HMG-CoA reductase inhibitors, commonly known as statins, are some of the most widely prescribed medications worldwide and have been shown to be effective at lowering cholesterol in numerous long-term prospective trials, yet there are significant limitations to their use. First, patients receiving statin therapy have relatively low levels of medication adherence compared with other drug classes. Next, numerous statin formulations are available, each with its own unique safety and efficacy profile, and it may be unclear to prescribers which treatment is optimal for their patients. Finally, statins have class-wide side effects of myopathy and rhabdomyolysis that have resulted in a product recall and dosage limitations. Recent evidence suggests that two genomic markers, KIF6 and SLCO1B1, may inform the therapy choice of patients initiating statins. Given the prevalence of statin usage, their potential health advantages and their overall cost to the healthcare system, there could be significant clinical benefit from creating personalized treatment regimens. Ultimately, if this approach is effective it may encourage higher adoption of generic statins when appropriate, promote adherence, lower rates of myopathy, and overall achieve higher value cardiovascular care. This paper will review the evidence for personalized prescribing of statins via KIF6 and SLCO1B1 and consider some of the implications for testing these markers as part of routine clinical care.
OBJECTIVES: To evaluate the association between social support and medication adherence. STUDY DESIGN: A search of articles published before November 2010 in peer-reviewed, healthcarerelated journals was conducted using PubMed, EMBASE, and Web of Science, and search terms related to social support (social support OR friend OR family OR agency) and adherence (patient compliance OR medication adherence), yielding 5331 articles. METHODS: Articles were included if they directly measured the relationship between medication adherence and some form of social support. Excluded were case studies, studies with participants < 18 years of age, and non-English language studies. Four social support categories were reported: structural, practical, emotional, and combination. Medication adherence was reported in the manner in which it was described in each study. RESULTS: Fifty studies were included in the final analysis. A greater degree of practical support was most consistently associated with greater adherence to medication; evidence for structural or emotional support was less compelling. However, most studies were limited in size and design, and substantial variability in designs and outcome measurement prohibited pooling of results, necessitating qualitative evaluation of the studies. CONCLUSIONS: This qualitative analysis found that practical social support was most consistently associated with greater medication adherence. Interventions that use existing contacts (friends or family) to engage patients in the mundane and practical aspects of medication purchasing and administration may be an effective approach to promoting better medication adherence.
BACKGROUND: Little is known about the use of warfarin in hemodialysis (HD) patients with atrial fibrillation (AF). We studied temporal trends of AF among older HD patients, and of warfarin use among those with AF. METHODS: We linked US Medicare and prescription claims from older patients undergoing HD in 2 Eastern US states. We established annual cohorts of prevalent HD patients; AF was ascertained from >2 claims (>7 days apart) in the same year, with a diagnosis code indicating AF. Among those with AF, we defined current and past warfarin use. Demographic and clinical characteristics were also ascertained for each cohort. We used repeated-measures logistic regression to define the odds of AF and of current or past versus absence of warfarin use. RESULTS: Of 6,563 unique patients, 2,185 were determined to have AF. The prevalence of AF increased from 26% in 1998 to 32% in 2005. In 2005, current warfarin use was present in 24% of AF patients and past use in 25%; 51% had no evidence of any warfarin use. No significant trends in utilization were observed from 1998 through 2005. Patients aged =85 years and nonwhites were less likely to have received warfarin; most comorbidities were not associated with warfarin use except for patients with past pulmonary embolism or deep venous thrombosis who were more likely than those without such history. CONCLUSION: While the prevalence of AF has been increasing among older HD patients, warfarin use was low and unchanged over time, perhaps reflecting the lack of evidence supporting its use.
