Abstract
Guidelines recommend attempting to re-initiate statins in patients who discontinue treatment. Prior experiences while taking a statin, including side effects, may reduce a person’s willingness to re-initiate treatment. We determined the percentage of adults who are willing to re-initiate statin therapy after treatment discontinuation. Factors associated with willingness to re-initiate a statin were also examined. A statin questionnaire was administered and study examination conducted among black and white US adults enrolled in the nationwide REasons for Geographic And Racial Differences in Stroke (REGARDS) study between 2013 and 2017. Among participants who self-reported ever having taken a statin (n=7,216, mean age 72 years, 53% women, 34% black), 1,081 (15%) reported having discontinued treatment. Among those who discontinued treatment, statin side effects, perceived lack of need for a statin, and cost were reported by 66%, 31%, and 3% of participants, respectively. Overall, 37% of participants who had discontinued treatment were willing to re-initiate statin therapy. Participants who discontinued treatment due to cost (prevalence ratio (PR) 1.61; 95% confidence interval (CI) 1.01, 2.57) were more likely to report a willingness to re-initiate therapy. Participants with a low-density lipoprotein-cholesterol ≥130 mg/dL versus <100 mg/dL (PR 0.69; 95%CI 0.53, 0. 88) and who discontinued treatment due to side effects (PR 0.51; 95%CI 0.41, 0.64) were less likely to report willingness to re-initiate statin therapy. In conclusion, a substantial proportion of participants who discontinued statin therapy were willing to re-initiate treatment. Healthcare providers should discuss re-initiation of statin therapy with their patients who have discontinued treatment.
Keywords: Statin, re-initiation, willingness
Statins are widely prescribed for the primary and secondary prevention of cardiovascular disease (CVD).1–3 Despite being well-tolerated by most individuals, many people discontinue statin treatment.4–6 Discontinuation due to muscle pain, memory problems, cost, and perceived lack of benefit from therapy has been reported.7,8 Prior studies have reported statin discontinuation to be associated with an increased risk for CVD events.9–12 Several guidelines and scientific statements recommend attempting to re-initiate patients on a statin after treatment discontinuation.1,13–15 Many patients remain on a statin long-term after re-initiation.16,17 Identifying factors associated with willingness to re-initiate a statin may allow personalized strategies for those reluctant to restart treatment. The purpose of this study was to determine the percentage of people reporting willingness to re-initiate statin therapy following discontinuation, and examine the association of reasons for discontinuation and side effects attributed to statins with willingness to re-initiate treatment in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a bi-racial cohort of men and women.
Methods
The REGARDS study is a nationwide study that enrolled participants from across the continental US.18 The study oversampled black participants, and approximately half of the sample was recruited from the eight southern US states referred to as the “stroke belt/buckle” (North Carolina, South Carolina, Georgia, Alabama, Mississippi, Tennessee, Arkansas, and Louisiana). Participants completed a telephone interview and an in-home study examination at baseline (January 2003-October 2007), and are contacted every 6 months to identify stroke and coronary heart disease events for subsequent adjudication. Between May 2013 and November 2016, 14,233 participants completed a second in-home examination and telephone interview. The current analysis included participants who completed the second study examination and a statin questionnaire administered on a single occasion during follow-up telephone interviews conducted between November 2015 and March 2017 (n=13,007). We restricted the current analysis to 7,216 participants who self-reported ever having taken a statin at the time of the statin questionnaire administration (Supplemental Figure 1). All components of the REGARDS study were approved by the Institutional Review Board at the University of Alabama at Birmingham. All participants provided written informed consent upon enrollment and again before completing the second study examination.
Data for the current analysis were collected through the REGARDS second study examination and a telephone interview. The statin questionnaire was administered to participants a median of 1.5 years (25th – 75th percentiles: 1 to 2 years) after the second examination. Statin discontinuation was defined as self-reporting stopping treatment for > 2 weeks for any reason and not taking a statin at the time of the questionnaire administration. Participants were asked about 3 potential reasons for discontinuation: cost, perceived lack of need, and side effects. Participants could report multiple reasons for discontinuing statin therapy (Supplemental Figure 2). Those responding “no” or “not sure” to all 3 reasons were categorized as having an “unknown” reason for discontinuation. For participants reporting side effects, we asked what side effects were experienced: muscle pain, tenderness or weakness (hereafter referred to as statin-associated muscle symptoms [SAMS] for conciseness), memory problems, or having an abnormal blood test for the liver or muscles. Participants could report multiple side effects and those responding “no” or “not sure” to experiencing all 3 side effects were categorized as having experienced “unknown” side effects.
