Informing Patient-Centered Care Through Stakeholder Engagement and Highly Stratified Quantitative Benefit-Harm Assessments.

OBJECTIVES: In a previous project aimed at informing patient-centered care for people with multiple chronic conditions, we performed highly stratified quantitative benefit-harm assessments for 2 top priority questions. In this current work, our goal was to describe the process and approaches we developed and to qualitatively glean important elements from it that address patient-centered care. METHODS: We engaged patients, caregivers, clinicians, and guideline developers as stakeholder representatives throughout the process of the quantitative benefit-harm assessment and investigated whether the benefit-harm balance differed based on patient preferences and characteristics (stratification). We refined strategies to select the most applicable, valid, and precise evidence. RESULTS: Two processes were important when assessing the balance of benefits and harms of interventions: (1) engaging stakeholders and (2) stratification by patient preferences and characteristics. Engaging patients and caregivers through focus groups, preference surveys, and as co-investigators provided value in prioritizing research questions, identifying relevant clinical outcomes, and clarifying the relative importance of these outcomes. Our strategies to select evidence for stratified benefit-harm assessments considered consistency across outcomes and subgroups. By quantitatively estimating the range in the benefit-harm balance resulting from true variation in preferences, we clarified whether the benefit-harm balance is preference sensitive. CONCLUSIONS: Our approaches for engaging patients and caregivers at all phases of the stratified quantitative benefit-harm assessments were feasible and revealed how sensitive the benefit-harm balance is to patient characteristics and individual preferences. Accordingly, this sensitivity can suggest to guideline developers when to tailor recommendations for specific patient subgroups or when to explicitly leave decision making to individual patients and their providers.

Outcome preferences of older people with multiple chronic conditions and hypertension: a cross-sectional survey using best-worst scaling.

BACKGROUND: Older people with hypertension and multiple chronic conditions (MCC) receive complex treatments and face challenging trade-offs. Patients' preferences for different health outcomes can impact multiple treatment decisions. Since evidence about outcome preferences is especially scarce among people with MCC our aim was to elicit preferences of people with MCC for outcomes related to hypertension, and to determine how these outcomes should be weighed when benefits and harms are assessed for patient-centered clinical practice guidelines and health economic assessments. METHODS: We sent a best-worst scaling preference survey to a random sample identified from a primary care network of Kaiser Permanente (Colorado, USA). The sample included individuals age 60 or greater with hypertension and at least two other chronic conditions. We assessed average ranking of patient-important outcomes using conditional logit regression (stroke, heart attack, heart failure, dialysis, cognitive impairment, chronic kidney disease, acute kidney injury, fainting, injurious falls, low blood pressure with dizziness, treatment burden) and studied variation across individuals. RESULTS: Of 450 invited participants, 217 (48%) completed the survey, and we excluded 10 respondents who had more than two missing choices, resulting in a final sample of 207 respondents. Participants ranked stroke as the most worrisome outcome and treatment burden as the least worrisome outcome (conditional logit parameters: 3.19 (standard error 0.09) for stroke, 0 for treatment burden). None of the outcomes were always chosen as the most or least worrisome by more than 25% of respondents, indicating that all outcomes were somewhat worrisome to respondents. Predefined subgroup analyses according to age, self-reported life-expectancy, degree of comorbidity, number of medications and antihypertensive treatment did not reveal meaningful differences. CONCLUSIONS: Although some outcomes were more worrisome to patients than others, our results indicate that none of the outcomes should be disregarded for clinical practice guidelines and health economic assessments.

Balance of benefits and harms of different blood pressure targets in people with multiple chronic conditions: a quantitative benefit-harm assessment.

