Self‐Administration of Aspirin After Chest Pain for the Prevention of Premature Cardiovascular Mortality in the United States: A Population‐Based Analysis
Journal of the American Heart Association
Abstract
Background
Aspirin, an effective, low‐cost pharmaceutical, can significantly reduce mortality if used promptly after acute myocardial infarction (AMI). However, many AMI survivors do not receive aspirin within a few hours of symptom onset. Our aim was to quantify the mortality benefit of self‐administering aspirin at chest pain onset, considering the increased risk of bleeding and costs associated with widespread use.
Methods and Results
We developed a population simulation model to determine the impact of self‐administering 325 mg aspirin within 4 hours of severe chest pain onset. We created a synthetic cohort of adults ≥ 40 years old experiencing severe chest pain using 2019 US population estimates, AMI incidence, and sensitivity/specificity of chest pain for AMI. The number of annual deaths delayed was estimated using evidence from a large, randomized trial. We also estimated the years of life saved (YOLS), costs, and cost per YOLS. Initiating aspirin within 4 hours of severe chest pain onset delayed 13 016 (95% CI, 11 643–14 574) deaths annually, after accounting for deaths due to bleeding (963; 926–1003). This translated to an estimated 166 309 YOLS (149391–185 505) at the cost of $643 235 (633 944–653 010) per year, leading to a cost‐effectiveness ratio of $3.70 (3.32–4.12) per YOLS.
Conclusions
For <$4 per YOLS, self‐administration of aspirin within 4 hours of severe chest pain onset has the potential to save 13 000 lives per year in the US population. Benefits of reducing deaths post‐AMI outweighed the risk of bleeding deaths from aspirin 10 times over.
Nonstandard Abbreviations and Acronyms
- ISIS‐2
- International Study of Infarct Survival
- YOLS
- years of life saved
Research Perspective
What Is New?
•
Over 13 000 deaths would be delayed per year if adults experiencing severe chest pain took aspirin within 4 hours without imposing significant harm or costs.
What Question Should Be Addressed Next?
•
Future research should investigate best practices for increasing awareness of heart attack symptoms as well as encouraging carrying and self‐administration of aspirin.
Acute myocardial infarction (AMI) is a leading cause of mortality in the United States (US), with > 300 000 deaths in 2019. The American Heart Association estimated that approximately every 40 seconds, someone in the United States has an AMI, translating into 605 000 incident cases.1 Aspirin is a cost‐effective pharmaceutical for reducing mortality after AMI. The International Study of Infarct Survival (ISIS‐2), one of the largest randomized control trials (RCTs) of aspirin use, found that 28‐day aspirin use initiated within 4 hours of symptom onset reduced cardiovascular mortality by 25%.2 The relative risk (RR) reduction of aspirin has been found to be highest when aspirin is administered earlier, closer to symptom onset.3
Yet, more than three quarters (78%) of AMI deaths occur outside the hospital.1 Only 45.5% of patients with chest pain who were later diagnosed as experiencing an AMI accessed medical care within 4 hours of symptom onset.4 Less than half of emergency medical dispatchers or technicians recommended or gave aspirin to patients with chest pain,5, 6 though the 2007 American College of Cardiology and American Heart Association Guideline for the Management of Patients with Unstable Angina and non‐ST‐Elevation Myocardial Infarction recommends that emergency medical dispatchers administer aspirin to patients experiencing chest pain. These guidelines do not encourage self‐administration of aspirin by patients after chest pain, possibly due to low specificity of chest pain as a symptom of AMI and for fear of side effects. Aspirin increases risk of gastrointestinal and intracranial bleeding, potentially leading to substantial and unnecessary loss of life.7 The 2014 Guideline for the Management of Patients With Non–ST‐Elevation Acute Coronary Syndromes suggests aspirin should be given to all patients with acute coronary syndromes without contraindications8 but does not explicitly mention chest pain symptoms and more recently the Guideline for the Evaluation and Diagnosis of Chest Pain does not mention aspirin use at all.9
Here we quantify the potential population‐level effect of self‐administering aspirin within 4 hours of severe chest pain onset to reduce mortality post‐AMI, using the US population as a case study, and estimate the increased risk of death due to bleeding. We also report the net impact on annual deaths, the years of life saved (YOLS), costs, and cost‐effectiveness of this intervention.
