A deep dive into the new 2025 AACE guideline on the pharmacologic management of adults with dyslipidemia. The discussion covers key changes since the 2017 guideline, introduces the GRADE methodology, explores practical implications for clinicians, and highlights gaps in current research.

Key Discussion Points & Insights

1. Introduction of the Experts and Their Backgrounds

• Dr. Shailesh Patel: Veteran endocrinologist focused on lipid metabolism and rare lipid disorders; foundational work on genetic disorders like sitosterolemia (ABCG5/8 genes); trained under Scott Grundy, a pioneer in lipid guidelines.
  • “My depth of lipid knowledge is really quite extensive...I was happy when I was asked to be chair of this particular guideline, especially...how we are proposing the guidelines for practice.” (01:29)
• Dr. Kathleen Wine: Clinical expertise in complex lipid disorders and type 1 diabetes; research roots in apolipoprotein physiology.
  • “I have this combination of lipid disorders and type 1 diabetes as my clinical specialties.” (03:13)

2. What’s New in the 2025 Dyslipidemia Guideline

• Incremental Updates:
  The guideline builds on 2017 recommendations, integrating new evidence and updates in pharmacotherapy.
• Incorporation of New Medications:
  Discussion of the latest FDA-approved lipid-lowering therapies, their benefits, and limitations.
• Adoption of GRADE Methodology:
  • “What is different is that we are going to be using the GRADE approach to actually propose the newer changes...” – Dr. Patel (04:37)

3. GRADE Methodology: A Paradigm Shift

• What is GRADE?
  GRADE = Grading of Recommendations, Assessment, Development and Evaluation.
  • “GRADE...takes not just the science base, but it actually looks at the applicability...and also takes into account the patient's perspective as well.” – Dr. Patel (08:02)
• How GRADE Impacted the Guideline:
  • Systematic, transparent, patient-centered assessment of evidence.
  • Ensures all available trial data is accounted for.
  • Involvement of primary care and patient feedback in the process.
  • “I truly felt...confident that we had looked at everything we possibly could.” – Dr. Wein (06:37)

Notable Moment:

• Practical feedback loop from primary care physicians and patients ensured recommendations are usable in real-world settings.
  • “Our primary care doctor would say, wait a minute, in reality, my patients can't drive two hours to the city to do this.” – Dr. Wein (10:11)

4. Surprises and Challenges in the Literature (11:10)

• Surprising lack of high-quality, actionable data in many areas:
  • “The majority of it is really not of adequate quality...I was disappointed that we didn’t find something...that could really give us good, strong recommendations.” – Dr. Wein (11:10)
• Mechanistic science gap:
  Many clinical trials focus on surrogate endpoints (cholesterol or triglyceride levels) rather than underlying lipoprotein particle metabolism.
  • “If you understand [mechanisms], you do a better job of actually treating your patient...clinical trials don’t address the particle metabolism.” – Dr. Patel (13:02)
• Key Table for Clinicians:
  • Table 3 in the guideline will provide a quick-reference summary for practice.
    • “The key table is going to be Table 3, which is a really wonderful summary that summarizes everything very quickly...” – Dr. Patel (12:40)

5. Implementing GRADE Recommendations in Practice (14:25)

• Shift in Recommendation Language:
  Less emphatic words; more nuanced expressions about certainty and size of effect.
  • “We don’t use words like strongly or maybe, but they get a little bit different. For example, the certainty is going to be is or probable or maybe.” – Dr. Patel (14:43)
• Clinician Guidance:
  Expect some missing recommendations due to lack of high-quality evidence.
  • “Some people are going to be disappointed because...we don’t have a recommendation because we don’t have data.” – Dr. Wein (16:12)

6. Gaps and Needs for Future Research (17:04)

Highlighted Gaps:

