Trajectories of P2Y12 inhibitor adherence in patients with acute coronary syndromes.

PURPOSE: P2Y12 inhibitors (P2Y12i) reduce cardiac events after acute coronary syndromes (ACS). However, suboptimal P2Y12i adherence persists. We aimed to examine P2Y12i non-adherence using group-based trajectory methods and to identify adherence predictors. METHODS: We conducted a population-based, retrospective cohort study using administrative data in Ontario, Canada of patients ≥65 years admitted for ACS between April 2014 and March 2018 with a P2Y12i dispensed within 7 days of discharge. We used group-based trajectory models to characterize longitudinal 1-year adherence patterns. Predictors associated with each adherence trajectory were identified by multinomial logistic regression. RESULTS: We included 11 917 patients using clopidogrel and 9763 using ticagrelor, aged [mean ± SD]: 77.33 ± 8.31/73.59 ± 6.79 years; men: 56.2%/65.4%, respectively. We identified 3 longitudinal adherence trajectories, that differed by agent: 75% of clopidogrel and 68% of ticagrelor patients showed a consistently adherent trajectory, while 13%/17% were gradually, and 12%/15% were rapidly non-adherent, respectively (p < 0.001). Differing baseline characteristics in each cohort were associated with observed adherence trajectories. Concomitant atrial fibrillation and prior bleeding history were associated with non-adherence among clopidogrel users. Among ticagrelor users, women and older persons were more likely to be rapidly non-adherent, adherence declining steeply starting 1 month post-ACS. CONCLUSIONS: We identified distinct adherence trajectories for clopidogrel and ticagrelor post-ACS, with 3 out of 4 clopidogrel patients but only 2 out of 3 ticagrelor patients in the consistently adherent trajectory. Intensive interventions targeted to the period of steep adherence decline post-ACS, particularly for women and older persons initiating ticagrelor, and patients with atrial fibrillation on clopidogrel should be considered and investigated further.

Evidence-Based Cardiovascular Disease Medicines' Availability in Low-Cost Generic Drug Programs in the United States : A Cross-Sectional Study.

BACKGROUND: Low-cost generic programs (LCGPs) that expand access to affordable cardiovascular disease (CVD) medicines can assist patients in achieving desired cardiovascular outcomes. It is important that LCGPs offer CVD medicines that promote evidence-based prescribing. OBJECTIVE: To evaluate LCGPs' coverage of evidence-based CVD medications using a clinical framework that examines coverage of core treatments, coverage of options with the highest-quality evidence, and the variety of medication options and strengths that create choices and allow dosing titration. DESIGN: Cross-sectional study. SETTING: Publicly available LCGPs in March and April 2023 in the United States. PARTICIPANTS: 19 LCGPs. MEASUREMENTS: Proportion of LCGPs that offered evidence-based CVD medicines within a clinical framework for 6 CVDs (atrial fibrillation, heart failure, hyperlipidemia, hypertension, post-acute coronary syndrome secondary prevention, and stable angina) according to 4 availability metrics (breadth, choice, high-quality evidence, and titratability). RESULTS: The availability of CVD medication varied by program, drug, and CVD condition. Some programs had more breadth and choice of coverage for most CVDs (H-E-B, Kroger, Mark Cuban Cost Plus Drug Company, and Walmart), whereas many had more focused coverage and others markedly limited offerings. Nearly all LCGPs offered angiotensin-converting enzyme inhibitors, ß-blockers, thiazides, and moderate-intensity statins, but availability was low for higher-cost or lower-use generics (antiplatelets and antiarrhythmics). Core pharmacotherapy coverage and choices were limited for atrial fibrillation and heart failure but widely available for hypertension and hyperlipidemia. LIMITATION: In-depth cost analysis was not investigated. CONCLUSION: Coverage of evidence-based medications for the 6 CVDs investigated varied by LCGP and condition. Because high availability of core CVD pharmacotherapy can enhance optimal disease state management, LCGPs should identify existing limitations in their coverage and continuously revise their formularies to improve the comprehensiveness of CVD medication coverage. PRIMARY FUNDING SOURCE: None.

Neoplasm Reports in Food and Drug Administration Adverse Event Reporting System Following Angiotensin Receptor Blocker Recalls.

