Trimethoprim sulfamethoxazole prophylaxis and serious infections in granulomatosis with polyangiitis treated with rituximab.

OBJECTIVE: To assess the association of trimethoprim sulfamethoxazole (TMP-SMX) prophylaxis with serious infections in rituximab-treated patients with granulomatosis with polyangiitis (GPA). METHODS: This retrospective cohort study included adults with GPA (2011-2020) within the United States Merative™ Marketscan® Research Databases with ≥6 months enrolment prior to first (index) rituximab treatment. We defined TMP-SMX prophylaxis as a ≥28-day prescription dispensed after or overlapping the index date. Serious infection was a hospital primary diagnosis for infection (excluding viral or mycobacterial codes). Secondary outcomes were outpatient infection, PJP, and adverse events potentially attributable to TMP-SMX. Cox proportional hazards regression assessed the association of time-varying TMP-SMX with outcomes of interest, adjusting for potential confounders. Individuals were followed until the outcome of interest, end of database enrolment, or Dec 31, 2020. RESULTS: Among 919 rituximab-treated individuals (53% female), mean age was 52.1 years (SD 16) and 281 (31%) were dispensed TMP-SMX within 30 days of index date. Over a median of 496 (IQR 138, 979) days, 130 serious infections occurred among 104 individuals (incidence 6.1 [95% CI 5.0-7.4] per 100 person-years). Time-varying TMP-SMX was negatively associated with serious infection (adjusted HR 0.5; 95% CI 0.3-0.9). The aHR for outpatient infections was 0.8 (95% CI 0.6-1.1). The estimate for PJP was imprecise (13 events, unadjusted HR 0.2; 95% CI 0.03-1.8). TMP-SMX was potentially associated with adverse events (aHR 1.3; 95% CI 0.9-1.9). CONCLUSIONS: TMP-SMX prophylaxis was associated with reduced serious infections in rituximab-treated GPA, but may increase adverse events, warranting further study of optimal prophylaxis strategies.

Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the United States of America: a retrospective cohort study.

BACKGROUND: Antibiotic prophylaxis is recommended during ANCA-associated vasculitis (AAV) induction. We aimed to describe the frequency, persistence, and factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) use in an adult population sample with granulomatosis with polyangiitis (GPA) treated with rituximab (RTX). METHODS: We identified adults with GPA treated with RTX within the Merative™ Marketscan® Research Databases (2011-2020). TMP-SMX prophylaxis was defined as a [Formula: see text] 28-day prescription dispensed within a month of starting RTX. We estimated TMP-SMX persistence, allowing prescription refill gaps of 30 days. Multivariable logistic regression and Cox proportional hazards regression assessed the factors associated with baseline TMP-SMX use and persistence, respectively. Covariates included age, sex, calendar year, insurance type, immunosuppressant use, hospitalization, and co-morbidities. RESULTS: Among 1877 RTX-treated GPA patients, the mean age was 50.9, and 54% were female. A minority (n = 426, 23%) received TMP-SMX with a median persistence of 141 (IQR 83-248) days. In multivariable analyses, prophylaxis was associated with prednisone use in the month prior to RTX ([Formula: see text] 20 mg/day vs none, OR 3.96; 95% CI 3.0-5.2; 1-19 mg/day vs none, OR 2.63; 95% CI 1.8-3.8), and methotrexate use (OR 1.48, 95% CI 1.04-2.1), intensive care (OR 1.95; 95% CI 1.4-2.7), and non-intensive care hospitalization (OR 1.56; 95% CI 1.2-2.1) in the 6 months prior to RTX. Female sex (OR 0.63; 95% CI 0.5-0.8) was negatively associated with TMP-SMX use. CONCLUSIONS: TMP-SMX was dispensed to a minority of RTX-treated GPA patients, more often to those on glucocorticoids and with recent hospitalization. Further research is needed to determine the optimal use and duration of TMP-SMX prophylaxis following RTX in AAV.

Anticoagulant Use and the Risk of Thromboembolism and Bleeding in Postoperative Atrial Fibrillation After Noncardiac Surgery.

BACKGROUND: An effective and safe oral anticoagulation (OAC) strategy for patients with new postoperative AF (POAF) after noncardiac surgery remains unclear. We aimed to determine the association between OAC use and 1) thromboembolic events and 2) major bleeding in patients with POAF after noncardiac surgery. METHODS: A retrospective cohort (1999-2015) was used to identify patients with new POAF after inpatient noncardiac surgery. Initiation of OAC was defined as prescription of an OAC within 30 days following hospital discharge. Times to first hospital admission or emergency department visit for a thromboembolic or major bleeding event were compared using Cox proportional hazards models. RESULTS: We identified 22,007 patients with new POAF after inpatient noncardiac surgery. The majority of patients had intermediate (CHA2DS2-VASc 2-3: 45%) to high (CHA2DS2-VASc ≥ 4: 42%) thromboembolic risk. During a mean follow-up of 4 years, a total of 1099 (5%) thromboembolic and 3250 (15%) bleeding events occurred. Compared with patients not on anticoagulation, anticoagulation did not reduce the risk for thromboembolic events (adjusted hazard ratio [aHR] 0.89, 95% CI 0.73-1.07). In patients initiated on anticoagulation, there was an association with a higher risk for major bleeding (aHR 1.14, 95% CI 1.04-1.25). CONCLUSIONS: In patients with new POAF after noncardiac surgery, anticoagulation was not associated with a reduction in long-term thromboembolic events; however, this was accompanied by an overall increased risk for major bleeding. Future prospective clinical studies are needed to better address the role for anticoagulation therapy in the setting of POAF after noncardiac surgery to understand the efficacy and safety of treatment.

