J Nurs Care Qual Vol. 25, No. 1, pp.

1721 Copyright c 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Using the Best Evidence to Change Practice

The purpose of this column is to present practical information for direct-care nurses and quality improvement leaders about using the best available evidence to change practice. This column is coordinated by June H. Larrabee, PhD, RN (jlarrabee@hsc.wvu.edu).

Aspirin for the Prevention of Cardiovascular Disease

Systematic Review
Brooke Adams Leaberry, MSN, RN, WHNP-BC, CVNP

ARDIOVASCULAR DISEASE (CVD) continues to be the number 1 cause of death and disability across the nation. Heart disease and stroke are the 2 main manifestations associated with CVD.1 Recently, the incidence of CVD has evolved from the traditional population of middle-aged men to include women and children of all races. Moreover, the disease is experienced in both affluent and developing populations across the globe.2 According to the World Health Organization, 17 million people around the world die from cardiovascular-related illnesses each year.3 This is an average of 1 death every 36 seconds. This disease claims more lives annually than cancer, chronic respiratory diseases, accidents, and diabetes mellitus combined. It is projected that by the year 2015, nearly 20 million persons will die from CVD annually.3 Because of the magnitude of this health problem, this review aims to provide nurses and nurse practitioners with a system-

Author Afliation: St Marys Medical Center, Huntington, West Virginia. Corresponding Author: Brooke Adams Leaberry, MSN, RN, WHNP-BC, CVNP, St. Marys Medical Center, 2900 1st Ave, Huntington, WV 25702 (bleaberry@verizon.net). Accepted for publication: May 20, 2009

atic review of the evidence related to the use of aspirin for the prevention of cardiovascular events, coupled with important implications for nursing practice. Coronary artery disease (CAD) is the main cause of morbidity and mortality associated with CVD. This condition is characterized by internal narrowing of the coronary arteries caused by atherosclerotic plaque. For the most part, this phenomenon is responsible for underlying myocardial ischemia, damage to structural and functional capacity of the heart, and acute coronary syndromes. According to the American Heart Association, CAD continues to cause nearly 700 000 deaths each year in the United States.1 The World Health Organization estimates that CAD accounts for 7.1 million deaths around the world annually.3 It is projected that this figure will increase to 11.1 million deaths by the year 2020. Absolute risk factors associated with CAD include tobacco use, hyperlipidemia, hypertension, diabetes, obesity, and sedentary lifestyle. Potential risk factors are associated with inflammation that includes low-grade infections, coronary artery calcification, and environmental pollution. Nonmodifiable risk factors include age, gender, race, and genetic factors.2 Research studies have investigated the usefulness of aspirin for the prevention of 17

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JOURNAL OF NURSING CARE QUALITY/JANUARYMARCH 2010 review, including 1 clinical guideline,5,6 systematic reviews,4,612 and 1 cohort study.13 CRITICAL APPRAISAL A critical appraisal was conducted by this author on each of the 10 documents using the appropriate appraisal tool.14,15 A clinical practice guideline (CPG) addressed the use of aspirin for the prevention of CVD events.5 In this guideline, aspirin is a class I (A) recommendation, per significant evidence from multiple randomized trials, for all patients at risk for cardiovascular events. Overall, the systematic methods for evidence search were clear and well documented with a strong link between recommendations and supporting evidence. Databases used for the literature search were clearly defined and included PubMed, EMBASE, and a Cochrane review. There were no clinical questions or clear objectives to the guideline; however, there was a written goal for each preventive measure. Limitations of the CPG included the lack of documentation that the guideline had been piloted and that benefits, side effects, and risks had been addressed. In addition, there was no evidence that the CPG had been externally reviewed by field experts, and no mechanism for the CPG to be updated was established. Eight meta-analyses of aspirin trials were also critically appraised employing the Scottish Intercollegiate Guidelines Networks methodology checklist for systematic reviews and meta-analysis.4,612,15 The Antiplatelet Trialists Collaboration studied the effects of antiplatelet therapy on vascular events in 1988 and again in 1994. The analysis completed in 1988 included a review of 25 randomized trials of antiplatelet treatment in persons with a history of transient ischemic attack, stroke, unstable angina, and myocardial infarction (MI). The aim was to study the effects of aspirin on nonfatal stroke, MI, vascular death, and nonvascular-related death. The overall effect of antiplatelet treatment showed a reduction in vascular mortality by 15% and a decrease in stroke and MI by 30%.