BACKGROUND: A worldwide voluntary recall of valsartan in July 2018 due to the potential carcinogen N-nitrosodimethylamine received extensive media and public attention. This was followed by more Food and Drug Administration (FDA) recalls regarding other contaminated ARB (angiotensin receptor blocker) products. Our study investigated the association between the FDA recalls and ARB neoplasm adverse events (AEs) reported to the FDA adverse event reporting system. METHODS: In this cross-sectional study, data were retrospectively collected from the FDA adverse event reporting system database from January 2015 to December 2019. Reporting odds ratios (RORs) were estimated to detect signals of association between ARBs (valsartan, irbesartan, and losartan) and reported neoplasm AEs using negative (amoxicillin and sertraline) and positive (omeprazole and ranitidine) control exposures. The χ2 was used to compare categorical variables. RESULTS: A total of 2 181 524 AEs, including 10 461 nonmetastatic neoplasm AEs were analyzed. Monthly RORs (95% CI) of valsartan-associated neoplasms versus controls (ROR*: valsartan/negative exposures; ROR†: valsartan/omeprazole; and ROR‡: valsartan/ranitidine) showed the highest signals after the recall date in July 2018 (7.64 [4.78-12.19]*; 4.77 [3.36-6.79]†; 4.13 [2.50-6.84]‡) and August 2018 (7.87 [5.19-11.94]*; 5.65 [4.12-7.75]†; and 7.20 [4.46-11.63]‡). In contrast, the highest cancer signals for the irbesartan and losartan recalls detected in March 2019 (4.80*; 4.06†; and 3.38‡) and April 2019 (3.63*; 3.69†; and 2.52‡) respectively, were lower. One-year postrecall reported neoplasm AEs were ≈2-fold higher for valsartan than irbesartan (OR, 1.77 [95% CI, 1.47-2.13], P<0.0001) and losartan (OR, 2.07 [95% CI, 1.85-2.32], P<0.0001). Although all ARBs had the same nitrosamine contamination, we found 1-year postrecall versus prerecall cancer signals for valsartan were 3-fold higher versus control exposures, while the changes in RORs for irbesartan and losartan were only 20-30% higher. CONCLUSIONS: Significantly more postrecall neoplasms were reported for valsartan, with higher valsartan-associated cancer signals compared with irbesartan and losartan, although they all contained the same carcinogenic contaminant. Extensive media coverage of the FDA valsartan recall may have alarmed patients and generated these abrupt, biologically infeasible cancer signals.

Examining the Nocebo Effect of Statins Through Statin Adverse Events Reported in the Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: This study aimed to evaluate whether the high frequency of reported statin adverse effects (AEs) may be associated with the nocebo effect. We compared nocebo-related subjective AEs with objective AEs and investigated factors potentially associated with the nocebo effect. METHODS: A retrospective cohort study was conducted using the Food and Drug Administration Adverse Event Reporting System between January 2010 and December 2019 for statins, including, atorvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin. Subjective AEs included fatigue, subjective muscular, and nervous system AEs. Objective AEs were defined as hepatic and objective muscular AEs. We compared the number of subjective and objective AEs using the Mann-Whitney U test and examined trends in the frequency of subjective versus objective reports over time using linear regression with interaction terms. We evaluated the association between AEs and gender and country using linear regression. Quantitative detection of signals was estimated using proportional reporting ratio and reporting odds ratio for simvastatin. RESULTS: Of 2 994 487 overall AE reports, more subjective than objective AEs were reported per quarter (mean±SD: 4777±1375.45 versus 999±276.95; P<0.0001), and over time during the study period (P<0.001). Women reported more subjective AEs than men per quarter (fatigue: 86.98 more per quarter, P=0.035; subjective muscular AE: 417.95, P<0.0001; nervous system AE: 273.60, P<0.0001), but fewer objective muscular AEs (-125.23 per quarter, P<0.0001). More subjective AEs and fewer objective AEs were reported per quarter in the United States relative to other countries. Simvastatin-associated reports showed signals for higher objective muscular AEs relative to all other statins (reporting odds ratio, 1.53 [95% CI, 1.49-1.58]). CONCLUSIONS: This study found that significantly more subjective than objective AEs are reported for statins. Subjective statin AEs, potentially related to the nocebo effect are reported more often by women than by men, and in the United States than in other countries.

Effects of intravenous immunoglobulin therapy and Fc gamma receptor polymorphisms on BK virus nephropathy in kidney transplant recipients.

BACKGROUND: BK virus nephropathy (BKVN) is a major complication in kidney transplant patients. This study aimed to investigate the efficacy of intravenous immunoglobulin (IVIG) therapy against persistent BKVN and to evaluate the association between persistent BKVN and Fc gamma receptor (FcγR) single nucleotide polymorphisms (SNPs). METHODS: A total of 86 patients out of 279 kidney recipients with BKVN were investigated in a single-center retrospective study. The majority of 86 patients were Hispanic and Asian (69.8% and 17.4%). Patients were treated with adjunctive IVIG or standard therapy (controls). Subgroup analysis was performed between IVIG responders and non-responders. BK virus copy number and serum creatinine (SCr) were measured to evaluate the impact of IVIG. We analyzed the association between the response to IVIG and genotype at FcγR3A (rs396991) and FcγR2A (rs1801274) SNPs. RESULTS: Viral load in IVIG non-responders was significantly higher than in responders at the time of diagnosis (219 271.8 vs 29 816.3 copies/mL, P = .015) and after 6 months of IVIG use (12 789.5 vs 1369.5 copies/mL, P < .001). However, analyses SNP of FcγR2A (OR = 0.807, CI = 0.435-1.496 P = .495) and FcγR3A (OR = 0.997, CI = 0.505-1.970, P = .993) SNPs showed no significant differences between the 2 groups. CONCLUSION: IVIG appears to lower BK DNA viral load significantly in patients with persistent BKVN. However, no associations were identified between BKVN and FcγR2A or FcγR3A SNPs.