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Early and sustained survival benefit associated with statin therapy at the time of percutaneous coronary intervention.

BACKGROUND: Long-term administration of statin therapy has been shown to reduce major coronary events and cardiac mortality within randomized clinical trials. In addition to lowering lipids, statins favorably affect platelet adhesion, thrombosis, endothelial function, inflammation, and plaque stability, which may potentially improve outcome after percutaneous coronary intervention (PCI). Therefore, we hypothesized that statin therapy has an early beneficial effect among patients undergoing PCI. METHODS AND RESULTS: Each year from 1993 to 1999, we prospectively collected data among the first 1000 patients undergoing PCI. Patients who presented with acute or recent myocardial infarction or cardiogenic shock were excluded from the analysis. Baseline, procedural, and 6-month data of statin-treated and non-statin-treated patients were compared. Propensity score and multivariate survival analysis were used to adjust for heterogeneity between the two groups. Of 5052 patients who completed follow-up, 26.5% were treated with statin at the time of the procedure. Statin therapy was associated with a mortality reduction at 30 days (0.8% versus 1.5%; hazard ratio, 0.53; P=0.048) and at 6 months (2.4% versus 3.6%; hazard ratio, 0.67; P=0.046). After adjusting for the propensity to receive statin therapy before the procedure and other confounders, statin therapy remained an independent predictor for survival at 6 months after coronary intervention (hazard ratio, 0.65; 95% CI, 0.42 to 0.99; P=0.045). CONCLUSIONS: In this large study cohort, statin therapy among PCI patients seems to be associated with a significant mortality advantage at early and intermediate-term follow-up.

Aged↗

Inhaled corticosteroids vs leukotriene receptor antagonists: health care costs across varying asthma severities.

BACKGROUND: The burden of asthma is substantial, and the overall cost of its management is growing. OBJECTIVE: To compare asthma-related charges and resource utilization across disease severity levels in the year after initial asthma treatment with any inhaled corticosteroid (ICS) or leukotriene receptor antagonist (LTRA). METHODS: This was a longitudinal, retrospective cohort study of claims data from managed care plans in the United States. All patients had a new prescription for an ICS or an LTRA between January 1999 and December 2000 and were enrolled in a managed care plan for at least 12 months before (preindex) and 12 months after (postindex) the initial claim. Asthma-related charges, hospitalizations, emergency department (ED) visits, physician visits, and asthma medication use were compared between the 2 cohorts. Propensity scores were calculated to control for baseline differences in patient characteristics and types of health care coverage. RESULTS: Claims from 31,860 patients were evaluated. Total postindex asthma-related charges were significantly lower in the ICS cohort than in the LTRA cohort (dollars 613 vs dollars 902, respectively; P < .001), as were asthma-related pharmacy charges (dollars 305 vs dollars 564, respectively; P < .001). Results were consistent for all propensity subclasses and all age groups. CONCLUSIONS: Results from this cohort study suggest that, across varying disease severities, treating asthma with an ICS as initial controller therapy leads to less health care resource utilization than does using an LTRA as initial therapy.

Administration, Inhalation↗

Selective cyclooxygenase-2 inhibition and cardiovascular effects: an observational study of a Medicaid population.

