Trends in Recurrent Coronary Heart Disease After Myocardial Infarction Among US Women and Men Between 2008 and 2017.

BACKGROUND: Rates for recurrent coronary heart disease (CHD) events have declined in the United States. However, few studies have assessed whether this decline has been similar among women and men. METHODS: Data were used from 770 408 US women and 700 477 US men <65 years of age with commercial health insurance through MarketScan and ≥66 years of age with government health insurance through Medicare who had a myocardial infarction (MI) hospitalization between 2008 and 2017. Women and men were followed up for recurrent MI, recurrent CHD events (ie, recurrent MI or coronary revascularization), heart failure hospitalization, and all-cause mortality (Medicare only) in the 365 days after MI. RESULTS: From 2008 to 2017, age-standardized recurrent MI rates per 1000 person-years decreased from 89.2 to 72.3 in women and from 94.2 to 81.3 in men (multivariable-adjusted P interaction by sex <0.001). Recurrent CHD event rates decreased from 166.3 to 133.3 in women and from 198.1 to 176.8 in men (P interaction <0.001). Heart failure hospitalization rates decreased from 177.4 to 158.1 in women and from 162.9 to 156.1 in men (P interaction=0.001). All-cause mortality rates decreased from 403.2 to 389.5 in women and from 436.1 to 417.9 in men (P interaction=0.82). In 2017, the multivariable-adjusted rate ratios comparing women with men were 0.90 (95% CI, 0.86-0.93) for recurrent MI, 0.80 (95% CI, 0.78-0.82) for recurrent CHD events, 0.99 (95% CI, 0.96-1.01) for heart failure hospitalization, and 0.82 (95% CI, 0.80-0.83) for all-cause mortality. CONCLUSIONS: Rates of recurrent MI, recurrent CHD events, heart failure hospitalization, and mortality in the first year after an MI declined considerably between 2008 and 2017 in both men and women, with proportionally greater reductions for women than men. However, rates remain very high, and rates of recurrent MI, recurrent CHD events, and death continue to be higher among men than women.

Cinacalcet and gastrointestinal bleeding risk in patients receiving hemodialysis.

PURPOSE: Secondary hyperparathyroidism (SHPT) is common among dialysis patients, and calcimimetics are a mainstay of treatment. This study assessed whether cinacalcet use is associated with gastrointestinal bleeding in a large hemodialysis cohort. METHODS: A linked database of clinical records and medical claims for patients receiving hemodialysis in a large dialysis organization, 2007-2010, was used. A nested case-control study was performed among patients aged ≥18 years who had received hemodialysis for ≥90 days, had Medicare Parts A, B, and D coverage for ≥1 year, and had clinical evidence of SHPT (parathyroid hormone >300 pg/mL). Cases were those who experienced death or hospitalization caused by gastrointestinal bleeding. Each case was matched to up to four controls. Exposure was measured by any cinacalcet use, current use, past use, cumulative exposure days, and cumulative dosage. Conditional logistic models were used to assess the association. RESULTS: Of 48 437 patients included, 2570 experienced gastrointestinal bleeding events (2498 non-fatal, 72 fatal), and 2465 (2397 non-fatal, 68 fatal) were matched to 9500 controls; 17.2% of cases and 15.8% of controls had cinacalcet exposure and 11.1% of both cases and controls had current use. The adjusted odds ratios (95% CI) of gastrointestinal bleeding for any use, current use, and past use of cinacalcet were 1.04 (0.91-1.19), 0.97 (0.83-1.13), and 1.22 (0.99-1.50), respectively, with no use as the reference. CONCLUSION: The results do not suggest an elevated risk of gastrointestinal bleeding resulting in hospitalization or death for hemodialysis patients exposed to cinacalcet.

Use of negative control outcomes to assess the comparability of patients initiating lipid-lowering therapies.

PURPOSE: Clinical trials have demonstrated efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in reducing risk of cardiovascular disease events, but effectiveness in routine clinical care has not been well-studied. We used negative control outcomes to assess potential confounding in an observational study of PCSK9i versus ezetimibe or high-intensity statin. METHODS: Using commercial claims, we identified U.S. adults initiating PCSK9i, ezetimibe, or high-intensity statin in 2015-2018, with other lipid-lowering therapy (LLT) use in the year prior (LLT cohort) or atherosclerotic cardiovascular disease (ASCVD) in the past 90 days (ASCVD cohort). We compared initiators of PCSK9i to ezetimibe and high-intensity statin by estimating one-year risks of negative control outcomes influenced by frailty or health-seeking behaviors. Inverse probability of treatment and censoring weighted estimators of risk differences (RDs) were used to evaluate residual confounding after controlling for covariates. RESULTS: PCSK9i initiators had lower one-year risks of negative control outcomes associated with frailty, such as decubitus ulcer in the ASCVD cohort (PCSK9i vs. high-intensity statin RD = -3.5%, 95% confidence interval (CI): -4.6%, -2.5%; PCSK9i vs. ezetimibe RD = -1.3%, 95% CI: -2.1%, -0.6%), with similar but attenuated associations in the LLT cohort. Lower risks of accidents and fractures were also observed for PCSK9i, varying by cohort. Risks were similar for outcomes associated with health-seeking behaviors, although trended higher for PCSK9i in the ASCVD cohort. CONCLUSIONS: Observed associations suggest lower frailty and potentially greater health-seeking behaviors among PCSK9i initiators, particularly those with a recent ASCVD diagnosis, with the potential to bias real-world analyses of treatment effectiveness.

