Population health impact and economic evaluation of the CARDIO4Cities approach to improve urban hypertension management.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, with 80% of that mortality occurring in low- and middle-income countries. Hypertension, its primary risk factor, can be effectively addressed through multisectoral, multi-intervention initiatives. However, evidence for the population-level impact on cardiovascular (CV) event rates and mortality, and the cost-effectiveness of such initiatives is scarce as long-term longitudinal data is often lacking. Here, we model the long-term population health impact and cost-effectiveness of a multisectoral urban population health initiative designed to reduce hypertension, conducted in Ulaanbaatar (Mongolia), Dakar (Senegal), and in the district of Itaquera in São Paulo (Brazil) in collaboration with the local governments. We based our analysis on cohort-level data among hypertensive patients on treatment and control rates from a real-world effectiveness study of the CARDIO4Cities approach (built on quality of care, early access, policy reform, data and digital, Intersectoral collaboration, and local ownership). We built a decision tree model to estimate the CV event rates during implementation (1-2 years) and a Markov model to project health outcomes over 10 years. We estimated the number of CV events averted and quality-adjusted life-years gained (QALYs through the initiative and assessed its cost-effectiveness based on the costs reported by the funder using the incremental cost effectiveness ratio (ICER) and published thresholds. A one-way sensitivity analysis was performed to assess the robustness of the results. The modelled patient cohorts included 10,075 patients treated for hypertension in Ulaanbaatar, 5,236 in Dakar, and 5,844 in São Paulo. We estimated that 3.3-12.8% of strokes and 3.0-12.0% of coronary heart disease (CHD) events were averted during 1-2 years of implementation in the three cities. We estimated that over the subsequent 10 years, 3.6-9.9% of strokes, 2.8-7.8% of CHD events, and 2.7-7.9% of premature deaths would be averted. The estimated ICER was USD 748 QALY gained in Ulaanbaatar, USD 3091 in Dakar, and USD 784 in São Paulo. With that, the intervention was estimated to be cost-effective in Ulaanbaatar and São Paulo. For Dakar, cost-effectiveness was met under WHO-CHOICE standards, but not under more conservative standards adjusted for purchasing power parity (PPP) and opportunity costs. The findings were robust to the sensitivity analysis. Our results provide evidence that the favorable impact of multisector systemic interventions designed to reduce the hypertension burden extend to long-term population-level CV health outcomes and are likely cost-effective. The CARDIO4Cities approach is predicted to be a cost-effective solution to alleviate the growing CVD burden in cities across the world.

Implementing a multisector public-private partnership to improve urban hypertension management in low-and middle- income countries.

BACKGROUND: Cardiovascular disease presents an increasing health burden to low- and middle-income countries. Although ample therapeutic options and care improvement frameworks exist to address its prime risk factor, hypertension, blood pressure control rates remain poor. We describe the results of an effectiveness study of a multisector urban population health initiative that targets hypertension in a real-world implementation setting in cities across three continents. The initiative followed the "CARDIO4Cities" approach (quality of Care, early Access, policy Reform, Data and digital technology, Intersectoral collaboration, and local Ownership). METHOD: The approach was applied in Ulaanbaatar in Mongolia, Dakar in Senegal, and São Paulo in Brazil. In each city, a portfolio of evidence-based practices was implemented, tailored to local priorities and available data. Outcomes were measured by extracting hypertension diagnosis, treatment and control rates from primary health records. Data from 18,997 patients with hypertension in primary health facilities were analyzed. RESULTS: Over one to two years of implementation, blood pressure control rates among enrolled patients receiving medication tripled in São Paulo (from 12·3% to 31·2%) and Dakar (from 6·7% to 19·4%) and increased six-fold in Ulaanbaatar (from 3·1% to 19·7%). CONCLUSIONS: This study provides first evidence that a multisectoral population health approach to implement known best-practices, supported by data and digital technologies, and relying on local buy-in and ownership, can improve hypertension control in high-burden urban primary care settings in low-and middle-income countries.

Fostering cardiovascular health at work - case study from Senegal.

