ASPIRIN is a drug that has been around

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1 Crit Care Nurs Q Vol. 31, No. 4, pp Copyright c 2008 Wolters Kluwer Health Lippincott Williams & Wilkins Aspirin for the Primary Prevention of Adverse Cardiovascular Events Krista Estes, MSN, ARNP; Jessica Thomure, MSN, ARNP 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. Key words: aspirin, bleeding complications, cardiovascular, low dose, prophylaxis ASPIRIN is a drug that has been around for more than 2000 years. The Greeks initially made salicylic acid by using bark and leaves from the willow tree to relieve fever and pain. The drug was then industrialized in the 19th century and was primarily utilized to reduce pain. It was in the 1960s that the antiplatelet effect of aspirin was discovered. Further studies revealed a beneficial effect of aspirin in individuals with coronary heart disease to prevent further cardiovascular events. 1 But what about aspirin use in healthy men and women to prevent adverse cardiovascular events? The use of aspirin for the primary prevention of adverse cardiovascular events in the healthy general population is controversial. Commercials on television propagate the idea that the daily use of aspirin is beneficial for all adults. The advertisements claim that aspirin could prevent myocardial infarctions and strokes. These commercials are misleading and may lead to medical complications in uneducated con- Author Affiliations: Shawnee Mission Medical Center (Ms Estes) and The University of Kansas Hospital (Ms Thomure), Kansas. Corresponding Author: Krista Estes, MSN, ARNP, University of Kansas School of Nursing, Family Nurse Practitioner Graduate Program, 3901 Rainbow Blvd, Kansas City, KS sumers. Oftentimes, daily aspirin is selfprescribed and a healthcare provider does not monitor the use. Approximately 36% of adults in the US population take aspirin regularly for primary prevention. 2 The general public views aspirin as a vitamin with minimal adverse effects and complications. The truth is, aspirin, like all other drugs, is a poison. 1 We do not know how much to give and for how long. Aspirin blocks synthesis of prostaglandins. Inappropriate aspirin use may lead to gastrointestinal problems such as ulcers that bleed and possibly perforate. The antiplatelet component of aspirin increases the tendency to bleed. This may increase the bleeding of gastrointestinal ulcers and could even cause hemorrhagic complications. Aspirin may also worsen hypertension and renal failure as well as aggravate asthma. Each year deaths are related to aspirin and other nonsteroidal anti-inflammatory drug use. 3 As healthcare providers, it is important to be aware of the complications aspirin may cause and to know what circumstances are appropriate to prescribe prophylactic aspirin. The decision to suggest daily aspirin intake for the primary prevention of adverse cardiovascular events is highly dependent on the patient s risks of damage to the gastrointestinal mucosa and increased bleeding versus the benefits of cardiovascular protection. Examination of research will provide a guideline