OBJECTIVE: Recent studies suggest that a systolic blood pressure (SBP) target of 120 mm Hg is appropriate for people with hypertension, but this is debated particularly in people with multiple chronic conditions (MCC). We aimed to quantitatively determine whether benefits of a lower SBP target justify increased risks of harm in people with MCC, considering patient-valued outcomes and their relative importance. DESIGN: Highly stratified quantitative benefit-harm assessment based on various input data identified as the most valid and applicable from a systematic review of evidence and based on weights from a patient preference survey. SETTING: Outpatient care. PARTICIPANTS: Hypertensive patients, grouped by age, gender, prior history of stroke, chronic heart failure, chronic kidney disease and type 2 diabetes mellitus. INTERVENTIONS: SBP target of 120 versus 140 mm Hg for patients without history of stroke. PRIMARY AND SECONDARY OUTCOME MEASURES: Probability that the benefits of a SBP target of 120 mm Hg outweigh the harms compared with 140 mm Hg over 5 years (primary) with thresholds >0.6 (120 mm Hg better), <0.4 (140 mm Hg better) and 0.4 to 0.6 (unclear), number of prevented clinical events (secondary), calculated with the Gail/National Cancer Institute approach. RESULTS: Considering individual patient preferences had a substantial impact on the benefit-harm balance. With average preferences, 120 mm Hg was the better target compared with 140 mm Hg for many subgroups of patients without prior stroke, especially in patients over 75. For women below 65 with chronic kidney disease and without diabetes and prior stroke, 140 mm Hg was better. The analyses did not include mild adverse effects, and apply only to patients who tolerate antihypertensive treatment. CONCLUSIONS: For most patients, a lower SBP target was beneficial, but this depended also on individual preferences, implying individual decision-making is important. Our modelling allows for individualised treatment targets based on patient preferences, age, gender and co-morbidities.

A randomized trial provided new evidence on the accuracy and efficiency of traditional vs. electronically annotated abstraction approaches in systematic reviews.

OBJECTIVES: Data Abstraction Assistant (DAA) is a software for linking items abstracted into a data collection form for a systematic review to their locations in a study report. We conducted a randomized cross-over trial that compared DAA-facilitated single-data abstraction plus verification ("DAA verification"), single data abstraction plus verification ("regular verification"), and independent dual data abstraction plus adjudication ("independent abstraction"). STUDY DESIGN AND SETTING: This study is an online randomized cross-over trial with 26 pairs of data abstractors. Each pair abstracted data from six articles, two per approach. Outcomes were the proportion of errors and time taken. RESULTS: Overall proportion of errors was 17% for DAA verification, 16% for regular verification, and 15% for independent abstraction. DAA verification was associated with higher odds of errors when compared with regular verification (adjusted odds ratio [OR] = 1.08; 95% confidence interval [CI]: 0.99-1.17) or independent abstraction (adjusted OR = 1.12; 95% CI: 1.03-1.22). For each article, DAA verification took 20 minutes (95% CI: 1-40) longer than regular verification, but 46 minutes (95% CI: 26 to 66) shorter than independent abstraction. CONCLUSION: Independent abstraction may only be necessary for complex data items. DAA provides an audit trail that is crucial for reproducible research.

A benefit-harm analysis of adding basal insulin vs. sulfonylurea to metformin to manage type II diabetes mellitus in people with multiple chronic conditions.

OBJECTIVES: The benefits and harms of diabetes treatments need to be carefully weighed in people with type II diabetes mellitus (DM) and multiple chronic conditions (MCCs). Our objective was to quantitatively assess the benefits and harms of the addition of basal insulin (insulin) vs. sulfonylurea (SU) to metformin in people with DM and MCCs. STUDY DESIGN AND SETTING: Data inputs into the benefit-harms analysis included (1) baseline risks of patient-centered outcomes (death, myocardial infarction, stroke, severe hypoglycemia, diarrhea, nausea) from cohorts and trials; (2) treatment effects for the addition of insulin vs. SU from a network meta-analysis; and (3) patient preference survey for outcome weights. Statistical analysis calculated the probability that adding insulin has greater benefits than harms, when compared with an SU, overall and by prespecified subgroups. RESULTS: Including the six outcomes, the probability of net benefit for insulin compared with SU was similar, across subgroups by age and diabetes duration (probability range, using conditional logit weights: 0.44-0.56). Adding patient preferences for treatment burden associated with insulin injections shifted the probability to favor SU over insulin (probability range, using conditional logit weights: 0.01-0.12). CONCLUSION: In people with DM and MCCs, we demonstrated incomplete evidence to conclude if basal insulin or SU should be added in people with DM and MCCs on metformin alone. The benefit-harm balance was sensitive to treatment preferences, that is., perceived treatment burden, indicating the importance of shared-decision making in caring for people with MCCs who are at high risk for experiencing harms associated with diabetes management.