BACKGROUND: Of the 15 million annual premature deaths from non-communicable diseases (NCDs), 85% occur in low- and middle-income countries (LMICs). Affecting individuals in the prime of their lives, NCDs impose severe economic damage to economies and businesses, owing to the high mortality and morbidity within the workforce. The Novartis Foundation urban health initiative, Better Hearts Better Cities, was designed to improve cardiovascular health in Dakar, Senegal through a combination of interventions including a workplace health program. In this study, we describe the labor policy environment in Senegal and the outcomes of a Novartis Foundation-supported multisector workplace health coalition bringing together volunteering private companies. METHODS: A mixed method design was applied between April 2018 and February 2020 to evaluate the workplace health program as a case study. Qualitative methods included a desk review of documents relevant to the Senegalese employment context and work environment and in-depth interviews with eight key informants including human resource representatives and physicians working in the participating companies. Quantitative methods involved an analysis of workplace health program indicators, including data on diagnosis, treatment and control of hypertension in employees, provided by the coalition companies, and a cost estimate of NCD-related ill-health as compared to the investment needed for hypertension screening and awareness raising events. RESULTS: Senegal has a legal and regulatory system that ensures employee protection, supports social security benefits, and promotes health and hygiene in companies. The Dakar Workplace Health Coalition comprised 18 companies, with a range of staff between 300 and 4'220, covering 36'268 employees in total. Interviews suggested that the main enablers for workplace program success were strong leadership support within the company and a central coordination mechanism for the program. The main barrier to monitor progress and outcomes was the reluctance of companies to share data. Four companies provided aggregated anonymized cohort data, documenting a total of 21'392 hypertension screenings and an increasing trend in blood pressure control (from 34% in Q4 2018 to 39% in Q2 2019) in employees who received antihypertensive treatment. CONCLUSION: Evidence on workplace health and wellness programs in Africa is scarce. This study highlights how private sector companies can play a significant role in improving cardiovascular population health in LMICs.

Variability in Price of Generic Antipsychotic Medications at Community Pharmacies.

OBJECTIVE: This study aimed to examine variability in pricing of generic antipsychotic medications in a diverse metropolitan area and to determine whether prices varied by pharmacy type. METHODS: A cross-sectional survey was conducted of pharmacy-level variability in retail cash prices for a 30-day supply of one first-generation and five generically available second-generation antipsychotic medications at community pharmacies in the Kansas City metropolitan area. All community pharmacies in the area were identified (N=281), and 94% (N=265, with 147 in Missouri and 118 in Kansas) responded to phone queries between April 25 and May 25, 2017, requesting the cash price of a 30-day supply of each of the six antipsychotics. All included pharmacies were categorized as a nationwide chain (N=182), grocery store (N=53), or independent pharmacy (N=30). RESULTS: Retail cash prices varied for all antipsychotic medications, with significant differences in price by pharmacy type. Price variation across all pharmacy types was lowest for haloperidol ($20-$102.99) and highest for aripiprazole ($29.99-$1,345.00). Pairwise comparisons showed that chain pharmacies had higher prices, compared with independent pharmacies, for all medications except haloperidol. Overall, chain pharmacies had the highest prices, with prices at grocery store pharmacies averaging $180 lower than chain pharmacies, and independent pharmacies averaging $415 lower than chain pharmacies. CONCLUSIONS: This report is the first on pharmacy-level variability in the costs of generic antipsychotic treatment options for schizophrenia. Appreciable differences were found in the costs of generic antipsychotics. Understanding variability in antipsychotic pricing may be important for providers serving uninsured patients.

Understanding Patient Perceptions of Hypertension for Optimal Management in a Student-Run Free Clinic.

The burden of hypertension (HTN) is disproportionately high among adults with low socio-economic status. Our objective was to examine the knowledge, attitudes and barriers related to HTN among this cohort. Using a mixed-methods approach, we interviewed twenty adults at a student-run safety-net health clinic. Most patients recognized HTN-related risks, but themes of denial, financial burden and misinformation emerged when addressing treatment adherence. Our findings highlight an urgent need to address patient-centric approaches in HTN management.

Impact of Glycoprotein IIb/IIIa Inhibition in Contemporary Percutaneous Coronary Intervention for Acute Coronary Syndromes: Insights From the National Cardiovascular Data Registry.