Sex differences in health behavior change after premature acute coronary syndrome.

BACKGROUND: Limited information is available on the health behavior profile of patients with premature acute coronary syndrome (ACS). The purpose of this study is to desribe the health bahvior of young patients with ACS at the baseline and 1 year post-ACS and examine sex differences. METHODS: GENESIS-PRAXY is a prospective cohort study of adults (18-55 years old) hospitalized with ACS from 26 centers located in Canada, United States, and Switzerland. Data on diet, physical activity, smoking, alcohol consumption, and recreational drug use were collected through self-administered questionnaires at baseline and 1 year post-ACS. RESULTS: Our analysis included 740 patients with complete data. At baseline, the health behavior profile of young patients with ACS was worse than that of the general population. Men had a lower fruit and vegetable intake, consumed alcohol more, and used recreational drugs more than women. Conversely, fewer men than women were smokers (34% vs 42%). At 1 year post-ACS, the proportion of those consuming ≥5 daily servings of fruits and vegetables increased modestly (+5% vs +1%, for men vs women) but remained lower than the general population. Among women, the prevalence of smoking remained about twice as high as the general population. Recreational drug use also remained higher than in the general population. CONCLUSIONS: Despite small improvements at 1 year post-ACS, the health behavior profile of young patients remained worse than that of the general population. Greater efforts to improve health behaviors post-ACS among young patients are needed, and a sex-based approach may be required to ensure successful behavioral changes.

Sex- and gender-related risk factor burden in patients with premature acute coronary syndrome.

BACKGROUND: Few contemporary data exist on traditional (TRF) and non-TRF (NTRF) burden in patients with premature acute coronary syndrome (ACS). METHODS: Prevalence of TRFs and NTRFs were measured in 1015 young (55 years old or younger) ACS patients recruited from 26 centres in Canada, the United States, and Switzerland. Risk factors were compared across sex and family history categories, and against a sample of the general Canadian population based on the 2000-2001 Canadian Community Health Survey. The 10- and 30-year risks of cardiovascular disease (CVD) were estimated using Framingham Risk Scores. RESULTS: Risk factors were more prevalent in premature ACS patients compared with the general population. Young women with a family history of coronary artery disease showed the greatest risk factor burden including TRFs of hypertension (67%), dyslipidemia (67%), obesity (53%), smoking (42%), and diabetes (33%), and NTRFs of anxiety (55%), low household income (44%), and depression (37%). The estimated median 10-year risk of CVD was 7% (interquartile range [IQR], 3%-9%) in women and 13% (IQR, 7%-17%) in men, whereas the 30-year risk of CVD was 36% (IQR, 22%-49%) in women and 44% (IQR, 31%-57%) in men. CONCLUSIONS: Patients with premature ACS, especially women with a positive family history, are characterized by a very high risk factor burden that is poorly captured by 10-year risk estimates but better captured by 30-year estimates. Consideration of NTRFs and use of 30-year risk estimates might better estimate risk in young individuals and improve the prevention of premature ACS.

Temporal trends in revascularization and outcomes after acute myocardial infarction among the very elderly.

BACKGROUND: Few data are available on time-related changes in use and outcomes of invasive procedures after acute myocardial infarction in very elderly patients. Our objective was to describe trends in revascularization procedures and outcomes in a provincial cohort of very elderly patients who had experienced acute myocardial infarction. METHODS: We used a database of hospital discharge summaries to identify all patients aged 80 years or older admitted for acute myocardial infarction in Quebec. We used the provincial database of physicians' services and medication claims to assess treatment and obtain data on survival. RESULTS: Between March 1996 and March 2007, 29 750 patients aged 80 years or older were admitted to hospital for acute myocardial infarction. During this period, use of percutaneous coronary interventions increased from 2.2% to 24.9%, and use of coronary artery bypass graft surgery increased from 0.8% to 3.1%. Evidence-based prescriptions of medication increased over time (p < 0.001). The prevalence of reported comorbidities was higher during the period of 2003-2006 than during the 1996-1999 period. One-year mortality improved over time (46.5% for 1996-1999 v. 40.9% for 2003-2006, p < 0.001) but remained unchanged in the subgroup of patients who did not undergo revascularization. INTERPRETATION: The use of revascularization, especially percutaneous coronary interventions, in the very elderly after acute myocardial infarction has been growing at a rapid pace, while the prevalence of reported comorbidities has been increasing in this population. Revascularization procedures are no longer restricted to younger patients. In the context of an aging population, it is imperative to determine whether these changes in practice are cost-effective.

