Although effective in secondary prevention of cardiovascular disease as well as in the treatment of myocardial infarction, acetylsalicylic acid use in primary prevention of cardiovascular disease has remained controversial. The journal article addresses the question of the effectiveness of acetylsalicylic acid in primary prevention of cardiovascular events in women. The study also addresses the controversy regarding the effects of acetylsalicylic acid in women health in the primary prevention of cardiovascular disease.
For this study, 39876 apparently healthy women aged 45 years and above were recruited to receive 100 milligrams of aspirin on alternate days and monitored for ten years for any major cardiovascular event such as nonfatal stroke, nonfatal myocardial infarction, or any other cardiovascular cases (Paul, et al. 1297). During follow-up, the aspirin group recorded 477 major cardiovascular events, while the placebo group had 522 major cardiovascular events. Analyses showed that there was a 17 percent decline with regard to individual end points in the risk of stroke in the aspirin group, as compared with placebo group. Aspirin also had no considerable effect on the death from cardiovascular cases or risk of myocardial infarction, as compared to placebo. Gastrointestinal bleeding was more common in the aspirin cluster than in placebo cluster. Subgroup follow-up showed that aspirin extensively lowered major cardiovascular events among women aged 65 years and above.
The journal article conclusively established that aspirin reduced the risk of stroke without affecting the myocardial infarction risk or fatality from cardiovascular causes.
Relevance of study
Cardiovascular events such as nonfatal stroke, nonfatal myocardial infarction and coronary artery disease, is among the leading causes of death in developed countries (Heart and Stroke Foundation of Canada 68). In developed countries, Thirty-six percent of deaths in men are attributable to cardiovascular related events while the percentage is slightly higher in women, at thirty-eight percent (Heart and Stroke Foundation of Canada 68). Aspirin is one of the most extensively used pharmacologic agents commonly prescribed for treatment and prevention of cardiovascular related ailments in the U S (Nelson and Knapp 18). Meta-analysis to evaluate the role of Aspirin in treatment and primary prevention of cardiovascular related ailments showed that Aspirin could to a large extent reduce risk of cardiovascular events. However, express evidence for use of aspirin for primary prevention of cardiovascular disease in women is limited.
Analysis of the study and outcomes
For this trial, 39876 apparently healthy women aged 45 years and above (mean age 54 years) were recruited to receive 100 milligrams of placebo or aspirin dose on alternate days and monitored for ten years for any major cardiovascular event or any other cardiovascular cases (Paul, et al. 1297). The females recruited were eligible if they had no cardiovascular disease history or a history of other major chronic illnesses. The recruits were also scrutinized for any history of side effects from any of the medications used in the study (Paul, et al. 1298). They were also required not to be under any nonsteroidal anti-inflammatory drugs during the follow-up or taking supplements of vitamins A, vitamins E or beta-carotene supplements; and were not taking corticosteroids or anticoagulants more than once a week (Paul, et al. 1298).
The main end point for this follow-up included the cumulative rate of the main cardiovascular events, including, stroke, myocardial infarction and cardiovascular related death while the secondary end points included the fatal, non-fatal and ischemic stroke, non-fatal myocardial infarction, hemorrhagic stroke (CCFP).
The well randomized and large sample used in this follow-up produced a proportionate placebo and aspirin groups. The trial showed no significant decrease in major cardiovascular events in the aspirin group as compared to the placebo group (Paul, et al. 1299). The trial also recorded a non-significant raise in hemorrhagic stroke risk in the aspirin group (Paul, et al. 1299). Aspirin had no momentous effect on fatal or non-fatal myocardial infarction risk as compared with placebo, (95 percent CI 0.84 to 1.25, RR 1.02) or death related to cardiovascular causes (95 percent CI 0.74 to 1.22, RR 0.95) (Paul, et al. 1299). However, subgroup analyses showed that aspirin considerably reduced risk of major cardiovascular events among women aged 65 years and above, (95 percent CI 0.59 to 0.92, RR 0.74), myocardial infarction (95 percent CI 0.44 to 0.97, RR 0.66) , and ischemic stroke (95 percent CI 0.49 to 1.00, RR 0.70) (Paul, et al. 1297).
Analysis of methodology
The follow up was well designed and had an excellent follow-up based on the principle of intention-to-treat (CCFP). This analysis has two limitations that can explain ineffectiveness of aspirin in prevention of major cardiovascular events. The first limitation of this assessment is that the general health of the sample used in the examination was not representative of the general population health (CCFP). This follow up sampled a group of very healthy women; 84.4 percent of these women had a ten year Framingham risk score of less than five percent. The US Preventive Services Task Force analytically reviewed the aspirin role in prevention of cardiovascular diseases and concluded that the effectiveness of aspirin in patients whose Framingham risk score lower than five percent was small (Hayden, Pignone, Phillips and Mulrow 192). The second limitation in this follow up is that this trial used 100 milligrams of aspirin each time. This dose is lower than ones used in previous prevention trials. The United States primary Preventive Task Force and the European Cardiologists Society recommend use of low-dose aspirin (75 mg/d to 100 mg/d) (Patrono, Bachmann, Baigent, Bode, De Caterina, Charbonnier, et al. 171; Hayden, et al. 192).
The balance of benefits and risks of aspirin in this study does not look approving, as indicated by the large Number Needed to Treat (NNT) with very wide confidence intervals of 95 percent and the small number needed to harm for quite a few serious complications. This trial reported a much larger and less attractive NNT than that found in previous prevention trials. In this follow up, women at high cardiovascular risk, especially those aged 65 years and above benefited from aspirin therapy more consistently.
CCFP Does low-dose ASA help prevent cardiovascular events in women? 2006. Web.
Heart and Stroke Foundation of Canada. “The changing face of heart disease and stroke in Canada” Toronto, Ont: Heart and Stroke Foundation of Canada; 1.1 (2000). 67–69
Hayden Michael, Pignone Michael, Phillips Christopher, and Cynthia Mulrow, “Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U. S. Preventive Services Task Force” Ann Intern Med. 2002, 161–172.
Patrono Carlo, Bachmann Fedor, Baigent Colin, and Bode Christopher, “Expert consensus document on the use of antiplatelet agents. The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European society of cardiology’ Eur Heart J. 2004, 166–181.
Paul Ridker, M.D., Nancy Cook, Sc.D., I-Min Lee, M.B., David Gordon, Michael Gaziano, JoAnn Manson, Charles Hennekens, and Julie E. Buring “A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women” New England Journal of medicine Volume 352. 13, 2005, 1293-1304
Nelson Cooper, Knapp Wesley. “Medication therapy in ambulatory medical care; National ambulatory medical care survey and national hospital ambulatory medical care survey, 1992”. National Center for Health Statistics, 290. 8 1997 1–24.