A Randomized Clinical Trial to Reduce Patient Prehospital Delay to Treatment in Acute Coronary Syndrome
Background— Delay from onset of acute coronary syndrome (ACS) symptoms to hospital admission continues to be prolonged. To date, community education campaigns on the topic have had disappointing results. Therefore, we conducted a clinical randomized trial to test whether an intervention tailored specifically for patients with ACS and delivered one-on-one would reduce prehospital delay time.
Methods and Results— Participants (n=3522) with documented coronary heart disease were randomized to experimental (n=1777) or control (n=1745) groups. Experimental patients received education and counseling about ACS symptoms and actions required. Patients had a mean age of 67±11 years, and 68% were male. Over the 2 years of follow-up, 565 patients (16.0%) were admitted to an emergency department with ACS symptoms a total of 842 times. Neither median prehospital delay time (experimental, 2.20 versus control, 2.25 hours) nor emergency medical system use (experimental, 63.6% versus control, 66.9%) was different between groups, although experimental patients were more likely than control to call the emergency medical system if the symptoms occurred within the first 6 months following the intervention (P=0.036). Experimental patients were significantly more likely to take aspirin after symptom onset than control patients (experimental, 22.3% versus control, 10.1%, P=0.02). The intervention did not result in an increase in emergency department use (experimental, 14.6% versus control, 17.5%).
Conclusions— The education and counseling intervention did not lead to reduced prehospital delay or increased ambulance use. Reducing the time from onset of ACS symptoms to arrival at the hospital continues to be a significant public health challenge.
Clinical Trial Registration— clinicaltrials.gov. Identifier NCT00734760.
Received February 1, 2009; accepted August 14, 2009.
Individuals who experience the signs and symptoms of acute coronary syndrome (ACS) often delay seeking treatment.1,2 Unfortunately, a delay of only a few hours can have a significant impact on patient survival,3 with a 30-minute delay reducing average life expectancy by 1 year.4 In recognition of the detrimental effect of prehospital delay on morbidity and mortality, the National Heart Attack Alert Program5 advocates a goal of 1 hour (ie, the “golden hour” similar to that in trauma care) from ACS symptom onset to opening the coronary artery by reperfusion or angioplasty. Unfortunately, the median prehospital delay times have remained far longer at 2.3 to 6 hours.6–8 More than three quarters of this delay time is related to the decision process undertaken by the patient, with less than one quarter related to transport time.9
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To date, all interventions to reduce prehospital delay in ACS have involved community education strategies designed to educate the general public.10 Interventions have focused on educating the public about the signs and symptoms of ACS, the importance of calling emergency services, and the availability of treatments such as fibrinolysis and primary coronary intervention. With a few exceptions, these community-based interventions have failed to reduce prehospital delay.10
Recognizing the complex cognitive, social, and emotional processes involved in having patients identify ACS symptoms correctly and seek care immediately, we conducted a randomized controlled trial to test an education and counseling intervention designed specifically for individuals at high risk for a future ACS event. The intervention was aimed at reducing the time from ACS symptom onset to arrival at the hospital by increasing patients’ knowledge about cardiac symptoms, and improving their attitudes and beliefs about seeking care immediately when they experience ACS symptoms by calling 911. The primary study hypothesis was that patients who received a face-to-face education and counseling intervention and who experienced symptoms of ACS during 2 years of follow-up would have reduced prehospital delay time compared to control. Secondary hypotheses focused on use of emergency medical services (EMS) and aspirin. We also examined the effect of the intervention on emergency department (ED) use.
WHAT IS KNOWN
The time from the onset of symptoms of acute coronary syndrome to arrival at the hospital continues to be far too long to achieve optimal benefit from reperfusion therapy in a majority of cases.
Three quarters of the time related to prehospital delay in acute coronary syndrome is the result of patients’ failure to call the emergency medical services.
Community education programs have been ineffective in changing prehospital delay times in acute coronary syndrome over the past 2 decades.
