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Background The plasma concentration of B-type natriuretic peptide (BNP) is a strong predictor of adverse cardiovascular events. The aim of this study was to determine whether the association between plasma BNP concentration and cardiovascular mortality is sustained or diminishes with increasing time after BNP is measured. Methods and Results Six thousand seven hundred forty patients with a history of myocardial infarction or unstable angina who participated in the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) trial had plasma BNP concentration measured at baseline and after 1 year. Associations with cardiovascular mortality were evaluated in landmark analyses 1 to <5, 5 to <10, and 10 to 16 years after randomization. There were 1640 cardiovascular deaths. The cardiovascular mortality rate increased progressively from 10.2 to 19.1 to 26.3/1000 patient-years from 1 to <5, 5 to <10, and 10 to 16 years after baseline, respectively. The average of baseline and 1-year BNP concentration was more strongly associated with cardiovascular mortality compared with baseline or 1-year BNP only. The hazard ratio (HR) for cardiovascular death associated with each doubling of average BNP concentration was similar during years 1 to <5 (HR, 1.53 [95% CI, 1.44-1.63]), years 5 to <10 (HR, 1.52 [95% CI, 1.44-1.60]), and years 10-16 (HR, 1.43 [95% CI, 1.36-1.50]), P <0.0001 for all. Conclusions BNP concentration remains an independent predictor of cardiovascular mortality more than a decade after it is measured. Because of random variation in plasma concentrations, the average of >1 BNP measurement improves long-term risk prediction.

Background Elevated plasma cystatin C levels reflect reduced renal function and increased cardiovascular risk. Less is known about whether the increased risk persists long-term or is independent of renal function and other important biomarkers. Methods and Results Cystatin C and other biomarkers were measured at baseline (in 7863 patients) and 1 year later (in 6106 patients) in participants in the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) study, who had a previous acute coronary syndrome. Outcomes were ascertained during the study (median follow-up, 6 years) and long-term (median follow-up, 16 years). Glomerular filtration rate (GFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration equations (first GFR-creatinine, then GFR-creatinine-cystatin C). Over 6 years, in fully adjusted multivariable time-to-event models, with respect to the primary end point of coronary heart disease mortality or nonfatal myocardial infarction, for comparison of Quartile 4 versus 1 of baseline cystatin C, the hazard ratio was 1.37 (95% CI, 1.07-1.74; P =0.01), and for major cardiovascular events was 1.47 (95% CI, 1.19-1.82; P <0.001). Over 16 years, the association of baseline cystatin C with coronary heart disease, cardiovascular, and all-cause mortality persisted (each P <0.001) and remained significant after adjustment for estimated GFR-creatinine-cystatin C. Cystatin C also predicted the development of chronic kidney disease for 6 years (odds ratio, 6.61; 95% CI, 4.28-10.20) independently of estimated GFR-creatinine and other risk factors. However, this association was no longer significant after adjustment for estimated GFR-creatinine-cystatin C. Conclusions Cystatin C independently predicted major cardiovascular events, development of chronic kidney disease, and cardiovascular and all-cause mortality. Prediction of long-term mortality was independent of improved estimation of GFR. Registration URL: https://anzctr.org.au; Unique identifier: ACTRN12616000535471.