BACKGROUND: Although consensus guidelines recommend insulin progression among patients with type 2 diabetes (T2DM) who fail to meet glycemic targets over time, many fewer patients are progressed than may benefit. We describe the rationale and design of the MOSAIc (Multinational Observational Study Assessing Insulin use) study, a multinational observational cohort study to identify patient-, physician, and health care environment-based factors associated with insulin progression for patients with T2DM in real-world practice. Methods/design We will enroll 4,500 patients with T2DM taking initial insulin therapy for [greater than or equal to]3 months across 175 physician practice sites in 18 countries. Extensive demographic, clinical, and psychosocial data at the patient and physician level and practice site characteristics will be collected at baseline and regular intervals during a 24-month follow-up period. We will use a multivariable logistic regression model to identify predictors of insulin progression and highlight potential opportunities for health behavior intervention to improve insulin progression rates. Secondary outcomes include evaluating factors associated with glycemic control, hypoglycemia, and treatment adherence among patients who do and do not progress beyond their initial insulin therapy and exploring geographic heterogeneity in treatment. DISCUSSION: Practice site and patient recruitment began in 2011 and baseline data will be available in late 2012. The MOSAIC study's longitudinal observational design as well as the breadth and depth of data will be used to explore and quantify predictors of insulin progression and to identify potential opportunities for health behavior intervention in order to improve T2DM treatment and clinical outcomes.
Given rising pharmaceutical expenditures and the widespread use of reference pricing as a costcontainment instrument abroad, we systematically reviewed the evidence evaluating reference pricing policies. We performed a structured electronic search of peer-reviewed journals for studies published before that reported on the effects of reference pricing policies on medication use, payer and patient spending, and resource consumption. Our search yielded 16 studies describing 9 reference-pricing policies from 6 countries. Reference-pricing policies led to decreases in drug prices and increases in utilization of targeted medications, while also reducing payer and patient expenditures. In addition, these policies did not lead to increased use of medical services, such as physician office visits and hospitalization. These results suggest that reference pricing may be an attractive policy strategy for the US healthcare system.
BACKGROUND: Controversy exists regarding the optimal preventative therapy for venous thromboembolism (VTE) after coronary artery bypass graft (CABG) surgery. We sought to compare the effectiveness and safety of the most commonly used regimens. METHODS AND RESULTS: We assembled a cohort of 92 699 patients who underwent CABG between 2004 and 2008, using the Premier database. Patients were categorized by method of VTE prevention initiated within 48 hours of surgery, including no preventative therapy (n=55 400), mechanical preventative therapy (n=21 162), subcutaneous unfractio--nated or low-molecular-weight heparin (n=10 718), subcutaneous fondaparinux (n=88), and concurrent mechanical-chemical therapy (n=5331). The incidence of VTE and major bleeding events within 6 weeks of CABG were compared, using multivariable and propensity score adjustment. The overall incidence of VTE for the entire cohort was 0.74%, and the incidence of major bleeding was 1.43%. VTE and bleeding events occurred with similar incidence in each of the patient categories (VTE: 0.70%, 0.79%, 0.81%, 1.14%, and 0.73%; major bleeding: 1.36%, 1.45%, 1.69%, 3.41%, 1.50%; no prevention, mechanical prevention, subcutaneous heparin, subcutaneous fondaparinux, concurrent mechanical-chemical prevention, respectively). Compared with receiving no prevention, the use of mechanical prevention or subcutaneous heparin did not significantly reduce the risk of VTE or change the risk of major bleeding (P=NS). CONCLUSION: Venous thromboembolism occurs infrequently after CABG. Compared with the use of no prevention, the administration of chemical or mechanical preventative therapies to CABG patients does not appreciably lower the risk of VTE. These data provide support for the common practice of administering no VTE preventative therapy after CABG, used for nearly 60% of patients within this cohort.
BACKGROUND: Dabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons. METHODS AND RESULTS: We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF]), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end point we studied was major hemorrhage. To address a lack of comparability between trial populations caused by the restriction of ROCKET-AF to high-risk patients, we conducted a subgroup analysis in patients with a CHADS(2) score >/=3. We found no statistically significant efficacy differences among the 3 drugs, although apixaban and dabigatran were numerically superior to rivaroxaban. Apixaban produced significantly fewer major hemorrhages than dabigatran and rivaroxaban. CONCLUSIONS: An indirect comparison of new anticoagulants based on existing trial data indicates that in patients with a CHADS(2) score >/=3 dabigatran 150 mg, apixaban 5 mg, and rivaroxaban 20 mg resulted in statistically similar rates of stroke and systemic embolism, but apixaban had a lower risk of major hemorrhage compared with dabigatran and rivaroxaban. Until head-to-head trials or large-scale observational studies that reflect routine use of these agents are available, such adjusted indirect comparisons based on trial data are one tool to guide initial therapeutic choices.