Low-density lipoprotein cholesterol reduction and statin intensity in myocardial infarction patients and major adverse outcomes: a Swedish nationwide cohort study.

AIMS: Clinical trials have demonstrated that a reduction in low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular (CV) events. This has, however, not yet been shown in a real-world setting. We aimed to investigate the association between LDL-C changes and statin intensity with prognosis after a myocardial infarction (MI). METHODS AND RESULTS: Patients admitted with MI were followed for mortality and major CV events. Changes in LDL-C between the MI and a 6- to 10-week follow-up visit were analysed. The associations between quartiles of LDL-C change and statin intensity with outcomes were assessed using adjusted Cox regression analyses. A total of 40 607 patients were followed for a median of 3.78 years. The median change in LDL-C was a 1.20 mmol/L reduction. Patients with larger LDL-C reduction (1.85 mmol/L, 75th percentile) compared with a smaller reduction (0.36 mmol/L, 25th percentile) had lower hazard ratios (HR) for all outcomes (95% confidence interval): composite of CV mortality, MI, and ischaemic stroke 0.77 (0.70-0.84); all-cause mortality 0.71 (0.63-0.80); CV mortality 0.68 (0.57-0.81); MI 0.81 (0.73-0.91); ischaemic stroke 0.76 (0.62-0.93); heart failure hospitalization 0.73 (0.63-0.85), and coronary artery revascularization 0.86 (0.79-0.94). Patients with ≥50% LDL-C reduction using high-intensity statins at discharge had a lower incidence of all outcomes compared with those using a lower intensity statin. CONCLUSIONS: Larger early LDL-C reduction and more intensive statin therapy after MI were associated with a reduced hazard of all CV outcomes and all-cause mortality. This supports clinical trial data suggesting that earlier lowering of LDL-C after an MI confers the greatest benefit.

Predictors of cinacalcet discontinuation and reinitiation in hemodialysis patients: results from 7 European countries.

BACKGROUND: The putative benefits of cinacalcet therapy for management of secondary hyperparathyroidism (SHPT) are thought to be most manifested when patients are taking it consistently and as prescribed. Real-world descriptions of cinacalcet prescription discontinuation and reinitiation in European hemodialysis patients are lacking. To address this knowledge gap, we used Dialysis Outcomes and Practice Patterns Study (DOPPS) data, based on dialysis facility medical records, from seven European countries to estimate rates and predictors of cinacalcet prescription discontinuation and reinitiation in hemodialysis patients and to describe the trajectories of CKD-MBD laboratory values after discontinuation. METHODS: Cox regression analyses were used to predict (1) cinacalcet discontinuation among 613 patients with ≥3 consecutive months without cinacalcet prescription immediately prior to a new cinacalcet prescription and (2) cinacalcet reinitiation among 415 patients with a newly discontinued cinacalcet prescription immediately after ≥3 consecutive months of prescribed use. RESULTS: Cinacalcet was discontinued in 21 and 35% of new users after 6 and 12 months, respectively. Cinacalcet was reinitiated in 38 and 49% of newly-discontinued users after 6 and 12 months, respectively. Predictors of discontinuation included lower parathyroid hormone (PTH) in the previous month (< 150 pg/ml vs. 150-299, HR = 2.57 [95% CI: 1.52-4.33]) and lower serum calcium in the previous month (< 8.4 mg/dl vs. 8.4-10.19, HR = 1.67 [95% CI: 1.08-2.59]). Predictors of reinitiation included higher PTH in the previous month (300-599 pg/ml vs. 150-299, HR = 1.88 [95% CI = 1.19-2.97]; 600+ pg/ml, HR = 3.02 [95% CI = 1.92-4.76]). After cinacalcet discontinuation, mean serum PTH increased from 408 to 510 pg/ml, mean serum calcium briefly rose from 9.12 to 9.22 mg/dl before declining to 9.06 mg/dl, and mean serum phosphorus showed little change. CONCLUSIONS: Nephrologist discontinuation of cinacalcet therapy is common in European countries. Additional research is needed to identify optimal cinacalcet treatment strategies for SHPT management, including comparisons of intermittent cinacalcet therapy versus sustained treatment with reduced dose or frequency.

