Routine Aspirin Research Articles

Highlights of This Issue

A region on chromosome 8q24 was previously identified as a prostate cancer risk locus. One allele within this region (the Broad11934905 A risk allele) is only present in people with African ancestry. Whitman and colleagues analyzed the association of six 8q24 SNPs (including the Broad11934905 A risk allele) with prostate cancer progression in 114 African-American prostate cancer patients. The authors found that patients carrying the Broad11934905 A risk allele were more likely to have higher pathologic stage tumors. In addition, the Broad11934905 A risk allele was associated with shorter time to biochemical recurrence. This is the first study to reveal prognostic potential of an SNP within the 8q24 region in African-American prostate cancer patients.The association of different dietary patterns with laryngeal cancer incidence was evaluated by Edefonti and colleagues in a case-control study of Italian hospital patients. Study participants completed food frequency questionnaires and, a posteriori dietary patterns were identified through principal component factor analysis using a set of 28 major nutrients. The authors identified a major dietary pattern (vitamins and fiber) that was inversely associated with laryngeal cancer. In contrast, both the animal products and the animal unsaturated fatty acids dietary patterns were directly associated with laryngeal cancer. These findings suggest that a diet rich in animal products, and animal fats may play a role in laryngeal cancer development.A recent study showing an inverse association between routine aspirin use and Hodgkin lymphoma risk suggested that aspirin may protect against Hodgkin lymphoma development. Chang and colleagues further explored this association by conducting a population-based case-control study in Northern Denmark, using prospectively collected data. The study involved 478 Hodgkin lymphoma cases identified in nationwide healthcare databases. The use of aspirin and other NSAIDs was ascertained by linkage to a population-based prescription database. The authors report evidence of a protective effect of low-dose aspirin, but not other NSAIDs against Hodgkin lymphoma development. Thus, routine aspirin use remains a theoretically promising means of reducing Hodgkin lymphoma risk.Pediatric cancer survivors are at increased risk of morbidity and mortality from cardiovascular disease compared with the general population. Meacham and colleagues utilized the large Childhood Cancer Survivor Study cohort to determine the association of cardiovascular disease risk factors with various cancer therapeutic modalities. The authors found that pediatric cancer survivors were more likely to take medications for hypertension, dyslipidemia, and diabetes. Radiation therapy, especially radiation exposure of the torso, was more highly associated with the development of cardiovascular disease risk factors. These findings reinforce the importance of vigilant healthcare maintenance for pediatric cancer survivors.

Aspirin and Other Nonsteroidal Anti-inflammatory Drugs in Relation to Hodgkin Lymphoma Risk in Northern Denmark

There are few known modifiable risk factors for Hodgkin lymphoma, but the recent finding of an inverse association between routine regular-strength aspirin use and Hodgkin lymphoma risk suggests that aspirin may protect against Hodgkin lymphoma development. To further investigate this association using prospectively collected data, we conducted a population-based case-control study in northern Denmark. A total of 478 incident Hodgkin lymphoma cases were identified in nationwide health-care databases from 1991 to 2008. Ten population controls were matched to each case on age, sex, and county using risk-set sampling. Use of aspirin, selective cyclooxygenase-2 inhibitors, and other nonsteroidal anti-inflammatory drugs (NSAIDs) from 1989 to 2007 was ascertained by linkage to a population-based prescription database. Conditional logistic regression was used to estimate odds ratios for associations between medication use and risk of Hodgkin lymphoma. The odds ratio (95% confidence interval) for ever use (>2 prescriptions) compared with never/rare use (< or =2 prescriptions) of low-dose aspirin was 0.7 (0.5-1.2). The association with low-dose aspirin use did not vary appreciably by recentness, duration, or intensity of use. Recent use (>2 prescriptions in the 1-2 years before the index date), short-term use (<7 years), and medium/high-intensity use (> or =25% of duration of use covered by prescription) of selective cyclooxygenase-2 inhibitors or other NSAIDs was associated with increased Hodgkin lymphoma risk possibly due to prodromal symptoms among cases. In conclusion, our results provide some evidence of a protective effect of low-dose aspirin, but not other NSAIDs, against Hodgkin lymphoma development.