2 Aspirin for the Primary Prevention of Adverse Cardiovascular Events 325 of current evidence-based practice findings to utilize in the healthcare setting. LITERATURE REVIEW The research analyzed for this literature review is divided into the following 3 tables. In Table 1, 4 articles are reviewed, which discuss the evaluation of effectiveness of prophylactic aspirin in men and women. Table 2 contains 5 articles that discuss the evaluation of risks versus benefits of prophylactic aspirin in men and women. Table 3 describes a current metaanalysis reviewing studies related to the use of aspirin for the primary prevention of adverse cardiovascular events in men compared with women. Studies reviewed contained subjects both with and without cardiovascular risk factors. SUMMARY AND CRITIQUE OF CURRENT RESEARCH LITERATURE The use of aspirin to prevent adverse cardiovascular events in healthy men and women is controversial. In reviewing 3 of the studies on low-risk subjects listed in Table 1, there are conflicting findings as to what beneficial effects prophylactic aspirin offers to healthy men and women. The British randomized trial 4 is one of the first studies that evaluated the use of prophylactic aspirin in healthy individuals. Physicians were chosen as the subjects with the belief that they would appreciate the need for the study and would be able to accurately report the experienced effects and outcomes of prophylactic aspirin from a personal standpoint. After the first year of this 6-year study, 19% of the physicians who were allocated to take aspirin stopped doing so, and in the next 5 years, an additional 5% stopped taking aspirin as well. Many of these physicians reported they stopped taking aspirin because of gastrointestinal problems. The study concluded there is a nonsignificant difference in the incidence of fatal and nonfatal myocardial infarctions or strokes. Aspirin was found to significantly reduce the rate of recurrence of transient cerebral ischemic attacks by about half. However, for subjects who suffered a stroke and took aspirin on a daily basis, the outcome was likely to be disabling or fatal. A limitation of this study is the lack of placebo control, which may result in biased results. Although this study was conducted in 1988, it has served as a foundation to many other studies as well as placebocontrolled studies on prophylactic aspirin. Ridker et al 5 performed a study that looked at the effect of aspirin in women over a 10- year period. Healthy women (N = ) aged 45 years and older were randomly assigned to receive 100 mg of aspirin or a placebo, to take every alternate day. They were monitored for a first major adverse cardiovascular event, such as a nonfatal myocardial infarction, nonfatal stroke, or death resulting from cardiovascular causes. In comparison to Peto et al, this study reported that aspirin had a nonsignificant reduction of 9% in the occurrence of a first major adverse cardiovascular event. There was no significant difference between the groups for risk of fatal stroke but the aspirin users had a decreased risk of nonfatal strokes. Aspirin was found to have a nonsignificant effect on the risk of fatal or nonfatal myocardial infarctions or death from cardiovascular causes. As Peto et al had discovered, this study also showed a significant reduction of 22% in the risk of transient ischemic attacks. With regard to adverse effects, Ridker et al found there was an increased occurrence of gastrointestinal bleeding in the group of women who took aspirin. At times, the bleeding was so severe that a blood transfusion was needed. In contrast to earlier findings by Peto et al, Ridker et al found a significant reduction (24%) in the risk of ischemic stroke and a nonsignificant increase in the risk of hemorrhagic stroke. Also, in subgroup analysis, aspirin was found consistently and significantly to reduce the risk of major adverse cardiovascular events by 26%, the risk of ischemic stroke by 30%, and myocardial infarctions in women 65 years of age and older. Chan et al 6 evaluated the influence of prophylactic aspirin on total mortality in female nurses with no cardiovascular

3 326 CRITICAL CARE NURSING QUARTERLY/OCTOBER DECEMBER 2008 Table 1. Evaluation of effectiveness of prophylactic aspirin in healthy men and women Study/purpose Sample/location Design/methods Measurement Findings Peto et al 4 evaluated whether daily prophylactic aspirin would reduce the incidence of and mortality from stroke, myocardial infarction, and other vascular problems Chan et al 5 assessed the influence of long-term use of aspirin on total mortality in women Healthy male doctors (N = 5139) of all ages (half were younger than 60 y) practicing medicine in the United Kingdom Women (N = ) with no history of cardiovascular disease or cancer. Women enrolled in the Nurses Healthy Study from all around the United States Six-year randomized trial. Experimental group took 500 mg of aspirin every day, whereas control group did not take aspirin Prospective, nested case-control study conducted over 24 y. A questionnaire was completed by all participants, which included detailed information on aspirin use and concurrent data on mortality risk factors. In 2004, researchers analyzed the cause of 9477 participant deaths Brief questionnaire completed every 6 mo regarding aspirin use and health, specifically about myocardial infarctions, strokes, transient ischemic attacks, migraines, cataracts, and peptic ulcers. National Health Service reported deaths Cause of death and concurrent years of aspirin use vs nonaspirin use Nonsignificant difference in rates of fatal/nonfatal myocardial infarctions or strokes. Significant reduction in frequency of transient ischemic attacks. Experimental group had a higher incidence of disabling strokes and gastrointestinal complications Low to moderate doses of aspirin are associated with a significant lower risk of all-cause mortality, mainly in older women and those with cardiac risk factors. In women who had used aspirin for 1 5 y, there was a significant reduction in cardiovascular mortality (continues)