• Diversity in Clinical Trials:
  Underrepresentation of non-English speakers, minorities, and women.
  • “That’s our goal, is to get people who don’t have English as a first language, people of different backgrounds involved in these trials.” – Dr. Wein (17:21)
• Refining Risk Factors:
  Uncertainty about the utility of markers (e.g., CAC, ApoB, Lp(a)); unable to endorse routine use due to insufficient evidence.
• Tricky Triglycerides:
  Lacking data to support specific targets or interventions for most patients.
• Peripheral Artery Disease:
  Insufficient interventional trials for this group.
• Elderly Patients (65+):
  “There’s not good data in age over age 65...has not really come through.” – Dr. Wein (19:06)
• Type 1 Diabetes:
  “We tried to include it, we asked the question and...there’s almost no data on cardiovascular intervention or prevention in type 1 diabetes. So it’s not in this guideline.” – Dr. Wein (19:27)

Pharmacotherapy-Specific Notes:

• Novel therapeutics (PCSK9 inhibitors, inclisiran, bempedoic acid):
  Limited trial data on broad populations and indications.

  • “There’s not enough evidence to support...their extensive use. So I think our guidelines is going to clarify when it is appropriate to use these novel therapeutics...” – Dr. Patel (20:15)

• Deprecation of Older Agents:

  • Fish oils and niacin: evidence does not support routine use.
    • “Our recommendation for niacin is that we really don’t see a very good role for it...” – Dr. Patel (21:03)

Notable Quotes & Memorable Moments

| Timestamp | Speaker | Quote | |-----------|---------|-------| | 01:29 | Dr. Patel | “I was happy when I was asked to be chair of this particular guideline, especially as we will get into it a little later how it has changed, how we are proposing the guidelines for practice.” | | 06:37 | Dr. Wein | “What I felt in using the GRADE is I really felt confident that we had called all the possible clinical trials, we had applied a standardized approach...I really feel confident that we’ve looked at all the possible data here and can give a good assessment...” | | 08:02 | Dr. Patel | “GRADE...takes not just the science base, but it actually looks at the applicability...cost effectiveness...the patient’s perspective as well.” | | 10:11 | Dr. Wein | “Our primary care doctor would say, wait a minute, in reality, my patients can’t drive two hours to the city to do this. It really helped us think of...how does this apply to everybody across the country?” | | 11:10 | Dr. Wein | “I was impressed at the volume of data that’s available, but the fact that the majority of it is really not of adequate quality...” | | 13:02 | Dr. Patel | “If you understand [mechanisms], you do a better job of actually treating your patient...the mechanisms where lipids are concerned is really to do with lipoprotein metabolism.” | | 14:43 | Dr. Patel | “So, for example, the certainty is going to be is or probable or maybe. And I think that as more and more guidelines around the country are going to be using grade, we need to make sure that that language becomes a little bit better and more comfortable...” | | 17:21 | Dr. Wein | “That’s our goal, is to get, you know, people who don’t have English as a first language, people of different backgrounds involved in these trials.” | | 19:27 | Dr. Wein | “There’s almost no data on cardiovascular intervention or prevention in type 1 diabetes. So it’s not in this guideline.” | | 21:03 | Dr. Patel | “Our recommendation for niacin is that we really don’t see a very good role for it to be part of most major therapeutic interventions...” |

Timestamps for Key Segments

• Panel Introductions & Expertise - 00:30–03:55
• Purpose & Major Updates in 2025 Guideline - 04:21–06:20
• GRADE Methodology & Its Impact - 06:20–10:53
• Practical Considerations, Patient & Primary Care Input - 10:53–12:26
• Unexpected Findings & Evidence Quality - 11:10–14:25
• How to Use the New Guidelines, Table 3 Highlight - 12:40–14:43
• Changes in Language & Certainty of Recommendations - 14:43–16:50
• Current Research Gaps & Needs for the Future - 17:04–22:54

Conclusion

The episode provides a thorough preview of the 2025 AACE Dyslipidemia Guideline, emphasizing a shift toward transparency and inclusivity in evidence review via the GRADE methodology, honest assessments of research limitations, and pragmatic advice for clinicians. Both Dr. Patel and Dr. Wein encourage future research to fill persistent gaps—especially in underrepresented populations, specific clinical subgroups, and mechanistic understanding of lipid metabolism. Notable agent-specific recommendations are previewed, especially regarding novel therapies and legacy agents such as niacin and fish oil.

The full guideline will include the key summary Table 3 and is expected to provide clinicians with actionable yet nuanced recommendations tailored to current evidence quality.