Modifiable statin characteristics associated with potential statin-related prescribing cascades.

STUDY OBJECTIVE: Clinicians may prescribe new medications (marker drug) to treat statin-related (index drug) adverse events, constituting a prescribing cascade. We aimed to identify modifiable statin characteristics (intensity and individual statin agents) associated with lower risk of prescribing cascades to inform clinical decisions in the presence of statin-related adverse events. DESIGN: A secondary analysis based on our previous work, a high-throughput sequence symmetry analysis screening for potential statin-related prescribing cascades. DATA SOURCE: MarketScan Commercial and Medicare Supplemental Insurance claims databases between 2005 and 2019. PATIENTS: Adults who initiated a statin between 2007 and 2018, and who were continuously enrolled in the same healthcare plan for at least 720 days before and 360 days after statin initiation. INTERVENTION: Among the previously identified 57 potential prescribing cascades, 42 statin-marker class dyad with a sample size of ≥ 500 were assessed in this study. MEASUREMENTS: We measured patients' baseline characteristics within -360 days of statin initiation and reported by modifiable statin characteristics. We also performed logistic regression and reported the adjusted odds ratios (aOR) with 95% confidence intervals (CI) of modifiable statin characteristics after adjusting for baseline characteristics. MAIN RESULTS: We identified 1,307,867 statin initiators who met the study criteria (21% elderly, 52% female). Compared with patients initiating low-intensity statins, those initiating moderate- or high-intensity statins had significantly greater odds to develop 29 (69%) prescribing cascades, including antidiabetic drugs such as dipeptidyl peptidase 4 (DPP-4) inhibitors (aOR 1.22; 95% CI, 1.11-1.35) and glucagon-like peptide-1 (GLP-1) analogs (aOR 1.31; 95% CI, 1.16-1.47), and opioids (aOR 1.18; 95% CI, 1.13-1.23). Individual statin agent selection also had a differential effect on 34 (81%) of the prescribing cascades. For example, compared with simvastatin initiators, the probability of initiating osmotically acting laxatives was significantly higher for lovastatin initiators (aOR 1.09; 95% CI, 1.03-1.15) and significantly lower in atorvastatin initiators (aOR 0.92; 95% CI, 0.89-0.94). CONCLUSION: Compared with low-intensity statins, high-intensity statins are associated with increased risk in many potential prescribing cascades, while the choice of individual statin agents affects the risk of prescribing cascades bidirectionally.

Trends in Prescribing of Non-steroidal Anti-inflammatory Medications in the US Ambulatory Care Setting From 2006 to 2016.

While opioid prescribing has significantly decreased from a peak in 2012, less is known about the national utilization of non-opioid analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (APAP) in the context of the opioid crisis. The objective of this study is to characterize the prescribing trends of NSAIDs and APAP in the US ambulatory care setting. We conducted repeated cross-sectional analyses using the 2006-2016 National Ambulatory Medical Care Survey. NSAID-involved visits were defined as patient visits among adults in which NSAIDs were ordered, supplied, administered, or continued. We used similarly-defined APAP visits as a referent group for context. After excluding aspirin and other NSAID/APAP combination products containing opioids, we calculated the annual proportion of NSAID-involved visits among all ambulatory visits. We conducted trend analyses using multivariable logistic regression adjusted for years, patient, and prescriber characteristics. From 2006 to 2016, there were 775.7 million NSAID-involved visits and 204.3 million APAP-involved visits. Most NSAIDs-involved visits were from patients aged 46-64 years (39.6%), female (60.4%), White (83.2%), and having commercial insurance (49.0%). There were significant increasing trends for the proportion of NSAID-involved visits (8.1-9.6%) and APAP-involved visits (1.7-2.9%) (both P < .0001). We observed an overall increase in NSAID and APAP-involved visits in US ambulatory care settings from 2006 to 2016. This trend may be attributed to decreasing opioid prescribing and raises safety concerns related to acute or chronic NSAID and APAP use. PERSPECTIVE: This study shows an overall increasing trend in NSAID use reported in nationally representative ambulatory care visits in the United States. This increase coincides with previously reported significant decreases in opioid analgesic use, particularly after 2012. Given the safety concerns related to chronic or acute NSAID use, there is a need to continue monitoring the use trends of this class of medication.

Initial Antihypertensive Regimens in Newly Treated Patients: Real World Evidence From the OneFlorida+ Clinical Research Network.