4 Aspirin for the Primary Prevention of Adverse Cardiovascular Events 327 Table 1. Evaluation of effectiveness of prophylactic aspirin in healthy men and women (Continued) Study/purpose Sample/location Design/methods Measurement Findings Ridker et al, 6 conducted the study to determine if aspirin lowered the risk of stroke without affecting the risk of myocardial infarction or death from cardiovascular causes Roncaglioni 7 investigated the efficacy of aspirin and vitamin E in the primary prevention of adverse cardiovascular events (both fatal and nonfatal) Women (N = ) aged 45 y or older with no known cardiovascular risk factors. Division of Preventative Medicine, Brigham and Women s Hospital, Boston, Massachusetts In the United States, 4495 men and women older than 50 y with 1 or more cardiovascular risk factors A randomized trial. Participants were randomly assigned to receive 100 mg of aspirin or placebo on alternative days and then monitored for 10 y for a first major adverse cardiovascular event (ie, nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) Randomized, controlled clinical trial. Patients received either 100 mg of aspirin or no aspirin with 300 mg vitamin E or without vitamin E Decreased occurrence of adverse cardiovascular disease/events in women receiving aspirin vs women not receiving aspirin Every 4 mo visit to patients home to check tolerance and compliance. Yearly clinical visits to reassess presence and level of cardiovascular risk factors and adverse events including stroke In subgroup analysis, aspirin consistently and significantly reduced the risk of major adverse cardiovascular events by 26%, the risk of ischemic stroke by 30%, and myocardial infarctions in women 65 y of age and older. Significant reduction (22%) in risk of transient ischemic attack Aspirin significantly lowered the frequency of fatal and nonfatal myocardial infarctions, nonfatal strokes, and total cardiovascular events. Severe bleeding more frequent with aspirin use, but was not associated with excess risk of hemorrhagic stroke

5 328 CRITICAL CARE NURSING QUARTERLY/OCTOBER DECEMBER 2008 Table 2. Evaluation of risks vs benefits of prophylactic aspirin in men and women Study/purpose Sample/location Design/methods Measurement Findings Hernandez-Diaz and Rodriguez. 8 assessed the risk of upper gastrointestinal (GI) tract complications (upper GI tract complications) of patients on low-dose daily aspirin for cardioprotection Meade and Brennan 9 evaluated risk vs benefit of low-dose prophylactic aspirin according to blood pressure and age in the primary prevention of coronary heart disease Patients (N = ) in the UK s General Practice Research Database and patients (N = 9129) in the Base de Datos para la Investigacion Farmacoepidemiologica en Atencion Primaria in Spain. Men and women aged y Men (N = 5499) aged y, at increased risk of coronary heart disease in 108 Medical Research Council general practices in London Random selection of dates in the databases during the year 2000 as snapshots of the population. Analyzed characteristics of aspirin users that put them at risk for GI problems such as history of upper GI problems and evaluated them based on sex, age, and nonsteroidal anti-inflammatory drug (NSAID) use Randomized, controlled trial. Four treatment groups were made: active warfarin and aspirin, active aspirin and placebo warfarin, active warfarin and placebo aspirin or placebo aspirin and active warfarin After evaluation of patients in the health databases, upper GI complication rates in aspirin users were estimated and compared with recent estimates reported in recent clinical trials. These findings were then compared with the control groups of the recent clinical trials Participant medical records were flagged and National Health Service notified of fatal and nonfatal events related to coronary heart disease, bleeding, and stroke. Significant findings were as follows: Of the aspirin users, 60% are older than 60 y. Of these patients, 13% use other NSAIDS. Gastric ulcers were present in 4% 6%. Cardiovascular and GI risk factors need to be considered when evaluating harm versus potential benefit of aspirin. GI complications may offset cardiovascular benefits in low-risk patients Aspirin significantly reduced nonfatal coronary events by 20% as well as strokes in men with lower systolic blood pressure (SBP). Men with high SBP did not benefit from aspirin because they may be at a greater risk for bleeding (continues)