OBJECTIVES: This study investigates the effects of glycoprotein IIb/IIIa inhibitors (GPIs) on outcomes after percutaneous coronary intervention (PCI). BACKGROUND: Ischemic complications are reduced after PCI when a GPI is added to heparin. However, there are limited data on the safety and efficacy in contemporary PCI. METHODS: We used the National Cardiovascular Data Registry CathPCI Registry data to assess the association between GPI use and PCI outcomes for acute coronary syndrome between July 2009 and September 2011. The primary outcome was all-cause in-hospital mortality. The secondary outcome was major bleeding. To adjust for potential bias, we used multivariable logistic regression, propensity-matched (PM) analysis, and instrumental variable analysis (IVA). RESULTS: There were 970,865 patients included; 326,283 (33.6%) received a GPI. Unadjusted mortality and major bleeding were more common with a GPI (2.4% vs. 1.4% and 3.7% vs. 1.5%, respectively; p < 0.001 for both). In contrast, GPI use was associated with lower mortality on adjusted analyses; relative risks range from 0.72 (95% confidence interval [CI]: 0.50 to 0.97) with IVA to 0.90 (95% CI: 0.86 to 0.95) with PM. The association of GPI use with bleeding remained in adjusted analyses (multivariable relative risk: 1.93, 95% CI: 1.83 to 2.04; PM relative risk: 1.83, 95% CI: 1.74 to 1.92; and IVA relative risk: 1.53, 95% CI: 1.27 to 2.13). Subgroup analysis revealed enhanced risk reduction with ST-segment elevation myocardial infarction, high predicted mortality, and heparin-based anticoagulation. CONCLUSIONS: In unselected acute coronary syndrome patients undergoing PCI, GPI use was associated with reduced in-hospital mortality and increased bleeding. In the modern era of PCI, there may still be a role for the judicious use of GPIs.

Relationship between stent type and quality of life after percutaneous coronary intervention for acute myocardial infarction.

BACKGROUND: Drug-eluting stents (DES) reduce restenosis, as compared with bare-metal stents (BMS); however, the relationship between stent type and health status is unknown. We examined whether stent type was associated with health status outcomes in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: We evaluated 6- and 12-month health status in 2,694 patients with acute myocardial infarction (AMI) enrolled in the TRIUMPH and PREMIER registries who underwent PCI with DES (n = 1,361) or BMS (n = 1,333). Health status was assessed with the Seattle Angina Questionnaire, Medical Outcomes Study Short Form-12, and Patient Health Questionnaire depression scale. Propensity matching was performed to account for baseline differences in patient characteristics, resulting in a comparison cohort of 784 patients treated with DES and 784 patients treated with BMS. Both groups experienced significant improvements in health status at 6 and 12 months after PCI. Drug-eluting stent use was associated with a small improvement in Seattle Angina Questionnaire quality of life and functional limitation scores at 6 months (3.6 [95% CI 0.96-6.21], P = .007, and 3.8 [1.55-6.01], P < .001, respectively), but not at 12 months (2.3 [-0.46 to 5.03], P = .10, and 0.3 [-2.04 to 2.48], P = .85, respectively). CONCLUSIONS: In patients with AMI undergoing PCI, DES use was associated with transient but unsustained health status benefits over 12 months after AMI.

Appropriate revascularization in stable angina: lessons from the BARI 2D trial.

BACKGROUND: The 2012 Guidelines for Diagnosis and Management of Patients with Stable Ischemic Heart Disease recommend intensive antianginal and risk factor treatment (optimal medical management [OMT]) before considering revascularization to relieve symptoms. The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial randomized patients with ischemic heart disease and anatomy suitable to revascularization to (1) initial OMT with revascularization if needed or (2) initial revascularization plus OMT and found no difference in major cardiovascular events. Ultimately, however, 37.9% of the OMT group was revascularized during the 5-year follow-up period. METHODS: Data from the 1192 patients randomized to OMT were analyzed to identify subgroups in which the incidence of revascularization was so high that direct revascularization without a trial period could be justified. Multivariate logistic analysis, Cox regression models of baseline data, and a landmark analysis of participants who did not undergo revascularization at 6 months were constructed. RESULTS: The models that used only data available at the time of study entry had limited predictive value for revascularization by 6 months or by 5 years; however, the model incorporating severity of angina during the first 6 months could better predict revascularization (C statistic = 0.789). CONCLUSIONS: With the possible exception of patients with severe angina and proximal left anterior descending artery disease, this analysis supports the recommendation of the 2012 guidelines for a trial of OMT before revascularization. Patients could not be identified at the time of catheterization, but a short period of close follow-up during OMT identified the nearly 40% of patients who underwent revascularization.