BACKGROUND: The differential effects of selective cyclooxygenase-2 (COX-2) inhibitors compared with nonspecific nonsteroidal anti-inflammatory agents (NSAIDs) on platelet aggregation and prostacyclin/thromboxane balance have led to concerns that COX-2 inhibitors may increase the risk for cardiovascular thrombotic events. Empirical studies have generally been limited to analyses of secondary end points with low event rates in clinical trials and single event rates in observational studies, all of which have come to conflicting conclusions. This observational cohort study examines the cardiovascular risk of COX-2 inhibitors compared with nonspecific NSAIDs in Maryland Medicaid enrollees, a high-risk population. METHODS: Medical and prescription claims were analyzed for noninstitutionalized Medicaid enrollees who received at least a 60-day supply of a COX-2 inhibitor or other prescription NSAID between June 2000 and June 2002 and who did not use these drugs for at least 6 months prior. Naproxen users were excluded. We developed a logistic model of propensity for treatment with COX-2 inhibitors and stratified patients by quintiles of their propensity score. The model adjusted for demographics, indications for COX-2 inhibitors, and cardiovascular risk factors. RESULTS: The study population comprised 1005 patients using COX-2 inhibitors and 5245 patients using a nonnaproxen NSAID. Of the 6250 patients, 70% were female, 50% were African American, and 30% were older than 50 years. Overall, 12% of the patients had at least 1 cardiovascular thrombotic event after treatment within the follow-up period. The propensity-adjusted odds ratio showed no significant effect of COX-2 inhibitor use on this percentage of patients (odds ratio, 1.09; 95% confidence interval, 0.90-1.33). CONCLUSION: We did not find that COX-2 inhibitors increased cardiovascular risk over nonnaproxen NSAIDs in a high-risk Medicaid population.

Adolescent↗

Association of epidural analgesia with cesarean delivery in nulliparas.

OBJECTIVE: To evaluate whether epidural analgesia during the first stage of labor is associated with an increased risk of cesarean delivery. METHODS: The association of epidural analgesia and cesarean delivery was examined in a retrospective study of 1733 low-risk, term nulliparas with singleton infants in vertex presentations, in which labor began spontaneously. To evaluate the effect of epidural analgesia on cesarean deliveries, independent of other factors influencing the use of epidural analgesia, we used propensity scores to create five subgroups (quintiles) of women who, based on characteristics discernible at admission, appeared equally likely to receive epidural analgesia. Multivariate logistic regression analysis was used to control for confounding. RESULTS: Overall, the cesarean rate among women receiving epidural analgesia was 17% (168 of 991), compared with 4% (30 of 742) among those who did not receive epidural analgesia. An increased cesarean rate among women receiving epidural analgesia was present in all propensity quintiles. In an adjusted logistic regression analysis, women receiving epidural analgesia were 3.7 times more likely to undergo a cesarean (95% confidence interval 2.4, 5.7). The greatest increase in cesarean risk was noted when epidural analgesia was administered earlier in labor, but there was a more than twofold increase regardless of the dilation and station at administration of epidural analgesia. CONCLUSIONS: Epidural analgesia may increase substantially the risk of cesarean delivery. Although the causal nature of this association remains open to debate, prenatal care providers should routinely discuss the risks and benefits of epidural analgesia with women during their pregnancies so that they can make informed decisions about the use of pain relief during labor.

Adult↗

The effect of pneumonia on mortality among patients hospitalized for acute stroke.

OBJECTIVE: To determine the effect of pneumonia on 30-day mortality in patients hospitalized for acute stroke. METHODS: Subjects in the initial cohort were 14,293 Medicare patients admitted for stroke to 29 greater Cleveland hospitals between 1991 and 1997. The relative risk (RR) of pneumonia for 30-day mortality was determined in a final cohort (n = 11,286) that excluded patients dying or having a do not resuscitate order within 3 days of admission. Clinical data were obtained from chart abstraction and were merged with Medicare Provider Analysis and Review files to obtain deaths within 30 days. A predicted-mortality model (c-statistic = 0.78) and propensity score for pneumonia (c-statistic = 0.83) were used for risk adjustment in logistic regression analyses. RESULTS: Pneumonia was identified in 6.9% (n = 985) of all patients and in 5.6% (n = 635) of the final cohort. The rates of pneumonia were higher in patients with greater stroke severity and features indicating general frailty. Unadjusted 30-day mortality rates were six times higher for patients with pneumonia than for those without (26.9% vs 4.4%, p < 0.001). After adjusting for admission severity and propensity for pneumonia, RR of pneumonia for 30-day death was 2.99 (95% CI 2.44 to 3.66), and population attributable risk was 10.0%. CONCLUSION: In this large community-wide study of stroke outcomes, pneumonia conferred a threefold increased risk of 30-day death, adding impetus to efforts to identify and reduce the risk of pneumonia in patients with stroke.