6 Aspirin for the Primary Prevention of Adverse Cardiovascular Events 329 Table 2. Evaluation of effectiveness of prophylactic aspirin in healthy men and women (Continued) Study/purpose Sample/location Design/methods Measurement Findings Augustovski et al, 10 conducted the study to evaluate the effects of aspirin in the primary prevention of adverse cardiovascular events in patients with different risk profiles Nelson et al 11 conducted the study to investigate the routine use of low-dose aspirin in men and women aged y without overt cardiovascular disease Cohorts of male and female patients aged y seen in a primary care setting. Each cohort is generated by a different number of cardiovascular risk factors from no risks to high-risk on the basis of Framingham Heart Study data, United States Men (N = ) and (N = ) women aged y with no cardiovascular disease. The state of Victoria, Australia Markov decision analytic model to evaluate expected duration and quality of life of the cohorts over 10 y. Experimental group was given low-dose aspirin prophylaxis and control was given no aspirin prophylaxis Epidemiological modeling in a hypothetical population. For 30 y, researchers observed/compared the occurrence of deaths and adverse events secondary to cardiovascular disease vs the adverse effects and deaths secondary to prophylactic use of aspirin Measured by the quality-adjusted survival. Outcomes measured included myocardial infarctions, stroke, gastrointestinal bleeding, ulcer, and death. Observed occurrence of first ever myocardial infarction or unstable angina, ischemic or hemorrhagic stroke, and major gastrointestinal hemorrhage. Significant findings that imply the decision to take aspirin to prevent adverse cardiovascular events depend on the patient s level of risk. Aspirin is a harmful intervention for patients with no risk factors and beneficial in moderate and high-risk patients The benefits of low dose aspirin on the risk of cardiovascular disease in men and women aged 70 y may be offset by adverse events.

7 330 CRITICAL CARE NURSING QUARTERLY/OCTOBER DECEMBER 2008 Table 3. Meta-analysis of risks vs benefits of prophylactic aspirin in men compared with women Study/purpose Sample/location Design/methods Measurement Findings For both women and men, prophylactic aspirin significantly reduced the risk of adverse cardiovascular events (12% in women and 14% in men). In women, there was a 17% reduction of stroke and in men there was a 32% reduction in MI. In both men and women, aspirin significantly increased the risk of bleeding. All study participants were reviewed to identify the following outcomes: nonfatal MI, nonfatal stroke, major bleeding, and cardiovascular mortality Evaluated the outcomes of aspirin therapy on the participants of 6 different randomized, controlled trials (N = men and women) Participants (N = ) without cardiovascular disease on the basis of data including the following: myocardial infarction (MI), stroke, and cardiovascular mortality. Department of Cardiovascular Medicine, Duke University, Durham, North Carolina Berger et al 12 conducted a study to determine whether the benefits and risks of aspirin treatment in the primary prevention of cardiovascular disease varies by gender disease over a period of 24 years. The women in this study chose whether or not to take aspirin, and aspirin use was monitored through questionnaires sent out 2 times a year. The nonrandomized assignment of subjects to aspirin therapy is a limitation to this study. Chan et al concluded that prophylactic aspirin does significantly lower risk of all cause mortality in no-risk women. In women who used aspirin for 1 to 5 years, there was a significant reduction in cardiovascular mortality. In subgroup analysis, both Ridker et al and Chan et al agree that the effect of aspirin is most beneficial in older women and those with cardiovascular risk factors. Roncaglioni 7 further explored the effectiveness of prophylactic aspirin. Instead of examining the effects of aspirin in the primary prevention of cardiovascular disease in no-risk individuals, this study examined the effect of aspirin in 4495 men and women (mean age 64 years) with at least 1 cardiovascular risk factor. These subjects were randomly assigned to treatment groups. Results revealed a significant reduction in the frequency of fatal and nonfatal myocardial infarctions, nonfatal strokes, and adverse cardiovascular events in individuals who took prophylactic aspirin. There was a significant increase in bleeding in the aspirin group. The findings of this study, as well as other trials, were so strong that on ethical grounds, the study was prematurely stopped at 3.6 years. In review of the research articles in Table 1, the use of aspirin is recommended in women and men with at least 1 cardiovascular risk factor. Results of these studies show that aspirin therapy can reduce the incidence of transient ischemic attacks in men and women and the risk of nonfatal stroke in women. In subgroup analysis of women, age modified the effect of aspirin therapy on the end point of both stroke and cardiovascular outcomes. These research findings support prophylactic aspirin use in older women (age > 65 years) and individuals with cardiovascular risks. There are conflicting outcomes regarding whether or not aspirin is effective in reducing adverse cardiovascular-related events

