Abstract
BACKGROUND:
Little is known about trends in statin use in United States (US) nursing homes.
OBJECTIVES:
To describe national trends in statin use in nursing homes and evaluate the impact of the introduction of generic statins, safety warnings, and guideline recommendations on statin use.
METHODS:
This study employed a repeated cross-sectional prevalence design to evaluate monthly statin use in long-stay US nursing home residents enrolled in Medicare fee-for-service using the Minimum Data Set 3.0 and Medicare Part D claims between April 2011– December 2016. Stratified by age in years (65–75, ≥76), analyses estimated trends and level changes with 95% confidence intervals (CI) following statin-related events (the availability of generic statins, American Heart Association/American College of Cardiology guideline updates, and US Food and Drug Administration safety warnings) through segmented regression models corrected for autocorrelation.
RESULTS:
Statin use increased from April 2011 to December 2016 (65–75 years: 38.6% to 43.3%; ≥76 years: 26.5% to 30.0%), as did high intensity statin use (65–75 years: 4.8% to 9.5%; ≥76 years: 2.3% to 4.5%). The introduction of generic statins yielded little impact on prevalence of statins in nursing home residents. Positive trend changes in high intensity statin use occurred following national guideline updates in December 2011 (65 to 75 years: β = 0.16; 95% CI: 0.09 to 0.22; ≥76 years: β = 0.09; 95% CI: 0.06 to 0.12) and November 2013 (65 to 75 years: β = 0.11; 95% CI: 0.09 to 0.13; ≥76 years: β = 0.04; 95% CI: 0.03 to 0.05). There were negative trend changes for any statin use concurrent with FDA statin safety warnings in March 2012 among both age groups (65–75 years: β trend change=−0.06; 95% CI: −0.10 to −0.02; ≥76 years: β trend change= −0.05; 95% CI: −0.08 to −0.01). The publication of a statin deprescribing trial results yielded a decrease in any statin use among the ≥76 years age group (β level change= −0.25, 95% CI: −0.48 to −0.09; β trend change= −0.03, 95% CI: −0.04 to −0.01) with both age groups observing a positive trend change with high intensity statins (65 to 75 year age group: β = 0.11; 95% CI: 0.02 to 0.21; ≥76 years age group: β = 0.05; 95% CI: 0.01 to 0.09).
CONCLUSION:
Overall, statin use in US nursing homes increased from 2011 to 2016. Guidelines and statin-related events appeared to impact use in the nursing home setting. As such, statin guidelines and messaging should provide special consideration for nursing home populations, who may have more risk than benefit from statin pharmacotherapy.
Keywords: statins, nursing homes, trends, black box warnings, guidelines, deprescribing
1. INTRODUCTION
Statins remain one of the most commonly prescribed medication classes in the United States (US) [1, 2]. Among adults ≥75 years of age, use of statins has grown considerably since the 1990s [3]. As of 2012–2013, nearly half of all older adults used statins for primary or secondary prevention of cardiovascular disease [4]. Despite widespread use in community-dwelling adults, statins in the nursing home population remain largely understudied. The few available estimates suggest statin prescribing is common, but include only limited sub-populations of nursing home residents [5–8]. No study to date has reported trends in the use of statins among a national sample of all US long-stay nursing home residents.
In the past, changes to recommendations and new public information (Figure 1) have been shown to influence the use of statins [9, 10]. The 2011 US Food and Drug Administration (FDA) black-box warning against the use of simvastatin 80 mg for patients aged ≥75 years was found to diminish use in community-dwelling adults, given reports of increased risk of severe muscle injury [9]. The American Heart Association/American College of Cardiology (AHA/ACC) guideline updates in 2011 and 2013 [11, 12], which called for more intensive and widespread use of statins, was followed by an increase in their overall use in subsequent years [10]. In 2015, a pragmatic clinical trial of older adults with an estimated life expectancy of one month and one year demonstrated statin deprescribing was not only safe, but also beneficial to quality of life [13]. The next year, the US Preventative Services Task Force (USPSTF) released a statement, abstaining from providing recommendations for any statin use in those over 75 years of age, citing insufficient evidence [14]. While these events have appeared to impact overall use of statins in the community-dwelling population, the effect of these events on use of statins in the nursing home environment is unknown.
Fig. 1.
Statin-related Events Timeline, 2011 – 2016
In the context of a dynamic environment of public reports and policy recommendations, this study focused on the use of statins in the US nursing home population over time. The study sought to: 1) describe recent trends in the use of statin among nursing home residents nationwide and 2) estimate the extent to which the prevalence of statin use in nursing homes was affected by the introduction of generic statins into the US market, updates to AHA/ACC guidelines, national safety warnings related to statins, and the publication of a statin deprescribing trial. We evaluated statin prescribing using a national, contemporaneous data resource that merged the Minimum Data Set (MDS) 3.0 and Medicare Part D Claims files from 2011–2016.
2. METHODS
2.1. Data Sources
The Minimum Data Set (MDS) 3.0 was merged to Medicare administrative data files consisting of the Medicare Beneficiary Summary File (enrollment data) and Medicare Part D (prescription drug claims). The MDS 3.0 is a comprehensive dataset of clinical nursing home assessment data federally mandated for all residents in Medicare- and Medicaid- certified nursing home facilities in the United States. The validated assessment tool includes information on the health status of nursing home residents in addition to sociodemographic, medical, and psychological information [15].