Acute Disease↗

Increase of 1-year mortality after perioperative beta-blocker withdrawal in endovascular and vascular surgery patients.

OBJECTIVES: To assess the relation between beta-blocker use, underlying cardiac risk, and 1-year outcome in vascular surgery patients, including the effect of beta-blocker withdrawal. DESIGN: Prospective survey. MATERIALS: 711 consecutive peripheral vascular surgery patients from 11 hospitals in the Netherlands between May and December 2004. METHODS: Patients were evaluated for cardiac risk factors, beta-blocker use and 1-year mortality. Low and high risk was defined according to the Revised Cardiac Risk Index. Propensity scores for the likelihood of beta-blocker use were calculated and regression models were used to study the relation between beta-blocker use and mortality. RESULTS: 285 patients (40%) received beta-blockers throughout the perioperative period (continuous users). Only 52% of the 281 high risk patients received continuous beta-blocker therapy. Beta-blocker therapy was started in 29 and stopped in 21 patients, respectively. One-year mortality was 11%. After adjustment for potential confounders and the propensity of its use, continuous beta-blocker use remained significantly associated with a lower 1-year mortality compared to non-users (HR=0.4; 95%CI=0.2-0.7). In contrast, beta-blocker withdrawal was associated with an increased risk of 1-year mortality compared to non-users (HR=2.7; 95%CI=1.2-5.9). CONCLUSIONS: We demonstrated an under-use of beta-blockers in vascular surgery patients, even in high-risk patients. Perioperative beta-blocker use was independently associated with a lower risk of 1-year mortality compared to non-use, while perioperative withdrawal of beta-blocker therapy was associated with a higher 1-year mortality.

Adrenergic beta-Antagonists↗

Benefit of postoperative adjuvant chemoradiotherapy in locoregionally advanced esophageal carcinoma.

OBJECTIVE: We sought to determine whether chemoradiotherapy after esophagectomy improves survival. METHODS: From 1994 to 2000, 31 patients with locoregionally advanced esophageal carcinoma (90% pT3, 81% pN1, and 13% pM1a) received postoperative adjuvant chemoradiotherapy. Concurrently, 52 patients with advanced carcinoma underwent esophagectomy alone and survived at least 10 weeks, the time frame for adjuvant therapy. A propensity score based on demographic, tumor, and surgical factors was used to identify matched pairs to determine the association of adjuvant therapy with outcomes. RESULTS: For patients receiving adjuvant therapy versus esophagectomy alone, risk-unadjusted median, 1-year, and 4-year survivals were 28 versus 14 months, 68% +/- 8.4% versus 60% +/- 6.8%, and 44% +/- 9.0% versus 17% +/- 5.6%, respectively (P =.05). Similarly, risk-unadjusted median time to recurrence was 25 versus 13 months (P =.15), and median recurrence-free survival was 22 versus 11 months (P =.04). Among propensity-matched patients, median, 1-year, and 4-year survivals for those receiving adjuvant therapy versus esophagectomy were 28 versus 15 months, 60% +/- 11.0% versus 65% +/- 10.7%, and 44% +/- 11.3% versus 0% (P =.05). Median time to recurrence was 25 versus 13 months (P =.04), and recurrence-free survival was 22 versus 10 months (P =.02). CONCLUSION: In patients with locoregionally advanced esophageal carcinoma, addition of postoperative adjuvant chemoradiotherapy to esophagectomy alone doubled survival time, time to recurrence, and recurrence-free survival. Patients with locoregionally advanced carcinoma after esophagectomy should be considered for adjuvant therapy.

