Aspirin in patients undergoing noncardiac surgery Devereaux, P J; Mrkobrada, Marko; Sessler, Daniel I ...
New England journal of medicine/The New England journal of medicine,
04/2014, Volume:
370, Issue:
16
Journal Article
Peer reviewed
Open access
There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those ...who are not.
Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days.
The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval CI, 0.86 to 1.15; P=0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients 4.6% vs. 188 patients 3.8%; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P=0.04). The primary and secondary outcome results were similar in the two aspirin strata.
Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).
Overt stroke after non-cardiac surgery has a substantial impact on the duration and quality of life. Covert stroke in the non-surgical setting is much more common than overt stroke and is associated ...with an increased risk of cognitive decline and dementia. Little is known about covert stroke after non-cardiac, non-carotid artery surgery.
We undertook a prospective, international cohort study to determine the incidence of covert stroke after non-cardiac, non-carotid artery surgery. Eligible patients were ≥65 yr of age and were admitted to hospital for at least three nights after non-cardiac, non-carotid artery surgery. Patients underwent a brain magnetic resonance study between postoperative days 3 and 10. The main outcome was the incidence of perioperative covert stroke.
We enrolled a total of 100 patients from six centres in four countries. The incidence of perioperative covert stroke was 10.0% (10/100 patients, 95% confidence interval 5.5–17.4%). Five of the six centres that enrolled patients reported an incident covert stroke, and covert stroke was found in patients undergoing major general (3/27), major orthopaedic (3/41), major urological or gynaecological (3/22), and low-risk surgery (1/12).
This international multicentre study suggests that 1 in 10 patients ≥65 yr of age experiences a perioperative covert stroke. A larger study is required to determine the impact of perioperative covert stroke on patient-important outcomes.
NCT01369537.
Indians have high rates of cardiovascular disease. Hypertension (HTN) is an important modifiable risk factor. There are no comprehensive reviews or a nationally representative study of the burden, ...treatments and outcomes of HTN in India. A systematic review was conducted to study the trends in prevalence, risk factors and awareness of HTN in India. We searched MEDLINE from January 1969 to July 2011 using prespecified medical subject heading (MeSH) terms. Of 3372 studies, 206 were included for data extraction and 174 were observational studies. Prevalence was reported in 48 studies with sample size varying from 206 to 167 331. A significant positive trend (P<0.0001) was observed over time in prevalence of HTN by region and gender. Awareness and control of HTN (11 studies) ranged from 20 to 54% and 7.5 to 25%, respectively. Increasing age, body mass index, smoking, diabetes and extra salt intake were common risk factors. In conclusion, from this systematic review, we record an increasing trend in prevalence of HTN in India by region and gender. The awareness of HTN in India is low with suboptimal control rates. There are few long-term studies to assess outcomes. Good quality long-term studies will help to understand HTN better and implement effective prevention and management programs.
Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial ...infarction and death without inducing hemodynamic instability.
We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days.
Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval CI, 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients 47.6% vs. 1854 patients 37.1%; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was associated with an increased rate of nonfatal cardiac arrest (0.3% 16 patients vs. 0.1% 5 patients; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02).
Administration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).
Abstract
Background
Myocardial injury after a hip fracture is common and has a poor prognosis. Patients with a hip fracture and myocardial injury may benefit from accelerated surgery to remove the ...physiological stress associated with the myocardial injury.
Purpose
To determine if accelerated surgery is superior to standard-care on the 90-day risk of vascular outcomes and death in patients with a hip fracture who presented with an elevated cardiac biomarker/enzyme at hospital arrival.
Methods
The HIP ATTACK-1 trial was a randomized controlled trial designed to determine whether accelerated surgery for hip fracture was superior to standard-care in reducing death or major complications. This substudy includes 1392/2970 patients with a cardiac biomarker/enzyme measurement (>99.9% had a troponin measurement) at hospital arrival. The primary outcome was all-cause mortality. The secondary composite outcome included all-cause mortality, myocardial infarction, stroke, and congestive heart failure at 90-days after randomization.