Engaging Stakeholders to Inform Clinical Practice Guidelines That Address Multiple Chronic Conditions.

BACKGROUND: Having more than one chronic condition is common and is associated with greater health care utilization, higher medication burden and complexity of treatment. However, clinical practice guidelines (CPGs) do not routinely address the balance between harms and benefits of treatments for people with multiple chronic conditions (MCCs). OBJECTIVE: To partner with the Kaiser Permanente Integrated Cardiovascular Health (ICVH) program to engage multiple stakeholders in a mixed-methods approach in order to: 1) identify two high-priority clinical questions related to MCCs, and 2) understand patients' and family caregivers' perceptions of meaningful outcomes to inform benefit/harm assessments for these two high-priority questions. These clinical questions and outcomes will be used to inform CPG recommendations for people with MCCs. DESIGN AND PARTICIPANTS: The ICVH program provided 130 topics rank-ordered by the potential for finding evidence that would change clinical recommendations regarding the topic. We used a modified Delphi method to identify and reword topics into questions relevant to people with MCCs. We used two sets of focus groups (n = 27) to elicit patient and caregiver perspectives on two important research questions and relevant patient-important outcomes on benefit/harm balance for people with MCCs. KEY RESULTS: Co-investigators, patients and caregivers identified "optimal blood pressure goals" and "diabetes medication management" as important clinical topics for CPGs related to people with MCCs. Stakeholders identified a list of relevant outcomes to be addressed in future CPG development including 1) physical function and energy, 2) emotional health and well-being, 3) avoidance of treatment burden, side effects and risks, 4) interaction with providers and health care system, and 5) prevention of adverse long-term health outcomes. CONCLUSIONS: Through the application of a mixed-methods process, we identified the questions regarding optimal blood pressure goals and diabetes medication management, along with related patient-centered outcomes, to inform novel evidence syntheses for those with MCCs. This study provides the lessons learned and a generalizable process for CPG developers to engage patient and caregivers in priority-setting for the translation of evidence into future CPGs. Ultimately, engaging patient and stakeholders around MCCs could improve the relevance of CPGs for the care of people with MCCs.

ACC/AHA Special Report: Clinical Practice Guideline Implementation Strategies: A Summary of Systematic Reviews by the NHLBI Implementation Science Work Group: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

BACKGROUND: In 2008, the National Heart, Lung, and Blood Institute convened an Implementation Science Work Group to assess evidence-based strategies for effectively implementing clinical practice guidelines. This was part of a larger effort to update existing clinical practice guidelines on cholesterol, blood pressure, and overweight/obesity. OBJECTIVES: Review evidence from the published implementation science literature and identify effective or promising strategies to enhance the adoption and implementation of clinical practice guidelines. METHODS: This systematic review was conducted on 4 critical questions, each focusing on the adoption and effectiveness of 4 intervention strategies: (1) reminders, (2) educational outreach visits, (3) audit and feedback, and (4) provider incentives. A scoping review of the Rx for Change database of systematic reviews was used to identify promising guideline implementation interventions aimed at providers. Inclusion and exclusion criteria were developed a priori for each question, and the published literature was initially searched up to 2012, and then updated with a supplemental search to 2015. Two independent reviewers screened the returned citations to identify relevant reviews and rated the quality of each included review. RESULTS: Audit and feedback and educational outreach visits were generally effective in improving both process of care (15 of 21 reviews and 12 of 13 reviews, respectively) and clinical outcomes (7 of 12 reviews and 3 of 5 reviews, respectively). Provider incentives showed mixed effectiveness for improving both process of care (3 of 4 reviews) and clinical outcomes (3 reviews equally distributed between generally effective, mixed, and generally ineffective). Reminders showed mixed effectiveness for improving process of care outcomes (27 reviews with 11 mixed and 3 generally ineffective results) and were generally ineffective for clinical outcomes (18 reviews with 6 mixed and 9 generally ineffective results). Educational outreach visits (2 of 2 reviews), reminders (3 of 4 reviews), and provider incentives (1 of 1 review) were generally effective for cost reduction. Educational outreach visits (1 of 1 review) and provider incentives (1 of 1 review) were also generally effective for cost-effectiveness outcomes. Barriers to clinician adoption or adherence to guidelines included time constraints (8 reviews/overviews); limited staffing resources (2 overviews); timing (5 reviews/overviews); clinician skepticism (5 reviews/overviews); clinician knowledge of guidelines (4 reviews/overviews); and higher age of the clinician (1 overview). Facilitating factors included guideline characteristics such as format, resources, and end-user involvement (6 reviews/overviews); involving stakeholders (5 reviews/overviews); leadership support (5 reviews/overviews); scope of implementation (5 reviews/overviews); organizational culture such as multidisciplinary teams and low-baseline adherence (9 reviews/overviews); and electronic guidelines systems (3 reviews). CONCLUSION: The strategies of audit and feedback and educational outreach visits were generally effective in improving both process of care and clinical outcomes. Reminders and provider incentives showed mixed effectiveness, or were generally ineffective. No general conclusion could be reached about cost effectiveness, because of limitations in the evidence. Important gaps exist in the evidence on effectiveness of implementation interventions, especially regarding clinical outcomes, cost effectiveness and contextual issues affecting successful implementation.