Methods
We parameterized and applied a group‐based population simulation model to quantify the effect of early self‐administration of aspirin on death from AMI versus deaths from gastrointestinal and intracranial bleeding (Figure 1). All adults over the age of 40 experiencing severe chest pain, with or without AMI, who self‐administered aspirin within 4 hours of chest‐pain onset were expected to experience 1 of 4 possible outcomes: fatal AMI, nonfatal AMI, death due to excessive bleeding (defined as gastrointestinal or intracranial hemorrhage), or AMI‐free survival. The main outcome of interest was net deaths delayed post‐AMI, accounting for aspirin‐related deaths from bleeding. Secondary outcomes of interest were YOLS, total cost of aspirin, and cost of aspirin per YOLS.
Figure 1. Model structure depicting the change in risk comparing usual care scenario with 100% adherence to an early aspirin intervention ≤4 hours of chest pain onset.
AMI indicates acute myocardial infarction; and MI, myocardial infarction.
Study Population and Data Sources
We created a synthetic cohort of US adults ≥ 40 years old by 5‐year age group and sex using the population data from the US Census 2019 (because data from the 2020 Census were not yet available).10 Table 111, 12, 13, 14, 15, 16, 17 summarizes the model parameters and sources of the data. All supporting data used to parameterize the model are available within the article and its online supplement. Simulation code and data files have also been made available online: https://github.com/rirusso/Aspirin‐Simulation.
| Parameter | Description | Value |
|---|---|---|
| US Population | Age*‐sex specific estimates for US population in 2019 from US Census Bureau10 | Total men ages ≥40 y: 74 652 614 Total women ages ≥40 y: 82 650 711 |
| MI, GIH, and ICH mortality rates | Age‐sex specific mortality rates from the Centers for Diseases Control and Prevention (CDC) Wonder 201911, 12, 13 | Tables S1 and S4 |
| Sensitivity of chest pain for MI | Pooled estimates of sex‐specific sensitivity of chest pain for MI from updated meta‐analysis‡ of 13 studies with 1 223 190 participants14 | Men: 84% (95% CI, 78%–88%) Women: 79% (95% CI, 74%– 84%) |
| PPV of chest pain for MI | Pooled estimate from 11 studies with 111 545 participants (Tables S2 and S3; Figures S2 and S3) | PPV: 0.1682 (95% CI, 0.13–0.21) |
| RR reduction for MI due to aspirin | RR reduction of death within 28 d post MI for 325 mg aspirin used within 4 h and between 4 and 24 h from a RCT with 17 187 cases of MI3 | RR reduction: ≥4 h 25% (SD 7) <4 h 21% (SD 5) |
| RR of excessive bleeding due to aspirin | RR of excessive gastrointestinal or intracranial bleeding among aspirin users, from meta‐analysis of 11 studies15 | RR: 1.47 (95% CI, 1.31–1.65) |
| 28‐d CFR | Age‐sex specific 28‐d case fatality rate for MI† from the Globorisk estimates for high‐income North American countries12 | Table S5 |
| Life expectancy estimates | Age‐sex specific life expectancy from the CDC's National Vital Statistics System16 | Table S6 |
| Current aspirin use | Proportion of individuals with chest pain experiencing AMI who received aspirin >4 h of symptom onset from the National Registry of Myocardial Infarction4 | 55.5% |
| Cost for aspirin | Oral chewable aspirin tablet, 325 mg17 | $0.10 per tablet |
CDC indicates Centers for Disease Control and Prevention; CFR, case fatality rate; GIH, gastrointestinal hemorrhage; ICH, intracranial hemorrhage; MI, acute myocardial infarction; PPV, positive predictive value; RCT, randomized control trial; RR, relative risk; and US, United States.
*
By 5‐y age groups.
