Low-dose Aspirin In Primary Prevention Research Articles

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Diabetes: A Meta-Analysis

IntroductionThe use of low-dose aspirin for primary prevention of cardiovascular events in patients with diabetes is recommended by existing guidelines, but definitive evidence supporting its efficacy is lacking. The authors undertook a meta-analysis of published trials to determine the effect of low-dose aspirin for primary prevention of cardiovascular events in patients with diabetes. MethodsRandomized controlled trials comparing low-dose aspirin versus placebo or no treatment in patients with diabetes (either exclusively or as a subgroup) with no previous history of cardiovascular disease were identified through MEDLINE and EMBASE databases. ResultsSeven randomized controlled trials met the inclusion criteria. Two studies included exclusively patients with diabetes, whereas the remaining 5 studies included patients with diabetes as a subgroup. Two studies were excluded because they did not provide diabetes-specific data. Overall, aspirin was associated with a nonsignificant reduction in the hazard rate of the composite endpoint of major cardiovascular events compared with control (hazard ratio = 0.89, 95% confidence interval: 0.70–1.13, P = 0.33). Similarly, there was a nonsignificant reduction in the hazard rate of the individual endpoints of myocardial infarction, stroke, cardiovascular and all-cause mortality. The risk of major bleeding increased nonsignificantly with aspirin compared with control (relative risk = 3.02, 95% confidence interval: 0.48–18.86, P = 0.24). DiscussionThe role of low-dose aspirin for primary prevention of cardiovascular events in patients with diabetes remains unproven, and its routine use cannot be justified at present. More trials are needed to definitively address this issue.

Aspirin for primary prevention of cardiovascular disease?

Cardiovascular disease (CVD) is a leading cause of mortality.1 For example, in 2000, it accounted directly for around 2 million deaths in the European Union.2 Worldwide, many people take aspirin daily in the belief that doing so helps to prevent CVD. This approach is established for the secondary prevention of recurrent vascular events. However, there has been some uncertainty about the place of aspirin for the primary prevention of cardiovascular events. In particular, there have been doubts about whether any benefits of aspirin in people with no history of CVD outweigh the risks (e.g. the fact that long-term low-dose aspirin therapy almost doubles the likelihood of gastrointestinal haemorrhage. Here we consider the place of low-dose aspirin in primary prevention of CVD. BNF 2.9.

Aspirin for primary prevention of cardiovascular disease?

Cardiovascular disease (CVD) is a leading cause of mortality.1 For example, in 2000, it accounted directly for around 2 million deaths in the European Union.2 Worldwide, many people take aspirin...

Incorrect Data in Text and Table in: Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Patients With Type 2 Diabetes: A Randomized Controlled Trial

Hisao Ogawa, MD, PhD; Masafumi Nakayama, MD, PhD; Takeshi Morimoto, MD, PhD; Shiro Uemura, MD, PhD; Masao Kanauchi, MD, PhD; Naofumi Doi, MD, PhD; Hideaki Jinnouchi, MD, PhD; Seigo Sugiyama, MD, PhD; Yoshihiko Saito, MD, PhD; for the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial Investigators

Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Patients with Type 2 Diabetes: A Randomized Controlled Trial

Conclusion: Low-dose aspirin as primary prevention does not reduce the risk of cardiovascular events in patients with type 2 diabetes. Summary: In patients with previous cardiovascular events, aspirin therapy can serve as a secondary prevention strategy. Clinical guidelines also recommend patients with risk factors for coronary heart disease should take aspirin for primary prevention. However, subgroup analyses of large trials of aspirin for primary prevention have not demonstrated significant effects in patients with diabetes. Because these analyses were subgroup analyses, it is possible they were underpowered to demonstrate primary prevention of cardiovascular events with aspirin in patients with diabetes. The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) Trial is reported here. The objective was to determine possible efficacy of low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes. This was a multicenter, prospective, randomized, open labeled, blinded end point trial conducted from December 2002 through April 2008 in 163 Japanese institutions. The study enrolled 2539 patients with type 2 diabetes who did not have a history of atherosclerotic disease. The median follow-up was 4.4 years. Patients in the aspirin group were treated with 81 or 100 mg daily. Primary end points included fatal or nonfatal stroke, fatal or nonfatal ischemic heart disease, and peripheral arterial disease. Secondary end points were each component of the primary end point, combinations of primary end points, and death from any cause. There were 154 atherosclerotic events comprising 68 events in the aspirin group (13.6 per 1000 person-years) and 86 events in the nonaspirin group (17.0 per 1000 person-years; hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.58-1.10; P = .16). The combined end point of fatal coronary events and fatal cerebrovascular events occurred in one patient in the aspirin group and in 10 patients in the nonaspirin group (HR, 1.10; 95% CI, 0.01-0.79; P = .0037). Death from any cause occurred in 34 patients in the aspirin group and 38 patients in the nonaspirin group (HR, 0.90; 95% CI, 0.57-1.14; P = .67). There was no difference in the aspirin and nonaspirin groups for the composite of hemorrhagic stroke and significant gastrointestinal bleeding. Comment: It is becoming frustrating to demonstrate any means of decreasing atherosclerotic events in patients with diabetes. Recent trials have suggested that strictly controlling plasma glucose levels is also ineffective in reducing cardiovascular events in patients with type 2 diabetes. Because of the low event rate in this trial and that it was conducted on an entirely Japanese population, it is probably too early to conclude that aspirin is ineffective as primary preventative therapy in patients with type 2 diabetes. Evidence is accumulating to that effect, however. See also the abstract “The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) Trial: Factorial Randomised Placebo Controlled Trial of Aspirin and Antioxidants in Patients with Diabetes and Asymptomatic Peripheral Arterial Disease” in this month's abstract section of Journal of Vascular Surgery.