Importance: Studies have shown that adverse events are associated with increasing inpatient care expenditures, but contemporary data on the association between expenditures and adverse events beyond inpatient care are limited., Objective: To evaluate whether hospital-specific adverse event rates are associated with hospital-specific risk-standardized 30-day episode-of-care Medicare expenditures for fee-for-service patients discharged with acute myocardial infarction (AMI), heart failure (HF), or pneumonia., Design, Setting, and Participants: This cross-sectional study used the 2011 to 2016 hospital-specific risk-standardized 30-day episode-of-care expenditure data from the Centers for Medicare & Medicaid Services and medical record-abstracted in-hospital adverse event data from the Medicare Patient Safety Monitoring System. The setting was acute care hospitals treating at least 25 Medicare fee-for-service patients for AMI, HF, or pneumonia in the United States. Participants were Medicare fee-for-service patients 65 years or older hospitalized for AMI, HF, or pneumonia included in the Medicare Patient Safety Monitoring System in 2011 to 2016. The dates of analysis were July 16, 2017, to May 21, 2018., Main Outcomes and Measures: Hospitals' risk-standardized 30-day episode-of-care expenditures and the rate of occurrence of adverse events for which patients were at risk., Results: The final study sample from 2194 unique hospitals included 44 807 patients (26.1% AMI, 35.6% HF, and 38.3% pneumonia) with a mean (SD) age of 79.4 (8.6) years, and 52.0% were women. The patients represented 84 766 exposures for AMI, 96 917 exposures for HF, and 109 641 exposures for pneumonia. Patient characteristics varied by condition but not by expenditure category. The mean (SD) risk-standardized expenditures were $22 985 ($1579) for AMI, $16 020 ($1416) for HF, and $16 355 ($1995) for pneumonia per hospitalization. The mean risk-standardized rates of occurrence of adverse events for which patients were at risk were 3.5% (95% CI, 3.4%-3.6%) for AMI, 2.5% (95% CI, 2.5%-2.5%) for HF, and 3.0% (95% CI, 2.9%-3.0%) for pneumonia. An increase by 1 percentage point in the rate of occurrence of adverse events was associated with an increase in risk-standardized expenditures of $103 (95% CI, $57-$150) for AMI, $100 (95% CI, $29-$172) for HF, and $152 (95% CI, $73-$232) for pneumonia per discharge., Conclusions and Relevance: Hospitals with high adverse event rates were more likely to have high 30-day episode-of-care Medicare expenditures for patients discharged with AMI, HF, or pneumonia.

Background: Little is known regarding the relationship between hospital performance on adverse event rates and hospital performance on 30-day mortality and unplanned readmission rates for Medicare fee-for-service patients hospitalized for acute myocardial infarction (AMI)., Methods and Results: Using 2009-2013 medical record-abstracted patient safety data from the Agency for Healthcare Research and Quality's Medicare Patient Safety Monitoring System and hospital mortality and readmission data from the Centers for Medicare & Medicaid Services, we fitted a mixed-effects model, adjusting for hospital characteristics, to evaluate whether hospital performance on patient safety, as measured by the hospital-specific risk-standardized occurrence rate of 21 common adverse event measures for which patients were at risk, is associated with hospital-specific 30-day all-cause risk-standardized mortality and unplanned readmission rates for Medicare patients with AMI. The unit of analysis was at the hospital level. The final sample included 793 acute care hospitals that treated 30 or more Medicare patients hospitalized for AMI and had 40 or more adverse events for which patients were at risk. The occurrence rate of adverse events for which patients were at risk was 3.8%. A 1% point change in the risk-standardized occurrence rate of adverse events was associated with average changes in the same direction of 4.86% points (95% CI, 0.79-8.94) and 3.44% points (95% CI, 0.19-6.68) for the risk-standardized mortality and unplanned readmission rates, respectively., Conclusions: For Medicare fee-for-service patients discharged with AMI, hospitals with poorer patient safety performance were also more likely to have poorer performance on 30-day all-cause mortality and on unplanned readmissions., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objectives: This study sought to assess whether baseline and change in contemporary sensitive troponin I (TnI) levels predicts coronary heart disease (CHD) death and myocardial infarction (MI), and to determine the effects of pravastatin on TnI levels., Background: The role of troponins in predicting long-term outcomes in patients with stable CHD is not clearly defined., Methods: The LIPID (Long-Term Intervention With Pravastatin in Ischaemic