8 Aspirin for the Primary Prevention of Adverse Cardiovascular Events 331 and strokes in healthy men and women and further longitudinal studies will need to be performed. All of the research articles agree that there is an increased risk of bleeding and gastrointestinal complications in aspirin users. As many of these articles have found, the benefits of prophylactic aspirin are counterbalanced with risks, specifically gastrointestinal complications and increased risk for bleeding. In Table 2, the risks versus benefits of prophylactic aspirin are reviewed. As implied in Table 1, daily aspirin use was associated gastrointestinal health complications. Hernandez-Diaz and Rodriguez 8 assessed the risk of upper gastrointestinal complications (UGIC) in men and women who take lowdose prophylactic aspirin on a daily basis. The study found that 60% of aspirin users are 60 years of age and older. Of these individuals, 4% to 6% had a recent history of peptic ulcers and 13% of these subjects took other NSAIDs simultaneously. Knowing that older age, male gender, NSAID use, and past medical history of gastrointestinal ulcers are risk factors for UGIC, this study concluded that gastrointestinal risk factors should be considered when assessing the use of aspirin for cardioprotective effects. The risk of UGIC may outweigh the cardioprotective benefits of aspirin. Nelson et al 11 evaluated another risk that is associated with aspirin: increased bleeding. This study investigated the use of low-dose prophylactic aspirin in men and women aged years with no known cadiovascular disease. The main outcome measures that were evaluated included MI, unstable angina, ischemic or hemorrhagic stroke, and major gastrointestinal hemorrhage. The findings of this study suggest that the beneficial reduction in ischemic stroke and myocardial infarction may be offset by increased risks of serious intracranial and gastrointestinal bleeding in the elderly. As mentioned in studies by Hernandez-Diaz and Rodriguez as well as Nelson et al, it is imperative that underlying risks are assessed and taken into consideration when prescribing prophylactic aspirin. Meade and Brennan 12 evaluated men aged 45 to 69 years at 108 different group practices (N = 5499) in London, who were taking part in a thrombosis prevention trial. They examined which groups of patients benefited or experienced harm from prophylactic aspirin use on the basis of low- or high blood pressure. The evidence from this trial found that low-dose aspirin had more significant benefits in men with lower blood pressure (defined as systolic < 130 mm Hg) than men with higher blood pressure (defined as systolic > 145 mm Hg). Men with low blood pressure who were on low-dose aspirin had a significant reduction of nonfatal coronary events by 20% as well as a reduced risk of stroke. Meade and Brennan caution that although there were benefits to prophylactic aspirin therapy, there is still a need to assess whether or not the benefits outweigh the risks. Men with high blood pressure were found to have no cardioprotective benefit from aspirin and were at higher risk for bleeding and hemorrhagic stroke. These findings suggest that men with lower blood pressure may have more cardioprotective benefits from prophylactic aspirin therapy than those with higher blood pressure. Augustovski et al 10 analyzed the effects of aspirin in the primary prevention of adverse cardiovascular events in men and women with different risk profiles. Measured outcomes included the following: myocardial infarctions, stroke, gastrointestinal bleeding, ulcer, and death. These outcomes were measured in quality-adjusted life years. Results found that the effects of aspirin varied according to the patients risk profile. Those individuals at lowest cardiovascular risk were the most harmed with a loss of 1.8 quality adjusted life days, whereas those who were at highest cardiovascular risk received the most benefits with a gain of 11.3 quality adjusted life days. These results suggest that the decision to take prophylactic aspirin should be made with a thorough evaluation of a patient s risk. In conclusion to the findings in Table 2, the studies show that the decision whether or not to take low-dose prophylactic aspirin is one that needs to be taken seriously. Evidence