Identification of novel single nucleotide polymorphisms associated with acute respiratory distress syndrome by exome-seq.

Acute respiratory distress syndrome (ARDS) is a lung condition characterized by impaired gas exchange with systemic release of inflammatory mediators, causing pulmonary inflammation, vascular leak and hypoxemia. Existing biomarkers have limited effectiveness as diagnostic and therapeutic targets. To identify disease-associating variants in ARDS patients, whole-exome sequencing was performed on 96 ARDS patients, detecting 1,382,399 SNPs. By comparing these exome data to those of the 1000 Genomes Project, we identified a number of single nucleotide polymorphisms (SNP) which are potentially associated with ARDS. 50,190SNPs were found in all case subgroups and controls, of which89 SNPs were associated with susceptibility. We validated three SNPs (rs78142040, rs9605146 and rs3848719) in additional ARDS patients to substantiate their associations with susceptibility, severity and outcome of ARDS. rs78142040 (C>T) occurs within a histone mark (intron 6) of the Arylsulfatase D gene. rs9605146 (G>A) causes a deleterious coding change (proline to leucine) in the XK, Kell blood group complex subunit-related family, member 3 gene. rs3848719 (G>A) is a synonymous SNP in the Zinc-Finger/Leucine-Zipper Co-Transducer NIF1 gene. rs78142040, rs9605146, and rs3848719 are associated significantly with susceptibility to ARDS. rs3848719 is associated with APACHE II score quartile. rs78142040 is associated with 60-day mortality in the overall ARDS patient population. Exome-seq is a powerful tool to identify potential new biomarkers for ARDS. We selectively validated three SNPs which have not been previously associated with ARDS and represent potential new genetic biomarkers for ARDS. Additional validation in larger patient populations and further exploration of underlying molecular mechanisms are warranted.

Regional pulse wave velocities and their cardiovascular risk factors among healthy middle-aged men: a cross-sectional population-based study.

BACKGROUND: Both carotid-femoral (cf) pulse wave velocity (PWV) and brachial-ankle (ba) PWV employ arterial sites that are not consistent with the path of blood flow. Few previous studies have reported the differential characteristics between cfPWV and baPWV by simultaneously comparing these with measures of pure central (aorta) and peripheral (leg) arterial stiffness, i.e., heart-femoral (hf) PWV and femoral-ankle (fa) PWV in healthy populations. We aimed to identify the degree to which these commonly used measures of cfPWV and baPWV correlate with hfPWV and faPWV, respectively, and to evaluate whether both cfPWV and baPWV are consistent with either hfPWV or faPWV in their associations with cardiovascular (CV) risk factors. METHODS: A population-based sample of healthy 784 men aged 40-49 (202 white Americans, 68 African Americans, 202 Japanese-Americans, and 282 Koreans) was examined in this cross-sectional study. Four regional PWVs were simultaneously measured by an automated tonometry/plethysmography system. RESULTS: cfPWV correlated strongly with hfPWV (r = .81, P < .001), but weakly with faPWV (r = .12, P = .001). baPWV correlated moderately with both hfPWV (r = .47, P < .001) and faPWV (r = .62, P < .001). After stepwise regression analyses with adjustments for race, cfPWV shared common significant correlates with both hfPWV and faPWV: systolic blood pressure (BP) and body mass index (BMI). However, BMI was positively associated with hfPWV and cfPWV, and negatively associated with faPWV. baPWV shared common significant correlates with hfPWV: age and systolic BP. baPWV also shared the following correlates with faPWV: systolic BP, triglycerides, and current smoking. CONCLUSIONS: Among healthy men aged 40 - 49, cfPWV correlated strongly with central PWV, and baPWV correlated with both central and peripheral PWVs. Of the CV risk factors, systolic BP was uniformly associated with all the regional PWVs. In the associations with factors other than systolic BP, cfPWV was consistent with central PWV, while baPWV was consistent with both central and peripheral PWVs.

Temporal trends and hospital variation in the management of severe hyperglycemia among patients with acute myocardial infarction in the United States.

