eMERGE - Mayo Statin Response Algorithm - Khan AK, Kullo IJ
Genomics of Response to Statins: An Electronic Medical Record-Based GenomeWide Association Study
As a first step we have constructed an algorithm (Figure 1) to quantify the magnitude of
lipid-lowering in response to HMG-CoA reductase inhibitor (statin) therapy.
Patients will be included in the study based on this algorithm.
Step 1:
Statin use will be ascertained via Natural Language Processing (NLP) or electronically
from pharmacy records. We will identify patients on a statin and determine date of first
ever mention of statin (Table 1), which would correspond to the date of initiation of statin
in the electronic medical record (EMR) for these patients. Statin type and dose will be
identified. Patients on statins other than simvastatin will be normalized to an equivalent
dose of simvastatin: 10 mg of simvastatin = 1.25, 5, 20, 20 and 40 mg of rosuvastatin,
atorvastatin, pravastatin, lovastatin and fluvastatin respectively.1,2
Step 2:
Other lipid lowering medications (Table 4) will be mined from the EMR that may
potentiate the lipid lowering response of statins. Patients will be excluded if they are on
any other lipid-lowering medication at the time of initiation of statin.
Step 3:
Laboratory data (Tables 3a & 3b) will be mined from EMR at baseline and after initiation
of statin therapy. Relevant laboratory data includes total cholesterol (TC), triglycerides,
high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL)
cholesterol levels. Base line laboratory data will include labs drawn 12 months before and
up to the date of initiation of statin, while followup laboratory data would include the first
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eMERGE - Mayo Statin Response Algorithm - Khan AK, Kullo IJ
lipid levels drawn ≥ 4 weeks and up to 1 year after date of initiation of statin. Inpatient
laboratory tests will be excluded considering acute disease states that may alter the
studied variables. Patients with a < 10% reduction in TC or LDL-cholesterol will be
excluded.
Step 4:
Demographic & anthropometric data and other relevant data (Table 2) pertinent to lipid
lowering response to statin therapy will be mined from the EMR using established
eMERGE phenotyping algorithms. Smoking status will be determined using NLP as
previously described.3 The entire EMR up to and six months after the date of initiation of
statin will be mined for smoking status.
References:
1.
Maron DJ, Fazio S, Linton MF. Current perspectives on statins. Circulation
2000;101:207-13.
2.
McKenney JM, Jones PH, Adamczyk MA, Cain VA, Bryzinski BS, Blasetto JW.
Comparison of the efficacy of rosuvastatin versus atorvastatin, simvastatin, and
pravastatin in achieving lipid goals: results from the STELLAR trial. Current
medical research and opinion 2003;19:689-98.
3.
Savova GK, Ogren PV, Duffy PH, Buntrock JD, Chute CG. Mayo clinic NLP
system for patient smoking status identification. Journal of the American Medical
Informatics Association 2008;15:25-8.
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eMERGE - Mayo Statin Response Algorithm - Khan AK, Kullo IJ
Figure 1. Algorithm for quantifying lipid-lowering response to HMG-CoA reductase
inhibitor therapy
Patients
Other lipid lowering
medications
Stain initiation
Exclude
Commonly used
statins
Baseline lipid profile
No
Exclude patietns
without lipid profile
Followup lipid profile
No
Laboratory data
Demographic &
anthropometric data
Patients for analysis
Statin = HMG-CoA reductase inhibitors.
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eMERGE - Mayo Statin Response Algorithm - Khan AK, Kullo IJ
Table 1. Commonly used HMG-CoA reductase inhibitors (statins)
Generic
Trade name(s)
Lovastatin
Altoprev, Mevacor
Amlodipine/Atorvastatin
Caduet
Rosuvastatin
Crestor
Fluvastatin
Lescol , Lescol XL
Atorvastatin
Lipitor
Pitavastatin
Livalo
Pravastatin
Pravachol
Simvastatin
Zocor
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eMERGE - Mayo Statin Response Algorithm - Khan AK, Kullo IJ
Table 2. Data elements to be mined from the EMR
Demographic &
Anthropometric
Medical record number (MR#)
Date of birth (DOB)
Age at initiation of statin
Sex
Height at the date of statins initiation (-12, +12 months).
Weight at the date of statins initiation (-12, +12 months).
BMI at the date of statins initiation (-12, +12 months).
Race
Statin therapy
History of smoking within -3 months, +6 months of date of
initiation of statin
Date of first ever mention (initiation) of statin (DIS)
Generic name of statin initiated (Table 1)
Dose of statin initiated
Unit of statin initiated in mg
Baseline
laboratory data
Followup
laboratory data
Table 3a
Other lipid
lowering
medications
Patients on following lipid lowering medications to be excluded
(Table 4)
Table 3b
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eMERGE - Mayo Statin Response Algorithm - Khan AK, Kullo IJ
Table 3a. Baseline laboratory data to be mined from EMR
Time range
-12 months, 0 months of date of initiation of statin
Test
Units
Total cholesterol
mg/dL
Triglycerides
mg/dL
LDL cholesterol
mg/dL
HDL cholesterol
mg/dL
AST
U/L
ALT
U/L
Serum creatinine (Cr) level
mg/dl
ALK
U/L
Total serum bilirubin level
mg/dl
HDL = high-density lipoprotein cholesterol, LDL = low-density lipoprotein
cholesterol, AST = aspartate aminotransferases, ALT = alanine aminotransferases,
ALK = alkaline phosphatase
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eMERGE - Mayo Statin Response Algorithm - Khan AK, Kullo IJ
Table 3b. Followup laboratory data to be mined from EMR
Time range
Test
First laboratory values ≥ 4 weeks, up to 1 year of date
of initiation of statin
Units
Total cholesterol
mg/dL
Triglycerides
mg/dL
LDL cholesterol
mg/dL
HDL cholesterol
mg/dL
AST
U/L
ALT
U/L
Serum creatinine (Cr) level
mg/dl
ALK
U/L
Total serum bilirubin level
mg/dl
HDL = high-density lipoprotein cholesterol, LDL = low-density lipoprotein
cholesterol, AST = aspartate aminotransferases, ALT = alanine aminotransferases,
ALK = alkaline phosphatase
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eMERGE - Mayo Statin Response Algorithm - Khan AK, Kullo IJ
Table 4. Other lipid-lowering medications.
Time range
Generic
-12 months, +12 months of date of
initiation of statin
Trade name(s)
Niacin/Lovastatin
Advicor
Niacin/Simvastatin
Simcor
Fenofibrate
Ezetimibe/Simvastatin
Antara, Fenoglide, Lipofen, Lofibra,
Tricor, Triglide, Trilipix
Vytorin
Fenofibric acid
Fibricor
Gemfibrozil
Lopid
Niacin, nicotinic acid
Niaspan
Ezetimibe
Zetia
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