Disease) study randomized patients with cholesterol levels of 155 to 271 mg/dl 3 to 36 months after MI or unstable angina to placebo or pravastatin 40 mg per day. TnI levels were measured at baseline and after 1 year in 7,863 patients. Median follow-up was 6 years. Change in TnI was defined as moving up or down 1 tertile or ≥50% change., Results: Baseline TnI tertiles were <0.006 ng/ml, 0.006 to <0.018 ng/ml, and ≥0.018 ng/ml. TnI levels were related to CHD death and MI after adjustment for 23 risk factors and treatment (≥0.018 ng/ml vs. <0.006 ng/ml hazard ratio [HR]: 1.64; 95% CI: 1.41 to 1.90; p < 0.001). TnI levels increased in 23.0%, were unchanged in 51.3%, and decreased in 25.7% of patients. Pravastatin decreased TnI levels by 0.003 ng/ml versus placebo (p = 0.002). In landmark analyses, increases in TnI levels were associated with increased numbers of CHD death and MI (HR: 1.31; 95% CI: 1.06 to 1.62) and decreases with decreased risk (HR: 0.90; 95% CI: 0.74 to 1.09; overall p = 0.01). Data were similar with 50% change criteria. Net reclassification improvement by adding TnI to the baseline model for CHD death and MI was 4.8% (p = 0.01)., Conclusions: Baseline TnI levels and change at 1 year are independent predictors of CHD death and MI. TnI levels are strong predictors of risk, and change modifies risk., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with coronary heart disease (CHD) in healthy individuals and in patients who have had ischemic events., Methods and Results: The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study randomized 9014 patients with cholesterol levels of 4.0 to 7.0 mmol/L to placebo or pravastatin 3 to 36 months after myocardial infarction or unstable angina and showed a reduction in CHD and total mortality. We assessed the value of baseline and change in Lp-PLA2 activity to predict outcomes over a 6-year follow-up, the effect of pravastatin on Lp-PLA2 levels, and whether pravastatin treatment effect was related to Lp-PLA2 activity change. Lp-PLA2 was measured at randomization and 1 year, and levels were grouped as quartiles. The prespecified end point was CHD death or nonfatal myocardial infarction. Baseline Lp-PLA2 activity was positively associated with CHD events (P < 0.001) but not after adjustment for 23 baseline factors (P = 0.66). In 6518 patients who were event free at 1 year, change in Lp-PLA2 was a significant independent predictor of subsequent CHD events after adjustment for these risk factors, including LDL cholesterol and LDL cholesterol changes (P < 0.001). Pravastatin reduced Lp-PLA2 by 16% compared with placebo (P < 0.001). After adjustment for Lp-PLA2 change, the pravastatin treatment effect was reduced from 23% to 10% (P = 0.26), with 59% of the treatment effect accounted for by changes in Lp-PLA2. Similar reductions in treatment effect were seen after adjustment for LDL cholesterol change., Conclusion: Reduction in Lp-PLA2 activity during the first year was a highly significant predictor of CHD events, independent of change in LDL cholesterol, and may account for over half of the benefits of pravastatin in the LIPID study.

Background: Traditional methods for analyzing clinical and epidemiological cohort study data have been focused on the first occurrence of a health outcome. However, in many situations, recurrent event data are frequently observed. It is inefficient to use methods for the analysis of first events to analyse recurrent event data., Methods: We applied several semi-parametric proportional hazards models to analyze the risk of recurrent myocardial infarction (MI) events based on data from a very large randomized placebo-controlled trial of cholesterol-lowering drug. The backward selection procedure was used to select the significant risk factors in a model. The best fitting model was selected using the log-likelihood ratio test, Akaike Information and Bayesian Information Criteria., Results: A total of 8557 persons were included in the LIPID study. Risk factors such as age, smoking status, total cholesterol and high density lipoprotein cholesterol levels, qualifying event for the acute coronary syndrome, revascularization, history of stroke or diabetes, angina grade and treatment with pravastatin were significant for development of both first and subsequent MI events. No significant difference was found for the effects of these risk factors between the first and subsequent MI events. The significant risk factors selected in this study were the same as those selected by the parametric conditional frailty model. Estimates of the relative risks and 95% confidence intervals were also similar between these two methods., Conclusions: Our study shows the usefulness and convenience of the semi-parametric proportional hazards models for the analysis of recurrent event data, especially in estimation of regression coefficients and cumulative risks.