Cardiovascular outcomes after a change in prescription policy for clopidogrel.

BACKGROUND: Drug-reimbursement policies may have an adverse effect on patient outcomes if they interfere with timely access to efficacious medications for acute medical conditions. Clopidogrel in combination with aspirin is the recommended standard of care for patients receiving coronary stents to prevent thrombosis. We examined the population-level effect of a change by a Canadian provincial government in a pharmacy-benefits program from a prior-authorization policy to a less restrictive, limited-use policy on access to clopidogrel among patients undergoing percutaneous coronary intervention (PCI) with stenting after acute myocardial infarction. METHODS: We conducted a population-based, retrospective, time-series analysis from April 1, 2000, to March 31, 2005, of all patients 65 years of age or older with acute myocardial infarction who underwent PCI with stenting in Ontario, Canada. The primary outcome was the composite rate of death, recurrent acute myocardial infarction, PCI, and coronary-artery bypass grafting at 1 year, with adjustment for sex and age. The secondary outcome was major bleeding. RESULTS: The rate of clopidogrel use within 30 days after hospital discharge following myocardial infarction increased from 35% in the prior-authorization period to 88% in the limited-use period. The median time to the first dispensing of a clopidogrel prescription decreased from 9 days in the first period to 0 days in the second period. The 1-year composite cardiovascular outcome significantly decreased from 15% in the prior-authorization group to 11% in the limited-use group (P=0.02). Rates of bleeding in the two groups did not change. CONCLUSIONS: The removal of a prior-authorization program led to improvement in timely access to clopidogrel for coronary stenting and improved cardiovascular outcomes.

Statins and cancer risk.

OBJECTIVE: Despite numerous randomized clinical trials and observational epidemiologic studies, evidence on the potential effectiveness of statins for prevention of cancer remains controversial. The objective of this study was to investigate the relation between lipophilic statin use and cancer occurrence. METHODS: We conducted a retrospective observational study based on a medical administrative database in the province of Quebec, Canada (1998-2004). Patients aged 45 years or more and discharged from the hospital alive after admission for acute myocardial infarction were included. High- and low-dose statin use were defined as a filled prescription, within 3 days after index discharge, at or above (below) the statin-specific target dose, for any of the 4 lipophilic statin medications: atorvastatin, simvastatin, lovastatin, or fluvastatin. Statin non-use was defined as non-use of any statins while simultaneously using major non-statin cardiac medications. A total of 30,076 patients, including high-dose statin users (n=6015), low-dose statin users (n=5323), and non-users (n=18,738), were followed for up to 7 years. Multivariable Cox regression analyses were performed to estimate associations between statin dose category and the incidence of admission to hospital with a diagnosis of any type of cancer. RESULTS: The crude incidence rates of hospital admission with the diagnosis of any type of cancer were 13.9, 17.2, and 26.0 per 1000 person-years in statin high-dose users, low-dose users, and non-users, respectively. The estimated adjusted hazard ratios were 0.75 (95% confidence interval [CI], 0.60-0.95) for statin use at high dose and 0.89 (95% CI, 0.75-1.07) for statin use at low dose. No significant time-dependence of the effect of statins at either dose was detected. CONCLUSION: The use of lipophilic statins at sufficiently high dose might be associated with a clinically important reduction in the incidence of cancer.

Utility of PSA doubling time in follow-up of untreated patients with localized prostate cancer.

OBJECTIVES: To evaluate the prostate-specific antigen (PSA) changes and the ability of PSA doubling time (PSADT) to predict disease progression in untreated patients with clinically localized prostate cancer. METHODS: A total of 104 patients with localized prostate cancer were followed up expectantly with serial PSA measurements and digital rectal examination (DRE). PSADT was calculated by linear regression analysis for the 94 patients who had a minimum of three PSA measurements and 12 months of follow-up. The median follow-up was 33 months. Of the 94 patients, 45 underwent repeat prostate biopsy to evaluate whether tumor progression occurred during the observation period. RESULTS: Twenty-seven percent of patients had rapid PSADTs (less than 48 months). Only the presence of palpable disease on DRE correlated with a PSADT of less than 48 months (P <0.05). However, a PSADT of less than 120 months consistently correlated with disease progression on DRE and on repeat biopsy, as well as with the presence of clinically significant cancer. PSADT did not correlate with the Gleason score. Furthermore, patients with a PSADT of less than 48 months did not differ significantly from those with a PSADT of 48 to 120 months with regard to Gleason score, disease progression on DRE or on repeat biopsy, and the presence of significant cancer. CONCLUSIONS: A PSADT of less than 120 months correlates with disease progression. However, its clinical utility remains limited to identify patients at risk of disease progression reliably.