2.2. Study Design
A repeated cross-sectional design was employed to estimate temporal trends from calendar years 2011 to 2016 via monthly point prevalence estimates of statin use. We estimated point prevalence on the first day of each month from April 1, 2011 through December 1, 2016. This study was approved by the University of Massachusetts Medical School Institutional Review Board.
2.3. Study Population
The study population included nursing home residents with an MDS 3.0 quarterly assessment within the three months before each point prevalence date. To be included in the denominator of each monthly point prevalence, on the first of the month residents had to: 1) be a current resident; 2) not be in the hospital, 3) be alive, 4) not be in a skilled nursing facility (SNF) stay, 5) have resided in the home ≥90 days (determined by the presence of an MDS quarterly assessment), and 6) had continuous Medicare Fee-for-Service Part A, B, and D coverage in the current month and three months before. Residents were excluded if they were aged <65 years, comatose, or enrolled in hospice. We excluded those enrolled in hospice or those in the midst of a skilled nursing facility stay given that medications of enrollees do not appear in Medicare Part D when receiving these services.
2.4. Statin Use
Statins were identified by generic drug names in Medicare Part D prescription drug claim files. Generic statins included atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin (Supplemental Table S1). Prevalent use was determined if a prescription of any individual or combination of generic statins (date filled + day supply) overlapped with the first day of each month. Statin use was operationally defined in two ways: first, as any use (yes/no), and then, according to high intensity use (yes/no) using ACC/AHA guidelines (Supplemental Table S2). High intensity- defined statin use was included as a proxy variable for medications that were targets of major FDA and AHA/ACC changes during the study period (2011–2016; Figure 1).
2.5. Resident Characteristics
Resident characteristics were extracted from either the most recent quarterly MDS assessment before the point prevalence date or if the variable of interest was not collected on the quarterly assessment, the most recent full MDS 3.0 assessment before the point prevalence date. Variables were selected based on evidence of factors that could affect statin use time trends, such as characteristics associated with medication prescribing (e.g., sociodemographic, polypharmacy status, cognitive impairment, physical health) and cardiovascular disease (e.g., myocardial infarction, acute ischemic stroke).
Variables included: age (based on the stratification of major guidelines related to statin treatment of cardiovascular disease: 65–75, ≥76 years), race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic/Latino, other), marital status (yes/no), cognitive impairment (none, mild, moderate, severe), functional dependence (none to limited assistance required, extensive assistance required, complete assistance required/ dependent), and atherosclerotic cardiovascular disease (ASCVD) risk, number of non-statin concurrent medications, and rejected care (yes/no).
To evaluate cognitive impairment, the Cognitive Function Scale (CFS) [16]. was used. The CFS is based on the Brief Interview for Mental Status (BIMS; scored 0–15) and the Cognitive Performance Scale (CPS; scored 0–6) if unable to self-report with the following categories for cognitive impairment: none (or cognitively intact; BIMS: 13–15), mild (BIMS: 8–12, CPS: 0–2), moderate (BIMS: 0–7, CPS: 3–4), and severe (CPS: 5–6). Functional dependence was based on the MDS-ADL Self-Performance Hierarchy [17] (scored 0–6) with the following categories: independent to limited assistance required (0–2), extensive assistance required (3–4), and dependent to total dependence (5–6) in performing activities of daily living (ADLs). The variable for ASCVD was operationally defined as having: (1) an ASCVD diagnosis (coronary artery disease, stroke, or peripheral vascular disease/peripheral artery disease), (2) ≥1 risk factor for ASCVD without the disease (diabetes, hyperlipidemia, or hypertension [3, 4]), and (3) neither ASCVD or risk factors for ASCVD.
2.6. Statistical Analysis
All analyses were stratified by age group (i.e., aged: 65–75 and ≥76 years) [18]. To evaluate the extent to which the nursing home resident characteristics remained relatively stable during the study time period, we calculated descriptive statistics of resident characteristics for all residents included in point prevalence estimates on April 1, 2011 and on December 1, 2016. The month was the unit of analysis. Point prevalence estimates were then calculated for each month from April 1, 2011 to December 1, 2016 for any statin use and for high-intensity statin use. These point prevalence estimates were graphed. Given the projected effect of statin-related events [19], changes in statin use before and after months outlined in Figure 1 were evaluated using segmented regression analysis of interrupted time series. For the time series analysis, first we evaluated the linearity of the relationship between statin use and each of the time segments based on the visual inspection of the graphs. With this information, a generalized linear model approach was used to estimate the immediate change in the use of statins and the gradual change in trend after each of the events outlined in Figure 1. A priori, we hypothesized that we would not see immediate changes in prevalence estimates. Following Wagner et al. (2002) [20], we used segmented regression models. For events occurring in the last week of the month (i.e., November 2011, February 2012, and March 2015), we defined the level change and trend change based on the following month. We created separate models to evaluate the effect of generic availability (Fluvastatin 20mg and 40mg in July 2012, Fluvastatin 80mg in September 2015, Rosuvastatin in May 2016), guideline updates (AHH/ACC in December 2011 & November 2013), safety warnings (March 2013 FDA safety label changes, March 2014 NLA Task Force on Statin Safety), and deprescribing trial results (April 2015). Doing so allowed for us to have a minimum of eight intervals between separate segments in accordance with interrupted time series analyses guidance [21]. We calculated Durbin-Watson statistics to check for autocorrelation for the 13 time points given the monthly unit of analysis. Autocorrelation was detected if the Durbin Watson statistic was close to a value of two. Backwards elimination techniques were used to identify the significant autocorrelation and then adjust for it analytically using PROC AUTOREG in SAS (version 9.4, Cary, NC). We estimated full segmented models for each month evaluated including the respective intercept, baseline trend, level change, and trend change coefficients (β) with 95% confidence intervals (CIs).