Adenocarcinoma↗

Use of the pulmonary artery catheter is not associated with worse outcome in the ICU.

STUDY OBJECTIVES: In critically ill patients, the impact of pulmonary artery catheter (PAC) use on outcome is debatable. We investigated the epidemiology of PAC use in European ICUs and its relation to outcome. DESIGN: International cohort, observational study. SETTING: One hundred ninety-eight European ICUs participating in the Sepsis Occurrence in Acutely Ill Patients Study. PATIENTS: All 3,147 adult patients admitted to one of the participating ICUs between May 1, 2002, and May 15, 2002. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients were classified according to whether or not they had a PAC at any time during their ICU stay, and were followed up until death, hospital discharge, or for 60 days. Propensity score case matching was performed, and matched pairs were examined for baseline characteristics and outcome. Of 3,147 patients, 481 patients (15.3%) had a PAC. Patients with a PAC were older, had a higher incidence of heart failure, a lower incidence of cancer, and were more commonly surgical admissions. Fluid balance was comparable between the two groups. ICU and hospital mortality rates were higher in patients with a PAC (28.1% vs 16.8% and 32.5% vs 22.5%, respectively; p < 0.001). However, PAC use was not an independent risk factor for 60-day mortality in multivariate analysis, and in 453 propensity-matched pairs ICU and hospital mortality rates were comparable between groups (26.7% vs 26.3% and 31.4% vs 32.8%, p = not significant). Survival to 60 days was similar between the two matched groups (log rank = 0.02; p = 0.894). CONCLUSIONS: This observational study suggests that PAC use is not associated with increased mortality in this heterogeneous population.

Catheterization↗

Internal thoracic artery grafting in the elderly patient undergoing coronary artery bypass grafting: room for process improvement?

OBJECTIVE: The acute and long-term benefits of internal thoracic artery grafting are clear in younger patients undergoing coronary artery bypass grafting. The elderly, however, face higher surgical risks and have shorter life expectancy, and thus the use of internal thoracic artery grafting in this age group has been debated. This study examined the use, complication risks, and operative (30-day) mortality associated with internal thoracic artery grafting in patients 75 years of age and older. METHODS: Between 1996 and 1999, 522,656 patients in the Society of Thoracic Surgeons National Cardiac Database underwent primary, nonemergency-salvage coronary artery bypass grafting; of these, 99,942 were 75 years of age or older. The influence of internal thoracic artery use on operative mortality and 5 major complications in this elderly group was examined by means of (1) risk adjustment (adjusting for 28 baseline risk factors and site) and (2) a treatment propensity score analysis that compares patients with similar baseline likelihood for receiving an internal thoracic artery graft. RESULTS: In the National Cardiac Database 77.4% of patients aged 75 to 84 years received an internal thoracic artery graft compared with 93.5% for those aged 55 years or less. In this elderly group use of the internal thoracic artery was strongly associated with decreased operative mortality (unadjusted mortality, 6.20% vs. 4.05%; P <.0001) that persisted after controlling for baseline risk and provider effects (adjusted odds ratio, 0.85; 95% confidence intervals, 0.79-0.91). This mortality benefit was seen among those with low-to-high baseline propensity for receiving an internal thoracic artery graft. CONCLUSIONS: Use of the internal thoracic artery in elderly patients undergoing coronary artery bypass grafting provides an acute survival benefit. This benefit is similar to that seen in younger patients and persists after adjusting for both patient and provider selection factors. The internal thoracic artery appears to be underused in elderly patients undergoing bypass grafting and is a potential area for quality improvement.

Age Factors↗

Intermediate term biochemical progression rates after radical prostatectomy and radiotherapy in patients with screen detected prostate cancer.