The primary outcome was self-reported willingness to re-initiate statin therapy. Participants who discontinued their statin were asked “Would you be willing to restart a statin?” Participants who responded “no” or “not sure” were additionally asked “Would you be willing to restart a statin at a lower dose or less frequently than every day?” Participants responding “yes” to either question were categorized as being willing to re-initiate therapy.
Socio-demographic factors, current cigarette smoking, comorbidities, medication use and adherence, stress, depressive symptoms and physical and mental function were collected during a telephone interview coinciding with the second examination. Medical records were adjudicated by trained abstracters to identify hospitalized CVD events between the first and second in-home examination. During the second in-home study visit, blood pressure was measured, blood samples were collected, and an electrocardiogram was performed following standardized protocols.18 Covariate definitions are listed in Supplemental Table 1.
Characteristics of participants who had ever taken a statin were calculated overall and by statin discontinuation status, using chi-square tests to determine the statistical significance of differences. We calculated frequencies of reported reasons for statin discontinuation. Next, the percentage of participants willing to re-initiate statin therapy was calculated, overall, and by participant characteristics and reasons for discontinuation. Participant characteristics included age, sex, race, region of residence, education, smoking status, perceived stress, depressive symptoms, physical and mental function, medication adherence, high blood pressure, antihypertensive medication use, diabetes, history of CVD, and low-density lipoprotein-cholesterol (LDL-C). Poisson regression with robust variance estimators was used to calculate prevalence ratios (PR) and 95% confidence intervals (CI) for willingness to re-initiate statin therapy associated with participant characteristics and reason for discontinuation. The first model included adjustment for age, sex, and race. The second model included all participant characteristics and reasons for discontinuation simultaneously.
Next, we restricted the analysis to participants who discontinued statin use due to side effects. Frequencies of reported side effects were calculated. We calculated the percentage of participants who were willing to re-initiate statin therapy, overall, by participant characteristics and side effect experienced. We calculated the PR for willingness to re-initiate statin therapy using Poisson regression as described previously. Missing data were imputed using fully conditional specification and 10 data sets.19 Two sided p-values <0.05 were considered statistically significant. Analyses were performed using SAS 9.4 (SAS Institute, Cary, NC).
Results
Among 7,216 participants who reported ever taking a statin, the mean age was 74 years, 34% were black and 53% were women (Table 1). Overall, 1,081 (15%) participants had discontinued statin treatment. Participants who discontinued statin therapy were younger, more likely to be women, have low medication adherence, and have higher LDL-C compared with participants who had not discontinued treatment. Participants who discontinued therapy were less likely to have a high school education, to be taking antihypertensive medication, have diabetes or a history of CVD.
Table 1.
Characteristics of participants who reported ever taking a statin, overall, and by statin discontinuation status.
