Lipid-Lowering Therapy Patterns in T2D With CV Disease Risk
Lipid-Lowering Therapy Patterns in T2D With CV Disease Risk
This was a retrospective cohort analysis using the IMS LifeLink PharMetrics Plus commercial claims from January 1, 2006 to June 30, 2012. This nationally representative, longitudinal database is comprised of managed care health plan information throughout the USA, with adjudicated medical and pharmacy claims of >150 million enrollees since 2006.
Eligible patients were diagnosed with type 2 diabetes (International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes are provided in online supplementary appendix A http://drc.bmj.com/content/3/1/e000132/suppl/DC1) aged ≥18 years with >1 outpatient pharmacy claims for statins and/or ezetimibe from January 1, 2007 to June 30, 2011 from the IMS LifeLink PharMetrics Plus data set. The initiation date of the first statin and/or ezetimibe was designated as the index date. The first statin associated with the index date was designated as the index statin. The second outpatient pharmacy claim for statins and/or ezetimibe had to be ≤6 months apart. All patients were required to have continuous health plan enrolment for ≥12 months preindex date (baseline period) and 12 months postindex date. The follow-up period for treatment patterns varied in length, from (and including) the index date to the end of continuous health plan eligibility or to the end of the study period (June 30, 2012), whichever occurred first.
Patients with ≥1 outpatient pharmacy claim for statin and/or ezetimibe in the 12 months prior to the first index statin and/or ezetimibe claim, and patients with medical claims indicating pregnancy or delivery (ICD-9 CM codes are provided in online supplementary appendix A http://drc.bmj.com/content/3/1/e000132/suppl/DC1) at any time during the baseline or follow-up period were excluded from the study. Also, patients with >2 different index statins on the index date were excluded. Patients with type 2 diabetes were stratified into the following three high CVD risk cohorts:
These three cohorts were selected since these patient groups have been identified by several US national guidelines as high-risk populations for CV outcomes.
Demographic and clinical characteristics of patients in each cohort were examined. Initial statin intensity (low, moderate, high) was also recorded and stratified by index year for each cohort. Using average daily dose, definitions of different statin intensities were adapted from the 2013 ACC/AHA guidelines (see online supplementary appendix B http://drc.bmj.com/content/3/1/e000132/suppl/DC1). The average daily dose was defined as the strength of the statin multiplied by the dose quantity and divided by the total days of supply.
Treatment modification (none, first, and second) and time-to-treatment modification (days) during the follow-up period were captured. Treatment modifications are defined in Table 1. Treatment modifications included dose escalation, dose reduction, augmentation, subtraction for patients receiving combination therapy, reinitiation of index therapy, switching, and permanent LLT discontinuation. Utilizing treatment modifications observed in claims data, patients with a first and/or second treatment modification were classified as possible statin intolerance, LLT intolerance, and statin/LLT intolerance and/or ineffectiveness (Table 2). For example, statin dose reduction and temporary discontinuation followed by reinitiation of the same statin were considered as a signal for possible LLT intolerance. LLT ineffectiveness, as used in the present study, was defined in a similar way as the AHA/ACC 2013 guidelines (ie, a less-than-anticipated therapeutic response), and treatment modifications like dose escalation and augmentation with a non-statin LLT were considered as possible signals for LLT ineffectiveness. To increase the likelihood that the treatment modification(s) are associated with treatment intolerance and/or ineffectiveness, we categorized and accounted for both the observed first and second treatment modification(s) (if any), into possible LLT intolerance and/or ineffectiveness issues, as defined in Table 2. Patients with no treatment modification or those who had a first treatment modification but no second treatment modification were classified into low-intensity/moderate-intensity statin and/or ezetimibe or high-intensity statin treatment with/without ezetimibe treatment depending on their statin intensity and/or ezetimibe treatment.
All measures, including patients' demographic and clinical characteristics, LLT treatment modification patterns and possible associated intolerance and/or ineffectiveness issues among the three cohorts were reported. Analyses for each cohort were stratified by age groups (<65 and ≥65 years) to investigate the impact (if any) of Medicare eligibility; since patients aged ≥65 years are primarily insured under Medicare Advantage. In addition, the Deyo-Charlson comorbidity index score was calculated for each patient; this widely published comorbidity index uses ICD-9-CM codes in claims databases to measure the severity of patients' comorbidities. Means and SDs were reported for continuous variables. Relative frequencies and percentages were calculated for categorical data. All analyses were performed with SAS, V.9.3 (SAS Institute Inc, Cary, North Carolina, USA).
Research Design and Methods
This was a retrospective cohort analysis using the IMS LifeLink PharMetrics Plus commercial claims from January 1, 2006 to June 30, 2012. This nationally representative, longitudinal database is comprised of managed care health plan information throughout the USA, with adjudicated medical and pharmacy claims of >150 million enrollees since 2006.