PURPOSE: We compared biochemical progression rates measured by increasing prostate specific antigen (PSA) levels using a standard definition of biochemical recurrence among patients with screen detected prostate cancer treated with radical prostatectomy (RP) or radiotherapy (RT). MATERIALS AND METHODS: A total of 1,939 patients diagnosed with clinically localized prostate cancer in a community based screening study from 1989 to 1998, followed through 2001, were treated with RP or RT and agreed to enroll in a followup study. This prospective cohort study (median followup 62 months, range 0.2 to 141) used adjusted Cox proportional hazards models to examine time to progression. Selection bias was addressed with propensity scores. Biochemical evidence of cancer progression was defined as PSA greater than 0.2 ng/ml in patients who underwent RP and 3 consecutive PSA increases as recommended by the American Society for Therapeutic Radiology and Oncology criteria for radiotherapy. RESULTS: Of the patients 17% had evidence of cancer progression. The percentage with progression-free survival at 5 and 9 years for RP was 84% and 76%, respectively, and for RT 80% and 70%, respectively. Cox proportional hazards models produced a hazard ratio of 1.63 (95% CI, 1.12, 2.38) for RT compared with RP, adjusting for clinical stage, Gleason grade, preoperative PSA, biopsy age, treatment year and propensity for treatment type. CONCLUSIONS: With intermediate term followup, patients treated with RT were more likely to have cancer progression than with RP adjusting for demographics, clinical factors, selection bias and treatment year.

Adult↗

[Invasive strategy in patients with advanced diabetes and non-ST-segment elevation acute coronary syndrome. Angiographic findings and clinical follow-up. PREDICAR study results].

INTRODUCTION AND OBJECTIVES: Advanced diabetes can be associated with diffuse coronary artery disease that is difficult to treat by revascularization. We studied angiographic findings and disease progression in patients with advanced diabetes (either insulin-dependent or taking antidiabetic drugs for >5 years) and non-ST-elevation acute coronary syndrome who were being treated using an invasive strategy. METHODS: The study included 141 patients. The extent of the coronary artery disease was quantified using a score derived from a 29-segment coronary angiogram. The composite endpoint was death, myocardial infarction, or readmission for unstable angina within one year of follow-up. RESULTS: The extent of coronary disease was associated with Killip class >1 at admission (P=.02), previous coronary surgery (P=.003), ST-segment depression (P=.01), and a poor ejection fraction (P=.0001). The more of these factors present (i.e., 0, 1, 2 or 3 factors), the greater the extent of the coronary disease (i.e., 12 [7], 15 [7], 21 [6] and 23 [7] points, respectively; P=.0001). There was a significant difference between patients with > or =2 factors and those with P=.02), even after adjustment using a revascularization propensity score (C-index 0.80). CONCLUSIONS: In patients with non-ST-elevation acute coronary syndrome and advanced diabetes being managed using an invasive strategy, a history of coronary surgery, ST-segment depression and poor left ventricular function were all associated with the presence of diffuse coronary artery disease. Clinical follow-up indicated that revascularization during hospital admission improved prognosis.

Acute Disease↗

Clinical results of Hancock II versus Hancock Standard at long-term follow-up.

OBJECTIVE: We performed a multi-institutional study to compare the long-term structural valve deterioration of isolated Hancock Standard versus Hancock II bioprostheses. METHODS: From 1983 to 2002, 714 Hancock Standard and 1293 Hancock II bioprostheses were implanted at hospitals of the Venetian territory (Padova, Treviso, and Venice). Follow-up on January 1, 2003, included 14,749 patient-years with a median of 12 years and was 96% complete: 115 Hancock Standard and 53 Hancock II bioprostheses were at risk at 15 years. The 2 series were nonconcomitant, and many covariates differed (Table 1). Survival was analyzed with Cox analysis, and durability was analyzed with Weibull analysis. Balancing analysis with the logistic propensity score model was performed. RESULTS: Perioperative mortality was 6% in Hancock II and 12% in Hancock Standard operations. The overall unadjusted 15-year survival was identical (39.7% +/- 2.3% vs 39.9% +/- 2.4%, respectively), but age-adjusted survival at 15 years was 46% versus 25% (P < .001). Late survival was unrelated to the prosthetic model, whereas it was adversely affected by older age, previous operations, aortic regurgitation, male sex, higher New York Heart Association class, atrial fibrillation, and coronary artery bypass grafting. In Hancock II patients aged 65 years and older, the cumulative hazard of structural valve deterioration at 15 years was 6%, versus 17.5% in Hancock Standard patients. In younger patients, it was 18% and 37%, respectively. Analysis of 541 propensity-balanced patients showed a hazard ratio of the Hancock Standard prosthesis of 2 and a risk reduction of older age of approximately 10% every 10 years. CONCLUSION: After balancing risk factors and calibrating age effects, Hancock II propensity-matched bioprostheses showed similar survival but definitely increased durability.