9 332 CRITICAL CARE NURSING QUARTERLY/OCTOBER DECEMBER 2008 suggests that gastrointestinal risks as well as risk for severe bleeding are contraindications to daily aspirin use, when the risks outweigh the cardioprotective benefits. Age and blood pressure are 2 variables that can influence the outcome of a patient s prophylactic aspirin therapy. These research articles imply that healthcare providers should be knowledgeable of their patient s health history and cardiovascular risks before suggesting daily aspirin prophylactic therapy. Do the benefits of prophylactic aspirin therapy in the primary prevention of cardiovascular events vary by gender? Ridker et al and Chan et al both agree that the effect of aspirin is most beneficial in older women and those with cardiac risk factors, whereas Peto et al found no significant difference in the incidence of nonfatal myocardial infarctions or stroke in healthy men. In Table 1 and Table 2, it was unclear as to whether or not women received the same benefit from aspirin as men and vice versa. However, in Table 3, Berger et al performed a meta-analysis in an attempt to evaluate the overall finding of 6 trials with a total of individuals. All studies were randomized, controlled trials in participants without cardiovascular disease. Outcomes of prophylactic aspirin therapy that were evaluated included the following: myocardial infarction, stroke, and cardiovascular mortality. In reviewing women in these studies, 1285 had a major adverse cardiovascular event. There was a significant reduction (12%) in adverse cardiovascular events with aspirin therapy among women. The rate of myocardial infarctions was the same between women taking aspirin and those who did not. Of these women, 625 had a stroke. Aspirin was associated with a significant 17% reduction in the odds of a stroke among women. When assessing the subtypes of stroke, there was a significant 24% reduction in ischemic stroke and no effect on hemorrhagic stroke. Of men, 2047 were reported to have a major adverse cardiovascular event. Aspirin therapy contributed to a 14% reduction in adverse cardiovascular events among men. Unlike the women, who did not have a reduction in the occurrence of myocardial infarctions but had a reduction of strokes, the men had a 32% reduction of myocardial infarctions and a nonsignificant increase in the odds of stroke. Prophylactic aspirin was actually found to have a significant increase in the odds of hemorrhagic stroke (69%). No aspirin effect on cardiovascular and all-cause mortality was noted among men or women. In examining Table 2, it was apparent that the use of aspirin was associated with the adverse effects of severe bleeding and gastrointestinal complications. Similar results were found in the Berger et al study, which concluded in their meta-analysis that there is a 70% increased risk of major bleeding. These combined results confirmed a significant increase in the odds of major bleeding events in both men and women. Overall, the metaanalysis concluded a significant reduction in the risk of adverse cardiovascular events among men and women on aspirin therapy, otherwise the other benefits of aspirin therapy varied according to sex. For women, the risk for stroke was significantly reduced, whereas there was no effect on their risk for myocardial infarction. Men benefited from aspirin therapy by significantly reducing risk for myocardial infarction. Men did not have a reduction in their risk of stroke and actually suffered a significant increase in hemorrhagic stroke. The main limitation to the Berger et al study is that it did not consider aspirin dose, duration of treatment, or duration of follow-up in their analysis. Also, the occurrence of stroke and myocardial infarctions among these healthy subjects was low, so further studies would be needed. Critique of current research findings Overall, it is apparent in this literature review as well as the meta-analysis that prophylactic aspirin therapy can be beneficial in lowering the risk of adverse cardiovascular events and stroke in both men and women, especially those older than 60 years and with cardiovascular risk factors. Current research has found there are serious adverse effects to the daily use of aspirin. The authors of