WHAT THE STUDY ADDS
This was the first randomized clinical trial of an educational intervention for patients at high risk for acute coronary syndrome.
The intervention did not result in reduced prehospital delay or increased emergency medical services use, but resulted in increased aspirin use by patients before hospital admission.
After review and approval of the study protocol by the institutional review boards at all the participating institutions, we enrolled 3522 patients with diagnosed ischemic heart disease into a randomized controlled trial known as PROMOTION (Patient Response to Myocardial Infarction Following a Teaching Intervention Offered by Nurses) from 2002 to 2004 and were followed for 2 years following their enrollment. Participants provided written informed consent before randomization. The study design has been described previously.11 Briefly, it consisted of randomization to 1 of 2 arms: (1) the experimental arm included a single face-to-face educational session conducted by a nurse with expertise in cardiology, followed by telephonic reinforcement at 1 month by the same nurse, or (2) the control arm consisting of usual care. Physicians caring for patients and nurses collecting follow-up data were blinded to study assignment.
Patients were recruited from in-hospital cardiovascular and cardiac catheterization units and from a variety of outpatient clinics, cardiac rehabilitation programs, and community medical practices in the United States (n=1985, 56%) and Australia or New Zealand (n=1537, 44%). Patients were eligible for the study if they had a diagnosis of ischemic heart disease, confirmed by their physician or hospital medical record, and if they lived independently (ie, not in an institutional setting). Patients were excluded if they had any of the following: complicating serious comorbidity such as a psychiatric illness or untreated malignancy, neurological disorder with impaired cognition, or inability to read or understand English.
Data were collected in 6 sites: Los Angeles, Calif; Lexington, Ky; San Diego, Calif; Seattle, Wash; Sydney, Australia; and Auckland, New Zealand. The University of California, San Francisco served as the project and data coordinating center.
Baseline data were collected by means of a face-to-face meeting conducted in a place convenient to the patient (eg, outpatient clinic, physician’s office, or patient’s home) after enrollment and before randomization. All data were collected using standardized paper and pencil instruments. Subsequent data using similar questionnaires were collected at 3, 12, and 24 months in the physician’s office or patient’s home, or by telephone after the patients had received a mailed copy of the data collection instruments. A summary of the study design and number of participants at each data collection point is presented in the Figure.
All patients were asked to inform the research office using a 24-hour toll-free number if they had sought medical treatment for symptoms of ACS. To encourage complete follow-up data, however, all participants were called every 6 months and asked if they had experienced ACS symptoms and sought medical care. In all cases of admission to the emergency department for a possible ACS event, medical records were reviewed to determine the admitting and discharge diagnoses, prehospital delay time, mode of transport to the hospital, and aspirin use before admission. Follow-up continued for 2 years. All data collected at each of the participating sites were entered via internet into a secure database specifically designed for the study with appropriate privacy safeguards as dictated by the Health Insurance Portability and Accountability Act.
The intervention was based on the Leventhal self regulatory model of illness behavior12,13 in which ACS symptoms serve as a stimulus that must be processed both cognitively and emotionally; an action plan is then developed, and its effectiveness is appraised by the patient, with the plan revised based on that appraisal. Patients received education in the 3 areas recommended to physicians by the National Heart, Lung, and Blood Institute Working Group on Educational Strategies to Prevent Prehospital Delay in Patients at High Risk for Acute Myocardial Infarction: namely, information about ACS, anticipated emotional issues, and social factors that could affect delay.5
Patients were given standardized information about typical and atypical symptoms of ACS and possible variability in symptom presentation. Patients were told that they might experience chest pressure or discomfort that was intermittent rather than constant, and that diaphoresis, shortness of breath, and pain radiation to parts of the body other than the left arm (eg, neck or back) were also possible symptoms of ACS. They were advised to call EMS immediately. At the time of the development of the educational intervention, patients who had no contraindiciations were encouraged to take one nonenteric coated aspirin before arrival at the hospital as well as nitroglygerin (if prescribed), and this instruction was included.14
Patients were asked to anticipate the emotional responses to ACS symptoms that might lead to delay, as well as to discuss their previous experiences accessing the medical system. The rewards of seeking treatment immediately were emphasized, and emotional issues were addressed through role playing scenarios that were standardized across intervention group patients.