Background Knowledge of real-world antihypertensive use is limited to prevalent hypertension, limiting our understanding of how treatment evolves and its contribution to persistently poor blood pressure control. We sought to characterize antihypertensive initiation among new users. Methods and Results Using Medicaid and Medicare data from the OneFlorida+ Clinical Research Consortium, we identified new users of ≥1 first-line antihypertensives (angiotensin-converting enzyme inhibitor, calcium channel blocker, angiotensin receptor blocker, thiazide diuretic, or ß-blocker) between 2013 and 2021 among adults with diagnosed hypertension, and no antihypertensive fill during the prior 12 months. We evaluated initial antihypertensive regimens by class and drug overall and across study years and examined variation in antihypertensive initiation across demographics (sex, race, and ethnicity) and comorbidity (chronic kidney disease, diabetes, and atherosclerotic cardiovascular disease). We identified 143 054 patients initiating 188 995 antihypertensives (75% monotherapy; 25% combination therapy), with mean age 59 years and 57% of whom were women. The most commonly initiated antihypertensive class overall was angiotensin-converting enzyme inhibitors (39%) followed by ß-blockers (31%), calcium channel blockers (24%), thiazides (19%), and angiotensin receptor blockers (11%). With the exception of ß-blockers, a single drug accounted for ≥75% of use of each class. ß-blocker use decreased (35%-26%), and calcium channel blocker use increased (24%-28%) over the study period, while initiation of most other classes remained relatively stable. We also observed significant differences in antihypertensive selection across demographic and comorbidity strata. Conclusions These findings indicate that substantial variation exists in initial antihypertensive prescribing, and there remain significant gaps between current guideline recommendations and real-world implementation in early hypertension care.

Buprenorphine Use Trends Following Removal of Prior Authorization Policies for the Treatment of Opioid Use Disorder in 2 State Medicaid Programs.

Importance: State Medicaid programs have implemented initiatives to expand treatment coverage for opioid use disorder (OUD); however, some Medicaid programs still require prior authorizations (PAs) for filling buprenorphine prescriptions. Objective: To evaluate the changes in buprenorphine use for OUD among Medicaid enrollees in states that completely removed buprenorphine PA requirements. Design Setting and Participants: This retrospective cross-sectional study analyzed the immediate and trend changes on buprenorphine use during 2013 to 2020 associated with removal of PA requirements using a controlled interrupted time series analysis to account for autocorrelation. Data were collected from Medicaid State Drug Utilization Data for 2 states (California and Illinois) that completely removed a buprenorphine PA during the study period, and buprenorphine prescriptions for OUD treatment were identified among Medicaid enrollees. Main Outcomes and Measures: Quarterly total number of buprenorphine prescriptions for each state was calculated, and stratification analyses were conducted by dosage form (films and tablets). Results: Among the 2 state Medicaid programs (California and Illinois) that removed buprenorphine PAs, there was a total of 702 643 and 415 115 eligible buprenorphine prescription claims, respectively. After removing PA requirements for buprenorphine, there was an immediate increase that was not statistically significant (rate ratio [RR], 1.11; 95% CI, 0.76-1.61) in the number of all buprenorphine prescriptions in California and a statistically significant increase (RR, 6.99; 95% CI, 4.67-10.47) in the number of all buprenorphine prescriptions in Illinois relative to the change in the control states (Alabama, Florida, Idaho, Kansas, Mississippi, Nevada, South Dakota, and Wyoming). Additionally, there was a statistically significant decreasing trend in the number of all buprenorphine prescriptions in California (RR, 0.88; 95% CI, 0.82-0.94) and a statistically significant increasing trend in Illinois (RR, 1.11; 95% CI, 1.05-1.19) relative to the trend in control states. Conclusions and Relevance: In this cross-sectional study, removal of buprenorphine PA requirements was associated with a statistically significant increase in the number of buprenorphine prescription fills among Medicaid populations in 1 of the 2 included states.

A Mapping Literature Review of Medical Cannabis Clinical Outcomes and Quality of Evidence in Approved Conditions in the USA from 2016 to 2019.