†
Ischemic heart disease is approximating MI since stable angina is chronic.
‡
Meta‐analysis was re‐pooled after identifying an article that met exclusion criteria for specific chest pain.
Usual Care Scenario
We quantified the number of incident AMI cases in the United States by age and sex using counts of AMI‐related deaths (defined using International Classification of Diseases, Tenth Revision [ICD‐10] codes I21, I22, I24, I45, I49, and I51), and 1‐year case fatality rates of ischemic heart disease from the United States and Canada, from a review of the global literature (Table S1).11, 12, 13 To estimate the number of AMI cases who experienced severe chest pain, we multiplied the age‐sex specific incidence of AMI with sex‐specific sensitivity of severe chest pain derived from an updated meta‐analysis of 13 studies.14
Self‐Administration of Aspirin Scenario
We examined the effect of full coverage of starting self‐administration of aspirin within 4 hours of severe chest pain onset using 325 mg aspirin tablets (which is the standard high‐dose formulation in the United States) and continuing treatment for 28 days if an AMI was diagnosed, regardless of need for emergent surgical procedures. This is consistent with guidelines that indicate aspirin may be continued throughout the perioperative period before cardiac surgery, without major risks.18 If severe chest pain did not lead to a diagnosis of AMI, patients would of course discontinue taking aspirin after the first dose. We applied the benefit only to individuals experiencing severe chest pain under the “usual care” scenario to receive aspirin either late or never (Figure S1). We approximated this target population by combining 2 different estimates. First, as a proxy for access to care after AMI, we used the proportion of AMI deaths occurring in a health care facility (defined as hospice facility, inpatient medical facility, outpatient medical facility, and nursing home/long‐term care) versus those occurring outside health care facilities. Data on this proportion were derived from the vital statistics report analyzed by the Center for Disease Control and Prevention for 2019 by age and sex.11 Almost all individuals who accessed care (97.4%) received aspirin within 24 hours of arrival, based on quality of care metric data from the American College of Cardiology Chest Pain‐MI Registry reported in the Heart Disease and Stroke Statistics Report for 2022. Disaggregated data by age and sex were not reported. Second, we used evidence on the proportion of patients receiving aspirin late (ie, >4 hours after symptom onset) from an analysis of hospital discharge data from almost half a million AMI patients enrolled in the National Registry of Myocardial Infarction, which found that 55.5% of all patients received aspirin >4 hours after the event.4
Benefits of Early Aspirin Use
We derived 2 mortality benefits from early aspirin use based on the relative reduction in mortality after 28 days of AMI from the ISIS‐2 trial.2 ISIS‐2 was a RCT with a 2 × 2 factorial design. Patients who presented within 24 hours of symptom onset were assigned 162.5 mg aspirin. Use of aspirin within 4 hours of symptom onset led to a 25% reduction in 28‐day cardiovascular mortality and starting aspirin between 4 to 24 hours of symptom onset led to a 21% reduction in 28‐day cardiovascular mortality compared with no use. Doses higher than 160 mg were not associated with additional benefits but could confer greater risk of bleeding; therefore, we did not scale the RR reduction in mortality associated with a 160 mg aspirin pill from the ISIS‐2 trial to 325 mg in the present analysis. To quantify the annual number of AMI deaths delayed, we applied a 5% mortality benefit to individuals who currently receive aspirin late but would now self‐administer within 4 hours of symptom onset, and the 25% mortality benefit to the individuals who currently receive no aspirin.
