MedicalResearch.com Interview with:
Dr. Jennifer Robinson, MD MPH
Professor, Departments of Epidemiology & Medicine
Director, Prevention Intervention Center
Department of Epidemiology
University of Iowa
MedicalResearch.com: What is the background for this study?
Response: Compared to previous placebo-controlled statin trials, the FOURIER trial where all patients were on high or moderate intensity statin, had no reduction in cardiovascular or total mortality and the reduction in cardiovascular events was less than expected. However, other PCSK9 inhibitor trials performed in populations with higher baseline low density lipoprotein cholesterol (LDL-C) had cardiovascular risk reductions similar to that in the statin trails.
MedicalResearch.com: What are the main findings?
Response: In meta-analyses of LDL-C lowering drug trials, we found that total and cardiovascular mortality were reduced only when the mean baseline LDL-C in the trial was >100 mg/dl. We also found the higher the baseline LDL-C the greater the reduction in the risk of total and cardiovascular mortality. For example, for each 40 mg/dl higher baseline LDL-C above , cardiovascular death was reduced by another 14%.
We also found the myocardial infarction, revascularizations, and major cardiovascular events were reduced when LDL-C was <100 mg/dl, but risk was reduced more when in trials with higher baseline LDL-C levels. Stroke risk was reduced similarly across the range of baseline LDL-C levels.
Notably, the results of our meta-analyses predicted the recent results of the ODYSSEY OUTCOMES trial, where total mortality and MACE risk with the PCSK9 inhibitor alirocumab only appeared to be reduce when baseline LDL-C was >100 mg/dl.
MedicalResearch.com: What should readers take away from your report?
Response: LDL-C lowering drugs reduce cardiovascular risk across the spectrum of cardiovascular risk. However, LDL-C lowering drugs will produce even greater benefits when used in patients with higher LDL-C levels.
Very high risk patients with cardiovascular disease and other high risk characteristics (for example, polyvascular disease, familial hypercholesterolemia, diabetes, or other poorly controlled risk factors) who are treated with maximally tolerated statin therapy may still benefit from adding a nonstatin LDL-C lowering drug to reduce the risk of nonfatal coronary events and stroke.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: We need to find all of our patients with genetic and familial hypercholesterolemia and treat them with statins and other LDL-C lowering drugs as needed to reduce their risk of death and nonfatal cardiovascular events.
We also need to find ways to encourage better adherence to statins, which have proven mortality benefits, are inexpensive and safe.
Disclosures: Research grants to institution from and scientific consultant for manufacturers of statins, ezetimibe, and PCSK9 inhibitors.
Navarese EP, Robinson JG, Kowalewski M, et al. Association Between Baseline LDL-C Level and Total and Cardiovascular Mortality After LDL-C LoweringA Systematic Review and Meta-analysis. JAMA.2018;319(15):1566–1579. doi:10.1001/jama.2018.2525
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