Aims: To determine the incidence and predictors of, and effects of fenofibrate on silent myocardial infarction (MI) in a large contemporary cohort of patients with type 2 diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study., Methods and Results: Routine electrocardiograms taken throughout the study were assessed by Minnesota-code criteria for the presence of new Q-waves without clinical presentation and analysed with blinding to treatment allocation and clinical outcome. Of all MIs, 36.8% were silent. Being male, older age, longer diabetes duration, prior cardiovascular disease (CVD), neuropathy, higher HbA(1c), albuminuria, high serum creatinine, and insulin use all significantly predicted risk of clinical or silent MI. Fenofibrate reduced MI (clinical or silent) by 19% [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69-0.94; P = 0.006], non-fatal clinical MI by 24% (P = 0.01), and silent MI by 16% (P = 0.16). Among those having silent MI, fenofibrate reduced subsequent clinical CVD events by 78% (HR 0.22, 95% CI 0.08-0.65; P = 0.003)., Conclusion: Silent and clinical MI have similar risk factors and increase the risk of future CVD events. Fenofibrate reduces the risk of a first MI and substantially reduces the risk of further clinical CVD events after silent MI, supporting its use in type 2 diabetes.

Background: Tobacco use is one of the major avoidable causes of cardiovascular diseases. We aimed to assess the risks associated with tobacco use (both smoking and non-smoking) and second hand tobacco smoke (SHS) worldwide., Methods: We did a standardised case-control study of acute myocardial infarction (AMI) with 27,089 participants in 52 countries (12,461 cases, 14,637 controls). We assessed relation between risk of AMI and current or former smoking, type of tobacco, amount smoked, effect of smokeless tobacco, and exposure to SHS. We controlled for confounders such as differences in lifestyles between smokers and non-smokers., Findings: Current smoking was associated with a greater risk of non-fatal AMI (odds ratio [OR] 2.95, 95% CI 2.77-3.14, p<0.0001) compared with never smoking; risk increased by 5.6% for every additional cigarette smoked. The OR associated with former smoking fell to 1.87 (95% CI 1.55-2.24) within 3 years of quitting. A residual excess risk remained 20 or more years after quitting (1.22, 1.09-1.37). Exclusion of individuals exposed to SHS in the never smoker reference group raised the risk in former smokers by about 10%. Smoking beedies alone (indigenous to South Asia) was associated with increased risk (2.89, 2.11-3.96) similar to that associated with cigarette smoking. Chewing tobacco alone was associated with OR 2.23 (1.41-3.52), and smokers who also chewed tobacco had the highest increase in risk (4.09, 2.98-5.61). SHS was associated with a graded increase in risk related to exposure; OR was 1.24 (1.17-1.32) in individuals who were least exposed (1-7 h per week) and 1.62 (1.45-1.81) in people who were most exposed (>21 h per week). Young male current smokers had the highest population attributable risk (58.3%; 95% CI 55.0-61.6) and older women the lowest (6.2%, 4.1-9.2). Population attributable risk for exposure to SHS for more than 1 h per week in never smokers was 15.4% (12.1-19.3)., Conclusion: Tobacco use is one of the most important causes of AMI globally, especially in men. All forms of tobacco use, including different types of smoking and chewing tobacco and inhalation of SHS, should be discouraged to prevent cardiovascular diseases.