BACKGROUND: Acute kidney injury is a frequent postoperative complication that confers increased mortality, morbidity, and costs. The purpose of this study was to evaluate whether preoperative statin use is associated with a decreased risk of postoperative acute kidney injury. METHODS: We assembled a retrospective cohort of 98,939 patients who underwent a major open abdominal, cardiac, thoracic, or vascular procedure between 2000 and 2010. Statin users were pair-matched to nonusers on the basis of surgery type, baseline kidney function, days from admission until surgery, and propensity score based on demographics, comorbid conditions, and concomitant medications. Acute kidney injury was defined based on changes in serum creatinine measurements applying Acute Kidney Injury Network and Risk-Injury-Failure staging systems, and on the need for renal replacement therapy. Associations between statin use and acute kidney injury were estimated by conditional logistic regression. RESULTS: Across various acute kidney injury definitions, statin use was consistently associated with a decreased risk: adjusted odds ratios (95% confidence intervals) varied from 0.74 (0.58-0.95) to 0.80 (0.71-0.90). Associations were similar among diabetics and nondiabetics, and across strata of baseline kidney function. The protective association of statins was most pronounced among patients undergoing vascular surgery and least among patients undergoing cardiac surgery. CONCLUSIONS: Preoperative statin use is associated with a decreased risk of postoperative acute kidney injury. Future randomized clinical trials are needed to determine causality.
OBJECTIVES: The aim of this study was to evaluate the impact of reductions in statin and clopidogrel copayments on cardiovascular resource utilization, major coronary events, and insurer spending. BACKGROUND: Copayments are widely used to contain health spending but cause patients to reduce their use of essential cardiovascular medications. Reducing copayments for post-myocardial infarction secondary prevention has beneficial effects, but the impact of this strategy for lower risk patients and other drugs remains unclear. METHODS: An evaluation was conducted of health care spending and resource use by a large self-insured employer that reduced statin copayments for patients with diabetes or vascular disease and reduced clopidogrel copayments for all patients prescribed this drug. Eligible individuals in the intervention company (n = 3,513) were compared with a control group from other companies without such a policy (n = 49,803). Analyses were performed using segmented regression models with generalized estimating equations. RESULTS: Lowering copayments was associated with significant reductions in rates of physician visits (relative change: statin users 0.80; 95% confidence interval [CI]: 0.57 to 0.98; clopidogrel users: 0.87; 95% CI: 0.59 to 0.96) and hospitalizations and emergency department admissions (relative change: statin users 0.90; 95% CI: 0.80 to 0.92; clopidogrel users: 0.89; 95% CI: 0.74 to 0.90) although not major coronary events. Patient out-of-pocket spending for drugs and other medical services decreased (relative change: statin users 0.79; 95% CI: 0.75 to 0.83; clopidogrel users 0.74; 95% CI: 0.66 to 0.82). Providing more generous coverage did not increase overall spending (relative change: statin users 1.03; 95% CI: 0.97 to 1.09; clopidogrel users 0.94; 95% CI: 0.87 to 1.03). CONCLUSIONS: Lowering copayments for statins and clopidogrel was associated with reductions in health care resource use and patient out-of-pocket spending. The policy appeared cost neutral with respect to overall health spending.
To the Editor: Direct-to-consumer advertising (DTCA) can influence the use of prescription drugs.1,2 The US Food and Drug Administration (FDA) regulates prescription drug advertising, including requirements to provide consumers with a ‚"fair balance"‚ of risks and benefits. When prescription drugs switch to over-the-counter (OTC) status, regulatory oversight of their advertising shifts to the Federal Trade Commission (FTC). Unlike the FDA, the FTC holds drug advertisements to the same standards as any consumer product: it applies a ‚"reasonable consumer"‚ standard of truthfulness and nondeception that does not require any balancing of potential benefits and harms. Such a shift may be associated with changes in content.
On January 31, 2012, Pfizer recalled nearly 1 million packs of birth control pills because of concerns that inert and active pills were miscounted and incorrectly ordered in their blister packs.1 This and other recent recalls highlight concerns about the potential clinical impact of defective and otherwise compromised drug products. However, little is known about the public health burden of drug recalls and whether health care providers are properly notified about clinically important recalls. We sought to quantify the frequency, cause, and extent of distribution of drug recalls in the United States and to evaluate the processes by which the US Food and Drug Administration (FDA) communicates clinically important recall information to health care providers.