The association between cinacalcet use and missed in-center hemodialysis treatment rate.

PURPOSE: Missed in-center hemodialysis treatments (MHT) are a general indicator of health status in hemodialysis patients. This analysis was conducted to estimate the association between cinacalcet use and MHT rate. METHODS: We studied patients receiving hemodialysis and prescription benefits services from a large dialysis organization. Incident cinacalcet users were propensity score matched to controls on 31 demographic, clinical, and laboratory variables. We applied inverse probability (IP) of censoring and crossover weights to account for informative censoring. Weighted negative binomial modeling was used to estimate MHT rates and pooled logistics models were used to estimate the association between cinacalcet use and MHT. RESULTS: Baseline demographic and clinical variables included serum calcium, phosphorus, parathyroid hormone, and vitamin D use, and were balanced between 15,474 new cinacalcet users and 15,474 matched controls. In an analysis based on intention-to-treat principles, 40.8% of cinacalcet users and 46.5% of nonusers were censored. MHT rate was 13% lower among cinacalcet initiators versus controls: IP of censoring weighted incidence rate ratio was 0.87 (95% confidence interval [CI]: 0.84-0.90 p < 0.001). In analyses based on as-treated principles, 72.8% and 61.5% of cinacalcet users and nonusers, respectively, crossed over or were censored. MHT rate was 15% lower among cinacalcet initiators versus controls: IP of censoring/crossover weighted incidence rate ratio was 0.85 (95%CI: 0.82-0.87 p < 0.001). CONCLUSIONS: After controlling for indication and differential censoring, cinacalcet treatment was associated with lower MHT rates, which may reflect better health status. Copyright © 2016 John Wiley & Sons, Ltd.

Geographic variation of parathyroidectomy in patients receiving hemodialysis: a retrospective cohort analysis.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is associated with adverse outcomes in patients receiving maintenance dialysis. Parathyroidectomy is a treatment for SHPT; whether parathyroidectomy utilization varies geographically in the US is unknown. METHODS: A retrospective cohort analysis was undertaken to identify all patients aged 18 years or older who were receiving in-center hemodialysis between 2007 and 2009, were covered by Medicare Parts A and B, and had been receiving hemodialysis for at least 1 year. Parathyroidectomy was identified from inpatient claims using relevant International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes. Patient characteristics and End-Stage Renal Disease Network (a proxy for geography) were ascertained. Adjusted odds ratios for parathyroidectomy were estimated from a logistic model. RESULTS: A total of 286,569 patients satisfied inclusion criteria, of whom 4435 (1.5%) underwent PTX. After adjustment for a variety of patient characteristics, there was a 2-fold difference in adjusted odds of parathyroidectomy between the most- and least-frequently performing regions. Adjusted odds ratios were more than 20% higher than average in four networks, and more than 20% lower in four networks. CONCLUSIONS: Parathyroidectomy use varies substantially by geography in the US; the factors responsible should be further investigated.

Variation in genes involved in the immune response and prostate cancer risk in the placebo arm of the Prostate Cancer Prevention Trial.

BACKGROUND: We previously found that inflammation in benign prostate tissue is associated with an increased odds of prostate cancer, especially higher-grade disease. Since part of this link may be due to genetics, we evaluated the association between single nucleotide polymorphisms (SNPs) in immune response genes and prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial. METHODS: We genotyped 16 candidate SNPs in IL1ß, IL2, IL4, IL6, IL8, IL10, IL12(p40), IFNG, MSR1, RNASEL, TLR4, and TNFA and seven tagSNPs in IL10 in 881 prostate cancer cases and 848 controls negative for cancer on an end-of-study biopsy. Cases and controls were non-Hispanic white and frequency matched on age and family history. We classified cases as lower (Gleason sum <7; N = 674) and higher (7-10; N = 172) grade, and used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for age and family history. RESULTS: The minor allele (C) of rs3212227 in IL12(p40) was associated with an increased risk of total (log additive: OR = 1.30, 95%CI 1.10-1.53; P-trend = 0.0017) and lower-grade (OR = 1.36, 95%CI 1.15-1.62; P-trend = 0.0004) prostate cancer. The minor allele (A) of rs4073 in IL8 was possibly associated with a decreased risk of higher-grade (OR = 0.81, 95%CI 0.64-1.02; P-trend = 0.07), but not total disease. None of the other candidates was associated with risk. The minor alleles of IL10 tagSNPs rs1800890 (A; OR = 0.87, 95%CI: 0.75-0.99; P-trend = 0.04) and rs3021094 (C; OR = 1.31, 95%CI 1.03-1.66, P-trend = 0.03) were associated with risk; the latter also with lower- (P-trend = 0.04) and possibly higher- (P-trend = 0.06) grade disease. These patterns were similar among men with PSA <2 ng/ml at biopsy. CONCLUSION: Variation in some immune response genes may be associated with prostate cancer risk. These associations were not fully explained by PSA-associated detection bias. Our findings generally support the role of inflammation in the etiology of prostate cancer.