Adult↗

Gender differences in outcomes after hospital discharge from coronary artery bypass grafting.

BACKGROUND: There are few comparative data regarding long-term nonfatal outcomes for women versus men after coronary artery bypass grafting (CABG). This study compares gender differences in cardiac events in a population of hospital survivors up to 11 years after isolated CABG surgery in Ontario, Canada. METHODS AND RESULTS: A population-based cohort study (n=68,774 patients, 15,043 women) between September 1, 1991, and April 1, 2002, was assembled with linked clinical and administrative databases. Cox modeling and propensity score matching were used to compare death, cardiac readmission (angina, heart failure, myocardial infarction), repeat revascularization (angioplasty or CABG), and stroke readmission between men and women. Women were older (65+/-17 versus 62+/-13 years), more likely to present with urgent or emergent status (64% versus 56%), and less likely to receive arterial grafts (70% versus 78%). Women had a higher rate of cardiac readmission in the first year after surgery (hazard ratio [HR] of 1.5, 95% confidence interval [CI] 1.36 to 1.56), and this increased risk persisted after 1 year (HR 1.2, 95% CI 1.14 to 1.31). This was primarily due to readmissions for unstable angina (HR 1.3, 95% CI 1.24 to 1.38) and congestive heart failure (HR 1.1, 95% CI 1.06 to 1.21). Propensity-matched women had similar rates of death (HR 0.9, 95% CI 0.83 to 0.98) and repeat revascularization (HR 1.0, 95% CI 0.91 to 1.06). CONCLUSIONS: Women have a more complex clinical preoperative presentation and are more likely to be readmitted with unstable angina and congestive heart failure after CABG but experience survival similar to those seen in men. Gender differences in outcomes may be improved through durable revascularization strategies and close postoperative follow-up care targeted to women.

Aged↗

Total arterial revascularization is safe: multicenter ten-year analysis of 71,470 coronary procedures.

BACKGROUND: The purpose of this study was to assess the use of arterial revascularization and to compare the in-hospital mortality with other CABG grafting strategies. METHODS: A total of 71,470 CABG patients (1992-2001) in 27 centers in the United Kingdom were studied. The proportion of patients with arterial revascularization was compared. In-hospital mortality was compared for various grafting strategies: all-arterial (n = 5,401), all non-all-arterial patients (n = 66,069), one artery any number of veins (n = 49,801). The groups were compared for in-hospital mortality using multivariate logistic regression to assess the independent effect of the grafting strategies on mortality; logistic EuroSCORE-predicted mortality was compared to actual mortality, and all arterial and one artery and veins patients were compared with propensity score analysis. RESULTS: There was a significant increase in the proportion of all-arterial patients over time (3.2% to 11.7%, p < 0.001) with evidence of variability across centers. Crude mortality for all-arterial patients was 2% vs 3% for all non-all-arterial patients (p < 0.001). In multivariate analysis, all-arterial was associated with a slight but insignificant increase in in-hospital mortality (odds ratio [OR] 1.13; [95% confidence interval {CI} 0.86-1.48], p = 0.36). There was a trend toward higher mortality in the all-arterial group when compared with the one artery and veins group (OR 1.19 [95% CI 0.91-1.56], p = 0.10). The one artery and veins group was the only group where actual mortality was significantly lower than predicted by EuroSCORE (p < 0.001). In propensity analysis the mortality was 1.51% for one artery and veins and 1.74% of all-arterial patients (p = 0.56). CONCLUSIONS: The use of arterial grafting has increased over time, varies by center, and appears to be safe in terms of in-hospital mortality.

