Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Device-associated infection rates and mortality in intensive care units of Peruvian hospitals: findings of the International Nosocomial Infection Control Consortium

OBJECTIVES: To measure device-associated infection (DAI) rates, microbiological profiles, bacterial resistance, and attributable mortality in intensive care units (ICUs) in hospitals in Peru that are members of the International Nosocomial Infection Control Consortium (INICC). METHODS: Prospective cohort surveillance of DAIs was conducted in ICUs in four hospitals applying the definitions for nosocomial infections of the U.S. Centers for Disease Control and Prevention National Nosocomial Infections Surveillance System (CDC-NNIS) and National Healthcare Safety Network (NHSN). RESULTS: From September 2003 to October 2007 1 920 patients hospitalized in ICUs for an aggregate of 9 997 days acquired 249 DAIs, accounting for a rate of 13.0% and 24.9 DAIs per 1 000 ICU-days. The ventilator-associated pneumonia (VAP) rate was 31.3 per 1 000 ventilator-days; the central venous catheter-associated bloodstream infections (CVC-BSI) rate was 7.7 cases per 1 000 catheter-days; and the rate for catheter-associated urinary tract infections (CAUTI) was 5.1 cases per 1 000 catheter-days. Extra mortality for VAP was 24.5% (RR 2.07, P < 0.001); for CVC-BSI the rate was 15.0% (RR 2.75, P = 0.028). Methicillin-resistant strains accounted for 73.5% of all Staphylococcus aureus DAIs; 40.5% of the Enterobacteriaceae were resistant to ceftriaxone, 40.8% were resistant to ceftazidime, and 32.0% were resistant to piperacillin-tazobactam. Sixty-five percent of Pseudomonas aeruginosa isolates were resistant to ciprofloxacin, 62.0% were resistant to ceftazidime, 29.4% were resistant to piperacillin-tazobactam, and 36.1% were resistant to imipenem. CONCLUSIONS: The high rates of DAIs in the Peruvian hospitals in this study indicate the need for active infection control. Programs consisting of surveillance of DAIs and implementation of guidelines for infection prevention can ensure improved patient safety in the ICUs and throughout hospitals

Device-associated infection rates and mortality in intensive care units of Peruvian hospitals: findings of the International Nosocomial Infection Control Consortium Tasas de infección asociadas a aparatos y mortalidad en unidades de cuidados intensivos de hospitales peruanos: datos del Consorcio Internacional para el Control de las Infecciones Nosocomiales