Aspirin for Cardiovascular Prevention in Patients With Diabetes

Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi M, Doi N, Jinnouchi H, Sugiyama S, Saito Y; Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial Investigators: Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA 300:2134-2141, 2008 Design. A multicenter, randomized trial. Subjects. A total of 2,539 Japanese patients aged 30-85 years with type 2 diabetes and no previous history of atherosclerotic disease. Mean age was 65 years, and ~ 45% of participants were female. Methods. Participants were randomized to receive low-dose aspirin or no aspirin in an open-label design. The primary outcome was any atherosclerotic event, defined as cardiovascular death, nonfatal myocardial infarction, unstable angina, new-onset stable angina, stroke (ischemic or hemorrhagic), transient ischemic attack, or new peripheral vascular disease. All outcomes were adjudicated by an independent committee blinded to intervention status. Median follow-up was 4.37 years (193 of 2,539 were lost to follow-up). Results. Aspirin use was associated with a nonstatistically significant reduction in the incidence rate of the primary outcome (13.6/1,000 patient-years in the aspirin group …

Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Patients With Type 2 Diabetes: A Randomized Controlled Trial

Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Patients With Type 2 Diabetes: A Randomized Controlled Trial

A Health Economic Evaluation of Aspirin in the Primary Prevention of Cardiovascular Disease in Japan

Low-dose aspirin is standard care in patients with a history of cardiovascular disease (CVD). But, the use of low-dose aspirin in primary prevention has not yet been fully established in Japan although meta-analyses and US/European guidelines support its use in persons at increased CVD risk. This study assessed the health economic consequences of the use of low-dose aspirin in the primary prevention of CVD in Japan. Based on results reported in two recent meta-analyses of Hayden (2002) and Eidelman (2003), a Markov model was constructed to predict the cost-effectiveness of low-dose aspirin in the primary prevention of CVD. The model consists of 5 health states: 1) no history of CVD, 2) history of stroke, 3) history of myocardial infarction, 4) history of CVD, and 5) death, with a 10-year time horizon and 1-year cycles. Direct costs from the insurers' perspective were used, while health outcome was expressed in Life-Years Gained (LYG). 'Discounting Rate' with 3% was applied on effectiveness and costs. For patients with a 1-year risk of coronary heart disease (CHD) of 1.5% (10-year risk of +/-15%), the model demonstrated 'dominance' of the 'aspirin' arm versus 'no aspirin' arm; the 10-year costs were Japanese Yen (JPY) 634,000 (Euro 4,857) and JPY 518,000 (Euro 3,968) in the 'no aspirin' arm and 'aspirin' arm, respectively, while LYG was 8.33 and 8.36, respectively. Low-dose aspirin treatment saved on average JPY 116,000 (Euro 889) [95% confidence interval (CI) JPY 57,077-175,151] per patient. Dominance was demonstrated (non-significant) in the first year of treatment and, low-dose aspirin was dominant to 'no aspirin' arm from an annual risk of 0.20%. Other results of sensitivity analysis on gastrointestinal (GI) bleeding rate, stroke rate, cost of each event and discounting showed the robustness of the results. Administering low-dose aspirin to patients with a 1-year risk of CHD of 1.5% and more is significantly cost-saving from the insurers' perspective in Japan.