3. RESULTS
3.1. Characteristics of Sample
While the sample varied for each month, distribution of sample characteristics remained stable among each age group. Table 1 shows that the sociodemographic characteristics of the sample were similar in April 2011 and December 2016 for residents aged 65 to 75 years and ≥76 years. Specifically, regardless of age group, the samples were mostly women (65 to 75 years: April 2011: 56.5%, December 2016: 55.5%; ≥76 years: April 2011: 79.7%, December 2016: 77.1%), non-Hispanic white (65 to 75 years: April 2011: 72.8%, December 2016: 73.4%; ≥76 years: April 2011: 83.0%, December 2016: 82.0%) with none to mild cognitive impairment (65 to 75 years: April 2011: 59.3%, December 2016: 66.5%; ≥76 years: April 2011: 59.1%, December 2016: 53.8%) and extensive or complete functional dependence (65 to 75 years: April 2011: 26.6%, December 2016: 72.2%; ≥76 years: April 2011: 76.0%, December 2016: 79.4%). The majority of residents regardless of age group were taking an average of six or more non-statin medications (65 to 75 years: April 2011: 70.3%, December 2016: 66.9%; ≥76 years: April 2011: 60.0%, December 2016: 54.3%). The majority (>85%) among each age group across time either had an ASCVD diagnosis or risk factors.
TABLE 1.
Characteristics of the U.S. nursing home population by time point
| Characteristics (%*) | 65–75 years | ≥76 years | ||
|---|---|---|---|---|
| April 1, 2011 (n=85,260) | December 1, 2016 (n=104,839) | April 1, 2011 (n=378,969) | December 1, 2016 (n=357,246) | |
| Women | 56.5 | 55.5 | 79.7 | 77.1 |
| Married | 20.4 | 19.4 | 15.5 | 17.2 |
| Race/Ethnicity | ||||
| Non-Hispanic white | 72.8 | 73.4 | 83.0 | 82.0 |
| Non-Hispanic black | 19.4 | 19.1 | 11.0 | 10.8 |
| Hispanic/Latino | 5.7 | 5.4 | 4.2 | 4.8 |
| Other | 2.1 | 2.2 | 1.9 | 2.4 |
| Cognitive Impairmenta | ||||
| None | 35.5 | 43.8 | 19.5 | 24.2 |
| Mild | 23.8 | 22.7 | 21.4 | 22.1 |
| Moderate | 28.3 | 23.8 | 42.9 | 40.7 |
| Severe | 12.4 | 9.7 | 16.2 | 13.1 |
| Functional Dependenceb | ||||
| None to limited assistance required | 29.8 | 27.8 | 24.0 | 20.6 |
| Extensive assistance required | 43.6 | 50.0 | 48.3 | 57.7 |
| Complete assistance required/dependent | 26.6 | 22.2 | 27.7 | 21.7 |
| Atherosclerotic Cardiovascular Disease (ASCVD)c Risk | ||||
| ASCVD diagnosis | 40.7 | 40.5 | 36.7 | 39.4 |
| ≥1 ASCVD risk factor + no ASCVD diagnosis | 45.7 | 48.6 | 49.4 | 50.5 |
| No ASCVD risk factors + no ASCVD diagnosis | 13.6 | 11.0 | 13.9 | 10.1 |
| Number of Non-statin Concurrent Medications | ||||
| 0–5 | 29.7 | 33.1 | 40.0 | 45.8 |
| 6–10 | 43.0 | 36.9 | 42.0 | 37.7 |
| 11+ | 27.3 | 30.0 | 18.0 | 16.6 |
| Care Status | ||||
| Rejects care | 11.9 | 8.8 | 11.4 | 8.0 |
May not total to 100% due to rounding. Missing April 2011 data for sex (n 65–75=1; n ≥76 = 10), race/ethnicity (n 65–75=1,713; n ≥76 = 7,920), married (n 65–75=1,096; n ≥76 = 3,109), cognitive impairment (n 65–74=1,142; n 76+ = 3,710), functional dependence (n 65–75=27; n ≥76 = 93), and rejects care (n 65–74=264; n ≥76 = 573). Missing December 2016 data for race/ethnicity (n 65–75=2,156; n ≥76 = 6,252), married (n 65–74=2,161; n ≥76 = 4,956), cognitive impairment (n 65–75=1,331; n ≥76 = 3,206), functional dependence (n 65–75=61; n ≥76 = 144), and rejects care (n 65–75=305; n ≥76 = 669).