Patients were asked to bring their spouse, another family member, or friend to the intervention session whenever possible. These individuals were “deputized” to act as the decision maker if the patient hesitated to call EMS. The potential reaction of the family member was discussed (eg, denial, fear, ambivalence, etc) and the importance of and rewards for quick action were underscored.
An advisory form5 that included the appropriate steps to take with onset of ACS symptoms was provided at the end of the intervention session. Patients were asked to post the advisory form in a prominent place in the house (eg, on the refrigerator or by the phone). The intervention was standardized with a flip chart so that patients and family members received the same information components, but it was tailored to the patient’s own past medical experience and unique living situation. The information was delivered in a quiet private outpatient setting such as a room in the clinic office or the patient’s home and was approximately 40 minutes in length. One month after the initial intervention session, the nurse who had provided the intervention called each patient and reviewed the main points from the initial session. The average length of the phone call was 15 minutes.
Time from symptom onset to hospital presentation was obtained from the hospital medical record or, in those cases with no notation in the medical record, from the EMS prehospital medical reports.
Mode of Transportation
Emergency department records were used to identify mode of transport to the hospital. To verify transport by the paramedic system, we checked all data against the EMS prehospital medical reports.
Aspirin use before hospital admission was evaluated by review of the ED medical record and verified by patient interview after emergency department admission.
Sociodemographic and Clinical Characteristics
All participants completed a paper and pencil questionnaire describing sociodemographic characteristics, insurance status, and clinical history. Race was obtained by self-report and was requested because previous researchers have identified race or ethnicity as variables influencing prehospital delay.2,8
Knowledge, Attitudes, and Beliefs About ACS
These variables were measured at baseline and at 3 and 12 months in both experimental and control groups as a test of the fidelity of the intervention using the ACS Response Index, an instrument originally developed for the Rapid Early Reaction for Coronary Treatment (REACT) study to measure knowledge, attitudes, and beliefs about coronary heart disease7 and modified for use in the current study.15 Reliability was tested using Cronbach α and was judged adequate at 0.82, 0.71, and 0.74, respectively for the 3 scales of knowledge, attitudes, and beliefs.
Baseline characteristics of the control and experimental groups were compared using χ2 tests for categorical data and independent t tests for continuous variables. To test the saliency of the intervention, we assessed knowledge, attitudes, and beliefs over time (baseline and at 3 and 12 months) using repeated measures ANOVA.
Because prehospital delay time was positively skewed, we used log-transformed prehospital delay times for all analyses to make the distribution more nearly Gaussian. Sample size was calculated based on the mean and median prehospital delay times previously identified in 474 AMI patients in sites similar to those proposed in the current study.16 In that study, mean delay was 11.2 (SD, 21.6) hours, with a median delay of 3.3 hours. Using the ln of the transformed mean (1.4) and SD (1.4), we targeted a 25% reduction in delay time, reflecting a small to medium effect size (0.2857, t =1.966). Using α=0.05 and β=0.20, data on 388 patients were required to have adequate power to detect a significant difference in the prehospital delay time between the 2 groups.17 Based on a previous study in which a reduction in delay to treatment of 30 minutes led to a significant reduction in morbidity and mortality,4 the target of a 25% reduction was identified as clinically significant.