BACKGROUND: In January 2008, the Food and Drug Administration (FDA) communicated concerns about the efficacy of ezetimibe, but did not provide clear clinical guidance, and substantial media attention ensued. We investigated the proportion of patients who discontinued therapy and switched to a clinically appropriate alternative after the FDA communication. METHODS: : Using claims data from a national pharmacy benefits manager, we created a rolling cohort of new users of ezetimibe between January 2006 and August 2008 and created a supply diary for each patient in the year after cohort entry. A patient was identified as nonpersistent if a gap of 90 days was seen in the diary. Using segmented linear regression, we compared rates of nonpersistence before and after the FDA communication and assessed patient-level characteristics associated with discontinuation. Among nonpersistent patients, we determined whether a patient made a clinically appropriate switch in the subsequent 90 days by adding a new cholesterol-lowering medication or by increasing the dose of an existing one. We used a weighted t test to compare the rates of appropriate switching before and after the communication. RESULTS: : Among 867,027 new ezetimibe users, 407,006 (46.9%) were nonpersistent in the first year. After the FDA communication, the monthly level of ezetimibe nonpersistence increased by 5.7 percentage points (P<0.0001). Younger patients, those who lived in low-income zip codes, and female patients were less likely to discontinue therapy (P<0.0001 for all). Among nonpersistent patients, rates of clinically appropriate switching increased from 10.8% before to 16.5% after the FDA warning (P=0.004). CONCLUSIONS: : A substantial increase in ezetimibe nonpersistence rates was seen after an FDA communication regarding its efficacy and following associated media attention, and a small proportion of patients made a clinically appropriate switch after discontinuation. Further consideration is needed to deliver messages that promote appropriate use of chronic therapy rather than simply reduce use.
OBJECTIVES To determine whether adherence interventions should be administered to all medication takers or targeted to nonadherers. DATA SOURCES AND STUDY SELECTION Systematic search (Medline and Embase, 1966-2009) of randomized controlled trials of interventions to improve adherence to medications for preventing or treating cardiovascular disease or diabetes. DATA EXTRACTION Articles were classified as (1) broad interventions (targeted all medication takers), (2) focused interventions (targeted nonadherers), or (3) dynamic interventions (administered to all medication takers; real-time adherence information targets nonadherers as intervention proceeds). Cohen's d effect sizes were calculated. DATA SYNTHESIS We identified 7,190 articles; 59 met inclusion criteria. Broad interventions were less likely (18%) to show medium or large effects compared with focused (25%) or dynamic (32%) interventions. Of the 33 dynamic interventions, 6 used externally generated adherence data to target nonadherers. Those with externally generated data were less likely to have a medium or large effect (20% vs. 34.8% self-generated data). CONCLUSION Adherence interventions targeting nonadherers are heterogeneous but may have advantages over broad interventions. Dynamic interventions show promise and require further study.
BACKGROUND: In the treatment of patients with refractory atrial fibrillation (AF), the safety and efficacy of atrioventricular nodal ablation (AVNA) versus pharmacotherapy alone remains unclear. Additionally, the impact of AVNA in patients with reduced systolic function is of growing interest. METHODS AND RESULTS: A total of 5 randomized or prospective trials were included for efficacy review (314 patients), 11 studies for effectiveness review (810 patients), and 47 studies for safety review (5632 patients). All-cause mortality was similar between AVNA and medical therapy (3.1% versus 3.3%; relative risk ratio, 1.05; 95% confidence interval [CI], 0.29-3.85). There was no significant difference in exercise duration or ejection fraction (EF) with AVNA relative to pharmacotherapy. In subgroup analysis, patients with baseline systolic dysfunction (116 patients; mean EF, 44%) showed significant relative improvement in EF after AVNA (+4% greater; 95% CI, 3.11-4.89). In pooled observational analysis, AVNA was also associated with significant improvement in EF only in patients with systolic dysfunction (+7.44%; 95% CI, 5.4-9.5). The incidence of procedure-related mortality (0.27%) and malignant arrhythmia (0.57%) was low. At mean follow-up of 26.5 months, the incidence of sudden cardiac death after AVNA was 2.1%. There was significant heterogeneity in quality-of-life scales used; compared with pharmacotherapy, AVNA was associated with significant improvement in several symptoms (palpitations, dyspnea). CONCLUSIONS: In the management of refractory AF, AVNA is associated with improvement in symptoms and quality of life, with a low incidence of procedure morbidity. In patients with reduced systolic function, AVNA demonstrates small but significantly improved echocardiographic outcomes relative to medical therapy alone.