Cognitive impairment = Cognitive Function Scale based on Brief Interview for Mental Status (BIMS; scored 0–15) and the Cognitive Performance Scale (CPS; scored 0–6) if unable to self-report: none (or cognitively intact; BIMS: 13–15), mild (BIMS: 8–12, CPS: 0–2), moderate (BIMS: 0–7, CPS: 3–4), and severe (CPS: 5–6)
Functional dependence = MDS-ADL Self-Performance Hierarchy: independent to limited assistance required (0–2), extensive assistance required (3–4), and dependent to total dependence (5–6) in performing activities of daily living (ADLs)
ASCVD = including diagnoses of coronary artery disease, peripheral artery disease, and stroke
3.2. Trends in Statin Use
3.2.1. Trends in any statin use
Overall, the prevalence of any statin use increased gradually from April 2011 (28.7%) to December 2016 (33.0%).
See Figure 2 for trends in any statin use by age group. Statin use prevalence across time appeared higher for the 65 to 75 age group than that of the group ≥76 years. For the 65 to 75 year age group, any statin use increased from an average of 38.6% in April 2011 to 43.3% in December 2016. For the ≥76 year age group, any statin use increased from an average of 26.5% in April 2011 to 30.0% in December 2016.
Fig. 2.
Monthly percent of any statin use among US nursing home residents, by age group
3.2.2. Trends in high intensity statin use
Overall, the prevalence of high intensity statin use also increased from April 2011 (2.8%) to December 2016 (5.6%). See Figure 3 for trends in high intensity statin use by age group. While overall high intensity statin use was uncommon among nursing home residents across time, the prevalence in the 65 to 75 year age group was often more than twice that of the ≥76 year age group (e.g., April 2011: 65 to 75 years: 4.8%, ≥76 years: 2.3%). For the 65 to 75 age group, high intensity statin use increased from an average of 4.8% in April 2011 to 9.5% in December 2016. For the ≥76 year age group, high intensity statin use increased from an average of 2.3% in April 2011 to 4.5% in December 2016.
Fig. 3.
Monthly percent of high intensity statin use among US nursing home residents, by age group
3.3. Impact of statin-related events on prevalence of statin use
The impact of statin-related events on the prevalence of statin use, evaluated in separate models, are shown in Tables 2 – 5. This includes the results of these models showing trend and level changes concurrent with the following statin-related events: the introduction of generic statins into the US market (Table 2), AHA/ACC guideline updates (Table 3), release of statin-related safety warnings (Table 4), and publication of statin deprescribing trial results (Table 5). In all models, statin use (any and high intensity use) is higher in 65–75 year age group relative to the ≥76 years age group.
TABLE 2.
Effect of generic availability of statins on the prevalence of any statin use and the prevalence of high intensity use in US nursing homes, stratified by age group
| 65–75 years* | ≥76 years** | |||||
|---|---|---|---|---|---|---|
| β Coefficient* | 95% Confidence Interval | β Coefficient | 95% Confidence Interval | |||
| Any Statin Use | ||||||
| Intercept | 38.8 | 38.56 | 39.04 | 26.58 | 26.39 | 26.77 |
| Baseline Trend | 0.09 | 0.07 | 0.11 | 0.08 | 0.07 | 0.10 |
| July 2012 | ||||||
| Level change | −0.05 | −0.23 | 0.13 | 0.18 | −0.02 | 0.38 |
| Trend change | −0.02 | −0.04 | 0.00 | −0.03 | −0.05 | −0.01 |
| September 2015 | ||||||
| Level change | 0.12 | −0.21 | 0.45 | −0.40 | −0.71 | −0.09 |
| Trend change | −0.02 | −0.08 | 0.04 | 0.03 | −0.03 | 0.09 |
| May 2016 | ||||||
| Level change | −0.10 | −0.56 | 0.36 | −0.08 | −0.46 | 0.30 |
| Trend change | 0.03 | −0.07 | 0.13 | −0.07 | −0.16 | 0.03 |
| High Intensity Statin Use | ||||||
| Intercept | 4.36 | 2.61 | 6.12 | 2.08 | 1.25 | 2.92 |
| Baseline Trend | 0.06 | 0.01 | 0.10 | 0.03 | 0.01 | 0.05 |
| May 2016 | ||||||
| Level change | −0.04 | −0.31 | 0.23 | −0.06 | −0.19 | 0.07 |
| Trend change | 0.11 | −0.01 | 0.23 | 0.04 | −0.02 | 0.10 |
Model for 65–75 years adjusted for AR(12) = −0.76 for any statins and AR(1)=−0.99 for high intensity statins.
Model adjusted for AR(10) =0.31 and AR(12) =−0.45 for any statins and AR(1)=−0.99 for high intensity statins.
July 2012: generic availability fluvastatin 20mg and 40mg; September 2015: generic availability fluvastatin 80mg; May 2016: generic availability rosuvastatin (high intensity)
TABLE 5.