Results
322/1392 (23%) patients had a troponin elevation at hospital arrival. Among patients with troponin elevation, median time from hip fracture diagnosis to surgery was 6 h (IQR 5–13) in the accelerated-care group and 29 h (IQR 19–52) in the standard-care group. Patients with an increased troponin had lower risk of mortality with accelerated surgery compared to standard-care (17/163 10% versus 36/159 23%; HR 0.43 95% CI 0.24–0.77); and lower risk of the composite outcome (23/163 14% versus 47/159 30%; HR 0.43 CI 95% 0.26-0.72).
Conclusion
One in 5 patients with hip fracture present with myocardial injury. Accelerated surgery demonstrated a lower risk of mortality and major cardiovascular outcomes compared with standard-care.
Summary Background The combination of three blood-pressure-lowering drugs at low doses, with a statin, aspirin, and folic acid (the polypill), could reduce cardiovascular events by more than 80% in ...healthy individuals. We examined the effect of the Polycap on blood pressure, lipids, heart rate, and urinary thromboxane B2, and assessed its tolerability. Methods In a double-blind trial in 50 centres in India, 2053 individuals without cardiovascular disease, aged 45–80 years, and with one risk factor were randomly assigned, by a central secure website, to the Polycap (n=412) consisting of low doses of thiazide (12·5 mg), atenolol (50 mg), ramipril (5 mg), simvastatin (20 mg), and aspirin (100 mg) per day, or to eight other groups, each with about 200 individuals, of aspirin alone, simvastatin alone, hydrochlorthiazide alone, three combinations of the two blood-pressure-lowering drugs, three blood-pressure-lowering drugs alone, or three blood-pressure-lowering drugs plus aspirin. The primary outcomes were LDL for the effect of lipids, blood pressure for antihypertensive drugs, heart rate for the effects of atenolol, urinary 11-dehydrothromboxane B2 for the antiplatelet effects of aspirin, and rates of discontinuation of drugs for safety. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00443794. Findings Compared with groups not receiving blood-pressure-lowering drugs, the Polycap reduced systolic blood pressure by 7·4 mm Hg (95% CI 6·1–8·1) and diastolic blood pressure by 5·6 mm Hg (4·7–6·4), which was similar when three blood-pressure-lowering drugs were used, with or without aspirin. Reductions in blood pressure increased with the number of drugs used (2·2/1·3 mm Hg with one drug, 4·7/3·6 mm Hg with two drugs, and 6·3/4·5 mm Hg with three drugs). Polycap reduced LDL cholesterol by 0·70 mmol/L (95% CI 0·62–0·78), which was less than that with simvastatin alone (0·83 mmol/L, 0·72–0·93; p=0·04); both reductions were greater than for groups without simvastatin (p<0·0001). The reductions in heart rate with Polycap and other groups using atenolol were similar (7·0 beats per min), and both were significantly greater than that in groups without atenolol (p<0·0001). The reductions in 11-dehydrothromboxane B2 were similar with the Polycap (283·1 ng/mmol creatinine, 95% CI 229·1–337·0) compared with the three blood-pressure-lowering drugs plus aspirin (350·0 ng/mmol creatinine, 294·6–404·0), and aspirin alone (348·8 ng/mmol creatinine, 277·6–419·9) compared with groups without aspirin. Tolerability of the Polycap was similar to that of other treatments, with no evidence of increasing intolerability with increasing number of active components in one pill. Interpretation This Polycap formulation could be conveniently used to reduce multiple risk factors and cardiovascular risk. Funding Cadila Pharmaceuticals, Ahmedabad, India.
This case report depicts a case of histopathologically confirmed polar lepromatous (LL) leprosy with a bacterial index of 4+. He experienced recurrent episodes of erythema nodosum leprosum (ENL) in ...the first 5 years after diagnosis. Skin smears became negative after 6 years of dapsone monotherapy and have remained negative since that time. At 23 years after diagnosis, the patient had developed cataracts and underwent intracapsular cataract extractions with broad-based iridectomies. In one of the iris specimens, histopathologic examination revealed a focal granuloma composed of epithelioid cells. Subsequently a lepromin skin test showed a positive Mitsuda reaction with a borderline tuberculoid histopathology. This clearly illustrates the immunological upgrading of a polar lepromatous patient, perceived first in the iris tissue.
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