A Multi-Country Economic Evaluation of Low-Dose Aspirin in the Primary Prevention of Cardiovascular Disease

Low-dose aspirin (acetylsalicylic acid) is standard care in patients with a history of cardiovascular disease (CVD). The use of low-dose aspirin in primary prevention is not yet fully established, although meta-analyses and US and European guidelines support its use in people at increased risk of CVD. The primary objective of this study was to assess the economic consequences of the use of low-dose aspirin in the primary prevention of CVD in four European countries (UK, Germany, Spain and Italy). Based on results (benefits and harms) reported in meta-analyses, a state-transition model was developed to predict the cost effectiveness of low-dose aspirin in the primary prevention of CVD. The model consists of five health states: no history of CVD, history of stroke, history of myocardial infarction (MI), history of stroke and MI, and death. A 10-year time horizon and 1-year cycles were used. Secondary prevention data were derived from the aspirin arm of the CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) study. Direct costs from the public healthcare payer's perspective were used (euro, 2003 values). Effects were expressed in life-years (LY) and QALYs gained. Quality weights were obtained from published data.Country-specific discounting was applied on effects and costs (3.5% for the UK, 5% for Germany and 3% for Spain and Italy). Univariate sensitivity analysis and Monte Carlo simulation were performed to assess uncertainty in the results. For patients with an annual risk of coronary heart disease (CHD) of 1.5%, the model resulted in 10-year savings with low-dose aspirin of on average euro 201 (95% CI 81, 331), euro 281 (95% CI 141, 422), euro 797 (95% CI 301, 1331) and euro 427 (95% CI 122, 731) per patient in the UK, Germany, Spain and Italy, respectively. Average total cost was almost 3- to 4-fold higher in Spain and Italy than in the UK and Germany. Savings (non-significant) start in the first year of treatment in all countries. Sensitivity analyses on cost of complications, utility, discounting, stroke rate and gastrointestinal bleeding rate showed the robustness of the results. From an annual risk of CHD of 0.236% for the UK, 0.324% for Germany, 0.244% for Spain and 0.560% for Italy, low-dose aspirin was cost saving compared with placebo. Monte Carlo analysis showed aspirin dominance in about 97% of cases for the three studied annual risks of CHD (0.6%, 1.0% and 1.5%) in the UK, Germany and Spain. In Italy, aspirin dominance in > 95% of cases was seen at annual risks of 1% and 1.5%. Administering low-dose aspirin to patients with an annual risk of CHD of > or = 1% appears to be significantly cost saving from the healthcare payer's perspective in all countries analysed. Sensitivity analyses (CHD risk and bleedings) suggested the results were robust.

Low-Dose Aspirin for Primary Prevention of Stroke in Women

Aspirin has been shown to reduce the risk for myocardial infarction (MI), but not stroke, in men (N Engl J Med 1989; 321:129). These researchers sought

Low-Dose Aspirin for Primary Prevention of Cardiovascular Disease

Progressive atherosclerosis followed by plaque rupture is the leading cause of acute cardiovascular events. Inhibition of platelet aggregation by acetylsalicylic acid (aspirin) reduces recurrent cardiovascular events in secondary prevention trials. By extracting data from available randomized trials that examined aspirin prevention in persons without previously known cardiovascular disease, we evaluated the use of aspirin as a primary prevention measure. Using the raw data presented in the source publication on death, fatal and nonfatal myocardial infarctions, and cerebrovascular accidents, all relative and absolute risk reductions were recalculated with confidence intervals. In healthy men above 45 years of age, men with an increased cardiovascular risk profile, and persons with diabetes mellitus or hypertension, the use of aspirin reduces the incidence of myocardial infarction and has a neutral effect on cerebrovascular events. The protective effect of aspirin is apparently most prominent in those persons with an increased risk of manifest atherosclerotic vascular disease. Notwithstanding these results, for each patient it remains essential to balance the cardiovascular risk profile against the small increased risk of bleeding complications when prescribing aspirin.