Effect of deprescribing trial results* on the prevalence of any statin use and the prevalence of high intensity use in US nursing homes, stratified by age group
| 65–75 years** | ≥76 years*** | |||||
|---|---|---|---|---|---|---|
| β Coefficient* | 95% Confidence Interval | β Coefficient | 95% Confidence Interval | |||
| Any Statin Use | ||||||
| Intercept | 38.95 | 38.75 | 39.16 | 26.78 | 26.63 | 26.93 |
| Baseline Trend | 0.07 | 0.07 | 0.08 | 0.07 | 0.06 | 0.07 |
| April 2015 | ||||||
| Level change | 0.07 | −0.11 | 0.25 | −0.25 | −0.48 | −0.09 |
| Trend change | −0.01 | −0.03 | 0.00 | −0.03 | −0.04 | −0.01 |
| High Intensity Statin Use | ||||||
| Intercept | 4.40 | 3.02 | 5.79 | 2.11 | 1.52 | 2.70 |
| Baseline Trend | 0.04 | −0.01 | 0.09 | 0.02 | 0.00 | 0.04 |
| April 2015 | ||||||
| Level change | −0.08 | −0.33 | 0.17 | 0.01 | −0.11 | 0.13 |
| Trend change | 0.11 | 0.02 | 0.21 | 0.05 | 0.01 | 0.09 |
Kutner JS, Blatchford PJ, Taylor DH, Jr., Ritchie CS, Bull JH, Fairclough DL et al. Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial. JAMA Intern Med. 2015;175(5):691–700.
Model for 65–75 years adjusted for AR(12) = −0.73 for any statins and AR(1)=−0.98 for high intensity statins.
Model adjusted for AR(10) =0.19 and AR(12) =−0.55 for any statins and AR(1)=−0.98 for high intensity statins.
TABLE 3.
Effect of American Heart Association/American College of Cardiology (AHA/ACC) guideline updates in 2011 and 2013 on the prevalence of any statin use and the prevalence of high intensity use in US nursing homes, stratified by age group
| 65–75 years* | ≥76 years** | |||||
|---|---|---|---|---|---|---|
| β Coefficient* | 95% Confidence Interval | β Coefficient | 95% Confidence Interval | |||
| Any Statin Use | ||||||
| Intercept | 38.63 | 38.28 | 38.98 | 26.46 | 26.18 | 26.75 |
| Baseline Trend | 0.13 | 0.06 | 0.19 | 0.10 | 0.05 | 0.16 |
| December 2011 | ||||||
| Level change | 0.09 | −0.21 | 0.38 | 0.09 | −0.19 | 0.36 |
| Trend change | −0.07 | −0.13 | 0.00 | −0.03 | −0.09 | 0.02 |
| November 2013 | ||||||
| Level change | 0.09 | −0.06 | 0.24 | 0.01 | −0.15 | 0.17 |
| Trend change | 0.01 | 0.00 | 0.02 | −0.03 | −0.04 | −0.02 |
| High Intensity Statin Use | ||||||
| Intercept | 4.09 | 3.74 | 4.44 | 2.38 | 2.21 | 2.56 |
| Baseline Trend | −0.13 | −0.19 | −0.08 | −0.07 | −0.10 | −0.04 |
| December 2011 | ||||||
| Level change | −0.10 | −0.31 | 0.11 | −0.04 | −0.14 | 0.05 |
| Trend change | 0.16 | 0.09 | 0.22 | 0.09 | 0.06 | 0.12 |
| November 2013 | ||||||
| Level change | −0.03 | −0.24 | 0.18 | −0.04 | −0.12 | 0.05 |
| Trend change | 0.11 | 0.09 | 0.13 | 0.04 | 0.03 | 0.05 |
Models for 65 to 75 year old nursing home residents adjusted for AR(12) = −0.77 for any statin use and AR(1) = −0.78 for high intensity statin use.
Model for 76+ year old nursing home residents adjusted for AR(10) = 0.23 and AR(12) =−0.54 for any statin use and AR(1) =−0.75 and AR(9)=0.25for high intensity statin use.
TABLE 4.
Effect of statin safety warnings on the prevalence of any statin use and the prevalence of high intensity use in US nursing homes, stratified by age group
| 65–75 years* | ≥76 years** | |||||
|---|---|---|---|---|---|---|
| β Coefficient* | 95% Confidence Interval | β Coefficient | 95% Confidence Interval | |||
| Any Statin Use | ||||||
| Intercept | 38.64 | 38.34 | 38.95 | 26.38 | 26.13 | 26.63 |
| Baseline Trend | 0.12 | 0.08 | 0.16 | 0.12 | 0.08 | 0.16 |
| March 2012 | ||||||
| Level change | −0.10 | −0.36 | 0.16 | −0.18 | −0.43 | 0.08 |
| Trend change | −0.06 | −0.10 | −0.02 | −0.05 | −0.08 | −0.01 |
| March 2014 | ||||||
| Level change | 0.16 | 0.01 | 0.31 | −0.09 | −0.25 | 0.08 |
| Trend change | 0.01 | −0.01 | 0.02 | −0.03 | −0.05 | −0.02 |
| High Intensity Statin Use | ||||||
| Intercept | 4.95 | 4.71 | 5.19 | 2.38 | 2.27 | 2.48 |
| Baseline Trend | −0.10 | −0.14 | −0.07 | −0.05 | −0.07 | −0.04 |
| March 2012 | ||||||
| Level change | −0.22 | −0.41 | −0.02 | −0.08 | −0.17 | 0.02 |
| Trend change | 0.15 | 0.12 | 0.19 | 0.08 | 0.06 | 0.10 |
| March 2014 | ||||||
| Level change | −0.08 | −0.27 | 0.11 | −0.07 | −0.16 | 0.01 |
| Trend change | 0.09 | 0.07 | 0.10 | 0.03 | 0.03 | 0.04 |
Model for 65 to 75 years adjusted for AR(12) = −0.77 for any statin use and AR(1) = −0.64 for high intensity statin use.