Aged↗

Stage III non-small cell lung cancer and metachronous brain metastases.

OBJECTIVES: This study was undertaken to identify management strategies that maximize survival of patients with stage III non-small cell lung cancer and metachronous brain metastases and to determine whether any apparent improved survival was due to treatment or simply to patient selection. METHODS: Treatment evaluations of both primary non-small cell lung cancer and brain metastases were performed in 91 patients. Optimal treatment was identified by multivariable analysis. Propensity scoring and multivariable analysis were used to separate treatment benefit from patient selection. RESULTS: Risk-unadjusted median, 12-, and 24-month survivals were 5.2 months, 22%, and 10%, respectively. Younger age (P =.006), good performance status (P =.003), stage IIIA (P =.001), lung resection (P =.02), no other systemic metastases at time of diagnosis of brain metastases (P =.02), and either metastasectomy (P <.001) or stereotactic radiosurgery (P <.001) predicted best survival. However, metastasectomy or stereotactic radiosurgery was more common after lung resection (P =.02) and in patients with good performance status (P =.006), no other systemic metastases at time of diagnosis of brain metastases (P =.01), and fewer brain metastases (P <.001), suggesting that the patients with the best risk profile were selected for aggressive therapy of both lung primary and brain metastases. Despite this selection, analysis of propensity-matched patients demonstrated the benefit of lung resection and metastasectomy or stereotactic radiosurgery (P <.001). CONCLUSIONS: Younger patients with resected stage IIIA non-small cell lung cancer who have isolated metachronous brain metastases and good performance status do best when treated with metastasectomy or stereotactic radiosurgery. This survival benefit is a brain treatment effect, not the result of selecting the best patients for aggressive therapy.

Brain Neoplasms↗

Early effects of statins in patients with coronary artery disease and high C-reactive protein.

Statins improve survival in patients with coronary artery disease, especially those with elevated C-reactive protein (CRP). Although some randomized studies have shown a delay in statin-related survival advantage of up to 2 years, recent studies demonstrated early (<2 months) survival benefit in certain patient groups. We hypothesized that this early benefit relates to baseline CRP concentration. Patients (n = 2,924) with significant, angiographically defined coronary artery disease (>/=70% stenosis in >/=1 coronary artery) were followed for an average of 2.4 years after discharged on a statin prescription. CRP was divided into tertiles (<1.2, 1.2 to 1.7, >1.7 mg/dl), and Kaplan-Meier methods were used to determine timing of statin benefit in both the overall population and a propensity score-matched subgroup. Cox regressions (multivariable and propensity score approaches) were used to predict mortality. Statins were prescribed for 28.4% of patients. In the first CRP tertile, no early statin benefit was observed (adjusted hazard ratio 0.69, 95% confidence interval [CI] 0.30 to 1.6, p = 0.39), and survival curves separated after >2 years. However, in the second and the third tertiles, statin survival curves separated much earlier ( approximately 3 months and 1 week, respectively) and statins predicted improved survival (second tertile: hazard ratio 0.63, 95% CI 0.32 to 1.2, p = 0.17; third tertile: hazard ratio 0.35, 95% CI 0.18 to 0.67, p = 0.002). Propensity score analysis confirmed both statin benefit and early timing. Thus, statin use in patients with high CRP provides not only a larger but also a significantly earlier absolute survival benefit than statin use in patients with lower CRP. This provides further evidence of an anti-inflammatory effect of statins.