cardiovascular-related events. Aspirin is classified as an antiplatelet agent that decreases the occurrence of thrombus formation4 by inhibiting the formation of platelet thromboxane A2 . It also has been found to help control the inflammatory response that is thought to be responsible for causing this phenomenon. Strong evidence suggesting that risk factors of CVD can be effectively modified and the disease process can be prevented continues to build. Healthcare providers are faced with the daunting task of finding creative treatments for the prevention of this disease. However, there remains a gap in the evidence related to the efficacy of daily aspirin therapy in the treatment and prevention of CVD and concerns regarding the sideeffect profile of this treatment. Therefore, the research question presented by the author was as follows: In adults, what is the effect of aspirin in the prevention of cardiovascular events? SEARCH STRATEGY The search strategy to identify the best evidence related to aspirin use for the prevention of cardiovascular events included an indepth search of National Guideline Clearinghouse, Cochrane Library, Academic Search Complete, CINAHL, and PubMed. Key words used for the search included adults, aspirin, prevention, and cardiovascular events. The initial search of these keywords revealed a large pool of hits, totaling 7953. The search was narrowed by the inclusion of only peer-reviewed journals, clinical trials, metaanalyses, and evidence-based materials, which produced 798 hits. The technique of snowballing yielded 3 additional relevant documents. Articles that presented other complex health issues and multiple medication regimens were excluded. The number of documents was further reduced by including only those that used daily aspirin therapy for the prevention of cardiovascular events. In the end, a total of 15 documents of relevance were obtained. Of these, 10 articles were selected for inclusion in this systematic

Aspirin for the Prevention of Cardiovascular Disease The literature search represented a rigorous effort to identify all the relevant studies. The 1994 Antiplatelet Trialists Collaboration study focused on the effects of longterm antiplatelet therapy on vascular events.8 In this study, a total of 145 randomized trials were reviewed that included more than 100 000 participants. Relevant randomized controlled trials (RCTs) were identified by computer-aided literature searches, manual searches of journals, evaluation of the reference lists of trials and review articles, review of abstracts of meeting proceedings, collaboration with the trial register, and inquiry of various manufacturers of antiplatelet agents. This was a rigorous process that took several years to complete. The results of the review showed a reduction of about one-third in nonfatal MI and nonfatal stroke and onesixth in vascular death in high-risk patients (P < .0001). Overall, most of the criteria in the above studies were met, indicating wellconducted studies. The next 6 studies (Bartolucci et al, Boltri et al, Eidelman et al, Hayden et al, Hebert et al, and Sanmuganathan et al) were metaanalyses of RCTs using aspirin for prevention of CVD.4,6,912 Each meta-analysis reviewed some of the same RCTs. However, each study added important details, including additional strength and risk benefit ratios, to the analysis. Boltri, Akerson, and Vogel analyzed information from 3 primary prevention studies of aspirin in low-risk participants.6 The aim of the study was to evaluate the relationship between aspirin use and mortality in low-risk individuals. This review showed no significant evidence to recommend for or against the use of aspirin therapy to decrease mortality and CVD in low-risk participants. The sample size for this source was very large, totaling more than 100 000 participants. Many participants included in this study did have hypertension and nicotine dependence. This fact could have affected the study results and altered the overall strength of the study. Hebert and Hennekens compiled information from 4 randomized trials of aspirin therapy in the primary prevention of vascular