Management of serum calcium reductions among patients on hemodialysis following cinacalcet initiation.

PURPOSE: Cinacalcet is indicated for treatment of secondary hyperparathyroidism in patients receiving hemodialysis. Cinacalcet reduces serum calcium concentrations by decreasing parathyroid hormone secretion, but the frequency and degree of calcium reduction following cinacalcet initiation, subsequent physician response, and ultimate calcium recovery in clinical practice are not well described. METHODS: Patients receiving hemodialysis at a large dialysis organization who enrolled in the organization's prescription benefits service and initiated cinacalcet at serum calcium ≥8.4 mg/dL were studied (N = 13 723). Patients were categorized by whether they experienced a reduction in calcium to <8.4 mg/dL and to what level (<7.5, 7.5-7.9, and 8.0-8.3 mg/dL). Baseline characteristics, frequency of subsequent intervention, and calcium recovery were compared. RESULTS: Of those who experienced a reduction in calcium to <8.4 mg/dL (n = 6437 [46.9%]), 6.6% had calcium <7.5 mg/dL and 24.5% had calcium 7.5-7.9 mg/dL, while the majority (68.9%) had a level of 8-8.3 mg/dL. Higher baseline parathyroid hormone and alkaline phosphatase were associated with lower resultant calcium. Among patients with calcium reductions, 45.6-63.5% received one or more directed clinical therapeutic responses, including 15.6-28.4% for whom cinacalcet was discontinued; the majority of patients recovered to calcium ≥8.4 mg/dL within 90 days of first detection. Only modest differences in recovery were noted between patients who did and did not receive any therapeutic response and patients who did and did not discontinue cinacalcet. CONCLUSION: Serum calcium reductions following cinacalcet initiation were common; declines <7.5 mg/dL were infrequent. Calcium recovery occurred in the majority of patients, with or without therapeutic intervention.

Dynamics of cinacalcet use and biochemical control in hemodialysis patients: a retrospective New-user cohort design.

BACKGROUND: Cinacalcet is used to treat secondary hyperparathyroidism among hemodialysis patients. Large-scale epidemiologic studies describing patterns of cinacalcet use, effects on parathyroid hormone (PTH), calcium, and phosphorous levels, and predictors of discontinuation have not been previously reported. METHODS: This retrospective cohort study used a clinical database of a large U.S. dialysis provider (2007-2010) merged with administrative data from the United States Renal Data System. Among new users of cinacalcet with Medicare coverage, trends in PTH, calcium, and phosphorus were measured in 30-day intervals following cinacalcet initiation. RESULTS: Seventeen thousand seven hundred sixty-three eligible initiators contributed 111,047 30-day follow-up intervals. Of these, 56 % discontinued cinacalcet by month 4. Of those discontinuing, 76.3 % reinitiated. Mean values of PTH, calcium, and phosphorus decreased to recommended levels within 4 months following initiation. Proximal PTH levels < 150 pg/mL were associated with discontinuation: HR = 1.23 (95 % CI: 1.12, 1.36), whereas low calcium (< 7.5 mg/dL) was suggestive of an association, HR = 1.09 (95 % CI 0.91, 1.32). Being in the Part D gap period increased discontinuation risk: HR = 1.09 (95 % CI: 1.03, 1.16). Low-income subsidy status decreased discontinuation risk: HR = 0.77 (95 % CI 0.69, 0.86). Predictors of reinitiation included low-income subsidy, HR = 1.32 (95 % CI 1.22, 1.43); higher albumin level, HR = 1.23 (95 % CI 1.10, 1.36) and higher calcium level, HR = 1.26 (95 % CI 1.19, 1.33). CONCLUSIONS: Substantial and expected declines in laboratory values occurred following cinacalcet initiation. Early discontinuation and reinitiation of cinacalcet were common and may have occurred for clinical and economic reasons.

The association between circulating high-sensitivity C-reactive protein concentration and pathologic measures of colonic inflammation.