ACC/AHA Special Report: Clinical Practice Guideline Implementation Strategies: A Summary of Systematic Reviews by the NHLBI Implementation Science Work Group: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

BACKGROUND: In 2008, the National Heart, Lung, and Blood Institute convened an Implementation Science Work Group to assess evidence-based strategies for effectively implementing clinical practice guidelines. This was part of a larger effort to update existing clinical practice guidelines on cholesterol, blood pressure, and overweight/obesity. OBJECTIVES: Review evidence from the published implementation science literature and identify effective or promising strategies to enhance the adoption and implementation of clinical practice guidelines. METHODS: This systematic review was conducted on 4 critical questions, each focusing on the adoption and effectiveness of 4 intervention strategies: (1) reminders, (2) educational outreach visits, (3) audit and feedback, and (4) provider incentives. A scoping review of the Rx for Change database of systematic reviews was used to identify promising guideline implementation interventions aimed at providers. Inclusion and exclusion criteria were developed a priori for each question, and the published literature was initially searched up to 2012, and then updated with a supplemental search to 2015. Two independent reviewers screened the returned citations to identify relevant reviews and rated the quality of each included review. RESULTS: Audit and feedback and educational outreach visits were generally effective in improving both process of care (15 of 21 reviews and 12 of 13 reviews, respectively) and clinical outcomes (7 of 12 reviews and 3 of 5 reviews, respectively). Provider incentives showed mixed effectiveness for improving both process of care (3 of 4 reviews) and clinical outcomes (3 reviews equally distributed between generally effective, mixed, and generally ineffective). Reminders showed mixed effectiveness for improving process of care outcomes (27 reviews with 11 mixed and 3 generally ineffective results) and were generally ineffective for clinical outcomes (18 reviews with 6 mixed and 9 generally ineffective results). Educational outreach visits (2 of 2 reviews), reminders (3 of 4 reviews), and provider incentives (1 of 1 review) were generally effective for cost reduction. Educational outreach visits (1 of 1 review) and provider incentives (1 of 1 review) were also generally effective for cost-effectiveness outcomes. Barriers to clinician adoption or adherence to guidelines included time constraints (8 reviews/overviews); limited staffing resources (2 overviews); timing (5 reviews/overviews); clinician skepticism (5 reviews/overviews); clinician knowledge of guidelines (4 reviews/overviews); and higher age of the clinician (1 overview). Facilitating factors included guideline characteristics such as format, resources, and end-user involvement (6 reviews/overviews); involving stakeholders (5 reviews/overviews); leadership support (5 reviews/overviews); scope of implementation (5 reviews/overviews); organizational culture such as multidisciplinary teams and low-baseline adherence (9 reviews/overviews); and electronic guidelines systems (3 reviews). CONCLUSION: The strategies of audit and feedback and educational outreach visits were generally effective in improving both process of care and clinical outcomes. Reminders and provider incentives showed mixed effectiveness, or were generally ineffective. No general conclusion could be reached about cost effectiveness, because of limitations in the evidence. Important gaps exist in the evidence on effectiveness of implementation interventions, especially regarding clinical outcomes, cost effectiveness and contextual issues affecting successful implementation.