In 2017, a National Academies of Sciences, Engineering, and Medicine (NASEM) report comprehensively evaluated the body of evidence regarding cannabis health effects through the year 2016. The objectives of this study are to identify and map the most recently (2016-2019) published literature across approved conditions for medical cannabis and to evaluate the quality of identified recent systematic reviews, published following the NASEM report. Following the literature search from 5 databases and consultation with experts, 11 conditions were identified for evidence compilation and evaluation: amyotrophic lateral sclerosis, autism, cancer, chronic noncancer pain, Crohn's disease, epilepsy, glaucoma, human immunodeficiency virus/AIDS, multiple sclerosis (MS), Parkinson's disease, and posttraumatic stress disorder. A total of 198 studies were included after screening for condition-specific relevance and after imposing the following exclusion criteria: preclinical focus, non-English language, abstracts only, editorials/commentary, case studies/series, and non-U.S. study setting. Data extracted from studies included: study design type, outcome definition, intervention definition, sample size, study setting, and reported effect size. Few completed randomized controlled trials (RCTs) were identified. Studies classified as systematic reviews were graded using the Assessing the Methodological Quality of Systematic Reviews-2 tool to evaluate the quality of evidence. Few high-quality systematic reviews were available for most conditions, with the exceptions of MS (9 of 9 graded moderate/high quality; evidence for 2/9 indicating cannabis improved outcomes; evidence for 7/9 indicating cannabis inconclusive), epilepsy (3 of 4 graded moderate/high quality; 3 indicating cannabis improved outcomes; 1 indicating cannabis inconclusive), and chronic noncancer pain (12 of 13 graded moderate/high quality; evidence for 7/13 indicating cannabis improved outcomes; evidence from 6/7 indicating cannabis inconclusive). Among RCTs, we identified few studies of substantial rigor and quality to contribute to the evidence base. However, there are some conditions for which significant evidence suggests that select dosage forms and routes of administration likely have favorable risk-benefit ratios (i.e., epilepsy and chronic noncancer pain). The body of evidence for medical cannabis requires more rigorous evaluation before consideration as a treatment option for many conditions, and evidence necessary to inform policy and treatment guidelines is currently insufficient for many conditions.

Trends in Use of Prescription Nonsteroidal Anti-inflammatory Medications Before vs After Implementation of a Florida Law Restricting Opioid Prescribing for Acute Pain.

Importance: Previous research has shown an immediate reduction in new opioid users and use after implementation of the opioid supply restriction laws. Assessment of the association between opioid restrictions and alternative treatment options, such as nonsteroidal anti-inflammatory drugs (NSAIDs), is needed to evaluate potential unintended consequences for patients requiring analgesia. Objective: To evaluate the association between an opioid restriction law in Florida and use of prescription NSAIDs. Design, Setting, and Participants: This quality improvement study used interrupted time series analyses accounting for autocorrelation to estimate immediate and trend changes in the prescribing and use of prescription NSAIDs in Florida before and after implementation of a state law limiting opioid prescriptions to a 3-day supply. Participants were enrollees in a single private health plan of a large university and health system employer in Florida from January 2015 to June 2019. Exposures: Prescriptions for NSAIDs, ascertained from pharmacy claims data. Main Outcomes and Measures: The following outcomes were calculated monthly per 1000 plan enrollees: (1) number of NSAID users; (2) mean days' supply of NSAIDs per prescription; and (3) mean number of NSAID prescriptions. Individuals were classified as NSAID users if they had at least 1 NSAID prescription in a given month. Analysis was stratified by route of NSAID administration (oral or nonoral). Results: Among 46 783 NSAID users with 79 089 NSAID prescriptions during the study period, the median age was 47 years (interquartile range, 35-57 years). After implementation of the opioid restriction law, the number of NSAID users immediately increased, but the difference was not significant (change, 0.82 per 1000 patients; 95% CI, -0.67 to 2.30 per 1000 patients). No significant change in the days' supply of oral NSAID users occurred (change, 0.21 days per prescription; 95% CI, -1.66 to 2.08 days per prescription). Before implementation of the law, there was a nonsignificant decreasing trend in NSAID prescriptions (rate of change, -0.03 per month per 1000 enrollees; 95% CI, -0.13 to 0.07 per month per 1000 enrollees; after implementation, there was a nonsignificant increase in the number of oral and nonoral NSAID prescriptions (change, 1.49 per 1000 enrollees; 95% CI, -3.38 to 6.37 per 1000 enrollees). Conclusions and Relevance: In this quality improvement study, prescribing and use of prescription NSAIDs did not increase after implementation of a law restricting opioid analgesic prescriptions in Florida. These findings suggest possible greater use of over-the-counter NSAIDs after implementation of the law, but further research is needed to evaluate changes in the use of nonopioid analgesics and alternative pain therapies.