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disease.11 The objective was to obtain reliable information on the effects of aspirin therapy on various vascular events, including MI, stroke, and death. The results of the review showed a 30% decrease in nonfatal MI (95% confidence interval) and a 13% reduction in important vascular events (95% confidence interval). The trials reviewed were high-quality RCTs that represented a large volume of study participants. Sanmuganathan, Ghahramani, Jackson, Wallis, and Ramsay conducted a similar study using the same 4 primary prevention randomized trials as used by Hebert and Hennekens.11,12 The reason for the study was to determine the cardiovascular and coronary risk thresholds at which aspirin used for primary prevention is safe and worthwhile. The odds ratios and confidence intervals showed significant reductions in cardiovascular events (reduced by 15%) and MI (reduced by 30%) with daily aspirin therapy. Studies included were well-conducted RCTs that included nearly 50 000 participants. Heterogeneity was discussed along with the statistical analysis. Hayden, Pignone, Phillips, and Mulrow and Eidelman, Hebert, Weisman, and Hennekens both completed a meta-analysis on the same 5 clinical trials.9,10 The purpose of both studies was to update existing knowledge about aspirin therapy. In addition, Hayden et al examined both benefits and risks of using aspirin for prevention of cardiovascular events.10 The results of the review revealed a 95% confidence interval of the total coronary heart disease events endpoint with long-term aspirin therapy. This was a large sample size of greater than 50 000 participants. The last systematic review was the most recent and contained the largest volume of study participants. Bartolucci et al completed an analysis of 6 primary prevention trials using aspirin for the prevention of cardiovascular events.4 The objective of the review was to combine information from the Womens Health Study to the previously investigated 5 prevention trials to enlarge the sample and the power and precision of the information.

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JOURNAL OF NURSING CARE QUALITY/JANUARYMARCH 2010 provide evidence that is strong enough to support the use of aspirin therapy for the prevention of CVD events. The literature demonstrated an obvious benefit associated with aspirin as the studies were compounded. NURSING IMPLICATIONS The findings from this review provide important evidence-based implications to consider when planning nursing care. Documentation of a thorough patient history is imperative to the delivery of care at all levels of nursing practice. Cardiovascular risk factors, including family history, nicotine use, physical activity, obesity, hypertension, diabetes, and elevated cholesterol levels, should be discussed in detail with patients.2 Every attempt should be made to modify risk factors as indicated; however, the evidence shows that patients with cardiovascular risk factors benefit from aspirin therapy.4 Furthermore, patients who have a history of cardiovascular events including MI should be treated with daily aspirin therapy indefinitely.1 Likewise, patients with a coronary artery intervention including stent placement should receive daily aspirin indefinitely.16 Absolute contraindications to aspirin therapy include true aspirin allergy.1 Careful consideration should be given in discontinuing therapy once it has been initiated, and the risks and benefits of doing so must be considered. Patients should be monitored for GI tract and bleeding complications. In addition, a complete blood cell count, platelet count, prothrombin time, liver function studies, serum urea nitrogen, and serum creatinine should be obtained periodically.17 Patients should be educated to monitor for bleeding complications and consult their cardiovascular provider before discontinuing antiplatelet therapy. CONCLUSION On the basis of the information gathered for this review, regular aspirin use is positively correlated with the reduction in

The systematic review included information collected from 6 well-executed RCTs. The review showed significant benefits with aspirin use for total coronary heart disease, nonfatal MI, and total CVD events (P < .001 in each case). One cohort study conducted by Goldstein et al was appraised using the Scottish Intercollegiate Guidelines Network checklist.13,15 This was a multicenter study to assess the role of aspirin in the progression of coronary heart disease in patients currently receiving therapy. The results of the study concluded significant outcomes related to long-term aspirin use in cardiac death, all-cause mortality, and nonfatal infarction (P = .005, .009, and .029, respectively). This study was not an RCT. SYNTHESIS The evidence collected through the evaluation of the 10 documents supports the use of aspirin for prevention of cardiovascular events. On the basis of the combined results of these studies, aspirin decreases total CVD events. Heterogeneity was present across some studies for outcomes including stroke and mortality. This was mainly attributed to the results of 3 different RCTs that concluded there was insufficient evidence for or against recommending aspirin for the prevention of CVD events. Possible reasons for the heterogeneity include patient selection, randomization, and the presence of baseline disease patterns. The remainder of the studies all possessed consistent and strong evidence that supports the use of aspirin for prevention of CVD events. Furthermore, Sanmuganathan et al12 and Hayden et al10 presented supplemental information regarding the benefits and risks of using aspirin for preventative therapy. Gaps in the evidence remain about the efficacy of aspirin use for prevention of CVD in women and dose-specific outcomes related to CVD. Further research is warranted in these areas to provide strong evidence to guide practice. Nine of the 10 data sources reviewed, though,