Evaluating Data Abstraction Assistant, a novel software application for data abstraction during systematic reviews: protocol for a randomized controlled trial.

BACKGROUND: Data abstraction, a critical systematic review step, is time-consuming and prone to errors. Current standards for approaches to data abstraction rest on a weak evidence base. We developed the Data Abstraction Assistant (DAA), a novel software application designed to facilitate the abstraction process by allowing users to (1) view study article PDFs juxtaposed to electronic data abstraction forms linked to a data abstraction system, (2) highlight (or "pin") the location of the text in the PDF, and (3) copy relevant text from the PDF into the form. We describe the design of a randomized controlled trial (RCT) that compares the relative effectiveness of (A) DAA-facilitated single abstraction plus verification by a second person, (B) traditional (non-DAA-facilitated) single abstraction plus verification by a second person, and (C) traditional independent dual abstraction plus adjudication to ascertain the accuracy and efficiency of abstraction. METHODS: This is an online, randomized, three-arm, crossover trial. We will enroll 24 pairs of abstractors (i.e., sample size is 48 participants), each pair comprising one less and one more experienced abstractor. Pairs will be randomized to abstract data from six articles, two under each of the three approaches. Abstractors will complete pre-tested data abstraction forms using the Systematic Review Data Repository (SRDR), an online data abstraction system. The primary outcomes are (1) proportion of data items abstracted that constitute an error (compared with an answer key) and (2) total time taken to complete abstraction (by two abstractors in the pair, including verification and/or adjudication). DISCUSSION: The DAA trial uses a practical design to test a novel software application as a tool to help improve the accuracy and efficiency of the data abstraction process during systematic reviews. Findings from the DAA trial will provide much-needed evidence to strengthen current recommendations for data abstraction approaches. TRIAL REGISTRATION: The trial is registered at National Information Center on Health Services Research and Health Care Technology (NICHSR) under Registration # HSRP20152269: https://wwwcf.nlm.nih.gov/hsr_project/view_hsrproj_record.cfm?NLMUNIQUE_ID=20152269&SEARCH_FOR=Tianjing%20Li . All items from the World Health Organization Trial Registration Data Set are covered at various locations in this protocol. Protocol version and date: This is version 2.0 of the protocol, dated September 6, 2016. As needed, we will communicate any protocol amendments to the Institutional Review Boards (IRBs) of Johns Hopkins Bloomberg School of Public Health (JHBSPH) and Brown University. We also will make appropriate as-needed modifications to the NICHSR website in a timely fashion.

Recommendations for kidney disease guideline updating: a report by the KDIGO Methods Committee.

Updating rather than de novo guideline development now accounts for the majority of guideline activities for many guideline development organizations, including Kidney Disease: Improving Global Outcomes (KDIGO), an international kidney disease guideline development entity that has produced guidelines on kidney diseases since 2008. Increasingly, guideline developers are moving away from updating at fixed intervals in favor of more flexible approaches that use periodic expert assessment of guideline currency (with or without an updated systematic review) to determine the need for updating. Determining the need for guideline updating in an efficient, transparent, and timely manner is challenging, and updating of systematic reviews and guidelines is labor intensive. Ideally, guidelines should be updated dynamically when new evidence indicates a need for a substantive change in the guideline based on a priori criteria. This dynamic updating (sometimes referred to as a living guideline model) can be facilitated with the use of integrated electronic platforms that allow updating of specific recommendations. This report summarizes consensus-based recommendations from a panel of guideline methodology professionals on how to keep KDIGO guidelines up to date.

Feasibility and impact of implementing a private care system's diabetes quality improvement intervention in the safety net: a cluster-randomized trial.