AIMS: Previous studies have suggested that upstream medical therapy to modulate the renin-angiotensin axis may facilitate left atrial remodelling and thereby prevent new-onset atrial fibrillation (AF). The purpose of this study was to evaluate the association between angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARB) on new-onset AF in a large cohort of patients with coronary artery disease (CAD). METHODS AND RESULTS: This was a population-based study of 28 620 patients, from community-dwelling Medicare beneficiaries who had been hospitalized for acute myocardial infarction or coronary revascularization (1995‚Äì2004). All patients, 65 years and older, had a mean follow-up period of upto 3.8 ¬± 3.0 years. Patients with a history of AF before and during hospitalization were excluded. ¬†We compared the incidence of new-onset AF between patients who were (N= 10 918) and were not (N= 17 702) prescribed ACEI and/or ARB within 1 month of hospital discharge following cardiac event. New-onset AF within 5 and 10 years was 39.1 and 61.1%, respectively, in patients who received ACEI/ARB, compared¬† 34.9 and 53.6% in patients who did not receive them [unadjusted hazard ratio (HR): 1.16; 95% confidence interval (CI): 1.11, 1.21]. Multivariable analysis adjusting for patient- and hospital-related characteristics indicated that ACEI/ARB use independently had no impact on the risk of developing new-onset AF compared with non-users (adjusted HR: 0.99; 95% CI: 0.94, 1.04). Adjustment for propensity-score and health-seeking behaviours yielded nearly identical results. CONCLUSION: Angiotensin converting enzyme inhibitor/ARB therapy initiated within 1 month after hospital discharge is not associated with a reduction in the risk of new-onset AF after myocardial infarction or coronary revascularization.
BACKGROUND: Disclosure of conflicts of interest in biomedical research is receiving increased attention. The authors sought to define current disclosure policies and how they relate to disclosure statements provided by authors in major oncology journals. METHODS: The authors identified all oncology journals listed in the Thomson Institute for Scientific Information and sought their policies on conflict-of-interest disclosure. For a subset of journals with an Impact Factor >2.0, they catalogued the number and type of articles and the details of the published disclosures in all papers from the 2 most recent issues. RESULTS: Disclosure policies were provided by 112 of 131 journals (85%); 99 (88%) of these requested that authors disclose conflicts of interest (mean Impact Factor for these journals: 4.6), whereas the remaining 13 (12%) did not (mean Impact Factor: 2.9). Ninety-three journals (94%) required financial disclosure, and 42 (42%) also sought nonfinancial disclosures. For a subset of 52 higher-impact journals (Impact Factor >2.0), we reviewed 1734 articles and identified published disclosures in 51 journals (98%). Many of these journals (31 of 51, 61%) included some disclosure statement in >90% of their articles. Among 27 journals that published editorials/commentaries, only 14 (52%) included disclosures with such articles. There was no publication of any nonfinancial conflicts of interest in any article reviewed. CONCLUSIONS: Disclosure policies and the very definition of conflict of interest varied considerably among journals. Although most journals had some policy in this area, a substantial proportion did not publish disclosure statements consistently, with deficiencies particularly among editorials and commentaries.
A substantial threat to the overall health of the American public is nonadherence to medications used to treat diabetes, as well as physicians' failure to initiate patients' use of those medications. To address this problem, we evaluated an integrated, pharmacy-based program to improve patients' adherence and physicians' initiation rates. The study included 5,123 patients with diabetes in the intervention group and 24,124 matched patients with diabetes in the control group. The intervention consisted of outreach from both mail-order and retail pharmacists who had specific information from the pharmacy benefit management company on patients' adherence to medications and use of concomitant therapies. The interventions improved patients' medication adherence rates by 2.1 percent and increased physicians' initiation rates by 38 percent, compared to the control group. The benefits were greater in patients who received counseling in the retail setting than in those who received phone calls from pharmacists based in mail-order pharmacies. This suggests that the in-person interaction between the retail pharmacist and patient contributed to improved behavior. The interventions were cost-effective, with a return on investment of approximately $3 for every $1 spent. These findings highlight the central role that pharmacists can play in promoting the appropriate initiation of and adherence to therapy for chronic diseases.