| Characteristics | Statin discontinuation |
p-value | ||
|---|---|---|---|---|
| Overall (n=7,216) |
Yes (n=1,081) |
No (n=6,135) |
||
|
| ||||
| Age (years) | ||||
| < 65 | 997 (14%) | 188 (17%) | 809 (13%) | <0.001 |
| 65 – 74 | 3,442 (48%) | 519 (48%) | 2,923 (48%) | |
| ≥ 75 | 2,777 (39%) | 374 (35%) | 2,403 (39%) | |
| Black | 2,463 (34%) | 355 (33%) | 2,108 (34%) | 0.33 |
| Woman | 3,840 (53%) | 672 (62%) | 3,168 (52%) | <0.001 |
| Residing in Stroke Belt/Buckle | 4,073 (56%) | 621 (58%) | 3,452 (56%) | 0.47 |
| Less than high school education | 491 (7%) | 54 (5%) | 437 (7%) | 0.01 |
| Current smoker* | 509 (7%) | 63 (6%) | 446 (7%) | 0.09 |
| High perceived stress* | 1,968 (28%) | 296 (27%) | 1,690 (28%) | 0.88 |
| Depressive symptoms* | 763 (11%) | 113 (11%) | 650 (11%) | 0.89 |
| SF-12 physical component score* | ||||
| < 40 | 2,093 (31%) | 357 (35%) | 1,736 (30%) | 0.01 |
| 40–50 | 1,894 (28%) | 266 (26%) | 1,628 (28%) | |
| > 50 | 2,836 (41%) | 409 (39%) | 2,427 (42%) | |
| SF-12 mental component score* | ||||
| < 50 | 1,060 (15%) | 167 (16%) | 893 (15%) | 0.61 |
| 50–60 | 4.078 (60%) | 600 (58%) | 3,478 (60%) | |
| > 60 | 1,685 (25%) | 265 (26%) | 1,420 (25%) | |
| Low medication adherence* | 2,135 (32%) | 346 (35%) | 1,789 (31%) | 0.04 |
| High blood pressure** | 1,017 (14%) | 165 (15%) | 852 (14%) | 0.23 |
| Antihypertensive medication use* | 3,874 (54%) | 510 (47%) | 3,364 (55%) | <0.001 |
| Diabetes mellitus* | 2,165 (31%) | 242 (22%) | 1,923 (32%) | <0.001 |
| History of CVD* | 2,214 (32%) | 261 (25%) | 1,953 (33%) | <0.001 |
| LDL-C (mg/dL)* | ||||
| < 100 | 4,267 (62%) | 278 (27%) | 3,989 (69%) | <0.001 |
| 100 – 129 | 1,491 (22%) | 306 (30%) | 1,185 (20%) | |
| ≥ 130 | 1,076 (16%) | 432 (43%) | 644 (11%) | |
Abbreviations –CVD, cardiovascular disease; LDL-C, low-density lipoprotein-cholesterol; SF-12, 12-item short form survey.
missing data for some participants
High blood pressure defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg.
Among participants who discontinued statin use, 66% reported discontinuing due to side effects, 31% due to perceived lack of need, 3% reported discontinuing due to cost, and 15% for unknown reasons (Figure 1). Overall, 37% of participants who discontinued statin therapy reported a willingness to re-initiate treatment. Additionally, 27% of participants who discontinued their statin due to side effects reported a willingness to re-initiate statin therapy, compared with 39%, 63%, and 59% of participants who discontinued their statin due to perceived lack of need, cost, and unknown reasons, respectively. The percentage of participants willing to re-initiate statin therapy across participant characteristics is presented in Supplemental Table 2, left column. After multivariable adjustment, participants living in the stroke belt/buckle versus other regions of the US, with a physical component score of >50 versus <40, and who discontinued statin use due to cost were more likely to report willingness to re-initiate treatment (Table 2). Participants with LDL-C ≥130 mg/dL versus LDL-C <100 mg/dL and those who discontinued their statin due to side effects were less likely to report a willingness to re-initiate therapy.
Figure 1.
Percentage of participants reporting each reason for statin discontinuation and percentage of participants willing to re-initiate treatment.
Percentages on the top of each column represent the proportion of participants who discontinued their statin due to side effects, perceived lack of need, cost, or unknown reasons. *Percentages within columns represent, among those who discontinued their statin for a particular reason, the proportion willing and not willing to be re-initiated on a statin. For example, 63% of participants who discontinued their statin due to cost were willing to re-initiate statin therapy.
Table 2.
Prevalence ratios for willingness to re-initiate a statin among participants who discontinued treatment.