BACKGROUND: Elevated blood glucose is associated with higher mortality in patients with acute myocardial infarction (AMI). Although clinical guidelines recommend targeted glucose control in this group, clinical trials have yielded inconclusive results. Our objective was to understand how this lack of evidence impacts the management of severe hyperglycemia in routine practice. METHODS: We examined insulin use among 4,297 AMI admissions with a mean hospitalization blood glucose of ≥200 mg/dL across 55 US hospitals from 2000 to 2008. Temporal trends and interhospital variation in 2 measures of insulin use during hospitalization-any (subcutaneous, intravenous [IV], short acting, long acting) and IV insulin-were examined using hierarchical Poisson regression models. RESULTS: Of the 4,297 admissions, 2,618 (61%) received any insulin and 538 (13%) received IV insulin. After multivariable adjustment, a slight increase in insulin use was observed per admission year (relative risk [RR] 1.06, 95% CI 1.01-1.11). There was a modest (albeit nonsignificant) increase in IV insulin use seen before May 2004 (RR 1.18, 95% CI 0.96-1.47), with no significant change thereafter (RR 0.99, 95% CI 0.92-1.09). Marked variability in insulin use was observed across hospitals (median rate ratio 1.5 [any insulin] and 1.8 [IV insulin]), which did not change over time. CONCLUSIONS: Insulin use among patients with AMI and severe hyperglycemia has remained low over the past decade, with substantial and persistent interhospital variation. These observations reflect marked clinical uncertainty with regard to glucose management in AMI, underscoring the imperative for a definitive clinical trial in this field.

Incidence and predictors of 30-day hospital readmission rate following percutaneous coronary intervention (from the National Heart, Lung, and Blood Institute Dynamic Registry).

Postdischarge outcomes after percutaneous coronary intervention (PCI) are important measurements of quality of care and complement in-hospital measurements. We sought to assess in-hospital and postdischarge PCI outcomes to (1) better understand the relation between acute and 30-day outcomes, (2) identify predictors of 30-day hospital readmission, and (3) determine the prognostic significance of 30-day hospital readmission. We analyzed in-hospital death and length of stay (LOS) and nonelective cardiac-related rehospitalization after discharge in 10,965 patients after PCI in the Dynamic Registry. From 1999 to 2006 in-hospital death rate and LOS decreased. Thirty-day cardiac readmission rate was 4.6%, with considerable variability over time and among hospitals. Risk of rehospitalization was greater in women and those with congestive heart failure, unstable angina, multiple lesions, and emergency PCI. Conversely, a lower risk of rehospitalization was associated with a larger number of treated lesions. Patients readmitted within 30 days had higher 1-year mortality than those free from hospital readmission. In conclusion, although in-hospital mortality and LOS after PCI have decreased over time, the observed 30-day cardiac readmission rate was highly variable and risk of readmission was more closely associated with underlying patient characteristics than procedural characteristics.

Use of drug-eluting stents as a function of predicted benefit: clinical and economic implications of current practice.

BACKGROUND: Benefits of drug-eluting stents (DES) in percutaneous coronary intervention (PCI) are greatest in those at the highest risk of target-vessel revascularization (TVR). Drug-eluting stents cost more than bare-metal stents (BMS) and necessitate prolonged dual antiplatelet therapy (DAPT), which increases costs, bleeding risk, and risk of complications if DAPT is prematurely discontinued. Our objective was to assess whether DES are preferentially used in patients with higher predicted TVR risk and to estimate if lower use of DES in low-TVR-risk patients would be more cost-effective than the existing DES use pattern. METHODS: We analyzed more than 1.5 million PCI procedures in the National Cardiovascular Data Registry (NCDR) CathPCI registry from 2004 through 2010 and estimated 1-year TVR risk with BMS using a validated model. We examined the association between TVR risk and DES use and the cost-effectiveness of lower DES use in low-TVR-risk patients (50% less DES use among patients with <10% TVR risk) compared with existing DES use. RESULTS: There was marked variation in physicians' use of DES (range 2%-100%). Use of DES was high across all predicted TVR risk categories (73.9% in TVR risk <10%; 78.0% in TVR risk 10%-20%; and 83.2% in TVR risk >20%), with a modest relationship between TVR risk and DES use (relative risk, 1.005 per 1% increase in TVR risk [95% CI, 1.005-1.006]). Reducing DES use by 50% in low-TVR-risk patients was projected to lower US health care costs by $205 million per year while increasing the overall TVR event rate by 0.5% (95% CI, 0.49%-0.51%) in absolute terms. CONCLUSIONS: Use of DES in the United States varies widely among physicians, with only a modest correlation to patients' risk of restenosis. Less DES use among patients with low risk of restenosis has the potential for significant cost savings for the US health care system while minimally increasing restenosis events.