PURPOSE: C-reactive protein (CRP), an inflammation marker, is associated with colorectal cancer (CRC) risk in some prospective studies. Whether increased CRP is indicative of colonic inflammation, a possible CRC cause, or of other sources of inflammation (e.g., adiposity), is unknown. Thus, we evaluated the association between CRP and colonic mucosal measures of inflammation. METHODS: 151 adults undergoing colonoscopy provided a blood sample and random left- and right-side colonic mucosal biopsies. Height and weight were measured, and lifestyle information was collected. High-sensitivity C-reactive protein (hsCRP) was measured by immunoturbidometric assay. A gastrointestinal pathologist evaluated biopsies for seven colonic inflammation measures. Of 119 participants with complete information, 24 had an inflammatory bowel disease (IBD) history and were analyzed separately. We calculated the number of colonic inflammation measures present in both biopsies, and separately for right and left biopsies. Adjusted geometric mean hsCRP was calculated using linear regression, overall, by demographic and lifestyle factors, and inflammation measures. RESULTS: Most participants had ≥ 1 colonic inflammation measure (0: 21 %, 1: 39 %, ≥ 2: 40 %). Adjusted mean hsCRP did not increase with increasing number of inflammation measures (0: 1.67; 1: 1.33; ≥ 2: 1.01 mg/L; p trend = 0.21). Obese (2.03 mg/L) and overweight (1.61 mg/L) participants had higher adjusted mean hsCRP than normal-weight participants (0.62 mg/L; p trend <0.0001). Patterns were similar for participants with a history of IBD. CONCLUSIONS: hsCRP concentration was not associated with colonic inflammation, although hsCRP increased with adiposity. The hsCRP-CRC association may be explained by residual confounding by other risk factors, such as adiposity, rather than by CRP marking colonic inflammation.

Glycated hemoglobin and cancer incidence and mortality in the Atherosclerosis in Communities (ARIC) Study, 1990-2006.

Diabetes is a risk factor for many cancers; chronic hyperglycemia is hypothesized to be, in part, explanatory. We evaluated the association between glycated hemoglobin, a time-integrated glycemia measure, and cancer incidence and mortality in nondiabetic and diabetic men and women. We conducted a prospective study of 12,792 cancer-free participants attending the second visit (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) Study. We measured glycated hemoglobin in whole-blood samples using HPLC. Incident cancers were ascertained from registries and hospital records through 2006. We estimated multivariable-adjusted hazard ratios (HR) of cancer incidence and mortality for nondiabetic participants with values ≥ 5.7% (elevated), nondiabetic participants with <5.0% (low) and diabetic participants all compared with nondiabetic participants with 5.0-5.6% (normal). We ascertained 2,349 incident cancer cases and 887 cancer deaths. Compared with nondiabetic women with normal glycated hemoglobin, nondiabetic women with elevated values had an increased risk of cancer incidence (HR:1.24; 95% CI:1.07,1.44) and mortality (HR:1.58; 95% CI:1.23,2.05) as did diabetic women (incidence, HR:1.30; 95% CI:1.06,1.60, mortality, HR:1.96; 95% CI:1.40,2.76). Nondiabetic women with low values also had increased risk. Diabetic women with good glycemic control (<7.0%) had a lower cancer risk than those with higher values. Glycated hemoglobin in nondiabetic and diabetic men, and diabetes were not statistically significantly associated with total cancer risk. Our findings support the hypothesis that chronic hyperglycemia, even in the nondiabetic range, increases cancer risk in women. Maintaining normal glycated hemoglobin overall, and good glycemic control among diabetic adults, may reduce the burden of cancer, especially in women.

Characterizing a Clinical Trial - Representative, Real-World Population with Heart Failure with Reduced Ejection Fraction.