| Prevalence ratio (95% CI) | ||
|---|---|---|
|
| ||
| Characteristics | Model 1 | Model 2 |
|
| ||
| Age (years) | ||
| < 65 | 1 (ref) | 1 (ref) |
| 65 – 74 | 0.92 (0.71, 1.20) | 1.04 (0.79, 1.36) |
| ≥ 75 | 0.83 (0.62, 1.10) | 0.94 (0.70, 1.26) |
| Black | 1.29 (1.05, 1.59) | 1.20 (0.97, 1.49) |
| Woman | 0.81 (0.66, 0.99) | 0.86 (0.69, 1.06) |
| Region of residence | ||
| Non-Belt/Buckle | 1 (ref) | 1 (ref) |
| Stroke Belt/Buckle | 1.18 (0.96, 1.44) | 1.25 (1.01, 1.53) |
| Less than high school education | 0.99 (0.62, 1.57) | 0.95 (0.59, 1.53) |
| Current smoker | 1.39 (0.97, 1.99) | 1.43 (0.99, 2.06) |
| High perceived stress | 1.05 (0.85, 1.31) | 1.04 (0.81, 1.34) |
| Depressive symptoms | 1.05 (0.76, 1.44) | 0.94 (0.64, 1.38) |
| SF-12 physical component score | ||
| < 40 | 1 (ref) | 1 (ref) |
| 40–50 | 1.28 (0.98, 1.67) | 1.24 (0.94, 1.64) |
| > 50 | 1.35 (1.06, 1.71) | 1.33 (1.01, 1.76) |
| SF-12 mental component score | ||
| < 50 | 1 (ref) | 1 (ref) |
| 50–60 | 0.95 (0.73, 1.24) | 0.87 (0.63, 1.18) |
| > 60 | 0.76 (0.55, 1.04) | 0.73 (0.50, 1.05) |
| Low medication adherence | 0.87 (0.70, 1.08) | 0.86 (0.69, 1.07) |
| High blood pressure* | 0.93 (0.70, 1.23) | 0.88 (0.66, 1.17) |
| Antihypertensive medication use | 1.02 (0.83, 1.25) | 1.06 (0.86, 1.31) |
| Diabetes mellitus | 1.14 (0.91, 1.44) | 1.12 (0.88, 1.43) |
| History of CVD | 0.86 (0.67, 1.09) | 0.89 (0.69, 1.15) |
| LDL-C (mg/dL) | ||
| < 100 | 1 (ref) | 1 (ref) |
| 100 – 129 | 0.78 (0.61, 1.00) | 0.85 (0.66, 1.09) |
| ≥ 130 | 0.61 (0.48, 0.78) | 0.69 (0.53, 0.88) |
| Reason for discontinuation** | ||
| Side effects | 0.50 (0.41, 0.62) | 0.51 (0.41, 0.64) |
| Lack of perceived need | 1.09 (0.89, 1.35) | 0.86 (0.68, 1.08) |
| Cost | 1.74 (1.10, 2.74) | 1.61 (1.01, 2.57) |
Abbreviations: CVD, cardiovascular disease; CI, confidence interval; LDL-C, low-density lipoprotein-cholesterol; SF-12, 12-item short form survey.
Model 1 includes age, race, and sex
Model 2 includes all covariates listed in table
High blood pressure defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg.
Prevalence ratios calculated comparing the proportion of participants reporting versus not reporting individual reasons for discontinuation.
Among 715 participants who discontinued taking a statin due to side effects, 83% reported doing so due to SAMS, 10% due to memory problems, 11% due to an abnormal muscle or liver blood test, and 12% due to unknown side effects (Figure 2). In addition, 28% of participants who discontinued their statin due to SAMS reported a willingness to re-initiate statin therapy, compared with 23%, 25%, and 24% who discontinued due to memory problems, abnormal muscle or liver blood tests, and unknown side effects, respectively. Among participants who discontinued taking their statin due to side effects, the percentage willing to re-initiate therapy across participant characteristics is presented in Supplemental Table 2, right column. After multivariable adjustment, participants with LDL-C ≥130 mg/dL versus LDL-C <100 mg/dL were less likely to report a willingness to re-initiate a statin (Table 3). None of the individual side effects studied were associated with a willingness to re-initiate therapy.
Figure 2.
Percentage of participants reporting side effects prior to discontinuation and percentage of participants willing to re-initiate treatment.
Percentages on the top of each column represent the proportion of participants who reported discontinuation due to SAMS, memory problems, an abnormal liver or blood test, or unknown reasons among those who discontinued their statin due to side effects. *Percentages within columns represent the proportion of participants willing and not willing to be re-initiated on a statin among those reporting particular side effects. For example, 29% of participants who discontinued their statin due SAMS reported a willingness to re-initiate statin therapy.
Abbreviations: SAMS, statin-associated muscle symptoms
Table 3.