BACKGROUND: Integrated health care delivery systems devote considerable resources to developing quality improvement (QI) interventions. Clinics serving vulnerable populations rarely have the resources for such development but might benefit greatly from implementing approaches shown to be effective in other settings. Little trial-based research has assessed the feasibility and impact of such cross-setting translation and implementation in community health centers (CHCs). We hypothesized that it would be feasible to implement successful QI interventions from integrated care settings in CHCs and would positively impact the CHCs. METHODS: We adapted Kaiser Permanente's successful intervention, which targets guideline-based cardioprotective prescribing for patients with diabetes mellitus (DM), through an iterative, stakeholder-driven process. We then conducted a cluster-randomized pragmatic trial in 11 CHCs in a staggered process with six "early" CHCs implementing the intervention one year before five "'late" CHCs. We measured monthly rates of patients with DM currently prescribed angiotensin converting enzyme (ACE)-inhibitors/statins, if clinically indicated. Through segmented regression analysis, we evaluated the intervention's effects in June 2011-May 2013. Participants included ~6500 adult CHC patients with DM who were indicated for statins/ACE-inhibitors per national guidelines. RESULTS: Implementation of the intervention in the CHCs was feasible, with setting-specific adaptations. One year post-implementation, in the early clinics, there were estimated relative increases in guideline-concordant prescribing of 37.6 % (95 % confidence interval (CI); 29.0-46.2 %) among patients indicated for both ACE-inhibitors and statins and 38.7 % (95 % CI; 23.2-54.2 %) among patients indicated for statins. No such increases were seen in the late (control) clinics in that period. CONCLUSIONS: To our knowledge, this was the first clinical trial testing the translation and implementation of a successful QI initiative from a private, integrated care setting into CHCs. This proved feasible and had significant impact but required considerable adaptation and implementation support. These results suggest the feasibility of adapting diverse strategies developed in integrated care settings for implementation in under-resourced clinics, with important implications for efficiently improving care quality in such settings. CLINICALTRIALS.gov: NCT02299791 .

Transparency matters: Kaiser Permanente's National Guideline Program methodological processes.

INTRODUCTION: The practice-guideline process of collecting, critically appraising, and synthesizing available evidence, then developing expert panel recommendations based on appraised evidence, makes it possible to provide high-quality care for patients. Unwanted variability in the quality and rigor of evidence summaries and Clinical Practice Guidelines has been a long-standing challenge for clinicians seeking evidence-based guidance to support patient care decisions. METHODS: A multidisciplinary group of stakeholders, with representation from all eight Kaiser Permanente Regions, is responsible for creating National Guidelines. Conducting high-quality systematic reviews and creating clinical guidelines are time-, labor-, and resource-intensive processes, which raises challenges for an organization striving to balance rigor with efficiency. For these reasons, the National Guideline Program elected to allow for the identification, assessment, and possible adoption of existing evidence-based guidelines and systematic reviews using the ADAPTE; Appraisal of Guidelines Research and Evaluation; Assessment of Multiple Systematic Reviews (AMSTAR); and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) frameworks. If no acceptable external guidelines are identified, the Guideline Development Team then systematically searches for relevant high-quality systematic reviews, meta-analyses, and original studies. Existing systematic reviews are assessed for quality using a measurement tool to assess systematic reviews (the AMSTAR systematic review checklist). STUDY APPRAISAL: Following the screening and selection process, the included studies (the "body of evidence") are critically appraised for quality, using the GRADE methodology, which focuses on four key factors that must be considered when assigning strength to a recommendation: balance between desirable and undesirable effects, quality of evidence, values and preferences, and cost. The evidence is then used to create preliminary clinical recommendations. The strength of these recommendations is graded to reflect the extent to which a guideline panel is confident that the desirable effects of an intervention outweigh undesirable effects (or vice versa) across the range of patients for whom the recommendation is intended. DISSEMINATION: The Care Management Institute disseminates all KP national guidelines to its eight Regions via postings on its Clinical Library Intranet site, a Web-based internal information resource.

Intensity of lipid-lowering therapy and low-density lipoprotein cholesterol goal attainment among the elderly before and after the 2004 National Cholesterol Education Program Adult Treatment Panel III update.