PURPOSE: Given known differences between real-world and clinical trial populations, we characterized demographics, clinical characteristics, and outcomes using real-world (RW) data for patients with heart failure with reduced ejection fraction (HFrEF), including those similar to subjects enrolled in an HFrEF clinical trial to better understand patient populations that could benefit from novel therapies. PATIENTS AND METHODS: Using Vanderbilt University Medical Center electronic health records (2006-2019), two RW cohorts of HFrEF patients were identified. The "Clinical Cohort" was based on a validated HFrEF algorithm and left ventricular ejection fraction (LVEF) ≤40%. The "GALACTIC-HF-like Cohort" mirrored enrollment requirements of the GALACTIC-HF clinical trial including hospitalizations, medications, laboratory values, and LVEF ≤35%. RESULTS: Median age at index for the Clinical Cohort (N = 3954) and GALACTIC-HF-like Cohort (N = 1541) were 65 and 61 years, respectively; both were 67% male and 80% white. Over half had coronary artery disease (55% Clinical vs 64% GALACTIC-HF-like); hypercholesterolemia was common (69% Clinical vs 74% GALACTIC-HF-like). Chronic kidney disease (31 vs 21%), atrial fibrillation (32 vs 29%), and cardiac resynchronization or implantable cardioverter defibrillator (26 vs 23%) were higher in the GALACTIC-HF-like Cohort. ACE inhibitor use was high in both groups but more common in the GALACTIC-HF-like Cohort (71% and 82%, respectively). Beta-blockers or loop diuretics were used by >90% of both cohorts. HF hospitalization rates were 261 (95% CI 224, 297) per 1000 person-years in Clinical versus 523 (484, 562) in GALACTIC-HF-like Cohort (median follow-up of 2.9 and 4.2 years, respectively). CONCLUSION: Approximately 40% of RW HFrEF patients met criteria for the GALACTIC-HF trial. While findings of ongoing clinical trials may be directly generalizable to this sizable proportion of patients, future trials should examine whether the majority of patients with lower prevalence of comorbidities and rate of HF hospitalization could benefit from emerging HF treatments.

Characteristics of patients with diabetes and a history of myocardial infarction initiating PCSK9 and SGLT2 inhibitors.

Study objective: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk for atherosclerotic cardiovascular disease (ASCVD) events in patients with diabetes and ASCVD. We assessed factors associated with initiating either medication among patients with diabetes and a prior myocardial infarction (MI). Setting/participants: US adults ≥19 years old with private health insurance (MarketScan) or government health insurance (Medicare) who had diabetes and a prior MI and initiated a PCSK9i or an SGLT2i in 2017 or 2018. Main outcome measures: PCSK9i or SGLT2i initiation was identified using pharmacy claims. Results: Overall, 8102 patients initiated a PCSK9i (n = 1501; 18.5%) or an SGLT2i (n = 6601; 81.5%). Patients with 2 and ≥3 versus 1 prior MI (risk ratio [RR]: 1.32 [95%CI: 1.17-1.48] and 1.68 [1.41-2.01], respectively), prior coronary revascularization (1.47 [1.31-1.64]), prior stroke (1.28 [1.06-1.56]), history of peripheral artery disease (1.27 [1.14-1.41]), receiving cardiologist care (1.51 [1.36-1.67]) or taking ezetimibe (2.57 [2.35-2.82]) were more likely to initiate a PCSK9i versus an SGLT2i. Patients with a history of short-term (RR 1.07 [95%CI 1.05-1.09]) or long-term (1.07 [1.04-1.09]) diabetes complications, and taking a low/moderate- and high-intensity statin dosage (1.61 [1.51-1.70] and 1.68 [1.58-1.77], respectively) were more likely to initiate an SGLT2i versus a PCSK9i. Among patients who initiated a PCSK9i, 2.9% subsequently initiated an SGLT2i; 0.8% who initiated an SGLT2i subsequently initiated a PCSK9i. Conclusion: The decision to initiate PCSK9i or SGLT2i is explained by having very high cardiovascular disease risk for those initiating PCSK9i and diabetes complications for those initiating SGLT2i.

Atherosclerotic Cardiovascular Disease Events in Adults With CKD Taking a Moderate- or High-Intensity Statin: The Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline uses risk stratification to guide the decision to initiate nonstatin lipid-lowering medication among adults with atherosclerotic cardiovascular disease (CVD). We determined atherosclerotic CVD (ASCVD) event rates among adults with chronic kidney disease (CKD) taking statin therapy within 2018 AHA/ACC cholesterol guideline risk categories. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Adults with CKD not on dialysis in the Chronic Renal Insufficiency Cohort (CRIC) study who were taking a moderate/high-intensity statin 1 year after enrollment (baseline for the current analysis, n = 1,753). EXPOSURE: 2018 AHA/ACC cholesterol guideline risk categories: without a history of ASCVD, a history of 1 major ASCVD event and multiple high-risk conditions, and a history of ≥2 major ASCVD events. OUTCOME: Adjudicated ASCVD events after the year 1 study visit. ANALYTICAL APPROACH: We calculated age-sex standardized rates for ASCVD events and age-sex adjusted hazard ratios for ASCVD events accounting for the competing risk of death. RESULTS: There were 394 ASCVD events over a median follow-up period of 8 years. The ASCVD event rates (with 95% CI) per 1,000 person-years among participants without a history of ASCVD, with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 21.7 (18.4-25.1), 45.0 (37.8-52.3), and 73.3 (53.3-93.4), respectively. Compared with participants without a history of ASCVD, the HR (95% CI) rates for ASCVD events among those with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 1.89 (1.52-2.36) and 2.50 (1.85-3.39), respectively. LIMITATIONS: Data on whether participants were taking a maximally tolerated statin dosage were unavailable. CONCLUSIONS: The 2018 AHA/ACC cholesterol guideline identifies adults with CKD who have very high ASCVD risk despite taking a moderate/high-intensity statin.