10 Aspirin for the Primary Prevention of Adverse Cardiovascular Events 333 these studies imply that healthcare providers need to weigh both the risks and benefits of prophylactic aspirin for each patient before initiating aspirin therapy. It is apparent that aspirin has different beneficial effects for men and women. Women seem to benefit differently by a reduction in the risk for stroke. As many of the studies have shown, men seem to have more cardioprotective effects from aspirin as compared with women. Among these research findings, all agree that aspirin therapy can contribute to gastrointestinal complications and severe bleeding. It is unanimous that both men and women who have cardiovascular risk factors will benefit more from aspirin than those who do not have risk factors. Evidence-based knowledge supports the use of aspirin in these high-risk patients (the benefit will outweigh the harm). Further longitudinal, randomized studies need to be done on aspirin therapy in the healthy general population. There is not enough evidence to support utilization of aspirin for cardioprotective benefits in all healthy men and women. Other areas needing further research include whether low-dose aspirin is as effective as high-dose aspirin as well as information on the adverse effects of aspirin in the elderly population. More research on the relationship between hemorrhagic stroke and low-dose aspirin are needed as well. EVALUATION OF CURRENT USE OF RESEARCH FINDINGS The prophylactic use of aspirin in healthy men and women is a common practice. In an interview with Gregory Muhlebach, MD, (personal communication, June 2, 2007) at the University of Kansas Medical Center, he shared his personal method of prescribing aspirin in the primary care setting. Dr Muhlebach stated that he follows the current Federal Drug Administration 2003 guidelines, which recommend the use of 50 to 325 mg of aspirin daily for the prevention of cardiovascular disease and stroke. Although not all patients raise a red flag of cardiovascular risk factors, he routinely recommends aspirin to his patients. Within the general population, however, there are those individuals whose risks outweigh the benefits of prophylactic aspirin use. Van Tran, MD, (personal communication, June 27, 2007) at Mission Family Health in Kansas City commented that practitioners must learn to balance the scales carefully between preventing cardiovascular disease and bleeding events. In her clinic, she utilizes an annual coronary event risk assessment tool similar to the Framingham Heart Study Tool (Appendix A). Dr Tran stated that until an absolute, all-encompassing statement is made concerning aspirin use for the primary prevention of adverse cardiovascular events in the general population, practitioners must continue to be educated on current literature and make the best clinical judgment possible. In speaking with registered nurses, many feel that the majority of their patients take prophylactic aspirin. Susan Salazar, a registered nurse (personal communication, June 23, 2007), in the presurgery clinic at Shawnee Mission Medical Center in Kansas, obtains health histories on patients over the phone to get them prepared for surgery. She has found that oftentimes many patients forget to mention that they take an 81 mg aspirin. Usually she has to specifically ask them whether or not they take aspirin. Susan went on to comment, knowing whether or not someone takes aspirin is really important. Aspirin can lead to increased bleeding during surgery and is generally stopped one week before surgery. In addition to aspirin, many patients unknowingly take other blood thinning medications as well. For example, patients take aspirin with fish oil, vitamin E, NSAIDS, and sometimes even with clopidogrel (Plavix) and warfarin (Coumadin). On a more personal note, Susan mentioned that her primary care physician told her that there are 3 supplements that every woman over the age of 50 should take: a multivitamin, calcium with vitamin D, and an 81 mg aspirin. Although Susan states that she has no cardiovascular risk factors and is fairly healthy, she takes an aspirin simply because her physician said to.