Model adjusted for AR(10) = 0.22 and AR(12) =−0.51 for any statin use and AR(1) = −0.56 for high intensity statin use.
March 2012 FDA safety label changes and March 2014 NLA Task Force on Statin Safety.
3.3.1. Impact of the introduction of generic statins on prevalence of statin use
Table 2 shows the results from the model with terms corresponding to the introduction of generic statins. Among the 65 to 75 year age group, no level changes or trend changes were observed during the time periods tied to the introduction of generic statins, overall and for high intensity statins. Among the ≥76 year age group, there was a slight negative trend change in any statin use corresponding to the introduction of generic fluvastatin 20 mg and 40 mg in July 2012 (β −0.03; 95% CI: −0.05 to −0.01) and a negative level change in any statin use corresponding with the introduction of fluvastatin 80 mg in September 2015 (β =−0.40; 95% CI: −0.71 to −0.09). In general, for the high intensity statin analysis, the model only included one term date for the introduction of one high intensity generic statin with no statistically significant changes following its introduction among both age groups.
3.3.2. Impact of updates to the AHA/ACC guidelines on prevalence of statin use
Table 3 shows the results from the model corresponding to the dates of the AHA/ACC guideline updates. For any statin use among the 65 to 75 year age group, a trend decrease corresponded to the December 2011 updated guidelines (β = −0.07; 95% CI: −0.13 to 0.00) and a trend increase corresponded with the November 2013 updated guidelines (β = 0.01; 95% CI: 0.00 to 0.02). For high intensity statin use, positive trend changes occurred among both age groups with the December 2011 updated guidelines (65 to 75 years: β = 0.16; 95% CI: 0.09 to 0.22; ≥76 years: β = 0.09; 95% CI: 0.06 to 0.12) and the November 2013 updated guidelines (65 to 75 years: β = 0.11; 95% CI: 0.09 to 0.13; ≥76 years: β = 0.04; 95% CI: 0.03 to 0.05).
3.3.3. Impact of safety warnings on prevalence of statin use
Table 4 shows the results of the model corresponding to the release of statin safety warnings in the US. Among the 65 to 75 year age group, the March 2012 FDA statin safety label warnings resulted in a negative trend change for any statin use (β =−0.06; 95% CI: −0.10 to −0.02), and for high intensity use, both a level change (β = −0.22; 95% CI: −0.41 to −0.02) and a trend change (β = 0.15; 95% CI: 0.12 to 0.19). For the same age group, the March 2014 NLA Task Force on Statin Safety report resulted in a positive level change for any use (β = 0.16; 95% CI: 0.01 to 0.31) and a positive trend change for high intensity statin use (β = 0.09; 95% CI: 0.07 to 0.10). Among the ≥76 year age group, a negative trend change in any statin use was observed coinciding with both the March 2012 FDA safety labeling warning (β = −0.05; 95% CI: −0.08 to −0.01) and the March 2014 NLA report (β = −0.03; 95% CI: −0.05 to −0.02). For high intensity use in the ≥76 year age group, there was a positive trend change with both the March 2012 (β = 0.08; 95% CI: 0.06 to 0.10) and March 2014 (β = 0.03; 95% CI: 0.03 to 0.04) updates.
3.3.4. Impact of the deprescribing trial on prevalence of statin use
Table 5 shows the changes in statin prevalence following the 2015 publication of a deprescribing trial results. For any statin use, both the 65 to 75 and ≥76 years age group had negative changes (65 to 75 years: trend change β = −0.01; 95% CI: −0.03 to 0.00; ≥76 years: level change β = −0.25; 95% CI: −0.48 to −0.09; trend change β = −0.03; 95% CI: −0.04 to −0.01). For high intensity statins, both age groups observed positive trend changes (65 to 75 years: β = 0.11; 95% CI: 0.02 to 0.21; ≥76 years: β = 0.05; 95% CI: 0.01 to 0.09).
