Metabolic risk factors and effect of alirocumab on cardiovascular events after acute coronary syndrome: a post-hoc analysis of the ODYSSEY OUTCOMES randomised controlled trial.

BACKGROUND: Many patients with acute coronary syndrome have concurrent metabolic risk factors that affect risk of major adverse cardiovascular events (MACE). We aimed to assess the effects of the PCSK9 inhibitor alirocumab compared with placebo on MACE according to baseline metabolic risk factors. METHODS: We performed a post-hoc analysis of the ODYSSEY OUTCOMES trial, which was a multicentre, double-blind, randomised controlled trial done in 1315 hospitals and outpatient clinics in 57 countries. Patients aged 40 years or older with recent acute coronary syndrome (ie, in the past 1-12 months) and elevated concentrations of atherogenic lipoproteins, despite high-intensity or maximum-tolerated statin treatment, were eligible for enrolment. Between Nov 2, 2012, and Feb 9, 2017, patients were randomly assigned (1:1) to 75 mg alirocumab by subcutaneous injection every 2 weeks or matching placebo, beginning 1-12 months after acute coronary syndrome and were followed up for a median of 2·8 years (IQR 2·3-3·4). Patients and investigators were masked to group assignment and treatment dose adjustment. The primary outcome was a composite of death from coronary artery disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. Analysis of MACE according to an ordinal number of metabolic risk factors was done post hoc. Metabolic risk factors were defined as blood pressure of at least 130/85 mm Hg or treatment with antihypertensive medication, triglyceride concentration of at least 150 mg/dL, HDL cholesterol concentration less than 40 mg/dL for men and 50 mg/dL women, fasting plasma glucose concentration of at least 100 mg/dL or treatment with glucose-lowering medication, and BMI of at least 30 kg/m2. Risk of MACE and effect of alirocumab were assessed according to the number of metabolic risk factors. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. FINDINGS: Of 18 924 patients, 3882 (41%) of 9462 in the alirocumab group and 3859 (41%) of 9462 in the placebo group had three or more metabolic risk factors. In the placebo group, MACE incidence increased monotonically with each metabolic risk factor from 7·8% (no risk factors) to 19·6% (five risk factors; HR 1·18, 95% CI 1·13-1·24 per metabolic risk factor). Alirocumab decreased relative risk of MACE consistently across categories defined by the number of metabolic risk factors (pinteraction=0·77), but absolute risk reduction (aRR) increased with the number of metabolic risk factors (no risk factors aRR 0·7%, -1·81 to 3·29 vs five risk factors aRR 3·9%, -1·45 to 9·25; pinteraction<0·001). Similarly, when patients with diabetes were excluded, the incidence of MACE in the placebo group increased from 7·7% in patients with no metabolic risk factors to 14·6% in those with five metabolic risk factors and aRR with alirocumab increased from 0·91% in patients with no metabolic risk factors to 3·82% in those with five factors. Alirocumab was well tolerated in all subgroups defined by the presence of metabolic risk factors. INTERPRETATION: Accumulation of metabolic risk factors was associated with higher risk of MACE in patients with recent acute coronary syndrome. Alirocumab reduced MACE consistently, but aRR increased with number of metabolic risk factors. FUNDING: Sanofi and Regeneron Pharmaceuticals.

Results of the first five years of the prehospital automatic external defibrillation project in Singapore in the "Utstein style".

In 1994, all emergency medical services (EMS) ambulance officers in Singapore were trained to perform pre-hospital defibrillation with semi-automated external defibrillators (AED). All non-traumatic cardiac arrest patients over 10 years old were included, excluding those who were obviously dead and children below 36 kg. The data were collected by the ambulance officers according to the Utstein guidelines. From 1 February 1994 to 31 January 1999; resuscitation was attempted in 968 non-trauma cardiac arrests. Fifteen percent of the cases were of non-cardiac origin. The overall survival rate was 40/968 (4.1%, 95% CI 2.9-5.6%). Of 968 patients, 22/136 (16.2%, 95% CI 10.4-23.5%), 18/622 (2.9%, 95% CI 1.7-4.5%) and 0/210 (0%, 95% CI 0-1.7%) survived in the EMS witnessed, bystander witnessed and un-witnessed groups, respectively (P < 0.001). Within the EMS witnessed group, those with an initial rhythm of VF/VT had a higher survival rate (30.6%) than those without VF/VT (4.1%). P < 0.001, OR = 10.3, 95% CI 2.9-36.9. Similarly, the VF/VT survival rate in the bystander witnessed group (4.5%) was higher than the non-VF/VT (1.0%) (P = 0.011, OR = 4.4, 95% CI 1.3-15.4). The survival rate of patients with bystander witnessed VF/VT arrest who received bystander CPR was 9.4% compared to 1.0% in those who did not (P = 0.037, OR = 4.4, 95% CI 1.01-20.1). Our survival rate of bystander witnessed VF/VT arrest is comparable to large metropolitan cities in the USA. The determinants of survival include EMS witnessed arrest and VF/VT arrest. Increased quantity and quality of bystander CPR rate may improve the outcome in bystander witnessed cardiac arrest.

Food groups and the risk of colorectal carcinoma in an Asian population.

BACKGROUND: Singapore Chinese have experienced a rapid transition toward a pattern of disease in which lifestyle-related, chronic, degenerative diseases are major public health concerns. The rates of colorectal carcinoma have increased 2-fold over the last 3 decades. It has long been known that dietary factors play a role in the risk of this disease, although studies in Asian populations, with their unique dietary intake, have been few. METHODS: The authors conducted a population-based case-control study that included 121 Chinese patients with colorectal carcinoma and 222 healthy control participants who provided information on usual intake of major food groups in the preceding 3 years, physical activity, family history of colorectal carcinoma, and demographic variables through an in-person questionnaire. RESULTS: High intake of red meat, but not other meats, indicated a predisposition to risk of colorectal carcinoma (adjusted odds ratio [OR] for the highest tertile vs. the lowest tertile, 2.2; 95% confidence interval [95%CI], 1.1-4.2). A low vegetable intake also was associated with a higher risk, and the combined effect appeared to be additive. Those in the highest tertile of meat intake and the lowest quartile of vegetable intake had an OR of 2.6 (95%CI, 1.0-6.7). The authors observed a slight, albeit nonsignificant, positive association with foods high in refined sugars. There was no association observed with fruit or soy-legume intake in this study. Among nondietary variables, a family history of colorectal carcinoma conferred a significant increase in risk (OR, 6.7; 95% CI 2.4-18.7). CONCLUSIONS: Meat intake and vegetable intake were associated significantly with risk of colorectal carcinoma in this Asian population, and further studies on the effects of changes in these specific types of food may shed light on how best to reduce the rapid increase in rates in similar populations.