11 334 CRITICAL CARE NURSING QUARTERLY/OCTOBER DECEMBER 2008 DECISION PLAN FOR UTILIZATION OF RESEARCH The decision to adopt, alter, or reject the use of aspirin for the primary prevention of adverse cardiovascular events in the general population is based on the evaluation of current literature. In summary of the literature review, it is evident that prophylactic aspirin use in individuals with cardiovascular risks is beneficial. However, the benefit of aspirin in healthy men and women to prevent adverse cardiovascular events and stroke will require further longitudinal studies. In current studies which specifically focused on risk versus benefits of prophylactic aspirin use, it was found that the 2 variables of age and blood pressure may be linked to negative outcomes such as gastrointestinal complications and hemorrhagic strokes. SUMMARY AND CONCLUSIONS The use of aspirin for the primary prevention of adverse cardiovascular events in the general population is a complex issue, one that healthcare providers will face every day. Many healthcare providers prescribe lowdose aspirin to adults in the general population in an effort to decrease adverse cardiovascular events. However, in congruence with the findings in the literature review, it is recommended that low-dose aspirin be prescribed to adults with cardiovascular risk factors through the utilization of an appropriate assessment tool. In individuals who present with risk factors for bleeding or gastrointestinal complications that outweigh cardiovascular benefits, the withholding of prophylactic aspirin should be considered. Although aspirin is viewed as a benign drug, healthcare providers need to be aware of these possible complications. Appendix B presents a patient prescription protocol for the recommendation of aspirin, utilizing findings from the literature review and the Framingham Heart Study Tool (Appendix A). Under the direction of the National Heart, Lung, and Blood Institute, the Framingham Heart Study identifies the common factors that contribute to coronary vascular disease. 13 REFERENCES 1. Tramèr MJ. Aspirin, like all other drugs, is a poison. Br Med J. 2002;321(7270): Hughes S. Low-dose aspirin best for CV disease prevention. do. Published Accessed June 18, Josefson D. Bayer made to tone down aspirin advertising. West J Med. 2000;172(3): Peto R, Gray R, Collins R, et al. Randomized trial of prophylactic daily aspirin in British male doctors. Br Med J. 1988;296: Ridker PM, Cook NR, Min L, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005;352(13): Chan AT, Manson JE, Feskanich D, Stampfer MJ, Colditz GA, Fuchs CS. Long-term aspirin use and mortality in women. Arch Intern Med. 2007;167: Roncaglioni M. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomized trial in general Practice. Lancet. 2001;357(9250): Hernandez-Diaz S, Garcia-Rodriguez LA. Cardioprotective aspirin users and their excess risk of upper gastrointestinal complications. BMC Med. 2006;4: Meade TW, Brennan PJ. Determination of who may derive most benefit from aspirin in primary prevention: subgroup results from a randomized controlled trial. Br Med J. 2000;321: Augustovski FA, Cantor SB, Thach CT, Spann SJ. Aspirin for the primary prevention of cardiovascular events. J Gen Intern Med. 1998;13: Nelson MR, Liew D, Bertram M, Vos T. Epidemiological modeling of routine use of low dose aspirin for the primary prevention of coronary heart disease and stroke in those aged 70. Br Med J. 2005; 330: /7503/ Berger JS, Roncaglioni MC, Avanzini F, Pagrazzi I, Tognoni G, Brown DL. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized control trials. JAMA. 2006;295(3): National Heart, Lung, and Blood Institute. Framingham Heart Study. framingham/index.html. Published Accessed May 15, 2008.

12 Appendix A Aspirin for the Primary Prevention of Adverse Cardiovascular Events 335 Estimate of 10-Year Risk for Coronary Heart Disease Framingham Point Scores Framingham Point Scores by age group Age, y Points Framingham Point Scores by age group and total cholesterol Total cholesterol Age y Age y Age y Age y Age y < Framingham Point Scores by age and smoking status Age y Age y Age y Age y Age y Nonsmoker Smoker

13 336 CRITICAL CARE NURSING QUARTERLY/OCTOBER DECEMBER 2008 Framingham Point Scores by high-density lipoprotein level High-density lipoprotein level Points <40 2 Framingham Point Scores by systolic blood pressure and treatment status Systolic BP If untreated If treated < year risk for men by total Framingham Point Scores Point total 10-y risk, % <0 <

14 Aspirin for the Primary Prevention of Adverse Cardiovascular Events 337 Estimate of 10-Year Risk for Women Framingham Point Scores by age group Age, y Points Framingham Point Scores by age group and total cholesterol Total cholesterol Age y Age y Age y Age y Age y < Framingham Point Scores by age and smoking status Age y Age y Age y Age y Age y Nonsmoker Smoker Framingham Point Scores by high-density lipoprotein level High-density lipoprotein level Points <40 2

15 338 CRITICAL CARE NURSING QUARTERLY/OCTOBER DECEMBER 2008 Framingham Point Scores by systolic blood pressure and treatment status Systolic blood pressure If untreated If treated < year risk for women by total Framingham Point Scores Point total 10-y risk, % <9 <

16 Appendix B Aspirin for the Primary Prevention of Adverse Cardiovascular Events 339 Aspirin Prescription Protocol