A mixed linear model was used to assess the effect of the intervention on log transformed prehospital delay with the intercept parameters specified as random. In those cases where prehospital delay time was missing in the medical record or EMS record, values were not imputed. Similarly, a random-effects logistic model was used to compare the use of ambulance during emergency room visits and aspirin use between the experimental and control groups, and missing values were not imputed. Random effects were used in all analyses to account for the within-patient correlation of the outcomes because some patients had more than one emergency visit. Treatment assignment, time since randomization, and the time-by-treatment interaction, as well as age, gender, body mass index, insurance coverage for ambulance use, and medical history were treated as fixed effects based on previous research,1,2,5,6 suggesting that these variables might influence patients’ adherence to the recommended actions, our interest in understanding whether patients were more likely to follow recommendations in the time immediately after the intervention (ie, within 6 months) compared to a time more distant from the intervention session, and baseline differences between the experimental and control groups. Tests were 2-sided, and probability values <0.05 were considered statistically significant. All analyses were run using Stata 9.0 (Stata Corp) or SPSS 15.0 (SPSS, Inc).
On average, patients who enrolled in the study were 67 (SD, 11) years old, and 68% were male. The majority was married (71%), employed (72%), being cared for by a cardiologist (83%), and had insurance for visits to the ED (96%). A check on randomization revealed no significant differences between groups on a variety of demographic and clinical variables except for body mass index (P=0.048), gender (with more females in the experimental group than control, P=0.02), and insurance for ambulance use (with more patients with insurance in the control group compared to the experimental group, P=0.04; Table 1⇓).
Despite having a history of coronary heart disease, 38% of patients had significant gaps in knowledge about ACS at baseline, as documented by scores of less than 70% on the knowledge scale of the ACS response index. The mean cardiac knowledge score for the entire sample on the ACS response index was 71% (SD, 12%) with a range of 8% to 100%.18 There was no significant difference in baseline knowledge scores on the ACS response index between the 2 treatment groups at baseline (Table 1⇑). In comparing the groups over time, all 3 scales were significantly higher in the experimental group compared to the control group over time (P<0.0005), indicating that the intervention increased knowledge and influenced attitudes and beliefs in the hypothesized direction.
Of the 3522 subjects originally enrolled, 142 (4%) were deceased at 24 months, 75 (4.3%) in the experimental group and 67 (3.8%) in the control group (P=0.426). One hundred eighty-three (5.2%) were lost to follow-up, and 110 (3.1%) withdrew from the study. Therefore, the 2-year follow-up was conducted on 3087 (87.6%) subjects. A total of 565 (16.0%) patients presented to the ED with symptoms of ACS for a total of 842 admissions. Of the 565 patients, 260 (46%) were in the control group and 305 (54%) were in the experimental group. Of the 842 ED admissions, 408 (48%) were in the control group and 434 (52%) were in the experimental group. The patients who sought care for ACS symptoms are described in Table 2. Delay time was recorded in the medical record in 595 (71%) of the 842 cases. Data were available on the mode of transport in 708 (97.0%) cases and on the use of nonenteric coated aspirin by the patient before ED admission in 674 (92.3%) of cases.
Clinical outcomes are summarized in Table 3. The median time from symptom onset to hospital admission was 2.20 hours for the experimental group compared to 2.25 hours for the control group. The regression coefficient for the treatment variable was the difference in log times between the experimental and control groups, and this difference was not significant (P=0.40). Mean prehospital delay time was 22 minutes shorter on average in the experimental group than the control group, but this difference was not significant and was primarily caused by a few patients in the control group who incurred exceedingly long prehospital delay times (ie, greater than 12 hours). In an unadjusted mixed linear model analysis, the intervention resulted in a decreased prehospital delay time of 3.3% (95% CI, −10.9% to 4.3%; P=0.40) with the percent change calculated as the difference in prehospital delay times between the experimental and control groups divided by the control group prehospital delay time. When potentially confounding variables (ie, time since randomization, age, gender, body mass index, insurance for ambulance use, and medical history) were adjusted in the analysis, the intervention resulted in a decreased prehospital delay time of 1.02% (95% CI, −9.59 to 7.54; P=0.82).