Background: We compared cost-effectiveness of pravastatin in a placebo-controlled trial in 5500 younger (31-64 years) and 3514 older patients (65-74 years) with previous acute coronary syndromes., Methods: Hospitalizations and long-term medication within the 6 years of the trial were estimated in all patients . Drug dosage, nursing home, and ambulatory care costs were estimated from substudies. Incremental costs per life saved of pravastatin relative to placebo were estimated from treatment effects and resource use., Results: Over 6 years, pravastatin reduced all-cause mortality by 4.3% in the older patients and by 2.3% in the younger patients. Older patients assigned pravastatin had marginally lower cost of pravastatin and other medication over 6 years (A dollar 4442 vs A dollar 4637), but greater cost offsets (A dollar 2061 vs A dollar 897) from lower rates of hospitalizations. The incremental cost per life saved with pravastatin was A dollar 55500 in the old and A dollar 167200 in the young. Assuming no treatment effect beyond the study period, the life expectancy to age 82 years of additional survivors was 9.1 years in the older and 17.3 years in the younger. Estimated additional life-years saved from pravastatin therapy were 0.39 years for older and 0.40 years for younger patients. Incremental costs per life-year saved were A dollar 7581 in the older and A dollar 14944 in the younger, if discounted at 5% per annum., Conclusions: Pravastatin therapy was more cost-effective among older than younger patients, because of their higher baseline risk and greater cost offsets, despite their shorter life expectancy.

Context: Patients with unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI) can be cared for with a routine invasive strategy involving coronary angiography and revascularization or more conservatively with a selective invasive strategy in which only those with recurrent or inducible ischemia are referred for acute intervention., Objective: To conduct a meta-analysis that compares benefits and risks of routine invasive vs selective invasive strategies., Data Sources: Randomized controlled trials identified through search of MEDLINE and the Cochrane databases (1970 through June 2004) and hand searching of cross-references from original articles and reviews., Study Selection: Trials were included that involved patients with unstable angina or NSTEMI who received a routine invasive or a selective invasive strategy., Data Extraction: Major outcomes of death and myocardial infarction (MI) occurring from initial hospitalization to the end of follow-up were extracted from published results of eligible trials., Data Synthesis: A total of 7 trials (N = 9212 patients) were eligible. Overall, death or MI was reduced from 663 (14.4%) of 4604 patients in the selective invasive group to 561 (12.2%) of 4608 patients in the routine invasive group (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.72-0.93; P = .001). There was a nonsignificant trend toward fewer deaths (6.0% vs 5.5%; OR, 0.92; 95% CI, 0.77-1.09; P = .33) and a significant reduction in MI alone (9.4% vs 7.3%; OR, 0.75; 95% CI, 0.65-0.88; P<.001). Higher-risk patients with elevated cardiac biomarker levels at baseline benefited more from routine intervention, with no significant benefit observed in lower-risk patients with negative baseline marker levels. During the initial hospitalization, a routine invasive strategy was associated with a significantly higher early mortality (1.1% vs 1.8% for selective vs routine, respectively; OR, 1.60; 95% CI, 1.14-2.25; P = .007) and the composite of death or MI (3.8% vs 5.2%; OR, 1.36; 95% CI, 1.12-1.66; P = .002). But after discharge, the routine invasive strategy was associated with fewer subsequent deaths (4.9% vs 3.8%; OR, 0.76; 95% CI, 0.62-0.94; P = .01) and the composite of death or MI (11.0% vs 7.4%; OR, 0.64; 95% CI, 0.56-0.75; P<.001). At the end of follow-up, there was a 33% reduction in severe angina (14.0% vs 11.2%; OR, 0.77; 95% CI, 0.68-0.87; P<.001) and a 34% reduction in rehospitalization (41.3% vs 32.5%; OR, 0.66; 95% CI, 0.60-0.72; P<.001) with a routine invasive strategy., Conclusions: A routine invasive strategy exceeded a selective invasive strategy in reducing MI, severe angina, and rehospitalization over a mean follow-up of 17 months. But routine intervention was associated with a higher early mortality hazard and a trend toward a mortality reduction at follow-up. Future strategies should explore ways to minimize the early hazard and enhance later benefits by focusing on higher-risk patients and optimizing timing of intervention and use of proven therapies.