Combinations of mineral and bone disorder markers and risk of death and hospitalizations in the international Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Prior studies have developed a chronic kidney disease-mineral and bone disorder (CKD-MBD) composite score based on combinations of calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) that have been shown to be associated with an increased risk of clinical outcomes in the USA. We examined this association in a contemporary, international cohort of hemodialysis patients. METHODS: We studied 19 313 patients surviving ≥12 months in the Dialysis Outcomes and Practice Patterns Study Phases 3-5 (2005-15) from Europe, Canada and the USA. The CKD-MBD composite score was defined as the number of markers above target levels (P, 3.5-5.5 mg/dL; Ca, 8.4-10.2 mg/dL; PTH, 150-600 pg/mL). Using Cox models, we estimated hazard ratios (HRs) for death and a composite event (death or hospitalization), contrasting MBD 2/3 (2-3 parameters above target) with MBD 0 (all in target), adjusted for a disease risk score (DRS). RESULTS: MBD 2/3 above target was observed in 10-14% of patients across regions and was associated with greater DRS-adjusted mortality {HR 1.41 [95% confidence interval (CI) 1.10-1.82]} and composite events [HR 1.23 (95% CI 1.10-1.38)] in the USA compared with MBD 0; the mortality association was stronger for patients ≥ 65 years of age [HR 1.82 (95% CI 1.28-2.58)] compared with patients <65 years of age [HR 1.11 (95% CI 0.80-1.55)]. HRs observed in Canada and Europe were generally consistent but weaker. Estimates for MBD 2/3 outside target (above or below) were slightly lower in all regions. CONCLUSIONS: Simultaneous consideration of Ca, P and PTH may help in identifying patients on dialysis with a higher risk of major clinical outcomes related to CKD-MBD.

Association of hospital transfusion use and infection-related rehospitalizations among patients receiving hemodialysis: A retrospective cohort study.

INTRODUCTION: Red blood cell transfusions have been associated with infection risk. We investigated whether hospital transfusions are associated with infections in maintenance hemodialysis patients requiring transfusions for chronic anemia. METHODS: In this retrospective cohort study, hemodialysis patients who experienced an incident hospitalization during 2012-2013 were identified from the Medicare end-stage renal disease database. Hospital transfusions were first categorized into one of five groups based on adjusted likelihood of administering red blood cell transfusions during inpatient hospital stays that occurred over the previous year (2011) among the general Medicare cohort. Next, in a patient-level analysis, patients were categorized according to transfusion use at the incident hospitalization hospital. Outcomes were infection-related rehospitalization and a composite of infection-related hospitalization and all-cause mortality during the 60 days following hospital discharge. We estimated adjusted rate ratios for the association between hospital transfusion use and risk of rehospitalization or the composite endpoint using Poisson regression models. FINDINGS: The study included 1578 hospitals and 61,455 hemodialysis patients. Patient characteristics were balanced across hospital transfusion use groups. The overall transfusion rate was 16.0%. The overall 30-day infection-related hospitalization rate (95% confidence interval) per 100 patient-months was 8.8 (8.6-9.1); rates did not differ by transfusion use group. Rate ratios for infection-related rehospitalization were 1.00 (0.91-1.10) over 30 days and 0.98 (0.91-1.05) over 60 days comparing the lowest and highest transfusion use groups. DISCUSSION: We found no differences in risk of infection-related rehospitalization for patients receiving maintenance hemodialysis across the varying blood transfusion rates of US hospitals.

Sex Differences in Incident and Recurrent Coronary Events and All-Cause Mortality.

BACKGROUND: Women have lower age-specific rates of incident coronary heart disease (CHD) than men. It is unclear whether women remain at lower risk for CHD events versus men following a myocardial infarction (MI). OBJECTIVES: This study assessed sex differences in recurrent MI, recurrent CHD events, and mortality among patients with MI and compared these associations with sex differences in a control group without a history of CHD. METHODS: This study analyzed data for 171,897 women and 167,993 men age 21 years or older with health insurance in the United States who had a MI hospitalization in 2015 or 2016. Patients with a MI were frequency matched by age and calendar year to 687,588 women and 671,972 men without CHD. Beneficiaries were followed until December 2017 for MI, CHD (i.e., MI or coronary revascularization), and in Medicare for all-cause mortality. RESULTS: Age-standardized rates of MI per 1,000 person-years were 4.5 in women and 5.7 in men without CHD (hazard ratio [HR]: 0.64; 95% confidence interval [CI]: 0.62 to 0.67) and 60.2 in women and 59.8 in men with MI (HR: 0.94; 95% CI: 0.92 to 0.96). CHD rates in women versus men were 6.3 versus 10.7 among those without CHD (HR: 0.53; 95% CI: 0.51 to 0.54) and 84.5 versus 99.3 among those with MI (HR: 0.87; 95% CI: 0.85 to 0.89). All-cause mortality rates in women versus men were 63.7 versus 59.0 among those without CHD (HR: 0.72; 95% CI: 0.71 to 0.73) and 311.6 versus 284.5 among those with MI (HR: 0.90; 95% CI: 0.89 to 0.92). CONCLUSIONS: The lower risk for MI, CHD, and all-cause mortality in women versus men is considerably attenuated following a MI.