Aspirin for the Primary Prevention of Adverse Cardiovascular Events

There is consideration controversy regarding the use of aspirin for the prophylaxis of certain cardiovascular conditions, such as coronary thrombosis and stroke. An exploration of current literature suggests that the decision to adopt a routine aspirin regimen must follow a careful analysis of potential risks as well as benefits. Nurses share a vital role in patient education related to aspirin regimens, to guard against potential complications of low-dose aspirin therapy, including gastrointestinal bleeding and stroke.

Ninety-day mortality after elective total hip replacement

Thromboprophylaxis after elective orthopaedic surgery remains controversial. Recent guidelines from the National Institute for Clinical Excellence (NICE) have suggested that low molecular weight heparin should be given to all patients undergoing total hip replacement. The British Orthopaedic Association is currently debating this guideline with NICE, as it is not clear whether published evidence supports this view. We present the early mortality in our unit after total hip replacement using aspirin as chemical thromboprophylaxis. The 30-day and 90-day mortality after primary total hip arthroplasty was zero. We compare this with that reported previously from our unit without using chemical thromboprophylaxis. With the introduction of routine aspirin thromboprophylaxis, deaths from cardiovascular causes have dropped from 0.75% to zero. These results demonstrate that there is a strong argument for the routine administration of aspirin after elective total hip replacement.

Does Routine Low-Dose Aspirin Protect Against Venous Thromboembolism?

Short-term aspirin therapy can lower the risk for venous thromboembolism (VTE) in high-risk patients. To test the efficacy of long-term aspirin therapy

Commentary: Aspirin and colorectal cancer an epidemiological success story

primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 2007;146:365–75. 19 U.S. Preventive Services Task Force. Routine aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2007;146:361–64. 20 Baron JA, Cole BF, Sandler RS et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003;348:891–99. 21 Sandler RS, Halabi S, Baron JA et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003;348:883–90. 22 Logan RFA, Grainge MJ, Shepherd VC, Armitage NC, Muir KR. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology 2007. (in press).

USPSTF Recommends Against Routine Aspirin or NSAIDs to Prevent Colorectal Cancer

The U.S. Preventive Services Task Force (USPSTF) has been releasing new and updated guidelines periodically (guidelines homepage).The USPSTF concludes

Routine Aspirin or Nonsteroidal Anti-inflammatory Drugs for the Primary Prevention of Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement

This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendation and supporting scientific evidence on routine use of aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer. The complete information on which this statement is based, including evidence tables and references, is available in the accompanying articles in this issue and on the USPSTF Web site (http://www.preventiveservices.ahrq.gov). The USPSTF is redesigning its recommendation statement in response to feedback from primary care clinicians. The USPSTF plans to release, later in 2007, a new, updated recommendation statement that is easier to read and incorporates advances in USPSTF methodology. The recommendation statement below is an interim version that combines existing language and elements with a new format. Although the definitions of grades remain the same, other elements have been revised.

A Prospective Study of Aspirin Use and the Risk for Colorectal Adenoma

Randomized, double-blind, placebo-controlled trials have established that regular aspirin use reduces the risk for recurrent colorectal adenoma. However, the effect of dose and duration of use, particularly in an average-risk population, is not well understood. To examine the influence of dose and duration of aspirin use in the primary prevention of colorectal adenoma. Prospective cohort study. Nurses' Health Study. 27 077 women, 34 to 77 years of age, without a history of adenoma, cancer, inflammatory bowel disease, or familial polyposis, who underwent lower endoscopy between 1980 and 1998. 1368 cases of confirmed distal colorectal adenoma were diagnosed between 1980 and 1998. Self-reported data on aspirin use were collected from biennial questionnaires. After other risk factors for adenoma were adjusted, women who regularly used aspirin (> or =2 standard aspirin tablets/wk) had a multivariate relative risk for adenoma of 0.75 (95% CI, 0.66 to 0.84) compared with nonregular users. Compared with women who denied any aspirin use, the multivariate relative risks for adenoma were 0.80 (CI, 0.70 to 0.93) for women who used 0.5 to 1.5 standard tablets per week, 0.74 (CI, 0.62 to 0.88) for those who used 2 to 5 tablets per week, 0.72 (CI, 0.61 to 0.85) for those who used 6 to 14 tablets per week, and 0.49 (CI, 0.36 to 0.65) for those who used more than 14 tablets per week (P < 0.001 for trend). Similar dose-response relationships were found among regular short-term users (< or =5 years; P < 0.001) and long-term users (>5 years; P < 0.001). In contrast, after adjustments were made for dose, increasing duration of aspirin use did not confer greater risk reduction (P > 0.2). Regular, short-term use of aspirin is inversely associated with risk for colorectal adenoma. However, the greatest protective effect is evident at substantially higher doses (>14 tablets/wk) than those recommended for the prevention of cardiovascular disease. Before aspirin can be recommended for chemoprevention in the general adult population, these results suggest the need for a more thorough evaluation of the risks and benefits of routine aspirin use at doses not previously considered.