Sixty-four percent of patients in the experimental group and 67% of patients in the control group used EMS. Comparing these values using an unadjusted random effects logistic model, the differences were not significant (P=0.89). However, using an adjusted random effects logistic model, we found an interaction between group assignment and time from randomization to symptom onset (P=0.009). We then compared patients who experienced symptoms within 6 months of study entry and those who experienced symptoms later than 6 months. Patients in the experimental group were more likely to use EMS if the ACS symptoms occurred early in the study (ie, within the first 6 months after group assignment; P=0.036). It was also noted that when all patients who used EMS were analyzed by country, 66.7% were Australian whereas only 33.3% were from the United States.
Approximately twice as many patients in the experimental group compared to control group took aspirin after symptom onset (22.3% versus 10.1% respectively), and the difference by group assignment was significant according to a mixed models random effects analysis (P=0.024). Using an adjusted random effects logistic model, the time from randomization to ED visit was a significant predictor of aspirin use (odds ratio, 1.93; CI, 1.09 to 3.43; P=0.024).
Receiving education and counseling about the need to respond quickly to ACS symptoms did not result in increased ED use. In fact, over the 2 years of follow-up 17.5% of patients in the control group sought care in an ED for symptoms of ACS compared to 14.6% of patients in the experimental group over the 2 years of follow-up. This difference in ED use between groups was not significant (P>0.05).
Today almost 14 million Americans have established coronary artery disease, which increases their risk for a future ACS event.19 Delay in contacting the health care system in the face of cardiac symptoms remains a major obstacle to definitive treatment of patients with acute myocardial infarction and may contribute to out-of-hospital cardiac deaths. The study reported here was the first randomized controlled trial designed specifically for a population at high risk for a future ACS event and targeting a reduction in prehospital delay. We documented the effects of a face-to-face tailored education and counseling intervention on prehospital delay time (the primary hypothesis), as well as EMS and aspirin use, as well as use of the ED (secondary hypotheses). The primary hypothesis was rejected. Although aspirin use was significantly higher in the experimental group, the use of EMS was not significantly different. However, use of ED resources was not significantly increased by the intervention.
The intervention was designed to encourage patients to personalize the message to seek care quickly in the face of ACS symptoms and to counter emotional coping mechanisms such as denial that might lead to prolonged prehospital delay time. The intervention protocol was based on the recommendations of the National Heart Attack Alert Program,5 and the findings were particularly disappointing given the tailored nature of the intervention and the high risk status of the sample for a future ACS event. Unlike previous interventions designed for community-dwelling individuals,7,10 the current study was tailored for patients aware of their risk for a future ACS event who could be expected to be more attentive to health messages than individuals living in the community.
On reflecting on the negative study findings of no difference in median prehospital delay times between the 2 experimental groups, several interpretations can be offered. First, data collection may have provided an unintended form of intervention in the control group. All patients enrolled in the current study completed questionnaires at baseline and at 3 and 12 months after enrollment and responded to questions in which they were asked to identify cardiac symptoms, describe their attitudes toward seeking help quickly if symptoms occurred, and state the level of their belief that the medical system had treatments that would help them if they sought care quickly. Reflecting on these questions at 3 different times and actively responding in writing to each of them may have sensitized control patients to the importance of seeking care early. Perhaps a third study arm that represented a true control without periodic assessment of knowledge, attitudes, and beliefs would have revealed that the data collection process itself was a form of intervention. The fact that, with the exception of the Physicians Health Study (median delay time of 114 minutes),20 the delay times in both the experimental and control groups was shorter than in all previous studies reported to date10 supports this interpretation.
Second, another explanation for the lack of effect of the face-to-face tailored intervention may be that the information presented did not address the variability of onset and the differing symptoms of ACS adequately or was not of sufficient intensity or duration to address the patients’ denial or inappropriate attribution of symptoms. The education and counseling session was delivered by a research nurse, not the patient’s physician. The latter may have been able to adapt the information provided the patient to the unique medical history, including the nature of previous ACS symptoms and patterns of response. Similarly, the fact that patients in the experimental group were more likely to call the EMS if ACS symptoms occurred early in the study (ie, in the first 6 months from enrollment) suggests that repetition of the information might increase the saliency of the intervention.