Prevalence ratios for willingness to re-initiate a statin among participants who discontinued treatment due to side effects.
| Prevalence ratio (95% CI) | ||
|---|---|---|
|
| ||
| Characteristics | Model 1 | Model 2 |
|
| ||
| Age (years) | ||
| < 65 | 1 (ref) | 1 (ref) |
| 65 – 74 | 1.05 (0.70, 1.57) | 1.10 (0.72, 1.66) |
| ≥ 75 | 0.91 (0.59, 1.42) | 0.97 (0.61, 1.53) |
| Black | 1.21 (0.89, 1.65) | 1.18 (0.85, 1.64) |
| Woman | 0.81 (0.60, 1.08) | 0.82 (0.60, 1.13) |
| Region of residence | ||
| Non-Belt/Buckle | 1 (ref) | 1 (ref) |
| Stroke Belt/Buckle | 1.27 (0.94, 1.70) | 1.25 (0.93, 1.70) |
| Less than high school education | 0.95 (0.49, 1.87) | 0.91 (0.46, 1.79) |
| Current smoker | 1.48 (0.89, 2.48) | 1.48 (0.88, 2.49) |
| High perceived stress | 1.11 (0.82, 1.52) | 1.10 (0.78, 1.56) |
| Depressive symptoms | 1.01 (0.63, 1.61) | 0.83 (0.47, 1.45) |
| SF-12 physical component score | ||
| < 40 | 1 (ref) | 1 (ref) |
| 40–50 | 1.25 (0.86, 1.81) | 1.30 (0.88, 1.92) |
| > 50 | 1.28 (0.91, 1.80) | 1.45 (0.98, 2.13) |
| SF-12 mental component score | ||
| < 50 | 1 (ref) | 1 (ref) |
| 50–60 | 0.84 (0.59, 1.22) | 0.75 (0.48, 1.17) |
| > 60 | 0.69 (0.44, 1.07) | 0.68 (0.40, 1.15) |
| Low medication adherence | 0.83 (0.60, 1.13) | 0.87 (0.63, 1.19) |
| High blood pressure* | 1.03 (0.70, 1.52) | 0.98 (0.65, 1.46) |
| Antihypertensive medication use | 1.21 (0.90, 1.62) | 1.24 (0.91, 1.67) |
| Diabetes mellitus | 1.20 (0.86, 1.66) | 1.13 (0.80, 1.60) |
| History of CVD | 1.06 (0.77, 1.47) | 1.05 (0.75, 1.48) |
| LDL-C (mg/dL) | ||
| < 100 | 1 (ref) | 1 (ref) |
| 100 – 129 | 0.74 (0.51, 1.07) | 0.75 (0.51, 1.09) |
| ≥ 130 | 0.63 (0.44, 0.89) | 0.63 (0.44, 0.91) |
| Side effects reported** | ||
| SAMS | 1.26 (0.85, 1.88) | 1.22 (0.81, 1.83) |
| Memory problems | 0.77 (0.46, 1.29) | 0.73 (0.43, 1.23) |
| Abnormal blood test | 0.90 (0.56, 1.44) | 0.91 (0.56, 1.47) |
Abbreviations: CVD, cardiovascular disease; CI, confidence interval; LDL-C, low-density lipoprotein-cholesterol; SAMS, statin-associated muscle symptoms; SF-12, 12-item short form survey.
Model 1 includes age, race, and sex
Model 2 includes all covariates listed in table
High blood pressure defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg.
Prevalence ratios calculated comparing the proportion of participants reporting versus not reporting each side effect.
Discussion
In this population-based sample of black and white adults, 15% of participants who reported ever taking a statin discontinued treatment. The most frequently reported reason for statin discontinuation was side effects. Over one-third of participants who discontinued taking a statin reported a willingness to re-initiate therapy. Although discontinuation due to side effects was associated with a lower likelihood for willingness to re-initiate therapy, a substantial percentage of participants who discontinued their statin due to side effects expressed a willingness to re-initiate treatment.
Statins are effective in lowering LDL-C concentrations and reducing the risk of CVD events.1–3 Despite the risk reduction benefits of statins, a high percentage of people discontinue treatment,16 especially within 12 months of initiation.4,5,16 The percentage of participants who had discontinued taking statins was lower in the current analysis when compared to previous studies.11 Statin discontinuation was only assessed at one time point in the current study and we were not able to account for multiple periods of discontinuation and re-initiation. The variation in the rates of statin discontinuation across studies may reflect differences in the criteria used to define discontinuation.