Moynihan 05

Aims: Postoperative thromboembolic stroke affects 2–3 per cent of patients undergoing carotid endarterectomy (CEA) and is preceded by 1–2 h of increasing embolization. The hypothesis underlying the current study was that preoperative administration of a platelet ADP antagonist (clopidogrel) would reduce embolization and was based on previous studies showing that the platelets of patients with the highest rates of postoperative embolization had increased platelet reactivity to ADP. Methods: Total 100 CEA patients on routine aspirin therapy (75 mg) with an accessible TCD window were randomized to 75 mg clopidogrel (n = 47) or placebo (n = 53) the night before surgery. Platelet function was assessed by flow cytometry. The number of emboli detected by transcranial Doppler within 3 h of CEA was independently quantified. Time taken from restoration of flow to skin closure was used as an indirect measure of the time to secure haemostasis. Results: Clopidogrel significantly reduced platelet activation in response to ADP (P < 0.05) whilst conferring a fourfold reduction in the number of patients with >10 emboli in the postoperative period (OR 4.4, 95 per cent CI: 1.4–14.4; P < 0.008). However, the time from flow restoration to skin closure was >40 min in 30 per cent of clopidogrel patients compared with 8 per cent of controls (P < 0.004). Conclusions: This is the first study to show that a CEA patient's postoperative thromboembolic potential can be significantly reduced by preoperative pharmacotherapy. It remains to be seen whether a lower dose of clopidogrel will confer a similar reduction in embolization whilst reducing the time to achieve haemostasis.

Clinical features and diagnosis of aspirin induced asthma

Although for therapeutic reasons it has become convenient to consider asthma as a single disease entity, this clearly is not the case, with many variants occurring. From a clinical standpoint,...

Scientific basis for the content of routine antenatal care. I. Philosophy, recent studies, and power to eliminate or alleviate adverse maternal outcomes.

Scope and content of antenatal care programs are ritualistic rather than evidence-based. We wanted to identify elements of antenatal care which are of proven benefit in preventing or ameliorating specific adverse outcomes in the mother: bleeding, anemia, preeclampsia, sepsis and genito-urinary infection and obstructed labor. Review of recent literature, especially randomized controlled trials. Recent trials indicate that fewer routine visits for low-risk women do not put pregnancies at increased risk but may lessen patient satisfaction. Bleeding in pregnancy has many causes, none of which can be eliminated through antenatal care. Risk factors can be identified by history-taking. Counselling and advice on what to do is the best option. Anemia in pregnancy is common, especially in developing countries. Routine iron supplementation is not necessary in well-nourished populations, but iron and folate should be provided for every pregnant woman in areas of high anemia prevalence; based on circumstantial evidence. Hemoglobin (Hb) determination as a routine test is more important late (around week 30) than early in pregnancy: high Hb is a danger signal. It is uncertain whether early detection of pre-eclampsia will reduce the incidence of eclampsia. Recent trials do not support routine aspirin to prevent pre-eclampsia among low risk women, nor is there evidence that anti-hypertensive treatment of mild pre-eclampsia will prevent more severe disease, but improved detection and care may still lead to better outcome. As to infections, urine culture and dipstick for leucocyte esterase and nitrite with subsequent treatment of positive cases will reduce the risk of pyelonephritis and appears to be cost-effective. Serological screening and treatment of syphilis is inexpensive and cost-effective. Obstructed labor can be anticipated in multiparas based on obstetrical history. Hospital delivery should be secured. Height of nulliparas should be recorded where hospital birth is not routine and a discriminatory level for hospital delivery decided locally. External version of breech lie does reduce the incidence of breech births and cesarean delivery.

Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials.

Most randomised trials of anticoagulant therapy for suspected acute myocardial infarction have been small and, in some, aspirin and fibrinolytic therapy were not used routinely. A systematic overview (meta-analysis) of their results is needed, in particular to assess the clinical effects of adding heparin to aspirin. Computer aided searches, scrutiny of reference lists, and inquiry of investigators and companies were used to identify potentially eligible studies. On central review, 26 studies were found to involve unconfounded randomised comparisons of anticoagulant therapy versus control in suspected acute myocardial infarction. Additional information on study design and outcome was sought by correspondence with study investigators. Patients with suspected acute myocardial infarction. No routine aspirin was used among about 5000 patients in 21 trials (including half of one small trial) that assessed heparin alone or heparin plus oral anticoagulants, and aspirin was used routinely among 68,000 patients in six trials (including the other half of one small trial) that assessed the addition of intravenous or high dose subcutaneous heparin. Death, reinfarction, stroke, pulmonary embolism, and major bleeds (average follow up of about 10 days). In the absence of aspirin, anticoagulant therapy reduced mortality by 25% (SD 8%; 95% confidence interval 10% to 38%; 2P = 0.002), representing 35 (11) fewer deaths per 1000. There were also 10 (4) fewer strokes per 1000 (2P = 0.01), 19 (5) fewer pulmonary emboli per 1000 (2P < 0.001), and non-significantly fewer reinfarctions, with about 13 (5) extra major bleeds per 1000 (2P = 0.01). Similar sized effects were seen with the different anticoagulant regimens studied. In the presence of aspirin, however, heparin reduced mortality by only 6% (SD 3%; 0% to 10%; 2P = 0.03), representing just 5 (2) fewer deaths per 1000. There were 3 (1.3) fewer reinfarctions per 1000 (2P = 0.04) and 1 (0.5) fewer pulmonary emboli per 1000 (2P = 0.01), but there was a small non-significant excess of stroke and a definite excess of 3 (1) major bleeds per 1000 (2P < 0.0001). The clinical evidence from randomised trials dose not justify the routine addition of either intravenous or subcutaneous heparin to aspirin in the treatment of acute myocardial infarction (irrespective of whether any type of fibrinolytic therapy is used).

Long term follow up of patients with anterior myocardial infarction complicated by left ventricular thrombus in the thrombolytic era.

To examine the appearance and resolution of left ventricular thrombi and to study the relation between thrombus and mortality during long term follow up after anterior myocardial infarction. Ninety nine consecutive patients were prospectively studied until the last included patient had been followed for one year. Streptokinase and aspirin were used routinely, anticoagulants only after a decision by the attending physician. Echocardiography was performed within 3 d of admission, before discharge, and after one, three, and 12 months. Umeå University Hospital, a teaching hospital in Northern Sweden. Left ventricular thrombus, segmental myocardial function, and mortality during follow up. Thirty patients (30%) had a thrombus on discharge. One month, three months, and 12 months after hospital discharge, the thrombus had resolved in 81%, 84%, and 90% of the patients, respectively. The proportion of resolved thrombi at one month was high irrespective of whether anticoagulants were given (10/11, 91%) or not (12/16, 75%), P = 0.4. New thrombi appeared in 12 patients after discharge and resolution and reapperance of thrombi continued during the follow up period. Patients who developed a thrombus during the hospital stay (n = 44, 44%) had more extensive myocardial dysfunction on discharge (P < 0.001) and significantly higher mortality during the follow up period than those without a thrombus (23% v 7%, P < 0.01). With routine thrombolytic and aspirin treatment of anterior myocardial infarction, left ventricular thrombi usually resolve during the first month after hospital discharge. Appearance and resolution of thrombi continue, however, in a significant proportion of the patients during long term follow up. A left ventricular thrombus during the initial hospital stay is associated with high long term mortality.