OBJECTIVES: To measure device-associated infection (DAI) rates, microbiological profiles, bacterial resistance, and attributable mortality in intensive care units (ICUs) in hospitals in Peru that are members of the International Nosocomial Infection Control Consortium (INICC). METHODS: Prospective cohort surveillance of DAIs was conducted in ICUs in four hospitals applying the definitions for nosocomial infections of the U.S. Centers for Disease Control and Prevention National Nosocomial Infections Surveillance System (CDC-NNIS) and National Healthcare Safety Network (NHSN). RESULTS: From September 2003 to October 2007 1 920 patients hospitalized in ICUs for an aggregate of 9 997 days acquired 249 DAIs, accounting for a rate of 13.0% and 24.9 DAIs per 1 000 ICU-days. The ventilator-associated pneumonia (VAP) rate was 31.3 per 1 000 ventilator-days; the central venous catheter-associated bloodstream infections (CVC-BSI) rate was 7.7 cases per 1 000 catheter-days; and the rate for catheter-associated urinary tract infections (CAUTI) was 5.1 cases per 1 000 catheter-days. Extra mortality for VAP was 24.5% (RR 2.07, P OBJETIVOS: Determinar las tasas de infecciones asociadas a aparatos (IAA), sus perfiles microbiológicos y la resistencia bacteriana, así como la mortalidad atribuible a estas infecciones en unidades de cuidados intensivos (UCI) de hospitales de Perú, miembros del Consorcio Internacional para el Control de las Infecciones Nosocomiales (INICC). MÉTODOS: Se hizo un seguimiento retrospectivo de cohorte de las IAA en las UCI de cuatro hospitales, según las definiciones de infección nosocomial del Sistema Nacional de Vigilancia de Infecciones Nosocomiales de los Centros para el Control y la Prevención de Enfermedades (CDC-NNIS) y de la Red Nacional de Seguridad Sanitaria (NHSN), de los Estados Unidos de América. RESULTADOS: De septiembre de 2003 a octubre de 2007, 1 920 pacientes hospitalizados en las UCI, con un total de 9 997 días, adquirieron 249 IAA, para una tasa de 13,0 por paciente (24,9 IAA por 1 000 días-UCI). La tasa de neumonía asociada a respiradores (NAR) fue de 31,3 casos por 1 000 días-ventilador; la tasa de infecciones circulatorias asociadas con cateterismo venoso central (IC-CVC) fue de 7,7 casos por 1 000 díascatéter; y la tasa de infecciones urinarias asociadas con el uso de catéteres (IUAC) fue de 5,1 casos por días-catéter. La mortalidad adicional por NAR fue de 24,5% (RR = 2,07; P < 0,001) y por IC-CVC fue de 15,0% (RR = 2,75; P = 0,028). De las IAA por Staphylococcus aureus, 73,5% se debían a cepas resistentes a la meticilina; de los aislamientos de Enterobacteriaceae, 40,5% eran resistentes a la ceftriaxona, 40,8% a la ceftazidima y 32,0% a la piperacilina-tazobactam. De los aislamientos de Pseudomonas aeruginosa, 65,0% eran resistentes a la ciprofloxacina; 62,0% a la ceftazidima; 36,1% al imipenem; y 29,4% a la piperacilina-tazobactam. CONCLUSIONES: Las elevadas tasas de IAA encontradas en los hospitales peruanos señalan la necesidad de un control activo de las infecciones. Se puede mejorar la seguridad de los pacientes de las UCI y de los hospitales en general mediante programas que abarquen la vigilancia de las IAA y la implementación de directivas para la prevención de infecciones

Risk categorization using New American College of Cardiology/American Heart Association guidelines for cholesterol management and its relation to alirocumab treatment following acute coronary syndromes

Background: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol ≥70 mg/dL or non−high-density lipoprotein cholesterol ≥100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. Methods: In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were randomly assigned to alirocumab or placebo. The primary trial outcome (major adverse cardiovascular events, ie, coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) was examined according to American College of Cardiology/American Heart Association risk category. Results: Of 18 924 participants followed for a median of 2.8 years, 11 935 (63.1%) were classified as VHR: 4450 (37.3%) had multiple prior ASCVD events and 7485 (62.7%) had 1 major ASCVD event and multiple high-risk conditions. Major adverse cardiovascular events occurred in 14.4% of placebo-treated patients at VHR versus 5.6% of those not at VHR. In the VHR category, major adverse cardiovascular events occurred in 20.4% with multiple prior ASCVD events versus 10.7% with 1 ASCVD event and multiple high-risk conditions. Alirocumab was associated with consistent relative risk reductions in both risk categories (hazard ratio=0.84 for VHR; hazard ratio=0.86 for not VHR; Pinteraction=0.820) and by stratification within the VHR group (hazard ratio=0.86 for multiple prior ASCVD events; hazard ratio=0.82 for 1 major ASCVD event and multiple high-risk conditions; Pinteraction=0.672). The absolute risk reduction for major adverse cardiovascular events with alirocumab was numerically greater (but not statistically different) in the VHR group versus those not at VHR (2.1% versus 0.8%; Pinteraction=0.095) and among patients at VHR with multiple prior ASCVD events versus a single prior ASCVD event (2.4% versus 1.8%; Pinteraction=0.661). Conclusions: The US guideline criteria identify patients with recent acute coronary syndrome and dyslipidemia who are at VHR for recurrent ischemic events and who may derive a larger absolute benefit from treatment with alirocumab. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Alirocumab and cardiovascular outcomes after acute coronary syndrome

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Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

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