4. DISCUSSION
Our study provides detailed information on national trends in statin use among US nursing home residents over the period from April 2011 to December 2016. This study also provides insight on the impact of statin-related events, including changes in statin use following the introduction of generic statins, statin-related guideline updates, statin-related safety warnings, and results of a major statin deprescribing trial in hospice eligible patients. After evaluating virtually all US long stay older nursing home residents enrolled in fee-for service Medicare, we found that any and high intensity statin use increased from 2011 to 2016. Positive trend changes in high intensity statin use coincided with AHA/ACC guideline changes in 2011 and 2013. The FDA 2012 safety label warning was associated with decreased trends in any statin use for both age groups, but positive trend changes in high intensity use. Statin-related events including guideline updates appear to impact the care of nursing home residents in whom the use of high intensity statins may not be appropriate nor evidence-based.
4.1. Overall statin trends
The overall statin use found in this study (April 2011 – December 2016: 29% – 33%) was similar to that of others evaluating such use in the nursing home [8, 22, 6]. Our evaluation of resident characteristics demonstrated little change in the case-mix of residents included in the analysis. Thus, the observed changes in trends could not be due to increases in need for statin therapy. In addition, other studies among US older adults have shown similar upward trends in statin use over time [23, 4, 10, 1]. This includes one retrospective cohort study that evaluated statin use from 2002 to 2013 using the US Medical Expenditure Panel Survey [4]. In this study, adults 65 to 74 years of age had an increase in use from 32.7% in 2002 to 2003 to 47.8% in 2012 to 2013 and those 75+ years had an increase of use from 30.0% in 2002 to 2003 to 48.6% in 2012 to 2013. Another similar observational retrospective study looked at high intensity statin use in the 30 days following hospital discharge for a myocardial infarction from 2011 to 2014 among Medicare beneficiaries aged 66 to 75 years [10]. This study showed that high intensity statin use increased from 24.8% in 2011 to 57.5% in 2014. Compared to our study, both of these studies showed higher overall rates of statin use and a greater percent increase in use from the start of each study. This is likely because of the different study populations and time periods. Regardless, these data convey a consistent upward trend in statin use over time among the US older adult population, which has appeared to extend to the nursing home setting.
4.2. Impact of the introduction of generic statins on prevalence of statin use
Consistent with our findings, other studies have also shown that changes in access have affected the use of statins[3, 1, 24]. The current study did not include data before April 2011. Other studies have demonstrated that statin use increased rapidly from 1987, when the first statin agent was introduced to the US market and in 2001, with the availability of the first generic statin (lovastatin) [3, 1]. Since then six major statin therapies had been approved in the US by the start of our study in April of 2011 (Supplemental Table S1). We found no impact following the introduction of generics on any statin use or high intensity statin use during the study period for the 65 to 75 age group. The lack of impact could be for several reasons. In the US, nursing homes are required by federal mandate to provide necessary medications regardless of residents’ source of insurance. Second, we included only nursing home residents with Medicare fee-for-service and Medicare Part D. For any statin use in the ≥76 year age group, the introduction of generic statins resulted in a decrease in any statin use, including a decreased trend in July 2012 and decreased level in September 2015, but had no effect on high intensity statin use. In nursing homes, every resident must have a drug regimen review every 30 days [25]. The majority of US nursing homes contract with large long-term care pharmacies that bundle the federally mandated drug regimen reviews into their service (except in New Jersey where it is against the law for consultant pharmacists to be employed by long term care pharmacies). Consultant pharmacists often make cost-savings recommendations. It is possible that in the context of drug regimen reviews consultant recommended discontinuation of statins, rather than shifting to generics. Our data do not allow us to evaluate this hypothesis.
4.3. Impact of updates to the AHA/ACC guidelines on prevalence of statin use
For high intensity statin use, major guidelines appeared play more of a role in influencing use of statins in the US nursing home setting. Before December 2011, the trend in the prevalence of statin use in both age groups was declining. Concurrent with the AHA/ ACC update to their 2006 recommendations for secondary prevention of vascular disease issued on November 29, 2011 [11], we observed a positive trend change in high intensity statin use for both age groups. These recommendations called for increased use of higher intensity statins to achieve lower low-density lipoprotein (LDL) cholesterol targets. In November 2013 the AHA/ACC released new guidelines [12], since the 2004 National Cholesterol Education Program’s Adult Treatment Panel (ATP) II Guideline Update, which lowered the criteria for statin treatment. Again, we observed a positive trend change in high intensity statin use for both age groups, albeit more modest than what was observed concurrent with the 2011 AHA/ACC guideline updates.
4.4. Impact of safety warnings on prevalence of statin use
Because our data had few data points before the June 2011 US FDA release of a black box warning for high dose (80 mg) simvastatin [9], we were unable to model the impact of the black box warning at that time. The March 2012 FDA statin safety label changes appeared to immediately result in decreased trends in any statin use for both age groups and a mixed effect in high-intensity use for each group. This appears to be aligned with the results of a systematic review on FDA drug risk communications, which noted that the impacts of such communications were “varied and unpredictable” [26]. The NLA Task Force on Statin Safety 2014 update to recommendations [27] concluded that statin therapy is generally safe and the potential benefits often outweigh the risks when indicated. Increases in the prevalence of statin use (any and high intensity) were observed in both age groups after this March 2014 report was released. This statistically significant uptake may have had less to do with the adverse effects reviewed in the report itself, but with increased public awareness of statins and its conclusion affirming the safety of statins.