BACKGROUND: In 2004, the Coordinating Committee of the National Cholesterol Education Program issued an update to the Adult Treatment Panel III guidelines on cholesterol management (the Update). Our objectives were to compare the proportion of elderly patients receiving intensive or minimal-guideline lipid-lowering therapy and the proportions meeting low-density lipoprotein cholesterol (LDL-C) goals before and after the update. METHODS: We used dispense records from Kaiser Permanente Northwest (Portland, OR) to identify elderly patients who received statin therapy in 2003 (n = 14425) and 2005 (n = 19422) and laboratory records to assess LDL-C goal attainment. RESULTS: Among new statin initiators, 85.4% of very-high-risk patients received minimal-guideline therapy in 2005, compared with 65.3% (P < .0001) in 2003. Of all new initiators, <1% received very aggressive therapy in either year (0.4% vs 0.3%, P = .315). Overall, 77.7% and 59.0% of ongoing users in 2005 and 2003, respectively, received minimal-guideline therapy (P < .0001). Low-density lipoprotein cholesterol goal attainment did not differ between 2003 and 2005 continuing statin users. Among very-high-risk patients who initiated statin treatment, a significantly greater proportion of patients in 2005 versus 2003 attained the optional goal of <70 mg/dL (45.5% vs 34.4% P = .014). However, there was no significant difference in the proportion attaining <100 mg/dL (77.8% vs 81.8%, P = .281). CONCLUSION: After the Update, more elderly patients were receiving intensive or minimal-guideline statin therapy. Low-density lipoprotein cholesterol goal attainment was isolated and appeared to occur by shifting already well-controlled patients to lower LDL-C levels. Although these findings may translate into less overall coronary heart disease risk, more aggressive lipid-lowering therapy would likely further reduce risk.

The association between fibrate use, change in high-density lipoprotein cholesterol, and the risk of cardiovascular disease: a retrospective chart review involving up to 8 years of follow-up.

BACKGROUND: Clinical trials have indicated that the use of fibric acid derivatives confers a benefit against cardiovascular disease (CVD) in selected populations. However, whether fibrates provide a CVD risk reduction independent of changes in the traditional lipoprotein fractions and other known CVD risk factors is not clear. OBJECTIVE: This study examined whether the use of fibrate therapy in a general clinical setting provided cardiovascular benefits independent of changes in the traditional lipoprotein fractions. METHODS: This was a matched, retrospective cohort study. From the electronic records of a large health maintenance organization in the northwestern United States, we identified a population that had newly initiated fibrate pharmacotherapy between January 1, 1996, and December 31, 2000. We then identified a comparator group of patients not using fibrates, matching them to fibrate users based on high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels, age, sex, and year of HDL-C and TG measurement. Subjects were followed until a CVD hospitalization, termination from the health plan, or December 31, 2003, whichever came first. We then used multivariate analysis accounting for differences in followup to identify predictors of CVD incidence. RESULTS: The study population included 1722 matched pairs (56.6% male; mean [SD] age, 57.3 [11.1] years). The patients who had newly initiated fibrate pharmacotherapy had low baseline HDL-C levels (mean, 37.4 mg/dL) and very high TG levels (617 mg/dL). The 2 groups were similar overall, with the only significant differences between fibrate users and nonfibrate controls being a greater prevalence of diabetes (37.7% vs 34.3%, respectively; P=0.040) and greater use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (56.6% vs 51.6%, respectively; P=0.003), beta-blockers (53.7% vs 49.0%; P=0.006), calcium channel blockers (25.1% vs 20.9%; P=0.004), and niacin (11.7% vs 7.4%; P<0.001). Overall, CVD risk was 26% lower for every 5-mg/dL increment in HDL-C. After adjustment for age, sex, smoking history, diabetes, existing diagnosis of CVD, weight, systolic blood pressure, baseline HDL-C, change in HDL-C, total cholesterol, TG, and use of statins, niacin, and other CVD drugs, fibrate use did not confer an additional CVD risk reduction. CONCLUSIONS: In this cohort with low baseline HDL-C levels and very high TG levels, fibrate use did not confer an independent CVD risk reduction after adjustment for CVD risk factors. Given the current obesity epidemic in the United States and the corresponding rise in the number of patients with the metabolic syndrome, the apparent risk reduction observed in association with higher HDL-C levels should not be ignored.