Background: Acute coronary syndrome continues to have significant long-term morbidity and mortality. This study sought to compare baseline characteristics, practice patterns and clinical outcomes for patients with non-ST elevation acute coronary syndrome from a broad range of low-, middle- and high-income countries., Methods and Results: We compared the data from a prospective registry of patients with non-ST elevation acute coronary syndrome involving 4615 patients from 65 centers in 8 low and middle income countries (OASIS registry 2) with those obtained from 7987 patients from 95 centers in 6 middle and high income countries (OASIS registry 1). Patients in the OASIS registry 2 were younger, were more often males and smokers, presented later to the hospital after symptom onset and had a lower prevalence of diabetes at admission [with the exception of India, which had the highest age-adjusted prevalence (39.1%)]. There were marked variations in the angiography and intervention rates during the hospital stay, but the uses of proven pharmacological therapies were comparable. The two-year mortality rates adjusted for baseline covariates ranged from 6.9% to 15%. Patients from China had the lowest two-year mortality rate (6.9%) and patients from India had the highest rate (15%). Combining the two registries, the covariate-adjusted rate of death or myocardial infarction did not differ across countries with in-hospital angiographic rates of > or = 50% (17.1%), 25-49% (16.7%) or < 25% (16.5%). However, the covariate-adjusted rates for subsequent myocardial infarction (7.6%, 9.2% and 10.8% respectively, p < 0.0001), refractory angina (21.3%, 27.7% and 35.4% respectively, p < 0.0001) and the composite of death, myocardial infarction or refractory angina (34.9%, 40.7% and 46.8% respectively, p < 0.0001) differed depending on the angiographic rates., Conclusions: Among the participating countries there was a marked heterogeneity in patient characteristics, coronary interventions, resulting in differences in the two-year composite rates of death, myocardial infarction and refractory angina among patients admitted with non-ST elevation acute coronary syndrome.

Background: The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial showed that pravastatin significantly reduced mortality and coronary heart disease (CHD) events in 9014 patients with known CHD and total cholesterol 4.0 to 7.0 mmol/L at baseline. Secondary objectives included assessment of CHD event reduction according to lipid levels., Methods and Results: We investigated the relationships of baseline and on-study lipids with subsequent CHD events in separate Cox models. Treatment effect on CHD event reduction was examined by baseline lipids and after adjustment for on-study lipid levels. Baseline lipids were significant predictors of CHD events. The adjusted relative risk per mmol/L (on placebo) was 1.24 (P=0.004) for total cholesterol, 1.28 (P=0.002) for low-density lipoprotein cholesterol, and 0.52 (P=0.004) for high-density lipoprotein cholesterol. Apolipoproteins A1 and B were strong predictors (each P=0.001). Pravastatin reduced the risk of the composite outcome of fatal CHD or nonfatal myocardial infarction by 24% (95% confidence interval [CI], 15% to 32%) and the expanded end point of fatal CHD, nonfatal myocardial infarction, unstable angina, or coronary revascularization by 17% (95% CI, 10% to 24%). Similar relative effects were observed for different categories of baseline lipids. The proportion of treatment effect explained by on-study lipid levels was 67% (95% CI, 27% to 106%) for the composite and 97% (95% CI, 49% to 145%) for the expanded end point. The most important lipids associated with event reduction were apolipoprotein B, low-density lipoprotein cholesterol, and the combination of total and high-density lipoprotein cholesterol., Conclusions: Changes in lipid levels can explain all or most of the observed benefit of pravastatin. Some treatment effect may also be mediated through nonlipid changes.