Glucose variability and mortality in patients hospitalized with acute myocardial infarction.

BACKGROUND: Mean blood glucose (BG) during acute myocardial infarction (AMI) is an important predictor of inpatient mortality but does not capture glucose variability (GV), which has been shown to be independently associated with mortality in critically ill patients. Whether GV is associated with in-hospital mortality during AMI, after accounting for mean BG, is unknown. METHODS AND RESULTS: We analyzed 18 563 consecutive patients with AMI with ≥3 BGs in the first 48 hours admitted to 61 US hospitals from 2000 to 2008. Five different GV metrics were compared for their ability to predict in-hospital mortality (range, standard deviation, mean amplitude of glycemic excursions, mean absolute glucose change, and average daily risk range) using hierarchical logistic regression models that sequentially adjusted for mean BG, hypoglycemia (<70 mg/dL), and multiple patient characteristics. In unadjusted analyses, range and average daily risk range had the highest C-indices (0.620 for range, 0.635 for average daily risk range; both P<0.0001). Greater GV was associated with higher mortality for all metrics (eg, mortality was 3.8%, 5.5%, 7.1%, and 11.3% for increasing quartiles of range, P<0.0001); however, the association between GV and mortality for each metric was no longer significant after multivariable adjustment. In contrast, mean BG remained an important predictor of survival (P<0.001, all models). CONCLUSIONS: Although greater GV is associated with increased risk of in-hospital mortality in patients with AMI in unadjusted analyses, GV is no longer independently predictive after controlling for multiple patient factors, including mean BG. These findings suggest that GV does not provide additional prognostic value above and beyond already recognized risk factors for mortality during AMI.

Global variation in the prevalence of elevated cholesterol in outpatients with established vascular disease or 3 cardiovascular risk factors according to national indices of economic development and health system performance.

BACKGROUND: Elevated serum cholesterol accounts for a considerable proportion of cardiovascular disease worldwide. An understanding of the relationship between country-level economic and health system factors and elevated cholesterol may provide insight for prioritization of cardiovascular prevention programs. METHODS AND RESULTS: Using hierarchical models, we examined the relationship between elevated total cholesterol (>200 mg/dL) in 53 570 outpatients from 36 countries, and tertiles of several country-level indices: (1) gross national income, (2) total expenditure on health as percentage of gross domestic product, (3) government expenditure on health as percentage of total expenditure on health, (4) out-of-pocket expenditures as percentage of private expenditure on health, and the World Health Organization indices of (5) Health System Achievement and (6) Performance/Efficiency. Overall, 38% of outpatients had total cholesterol >200 mg/dL (>5.18 mmol/L), and 9.3% of the total variability in elevated cholesterol was at the country level; this proportion was higher for patients with (12.1%) versus without (7.4%) history of hyperlipidemia. Among patients with history of hyperlipidemia, countries in the highest tertile of gross national income or World Health Organization Health System Achievement had lower odds of elevated cholesterol than lower tertiles (P<0.001, for both). Countries in the highest tertile of out-of-pocket health expenditures had higher odds of elevated cholesterol than those in the lowest tertile (P<0.001). No significant associations were found for patients without history of hyperlipidemia. CONCLUSIONS: Global variations in the prevalence of elevated cholesterol among patients with history of hyperlipidemia are associated with country-level economic development and health system indices. These results support the need for strengthening efforts toward effective cardiovascular disease prevention and control and may provide insight for health policy setting at the national level.

Trends in the incidence of acute kidney injury in patients hospitalized with acute myocardial infarction.