Aspirin for the Prevention of Cardiovascular Disease total cardiovascular events including cardiovascular death and nonfatal MI. Daily aspirin therapy is recommended for individuals with positive cardiovascular risk factors, patients who have experienced cardiovascular events, and those who have had cardiovascular interventional procedures. Limitations of this review include the use of information based on the literature results without review of the raw data. However, this practice is generally accepted.

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The best intervention for the effective prevention of CVD is a combination of modalities including risk factor modification and daily aspirin therapy. The burden of CVD across the nation is immense. The disease process can be overwhelming to individuals, families, communities, and the healthcare system. Providing strategies for the prevention of CVD would reduce overall mortality, provide increased quality of life, and decrease the rising costs of healthcare.

REFERENCES
1. Heart disease. American Heart Association Web site. http://www.americanheart.org/downloadable/ heart/123783441267009Heart%20and%20Stroke%20 Update.pdf. Published March 2009. Accessed March 9, 2009. 2. Moser D, Riegel B. Cardiac Nursing. St Louis, MO: Elsevier; 2008. 3. World Health Organization. Cardiovascular diseases. http://www.who.int/mediacentre/factsheets/fs317/ en/index.html. Published February 2007. Accessed December 22, 2008. 4. Bartolucci A, Howard G. Meta-analysis of data from the six primary prevention trials of cardiovascular events using aspirin. Am J Cardiol. 2006;98(6):746 750. 5. Smith S, Allen J, Blair S, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation. 2006;113(19):23632372. 6. Boltri J, Akerson M, Vogel RL. Aspirin prophylaxis in patients at low risk for cardiovascular disease: a systematic review of all-cause mortality. J Fam Pract. 2002;51(8):700704. 7. Secondary prevention of vascular disease by prolonged antiplatelet treatment: Antiplatelet Trialists Collaboration. BMJ. 1988;296(6618):320331. 8. Collaborative overview of randomized trials of antiplatelet therapy, I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients: Antiplatelet Trialists Collaboration. BMJ. 1994;308(6921):81 106. 9. Eidelman R, Hebert P, Weisman S, Hennekens CH. An update on aspirin in the primary prevention of cardiovascular disease. Arch Intern Med. 2003;163(17): 20062010. 10. Hayden M, Pignone M, Phillips C, Mulrow C. 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;136(2): 161172. 11. Hebert P, Hennekens CH. An overview of the 4 randomized trials of aspirin therapy in the primary prevention of vascular disease. Arch Intern Med. 2000;160(20):31233127. 12. Sanmuganathan P, Ghahramani P, Jackson P, Wallis E, Ramsay LE. Aspirin for primary prevention of coronary heart disease: safety and absolute benefit related to coronary risk derived from meta-analysis of randomised trials. Heart. 2001;85(3):265271. 13. Goldstein R, Andrews M, Hall J, Moss AJ. Marked reduction in long-term cardiac deaths with aspirin after a coronary event: Multicenter Myocardial Ischemia Research Group. J Am Coll Cardiol. 1996;28(2):326 330. 14. The Appraisal of Guidelines Research & Evaluation Research Trust. AGREE Appraisal Tool. http://www. agreetrust.org/docs/AGREE Instrument English.pdf. Published 2006. Accessed November 28, 2008. 15. Scottish Intercollegiate Guidelines Network. SIGN Appraisal Tool. http://www.sign.ac.uk/ methodology/checklists.html. Published 2007. Accessed July 3, 2007. 16. The American College of Cardiology Foundation, American Heart Association. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention. http://www.guideline.gov/summary/ summary.aspx?doc id=121938nbr=006290&string= heart+AND+diseasse. Published Revision December 2008. Accessed March 9, 2009. 17. Beers MF. Physicians Drug Handbook. 11th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.