Marc S. Sabatine, MD, MPH  Chairman | TIMI Study Group  Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine Brigham and Women's Hospital  Professor of Medicine | Harvard Medical School

When It Comes to LDL-C, “You Really Can’t Be Too Low”

MedicalResearch.com Interview with:

Marc S. Sabatine, MD, MPH  Chairman | TIMI Study Group  Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine Brigham and Women's Hospital  Professor of Medicine | Harvard Medical School

Dr. Marc Sabatine

Marc S. Sabatine, MD, MPH
Chairman | TIMI Study Group
Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine
Brigham and Women’s Hospital
Professor of Medicine | Harvard Medical School

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for cardiovascular disease.

The initial statin trials studied patients with high levels of LDL-C, and showed a benefit by lowering LDL-C.

We and others did studies in patients with so-called “average” levels of LDL-C (120-130 mg/dL), and also showed clinical benefit with lowering.

MedicalResearch.com But the question is: how low should you go?

Response: The answer is clear: you really can’t be too low.

MedicalResearch.com: What are the main findings of this study? 

Response: Current guidelines are still tethered to older data wherein we targeted LDL-C of ~70 mg/dL..

  • We looked at 4 populations of patients with atherosclerotic cardiovascular disease from clinical trials who were starting with an average LDL-C <=70mg/dL.
  • These are patients for whom currently most guidelines would say one does not need to intensify LDL-C lowering therapy.

Our findings:

1) Whether it was statins, ezetimibe, or a PCSK9 inhibitor, all of them reduced cardiovascular events. Therefore, even patients with LDL-C <=70 mg/dL need more LDL-C lowering.

2) The magnitude of the benefit was not attenuated at these low levels.
In older statin trials there was a 20% relative risk reduction for each mmol/L (~40 mg/dL) lowering of LDL-C.

In these modern studies with much lower starting LDL-C, we found the same relationship: a ~20% relative risk reduction for each mmol/L (~40 mg/dL) lowering of LDL-C.

3) The benefit was seen in patients populations with a starting average LDL-C of 63 mg/dL, and the benefit was seen dropping LDL-C down to an average of 21 mg/dL (meaning half of the patients achieved an LDL-C below this level!).

4) There was no excess in adverse events.

MedicalResearch.com: What should readers take away from your report?

Response: So the take home message is that for patients with atherosclerotic cardiovascular disease (ie, history of heart attack, stroke, or peripheral arterial disease), we should be targeting an LDL-C <40 mg/dL and personally I target ~20 mg/dL. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: These data were in patients with known atherosclerotic cardiovascular disease (eg, heart attack, stroke, or peripheral arterial disease).

Future studies should examine achieving very low levels of LDL-C in primary prevention so as to prevent initial occurrence of cardiovascular disease. 

Disclosures listed in paper.

Citation:

Sabatine MS, Wiviott SD, Im K, Murphy SA, Giugliano RP. Efficacy and Safety of Further Lowering of Low-Density Lipoprotein Cholesterol in Patients Starting With Very Low LevelsA Meta-analysisJAMA Cardiol.Published online August 01, 2018. doi:10.1001/jamacardio.2018.2258

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Last Updated on August 3, 2018 by Marie Benz MD FAAD