Aged↗

Is medical therapy still the optimal treatment strategy for patients with acute type B aortic dissections?

OBJECTIVE: The optimal treatment of patients with acute type B dissections continues to be debated. METHODS: A 36-year clinical experience of medical and surgical treatments in 189 patients was retrospectively analyzed (multivariable Cox proportional hazards model) with respect to three outcome end points: all deaths, freedom from reoperation, and freedom from late aortic complications or death. Propensity score analysis identified 2 quintiles (quintiles I and II, consisting of 142 comparable patients) for further comparison of the effects of surgical versus medical treatment. RESULTS: Shock (hazard ratio 14.5, 95% confidence interval 4.7-44.5, P <.001) and visceral ischemia (hazard ratio 10.9, 95% confidence interval 3.9-30.3, P <.001) largely predominated as determinants of death, along with 6 other risk factors (arch involvement, rupture, stroke, previous sternotomy, and coronary or lung disease), which roughly doubled the hazard of death. Female sex was a significant but weaker predictor of death. Renal dysfunction, year of presentation, age, and mode of therapy (medical vs surgical) had no important bearing on overall survival. The actuarial survival estimates for all patients were 71%, 60%, 35%, and 17% at 1, 5, 10, and 15 years, respectively, and were similar for the medical and surgical patients. Reoperation and late aortic complications were predicted by the presence of Marfan syndrome. For the propensity-matched patients in quintiles I and II, survival, freedom from reoperation, and freedom from aortic complications were almost identical in the medically treated and surgical subsets. CONCLUSIONS: The prognosis for patients with acute type B aortic dissection is bleak and determined primarily by dissection-related and patient-specific risk factors, which do not appear to be readily modifiable.

Acute Disease↗

Systemic lupus erythematosus in three ethnic groups: XVI. Association of hydroxychloroquine use with reduced risk of damage accrual.

OBJECTIVE: To examine whether hydroxychloroquine (HCQ) usage is associated with a reduced risk of damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: Patients (n = 518) meeting the American College of Rheumatology criteria for diagnosis of SLE and with </=5 years disease duration at study entry were followed up annually. Socioeconomic, demographic, clinical, and serologic manifestations as well as disease activity (by the Systemic Lupus Activity Measure [SLAM]) and damage (by the Systemic Lupus International Collaborating Clinics damage index [SDI]) were measured. Propensity scores were calculated to adjust for confounding factors affecting treatment assignment. A Cox proportional hazards model was used to compare the risk of developing new damage according to HCQ use at enrollment into the study. RESULTS: Fifty-six percent of the patients were treated with HCQ at the time of study enrollment. Patients who were not treated with HCQ on enrollment had higher SLAM and SDI scores than patients who were treated. Untreated patients were significantly more likely to have major organ involvement such as renal disease (P < 0.0001) or central nervous system disease (P < 0.0025). Results of unadjusted analysis suggested that treated patients were less likely to accrue damage (hazard ratio [HR] 0.68). With adjustment for differences in treatment assignment, HCQ usage was still associated with a reduced risk of developing new damage, with an HR of 0.68 (95% confidence interval [95% CI] 0.53-0.93) (P = 0.014). With adjustment for differences in treatment assignment, HCQ usage was still associated with a reduced risk of developing new damage (HR 0.73 [95% CI 0.52-1.00]) (P = 0.05). However, patients receiving HCQ who had no damage at study entry had a statistically significant decrease in the risk of damage accrual (HR 0.55 [95% CI 0.34-0.87]) (P = 0.0111), whereas those receiving HCQ who had damage at study entry did not (HR 1.106 [95% CI 0.70-1.74]) (P = 0.6630). CONCLUSION: These findings indicate that, after adjustment for propensity to receive HCQ, HCQ usage is independently associated with a reduced risk of damage accrual in SLE patients who had not yet accrued damage at the time of treatment initiation.

Adult↗