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
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.
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.
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-analysis. JAMA Cardiol.Published online August 01, 2018. doi:10.1001/jamacardio.2018.2258
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