Importance: Patient safety is a US national priority, yet lacks a comprehensive assessment of progress over the past decade.Objective: To determine the change in the rate of adverse events in hospitalized patients.Design, Setting, and Participants: This serial cross-sectional study used data from the Medicare Patient Safety Monitoring System from 2010 to 2019 to assess in-hospital adverse events in patients. The study included 244 542 adult patients hospitalized in 3156 US acute care hospitals across 4 condition groups from 2010 through 2019: acute myocardial infarction (17%), heart failure (17%), pneumonia (21%), and major surgical procedures (22%); and patients hospitalized from 2012 through 2019 for all other conditions (22%).Exposures: Adults aged 18 years or older hospitalized during each included calendar year.Main Outcomes and Measures: Information on adverse events (abstracted from medical records) included 21 measures across 4 adverse event domains: adverse drug events, hospital-acquired infections, adverse events after a procedure, and general adverse events (hospital-acquired pressure ulcers and falls). The outcomes were the total change over time for the observed and risk-adjusted adverse event rates in the subpopulations.Results: The study sample included 190 286 hospital discharges combined in the 4 condition-based groups of acute myocardial infarction, heart failure, pneumonia, and major surgical procedures (mean age, 68.0 [SD, 15.9] years; 52.6% were female) and 54 256 hospital discharges for the group including all other conditions (mean age, 57.7 [SD, 20.7] years; 59.8% were female) from 3156 acute care hospitals across the US. From 2010 to 2019, the total change was from 218 to 139 adverse events per 1000 discharges for acute myocardial infarction, from 168 to 116 adverse events per 1000 discharges for heart failure, from 195 to 119 adverse events per 1000 discharges for pneumonia, and from 204 to 130 adverse events per 1000 discharges for major surgical procedures. From 2012 to 2019, the rate of adverse events for all other conditions remained unchanged at 70 adverse events per 1000 discharges. After adjustment for patient and hospital characteristics, the annual change represented by relative risk in all adverse events per 1000 discharges was 0.94 (95% CI, 0.93-0.94) for acute myocardial infarction, 0.95 (95% CI, 0.94-0.96) for heart failure, 0.94 (95% CI, 0.93-0.95) for pneumonia, 0.93 (95% CI, 0.92-0.94) for major surgical procedures, and 0.97 (95% CI, 0.96-0.99) for all other conditions. The risk-adjusted adverse event rates declined significantly in all patient groups for adverse drug events, hospital-acquired infections, and general adverse events. For patients in the major surgical procedures group, the risk-adjusted rates of events after a procedure declined significantly.Conclusions and Relevance: In the US between 2010 and 2019, there was a significant decrease in the rates of adverse events abstracted from medical records for patients admitted for acute myocardial infarction, heart failure, pneumonia, and major surgical procedures and there was a significant decrease in the adjusted rates of adverse events between 2012 and 2019 for all other conditions. Further research is needed to understand the extent to which these trends represent a change in patient safety. [ABSTRACT FROM AUTHOR]

Background: Traditional methods for analyzing clinical and epidemiological cohort study data have been focused on the first occurrence of a health outcome. However, in many situations, recurrent event data are frequently observed. It is inefficient to use methods for the analysis of first events to analyse recurrent event data. Methods: We applied several semi-parametric proportional hazards models to analyze the risk of recurrent myocardial infarction (MI) events based on data from a very large randomized placebo-controlled trial of cholesterol-lowering drug. The backward selection procedure was used to select the significant risk factors in a model. The best fitting model was selected using the log-likelihood ratio test, Akaike Information and Bayesian Information Criteria. Results: A total of 8557 persons were included in the LIPID study. Risk factors such as age, smoking status, total cholesterol and high density lipoprotein cholesterol levels, qualifying event for the acute coronary syndrome, revascularization, history of stroke or diabetes, angina grade and treatment with pravastatin were significant for development of both first and subsequent MI events. No significant difference was found for the effects of these risk factors between the first and subsequent MI events. The significant risk factors selected in this study were the same as those selected by the parametric conditional frailty model. Estimates of the relative risks and 95% confidence intervals were also similar between these two methods. Conclusions: Our study shows the usefulness and convenience of the semi-parametric proportional hazards models for the analysis of recurrent event data, especially in estimation of regression coefficients and cumulative risks. [ABSTRACT FROM AUTHOR]