A third interpretation relates to difference between the 2 study groups. Despite randomization, there were significantly more women in the experimental group than the control group (34 versus 30% respectively, P=0.02). This difference may have contributed to the finding of no difference in median delay times, although gender was used as a covariate in the analysis. Although gender was not significantly different in the 2 groups who sought care for ACS symptoms (38 versus 32% in the experimental and control groups respectively, P=0.11), the difference in percentages may have favored longer median delay times in the experimental group. Some investigators6 have noted that women delay longer than men in seeking care for cardiac symptoms, although the reason for this difference by gender remains unknown. Similarly, the 2 groups who presented to the ED for symptoms of ACS were significantly different in their annual incomes and ambulance insurance, with the experimental group reporting lower income and less insurance coverage. Both factors would favor longer delays in the experimental group if patients were concerned about the cost of care and therefore may have contributed to the finding of no difference between the groups; however, these differences were handled as covariates in the analysis and therefore do not provide a strong explanation for the findings of no difference in prehospital delay times.
We were surprised at the high EMS use in both groups, which was twice the level of the 33% EMS use documented in REACT at baseline7 or the National Registry of Myocardial Infarction.21 Our findings may be a reflection of the large proportion of patients recruited from Australia and New Zealand (44%), where ambulance use is generally high and is covered by universal health care. In fact, 87% of all patients in the study had insurance coverage for EMS use, which may have contributed to the high ambulance use and the relatively short prehospital delay. Many investigators7,22 have noted the importance of accessing EMS to reduce prehospital delay time, as well as minimize delay to treatment once the patient is admitted to the hospital.
Although the intervention did not influence prehospital delay times or EMS use, it did result in a significantly higher percentage of patients who took aspirin in the face of acute symptoms. It is important to note that researchers have suggested that self treatment is a source of delay,23 and therefore the recommendation to take aspirin before hospital arrival is no longer given.24 However, our findings suggest that patients are willing to adopt this behavior, which is a relatively simple one compared to calling EMS. The significant difference between groups on this one outcome underscores the complexity of designing an intervention that will reduce the many psychological barriers to calling 911 that exist for patients and their family members in the face of ACS symptoms. Behaviors such as taking aspirin appear to be easier to change than calling EMS or seeking care in an ED immediately on onset of cardiac symptoms.
One of the concerns about conducting a large-scale intervention to decrease prehospital delay in ACS is that patients will become anxious and emergency department use will increase inappropriately. It is important to note that the intervention did not increase emergency room use in the experimental group, a finding that is similar to that of other community intervention studies.7,18,25
A relatively short, one-on-one education and counseling intervention significantly increased knowledge, attitudes, and beliefs about ACS and response to ACS symptoms. The intervention did not reduce prehospital delay time or increase EMS use, although it did increase the patients’ use of aspirin before arrival at the hospital. The decision to seek care promptly with the onset of ACS symptoms and use of EMS rather than other modes of transportation continues to be a significant public health challenge. Further research is required to determine how best to encourage patients who experience symptoms of ACS to seek care promptly.
The authors acknowledge Beverly Carlson, RN, MS, Sharp HealthCare, San Diego; Leanne M. Aitken, RN, PhD, Griffith University, Brisbane, Australia; Andrea Marshall, RN, PhD, University of Sydney, Sydney, Australia; Patricia Howard, RN, PhD, University of Kentucky; and Valerie Rose, BS, University of Washington, for their contributions to the study related to subject enrollment and data acquisition. They also acknowledge Yoshimi Fukuoka, RN, PhD, University of California, San Francisco, for her assistance with the statistical analysis.
Sources of Funding
The study was funded by the National Institutes of Health, National Institute of Nursing Research (R01 NR05323; Kathleen Dracup, principal investigator). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research or the National Institutes of Health.
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