Study Population
Eligible patients were diagnosed with type 2 diabetes (International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes are provided in online supplementary appendix A http://drc.bmj.com/content/3/1/e000132/suppl/DC1) aged ≥18 years with >1 outpatient pharmacy claims for statins and/or ezetimibe from January 1, 2007 to June 30, 2011 from the IMS LifeLink PharMetrics Plus data set. The initiation date of the first statin and/or ezetimibe was designated as the index date. The first statin associated with the index date was designated as the index statin. The second outpatient pharmacy claim for statins and/or ezetimibe had to be ≤6 months apart. All patients were required to have continuous health plan enrolment for ≥12 months preindex date (baseline period) and 12 months postindex date. The follow-up period for treatment patterns varied in length, from (and including) the index date to the end of continuous health plan eligibility or to the end of the study period (June 30, 2012), whichever occurred first.
Patients with ≥1 outpatient pharmacy claim for statin and/or ezetimibe in the 12 months prior to the first index statin and/or ezetimibe claim, and patients with medical claims indicating pregnancy or delivery (ICD-9 CM codes are provided in online supplementary appendix A http://drc.bmj.com/content/3/1/e000132/suppl/DC1) at any time during the baseline or follow-up period were excluded from the study. Also, patients with >2 different index statins on the index date were excluded. Patients with type 2 diabetes were stratified into the following three high CVD risk cohorts:
History of CVE: Patients with a history of CVEs, defined as ≥1 non-diagnostic medical claim (inpatient or outpatient) with a diagnosis or procedure code for myocardial infarction, unstable angina, ischemic stroke, coronary artery bypass graft surgery, percutaneous coronary intervention, or transient ischemic attack (ICD-9-CM codes are provided in online supplementary appendix A http://drc.bmj.com/content/3/1/e000132/suppl/DC1) during the baseline period;
Two risk factors: Patients with the following two risk factors: older age (men aged ≥45 years, women aged ≥55 years) and hypertension (diagnosis or antihypertensive medication)) but no history of CVE or other cardiovascular risk equivalent (CVRE) conditions other than type 2 diabetes during the baseline period. Excluded patients with other CVREs were defined as ≥1 non-diagnostic medical claim (inpatient or outpatient) with a diagnosis or procedure code for peripheral artery disease, abdominal aortic aneurysm, ischemic heart disease, or stable angina (ICD-9 CM codes are provided in online supplementary appendix A http://drc.bmj.com/content/3/1/e000132/suppl/DC1). Owing to data limitation, other risk factors (eg, smoking status, high-density lipoprotein cholesterol, etc) could not be accounted for in the study; and
Aged ≥40 years: Patients aged ≥40 years on the index date. This cohort includes a broader group of patients with type 2 diabetes but also encompasses patients in the two risk factors cohort.
These three cohorts were selected since these patient groups have been identified by several US national guidelines as high-risk populations for CV outcomes.
Study Outcomes
Demographic and clinical characteristics of patients in each cohort were examined. Initial statin intensity (low, moderate, high) was also recorded and stratified by index year for each cohort. Using average daily dose, definitions of different statin intensities were adapted from the 2013 ACC/AHA guidelines (see online supplementary appendix B http://drc.bmj.com/content/3/1/e000132/suppl/DC1). The average daily dose was defined as the strength of the statin multiplied by the dose quantity and divided by the total days of supply.
Treatment modification (none, first, and second) and time-to-treatment modification (days) during the follow-up period were captured. Treatment modifications are defined in Table 1. Treatment modifications included dose escalation, dose reduction, augmentation, subtraction for patients receiving combination therapy, reinitiation of index therapy, switching, and permanent LLT discontinuation. Utilizing treatment modifications observed in claims data, patients with a first and/or second treatment modification were classified as possible statin intolerance, LLT intolerance, and statin/LLT intolerance and/or ineffectiveness (Table 2). For example, statin dose reduction and temporary discontinuation followed by reinitiation of the same statin were considered as a signal for possible LLT intolerance. LLT ineffectiveness, as used in the present study, was defined in a similar way as the AHA/ACC 2013 guidelines (ie, a less-than-anticipated therapeutic response), and treatment modifications like dose escalation and augmentation with a non-statin LLT were considered as possible signals for LLT ineffectiveness. To increase the likelihood that the treatment modification(s) are associated with treatment intolerance and/or ineffectiveness, we categorized and accounted for both the observed first and second treatment modification(s) (if any), into possible LLT intolerance and/or ineffectiveness issues, as defined in Table 2. Patients with no treatment modification or those who had a first treatment modification but no second treatment modification were classified into low-intensity/moderate-intensity statin and/or ezetimibe or high-intensity statin treatment with/without ezetimibe treatment depending on their statin intensity and/or ezetimibe treatment.
Statistical Analysis
All measures, including patients' demographic and clinical characteristics, LLT treatment modification patterns and possible associated intolerance and/or ineffectiveness issues among the three cohorts were reported. Analyses for each cohort were stratified by age groups (<65 and ≥65 years) to investigate the impact (if any) of Medicare eligibility; since patients aged ≥65 years are primarily insured under Medicare Advantage. In addition, the Deyo-Charlson comorbidity index score was calculated for each patient; this widely published comorbidity index uses ICD-9-CM codes in claims databases to measure the severity of patients' comorbidities. Means and SDs were reported for continuous variables. Relative frequencies and percentages were calculated for categorical data. All analyses were performed with SAS, V.9.3 (SAS Institute Inc, Cary, North Carolina, USA).
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