BACKGROUND: Acute kidney injury (AKI) is common in patients with acute myocardial infarction (AMI) and is associated with permanent renal impairment and death. Although guidelines increasingly emphasize AKI prevention, whether increased awareness has translated into reduced AKI rates is unclear. METHODS: Among 33,249 consecutive hospitalizations in 31,532 unselected patients with AMI across 56 US centers from Cerner Corporation's Health Facts database, we examined the temporal trends in AKI incidence from 2000 to 2008. Acute kidney injury was defined as an absolute increase in creatinine level of at least 0.3 mg/dL or a relative increase of at least 50% during hospitalization. RESULTS: From 2000 to 2008, the mean age of patients increased (from 66.5 to 68.6 years), as did the known AKI risk factors, including chronic kidney disease, cardiogenic shock, diabetes mellitus, heart failure, coronary angiography, and percutaneous coronary intervention. Despite this, AKI incidence declined from 26.6% in 2000 to 19.7% in 2008 (P < .001). After multivariate adjustment, the trend of decreasing AKI rates persisted (4.4% decline per year; P < .001). In addition, in-hospital mortality also declined over time among patients developing AKI, from 19.9% in 2000 to 13.8% in 2008 (P = .003). CONCLUSIONS: In a large national study, AKI incidence in patients hospitalized with AMI declined significantly from 2000 to 2008 despite the aging population and rising prevalence of AKI risk factors. These findings may reflect increased clinician awareness, better risk stratification, or greater use of AKI prevention efforts during this time period.

Serum potassium levels and mortality in acute myocardial infarction.

CONTEXT: Clinical practice guidelines recommend maintaining serum potassium levels between 4.0 and 5.0 mEq/L in patients with acute myocardial infarction (AMI). These guidelines are based on small studies that associated low potassium levels with ventricular arrhythmias in the pre-ß-blocker and prereperfusion era. Current studies examining the relationship between potassium levels and mortality in AMI patients are lacking. OBJECTIVE: To determine the relationship between serum potassium levels and in-hospital mortality in AMI patients in the era of ß-blocker and reperfusion therapy. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study using the Cerner Health Facts database, which included 38,689 patients with biomarker-confirmed AMI, admitted to 67 US hospitals between January 1, 2000, and December 31, 2008. All patients had in-hospital serum potassium measurements and were categorized by mean postadmission serum potassium level (<3.0, 3.0-<3.5, 3.5-<4.0, 4.0-<4.5, 4.5-<5.0, 5.0-<5.5, and ≥5.5 mEq/L). Hierarchical logistic regression was used to determine the association between potassium levels and outcomes after adjusting for patient- and hospital-level factors. MAIN OUTCOME MEASURES: All-cause in-hospital mortality and the composite of ventricular fibrillation or cardiac arrest. RESULTS: There was a U-shaped relationship between mean postadmission serum potassium level and in-hospital mortality that persisted after multivariable adjustment. Compared with the reference group of 3.5 to less than 4.0 mEq/L (mortality rate, 4.8%; 95% CI, 4.4%-5.2%), mortality was comparable for mean postadmission potassium of 4.0 to less than 4.5 mEq/L (5.0%; 95% CI, 4.7%-5.3%), multivariable-adjusted odds ratio (OR), 1.19 (95% CI, 1.04-1.36). Mortality was twice as great for potassium of 4.5 to less than 5.0 mEq/L (10.0%; 95% CI, 9.1%-10.9%; multivariable-adjusted OR, 1.99; 95% CI, 1.68-2.36), and even greater for higher potassium strata. Similarly, mortality rates were higher for potassium levels of less than 3.5 mEq/L. In contrast, rates of ventricular fibrillation or cardiac arrest were higher only among patients with potassium levels of less than 3.0 mEq/L and at levels of 5.0 mEq/L or greater. CONCLUSION: Among inpatients with AMI, the lowest mortality was observed in those with postadmission serum potassium levels between 3.5 and <4.5 mEq/L compared with those who had higher or lower potassium levels.

Survival benefit with drug-eluting stents in observational studies: fact or artifact?