Benefit of Low-Dose Aspirin in Primary Prevention

Although clinical trial results have shown that aspirin has some primary-preventive cardiovascular effects, whether general practitioners should

Effects of sex steroids on women's health: implications for practitioners

Androgen excess in women is manifested typically by clinical features that may include hirsutism, acne, central obesity, male-pattern baldness, upper torso widening, increased waist-to-hip ratio, clitoral hypertrophy, and deepening of the voice. The differential diagnosis includes androgen-producing ovarian and adrenal neoplasms, Cushing's syndrome, polycystic ovary syndrome, and the intake of exogenous androgens. Physicians treating patients for one symptom of androgen excess must be alert for other symptoms and signs. The cosmetic manifestations of androgen excess belie the serious health risks associated with this condition, including cardiovascular disease, intravascular thrombosis, and insulin resistance. Prompt clinical recognition of androgen excess, understanding of the androgen-related biochemical abnormalities underlying the risks associated with this condition, and implementation of risk modification can reduce the incidence of associated morbidity and mortality. An interdisciplinary approach to management is strongly recommended. Risk reduction strategies include correction of dyslipidemias, low-dose aspirin for primary prevention of myocardial infarction, maintenance of ideal weight, smoking cessation, exercise, use of oral contraceptives containing a low-androgenic progestin, and postmenopausal estrogen replacement. Combination oral contraceptives containing low-androgenic progestins are effective not only in reducing signs of androgen excess but also in potentially retarding the progression of long-term sequelae such as cardiovascular disease.

Haematological profile of healthy elderly Australians.

To determine normal values for haematological parameters in healthy elderly persons, and document any changes in these over a 12 month period. The study was conducted as part of a randomised controlled trial of low-dose aspirin for primary prevention of cardiovascular disease in the elderly. All participants (380) had a full blood examination performed at entry, which was repeated after 12 months. The baseline results for all patients and the 12 month findings in a cohort of 162 persons allocated placebo were used in the present study. Community-based (general practices and residential retirement villages). Persons aged 70 years and over (53% females) who were ambulatory, living independently, and volunteered to participate. None had significant vascular disease, peptic ulceration, haemorrhagic symptoms or were currently taking non-steroidal anti-inflammatory drugs. Full blood examination (excluding white cell differential counts) performed with a Technicon H1 analyser. The mean haemoglobin level +/- standard deviation (SD) was 14.69 +/- 1.10 g/dL (for men) and 13.72 +/- 1.05 g/dL (for women). Significant differences (P less than 0.001) in packed cell volume, red cell and platelet counts were observed between the two sexes. No clinically significant change was observed in any of the parameters over a 12 month period. Haematological reference values for healthy elderly Australians are consistent with normal values reported in younger populations for both sexes. As a result recommendations are provided for normal reference values among this group in an Australian setting.

Aspirin Use and Cardiovascular Disease in Women-Reply

In Reply. —We thank Dr D'Agostino and colleagues for sharing their interesting data from the Framingham Heart Study. In their data, as in ours, the use of one through six aspirin per week was associated with decreased risks of CVD, whereas seven or more was not. Whether the absence of benefit in the latter group is attributable to the higher dose or frequency of aspirin ingestion or to confounding by the underlying indication for aspirin or related health habits remains unclear. It is of interest that low-dose aspirin was associated with greater reductions in stroke than in MI in the Framingham data. We agree that further investigation is warranted and believe that only randomized clinical trials of adequate sample size will provide conclusive evidence on the risk:benefit ratio of low-dose aspirin in primary prevention of CVD in women. Dr Yawn comments on the potential importance of the indications for aspirin

Effect of alternate-day regular and enteric-coated aspirin on platelet aggregation, bleeding time, and thromboxane A 2 levels in bleeding-time blood

The effectiveness of low-dose aspirin for primary prevention of cardiovascular mortality is being assessed among the nearly 22,000 United States physicians currently participating in the Physicians' Health Study. Because of occasional reports of gastric irritation among study participants, two enteric-coated aspirin preparations were tested as possible alternatives to regular compressed aspirin for platelet inhibition. Thirty-three volunteers were assigned randomly to one of four treatment groups: regular aspirin (325 mg), placebo, and two enteric-coated aspirin preparations (325 mg). Pills were administered every other day, duplicating the regimen used in the Physicians' Health Study. Bleeding times, platelet aggregation, and thromboxane A 2 levels produced by aggregating platelets in vitro, as well as in collected bleeding-time blood, were determined. Measurements were taken before and after a single dose as well as after seven alternate-day doses. Regular and enteric-coated aspirin preparations were equally efficacious in prolonging the bleeding time, inhibiting platelet aggregation, and suppressing thromboxane A 2 production. There was virtually complete suppression of thromboxane A 2 production (over 99 percent), by platelets in vitro and in collected bleeding-time blood. The levels were still profoundly reduced (89 percent) 48 hours after the last dose. Enteric-coated aspirin may provide an alternative to regular aspirin in a low-dose regimen designed to inhibit platelet activity.