Lipid Testing Trends in the US Before and After the Release of the 2013 Cholesterol Treatment Guidelines.

BACKGROUND: The 2013 ACC/AHA cholesterol treatment guidelines removed the recommendation to treat adults at risk of cardiovascular disease to goal levels of low-density lipoprotein cholesterol (LDL-C). We anticipated that the frequency of LDL-C testing in clinical practice would decline as a result. To test this hypothesis, we evaluated the frequency of LDL-C testing before and after the guideline release. METHODS: We used the MarketScan® Commercial and Medicare Supplemental claims data (1/1/2007-12/31/2016) to identify four cohorts: 1) statin initiators (any intensity), 2) high-intensity statin initiators, 3) ezetimibe initiators, and 4) patients at very high cardiovascular risk (≥2 hospitalizations for myocardial infarction or ischemic stroke, with prevalent statin use). Rates of LDL-C testing by calendar year quarter were estimated for each cohort. To estimate rates in the absence of a guideline change, we fit a time-series model to the pre-guideline rates and extrapolated to the post-guideline period, adjusting for covariates, seasonality, and time trend. RESULTS: Pre- and post-guideline rates (LDL-C tests per 1,000 persons per quarter) were 248 and 235, respectively, for 3.9 million statin initiators; 263 and 246 for 1.3 million high-intensity statin initiators; 277 and 261 for 323,544 ezetimibe initiators; and 180 and 158 for 42,108 very high-risk patients. For all cohorts, observed post-guideline rates were similar to model-predicted rates. On average, the difference between observed and predicted rates was 8.5 for patients initiating any statin; 2.6 for patients initiating a high-intensity statin; 11.4 for patients initiating ezetimibe, and -0.5 for high-risk patients. CONCLUSION: We observed no discernible impact of the release of the 2013 ACC/AHA guidelines on LDL-C testing rates. Rather, there was a gradual decline in testing rates starting prior to the guideline change and continuing throughout the study period. Our findings suggest that the guidelines had little to no impact on use of LDL-C testing.

Excess Risk for Atherosclerotic Cardiovascular Outcomes Among US Adults With HIV in the Current Era.

Background In the 2000s, adults with HIV had a higher risk for atherosclerotic cardiovascular disease (ASCVD) compared with those without HIV. There is uncertainty if this excess risk still exists in the United States given changes in antiretroviral therapies and increased statin use. Methods and Results We compared the risk for ASCVD events between US adults aged ≥19 years with and without HIV who had commercial or supplemental Medicare health insurance between January 1, 2011, and December 31, 2016. Beneficiaries with HIV (n=82 426) were frequency matched 1:4 on age, sex, and calendar year to those without HIV (n=329 704). Beneficiaries with and without HIV were followed up through December 31, 2016, for ASCVD events, including myocardial infarction, stroke, and lower extremity artery disease hospitalizations. Most beneficiaries were aged <55 years (79%) and men (84%). Over a median follow-up of 1.6 years (maximum, 6 years), there were 3287 ASCVD events, 2190 myocardial infarctions, 891 strokes, and 322 lower extremity artery disease events. The rate per 1000 person-years among beneficiaries with and without HIV was 5.53 and 3.49 for ASCVD, respectively, 3.58 and 2.34 for myocardial infarction, respectively, 1.49 and 0.94 for stroke, respectively, and 0.65 and 0.31 for lower extremity artery disease hospitalizations, respectively. The multivariable-adjusted hazard ratio (95% CI) for ASCVD, myocardial infarction, stroke, and lower extremity artery disease hospitalizations comparing beneficiaries with versus without HIV was 1.29 (1.18-1.40), 1.26 (1.13-1.39), 1.30 (1.11-1.52), and 1.46 (1.11-1.92), respectively. Conclusions Adults with HIV in the United States continue to have a higher ASCVD risk compared with their counterparts without HIV.