Objective: Diabetes, a major health problem worldwide, increases the risk of cardiovascular disease and its associated mortality: The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial showed that cholesterol-lowering treatment with pravastatin reduced mortality and coronary heart disease (CHD) events in 9014 patients aged 31-75 years with CHD and total cholesterol 4.0-7.0 mmol/l. We measured the effects of pravastatin therapy, 40 mg/day over 6.0 years, on the risk of CHD death or nonfatal myocardial infarction and other cardiovascular outcomes in 1,077 LIPID patients with diabetes and 940 patients with impaired fasting glucose (IFG).Results: In patients allocated to placebo, the risk of a major CHD event was 61% higher in patients with diabetes and 23% higher in the IFG group than in patients with normal fasting glucose, and the risk of any cardiovascular event was 37% higher in the diabetic group and 19% higher in the IFG group. Pravastatin therapy reduced the risk of a major CHD event overall from 15.9 to 12.3% (relative risk reduction [RRR] 24%, P < 0.001) and from 23.4 to 19.6% in the diabetic group (19%, P = 0.11); in the diabetic group, the reduction was not significantly different from the reductions in the other groups. Pravastatin reduced the risk of any cardiovascular event from 52.7 to 45.2% (21%, P < 0.008) in patients with diabetes and from 45.7 to 37.1% (26%, P = 0.003) in the IFG group. Pravastatin reduced the risk of stroke from 9.9 to 6.3% in the diabetic group (RRR 39%, CI 7-61%, P = 0.02) and from 5.4 to 3.4% in the IFG group (RRR 42%, CI -9 to 69%, P = 0.09). Pravastatin did not reduce the incidence of diabetes. Over 6 years, pravastatin therapy prevented one major CHD event (CHD death or nonfatal myocardial infarction) in 23 patients with IFG and 18 patients with diabetes. A meta-analysis of other major trials confirmed the high absolute risks of diabetes and IFG and the absolute benefits of statin therapy in these patients.Conclusions: Cholesterol-lowering treatment with pravastatin therapy prevents cardiovascular events, including stroke, in patients with diabetes or IFG and established CHD. [ABSTRACT FROM AUTHOR]

SummaryBackground: The LIPID study is a major trial of secondary prevention of coronary-heart-disease events that includes hospital admission with unstable angina (as well as myocardial infarction) as a qualifying event. In this substudy of LIPID, we compared subsequent cardiovascular risks and the effects of pravastatin in patients with previous unstable angina or previous myocardial infarction.Methods: 3260 patients diagnosed with unstable angina and 5754 with acute myocardial infarction 3-36 months previously were randomly assigned 40 mg pravastatin daily or placebo over a mean of 6.0 years. The risk reduction of a range of cardiovascular events was estimated by means of the hazard ratio in Cox's proportional hazards model.Findings: Among patients assigned placebo, survival in the two diagnosis groups was similar. The relative risk reduction for mortality with pravastatin was 20.6% in the myocardial infarction group and 26.3% in the unstable angina group (p=0.55). Pravastatin significantly reduced the rates of all prespecified coronary endpoints in the myocardial infarction group. In patients with previous unstable angina, coronary heart disease mortality, total mortality, myocardial infarction, a need for coronary revascularisation, the number of admissions to hospital, and the number of days in hospital were significantly lower with pravastatin. Overall, hospital admission for unstable angina was the most common endpoint (24.6% of the placebo group; 22.3% of the pravastatin group).Interpretation: Patients who have survived acute myocardial infarction or unstable angina have a similar long-term prognosis, a high occurrence of subsequent unstable angina, and benefit similarly from therapy with pravastatin. [ABSTRACT FROM AUTHOR]