BACKGROUND: Recently, there has been increased interest in leveraging observational studies for comparative effectiveness research. Without robust and valid risk adjustment, however, findings from these nonrandomized studies may remain biased. Previous studies examining long-term mortality with drug-eluting stents (DESs) have demonstrated discordant results between randomized trials and observational studies. To examine the impact of treatment selection bias on these findings, we used data from a prospective percutaneous coronary intervention (PCI) registry (EVENT [Evaluation of Drug Eluting Stents and Ischemic Events]) to compare clinical outcomes between DESs and bare metal stents (BMSs) using conventional (multivariable regression and propensity matching) and novel (instrumental variable analysis) risk-adjustment techniques. METHODS AND RESULTS: The study population consisted of 9266 patients who underwent nonemergent PCI with stent placement at 55 US centers between 2004 and 2007. All-cause mortality and target lesion revascularization (TLR) were assessed prospectively over 1 year of follow-up. Overall, 8171 patients (88%) received DES, but this proportion substantially differed by treatment year (93% in 2004-2006 and 73% in 2007; P<0.001). One-year rates of death and TLR were significantly lower with DES versus BMS (death, 2.5% versus 5.6%; TLR, 4.2% versus 6.9%; P<0.001 for both), findings that persisted in both multivariable-adjusted and propensity-matched analyses. In contrast, instrumental variable analysis, using enrollment period (2004-2006 versus 2007) as the instrument, demonstrated no significant difference in 1-year mortality (predicted absolute difference, 2.0%; 95% CI, -1.8% to 5.7%; P=0.30) and a strong trend toward reduced TLR with DES use (predicted absolute difference, -4.2%; 95% CI, -8.8% to 0.4%; P=0.07). CONCLUSIONS: Among unselected PCI patients in contemporary practice, DES use tended to be associated with a consistent reduction in TLR regardless of risk-adjustment method but showed discordant effects on mortality with conventional risk adjustment compared with instrumentable variable analysis. These findings underscore the limitations of standard risk-adjustment methods to adequately address treatment selection bias in nonrandomized studies and have important implications for comparative effectiveness research using observational data.

Clinical and economic outcomes of liberal versus selective drug-eluting stent use: insights from temporal analysis of the multicenter Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) registry.

BACKGROUND: Although the benefits of drug-eluting stents (DES) for reducing restenosis after percutaneous coronary intervention are well established, the impact of alternative rates of DES use on population-level outcomes is unknown. METHODS AND RESULTS: We used data from the Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) registry to examine the clinical impact and cost-effectiveness of varying DES use rates in routine care. Between 2004 and 2007, 10,144 patients undergoing percutaneous coronary intervention were enrolled in the EVENT registry at 55 US centers. Clinical outcomes and cardiovascular-specific costs were assessed prospectively over 1 year of follow-up. Use of DES decreased from 92 in 2004 to 2006 (liberal use era; n=7587) to 68 in 2007 (selective use era; n=2557; P<0.001). One-year rates of death or myocardial infarction were similar in both eras. Over this time period, the incidence of target lesion revascularization increased from 4.1 to 5.1, an absolute increase of 1.0 (95 confidence interval, 0.1 to 1.9; P=0.03), whereas total cardiovascular costs per patient decreased by $401 (95 confidence interval, 131 to 671; P=0.004). The risk-adjusted incremental cost-effectiveness ratio for the liberal versus selective DES era was $16,000 per target lesion revascularization event avoided, $27,000 per repeat revascularization avoided, and $433 000 per quality-adjusted life-year gained. CONCLUSIONS: In this prospective registry, a temporal reduction in DES use was associated with a small increase in target lesion revascularization and a modest reduction in total cardiovascular costs. These findings suggest that although clinical outcomes are marginally better with unrestricted DES use, this approach represents a relatively inefficient use of healthcare resources relative to several common benchmarks for cost-effective care.

The prevalence and predictors of an abnormal ankle-brachial index in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

OBJECTIVE: To examine ankle-brachial index (ABI) abnormalities in patients with type 2 diabetes and coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: An ABI was obtained in 2,240 patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial. ABIs were classified as: normal, 0.91-1.3; low, ≤ 0.9; high, >1.3; or noncompressible artery (NC). Baseline characteristics were examined according to ABI and by multivariate analysis. RESULTS ABI was normal in 66%, low in 19%, and high in 8% of patients, and 6% of patients had NC. Of the low ABI patients, 68% were asymptomatic. Using normal ABI as referent, low ABI was independently associated with smoking, female sex, black race, hypertension, age, C-reactive protein, diabetes duration, and lower BMI. High ABI was associated with male sex, nonblack race, and higher BMI; and NC artery was associated with diabetes duration, higher BMI, and hypertension. CONCLUSIONS: ABI abnormalities are common and often asymptomatic in patients with type 2 diabetes and CAD.