4.5. Impact of the deprescribing trial on prevalence of statin use
Nursing homes are a common site of death for older adults, with more than 20–25% of the aged dying in nursing homes [28]. Further, many nursing home residents have limited life expectancy; the median survival of nursing home residents is estimated to be 2.2 years [29]. Therefore, the older adults in our study may have had limited life expectancy, similar to those included in the statin de-prescribing study [13]. While we could not definitively identify hospice eligible patients with our data, we did find a greater impact on the effect of this deprescribing trial on any statin use in the ≥76 years age group than on the 65–75 year age group. We also observed an increase in high intensity statin use at the same time, and the reasons for this are unclear. One possibility is that residents may have had high intensity statin initiated as the result of a hospitalization for an acute cardiovascular event, but we were unable to evaluate this possibility with our data.
4.5. Study considerations
These data must be interpreted with some caveats in mind. Our approach may underestimate changes in the prevalence of statin use associated with delayed effects of guideline, USA FDA warnings, or deprescribing trial results. However, our analyses detected an overall upward trend in statin use over time in both older age groups with downward deflections corresponding to key statin-related events. It is quite possible that all major guideline updates did impact statin use, but not immediately in all circumstances. Nonetheless, it is not surprising that the ≥ 76 years age group would be more affected by major guideline changes. Advanced age is significantly associated with cardiovascular events which precipitates statin use [30]. As a result, the guideline changes are more likely to impact older adults. Ironically, it is this age group that guidelines often exclude in their recommendations but are subsequently applied to this population anyway. The guidelines do not specify statin recommendations for specific older populations such as frail nursing home residents. It is important to bear in mind that statins are prescribed prophylactically with a delayed mortality benefit of at least one to two years [31]. In light of the delayed efficacy and potential adverse effects of statins [31, 32], nursing home residents near the end-of-life may experience more harm than benefit from initiation or continuation of statins. Considering the impact of guidelines on this population and potential harm from overuse, special consideration should be given to older patients in long-term care environments when new guidelines are released.
4.6. Limitations
The study was limited to Medicare Fee-for-Service claims data, and thus the reliability of the results are dependent on the validity of secondary claims data. In addition, those with other insurance coverage such as Medicare Advantage or uninsured, were excluded. There is also potential for unmeasured confounding from data unavailable to the study team including the indication for statin therapy, past history of statin use, inpatient statin prescriptions, and data before or after the study period from 2011 to 2016. Since statins were introduced in 1987 and new guidelines from the United States Preventative Services Task Force (USPSTF) were released in late 2016, we would have preferred to include a longer time period to evaluate trends over time. Unfortunately, such data were not available to our research team. Regardless, this is the first study (to the best of our knowledge) to evaluate national statin trends in US nursing homes over time.
5. CONCLUSIONS
The percent of statin use among US nursing home residents has increased from 2011 to 2016. This includes any and high intensity statin use for residents aged 65 to 75 years and ≥76 years. Statin-related guideline and publications appeared to impact statin use. Therefore, the overall increase in statin use could in part be due to the fact that national guidelines have continued to lower threshold for statin treatment, likely contributing to the proliferation of statin use in the nursing home setting. Given the high rate of polypharmacy in nursing home settings and potential overuse in frail older adults, special consideration should be given to this population when guideline updates are being considered.
Supplementary Material
Key Points:
This cross-sectional study of virtually all US long stay older nursing home residents enrolled in fee-for service Medicare found that statin use and high intensity statin use increased over the 2011–2016 time period.
Positive trend changes in high intensity statin use coincided with American Heart Association/American College of Cardiology guideline changes in 2011 and 2013.
The US Food and Drug Administration safety label changes reduced the prevalence of any statin use in both age groups, but positive trend changes occurred in the prevalence of high intensity statin use.
The recommendations from national guideline updates may extend into the care of nursing home residents in whom the use of high intensity statins may not be appropriate nor evidence-based.
ACKNOWLEDGMENTS:
We thank Robert Goldberg, PhD for his guidance with this manuscript. The work was supported by the National Center for Advancing Translational Sciences, National Institutes of Health (TL1 TR001454), the National Institute on Aging (K24AG0268300), and the Agency for Healthcare Research and Quality (R36 HS026840). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality.
Funding:
The work was supported by the National Center for Advancing Translational Sciences, National Institutes of Health (TL1 TR001454, PI: Lapane), (K24AG068300, PI: Jennifer Tjia), and the Healthcare Research and Quality Agency for (R36 HS026840, PI: Mack).
Declarations:
This project was supported by grant number R36HS026840 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality.
Footnotes
Ethical Approval: This study used routinely- collected administrative and claims dataset and was approved by the University of Massachusetts Medical School Institutional Review Board (protocol number H00016995).
Conflict of Interest: Dr. Jennifer Tjia is a consultant for CVS Health and Omnicare Long Term Care Pharmacy. Drs. Mack, Hume, and Lapane have declared no conflicts of interest for this article.
Availability of data and material: The authors are unable to share the data used to conduct this study per their Data Use Agreement with the Centers for Medicare and Medicaid Services via RESDAC.
Code availability: SAS code will be made available on request to the authors.
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