Many guidelines recommend that healthcare providers attempt to re-initiate a statin after a patient discontinues treatment. The suggested course of re-initiation by the National Lipid Association includes using the same dose, dose-reduction, statin substitution, or lipid-lowering therapy combinations depending on a patient’s CVD risk and prevention needs.20 Other organizations make similar recommendations.1,15,21 Evidence from randomized trials suggests that many patients re-initiating therapy after a documented statin-related adverse event maintain treatment adherence.22–24 In the ODYSSEY ALTERNATIVE trial, 67% of participants with intolerance to ≥2 statins who were re-initiated on atorvastatin remained on treatment over 6 months.25 The high likelihood for statin tolerability after re-initiation should be considered when balancing statin risks and benefits.
In the current study, high physical function was associated with an increased willingness to re-initiate therapy. Health conscious individuals may be more inclined to accept treatments that improve their CVD risk. In contrast, participants reporting SAMS, the most commonly reported side effect, were less likely to report willingness to re-initiate a statin. This is consistent with a qualitative study where primary care physicians reported SAMS as the most substantial barrier to statin re-initiation.26 Discussing the high percentage of people who can tolerate a statin despite having previously experienced side effects16 and encouraging shared decision making in re-initiating treatment may minimize this barrier. Higher LDL-C was also associated with being less willing to re-initiate a statin, which warrants further investigation. Listening to patients’ concerns, explaining the benefits of statins, and considering various therapeutic schedules may improve willingness to re-initiate treatment.27
Participants living in the stroke belt/buckle region of the US were more likely to report willingness to re-initiate a statin. Previous research reported low rates of statin adherence in the southeastern regions of the US relative to other regions, but did not focus on attitudes toward treatment re-initiation.28 Further research is warranted to investigate regional differences related to patterns of statin use. Willingness to re-initiate treatment did not differ between participants with and without a history of CVD or diabetes, two high risk populations likely to receive substantial CVD risk reduction benefits from taking statins. Discussing the CVD risk reduction benefits of statins may increase the willingness to re-initiate therapy among high risk groups.
The findings of the current study should be interpreted in the context of certain limitations. Statin use, the prevalence of discontinuation, and reasons for discontinuation were identified through self-report. Medical records were not available to confirm treatment patterns. The statin questionnaire was administered a median of 1.5 years after the second in-home examination. Duration of statin use, changes in statin type, titration prior to a participant discontinuing their statin, and the time at which a participant discontinued their statin was not available. The current analysis was cross-sectional and we were unable to account for changes in CVD risk over time, which may influence treatment decisions.
In conclusion, results from the current study indicate that over one third of individuals who discontinue a statin may be willing to re-initiate treatment. Even among participants who discontinued taking their statin due to side effects, a substantial percentage reported a willingness to re-initiate treatment. Healthcare providers should discuss treatment re-initiation with their patients who have discontinued taking a statin. Discussing side effects and tolerability, emphasizing the benefits of statins, and offering various therapeutic schedules may improve patients’ willingness to re-initiate a statin.
Supplementary Material
Acknowledgements:
The REGARDS research project is supported by a cooperative agreement U01NS041588 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Service. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health. Representatives of the funding agency have been involved in the review of the manuscript but not directly involved in the collection, management, analysis or interpretation of the data. All authors had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors thank the other investigators, the staff, and the participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions can be found at http://www.regardsstudy.org
Funding:
The current study was funded by an industry/academic collaboration between Amgen Inc., University of Alabama at Birmingham and the Icahn School of Medicine at Mount Sinai. Additional support for GST was received through grant 5T32 HL00745733 from the NHLBI at the NIH.
Footnotes
Disclosures: MTM, GST, RMT, and LDC have no disclosures. KLM works in the Center for Observational Research at Amgen and is a stockholder of Amgen. RD is employed by Amgen and is a stockholder of Amgen. MEF receives research support from Amgen. RSR receives research support from Akcea, Amgen, Medicines Company, and Sanofi. He has participated in Advisory Boards for Akcea, Amgen, Regeneron and Sanofi. He consults for C5 and CVS Caremark. He receives honoraria from Akcea, Kowa and Pfizer, and royalties from UpToDate. MMS receives research support from Amgen. She has participated in Advisory Boards for Amgen. PM receives has received grant support and honoraria from Amgen.
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