Harms of Aspirin Use
To assess potential harms, we considered risk of death from gastrointestinal and intracranial hemorrhaging, which may be increased from aspirin use. Individuals who were eligible to receive aspirin under the intervention were at risk for bleeding deaths. This translates to the population of adults >40 years old receiving aspirin never or >4 hours of chest pain onset. We quantified the estimated number of bleeding deaths using the following: (1) the estimated number of people experiencing severe chest pain each year who do not receive aspirin within ≤4 hours, (2) the RR of severe gastrointestinal hemorrhage and intracranial hemorrhage associated with one‐time aspirin15 use by age and sex, and (3) annual mortality rates from gastrointestinal hemorrhage and intracranial hemorrhage obtained from Centers for Disease Control (CDC) Wide‐ranging Online Data for Epidemiologic Research (WONDER) in 2019 (Table S3).11 In addition to the populations experiencing AMI but receiving aspirin >4 hours, to whom we applied both mortality benefits and risks, we also included individuals experiencing severe chest pain with no AMI to quantify mortality risks. We estimated this population by subtracting the positive predictive value (PPV) of severe chest pain (ie, the ratio of AMI cases with chest pain to all individuals who experience severe chest pain for each age‐sex group), from the annual AMI incidence with chest pain and then dividing by the PPV of severe chest pain for AMI.
To quantify the PPV, we conducted a de novo systematic review and meta‐analysis of studies examining the incidence of AMI among individuals experiencing undifferentiated severe chest pain. Studies were primarily hospital‐based, in which patients being admitted to the emergency room with the chief complaint of chest pain were followed up for the occurrence of AMI. Eleven articles met our inclusion criteria (Tables S4 and S5; Figures S2 and S3), and the pooled PPV was 16.82%, (ie, 17% of patients who experienced severe chest pain had an AMI).
To quantify the relative risk of excessive bleeding from 325 mg aspirin daily, we used evidence from a meta‐analysis of 11 randomized control trials that reported a RR of 1.47 for long‐term daily aspirin use. Considering that the average cumulative dose of aspirin in the 11 trials was 331 g and using a log‐linear dose–response curve, the RR of bleeding for 28‐day daily 325 mg aspirin use was estimated to be 1.011 (ie ). We added an additional 325 mg to the cumulative dose when estimating the additional bleeding risk for patients who received aspirin >4 hours but <24 hours after an AMI.
Net Deaths Delayed and YOLS and Associated Costs
We quantified the net impact of early self‐administration of aspirin on mortality post‐AMI by subtracting aspirin‐related bleeding deaths from deaths delayed from AMI, for each age‐sex group. The number of YOLS was estimated as the product of net deaths delayed and life expectancy at the midpoint of the 5‐year age interval from the CDC's National Vital Statistics Life Expectancy Tables (Table S6).16 Total cost of aspirin was calculated as the product of the cost of 28‐day daily 325 mg aspirin (US $0.10 per tablet in 2021)17 and the number of individuals eligible for the early aspirin intervention. We reported cost per YOLS by age and sex and for the entire adult population of the United States.
Sensitivity Analysis
We varied the ICD‐10 codes used to define AMI‐related deaths (ie, deaths directly due to AMI or deaths from consequences of an AMI). In our most conservative approach, we restricted AMI‐related deaths to include only acute AMI and cardiac arrest (ICD‐10 codes I21 and I49), resulting in an estimated 347 232 cases of incident AMI in 2019 (Table S7). In our least conservative approach, we added a proportion of deaths from heart failure (ICD‐10 code 50.9), using 34% as the best estimate of heart failure cases attributable to coronary artery disease,19 resulting in an estimated 516 192 cases of incident AMI in 2019 (Table S7). We also restricted the meta‐analysis for the PPV of severe chest pain for AMI to include only studies conducted in the United States (n=5; Figure S4) and explored using the less conservative estimate of the PPV at 19.6% (Table S8).
Statistical Uncertainty Analysis
We propagated sampling uncertainty for deaths delayed, aspirin‐related bleeding deaths, and net deaths delayed using the standard errors of the input parameters.20, 21 Uncertainty estimates of input parameters were available for sex‐specific sensitivity of severe chest pain for AMI, emergency medical services‐administered aspirin, 4‐hour delay to care, the RR reduction of aspirin on AMI mortality, the RR of excess bleeding due to aspirin as well as our pooled effect‐estimate of the PPV of severe chest pain for AMI. We simulated distributions based on input parameter uncertainty estimates and took 10 000 independent random samples to calculate effect sizes and uncertainty of our 3 outcomes of interest. The median of the 10 000 simulations was used as the point estimate for each outcome, and 95s) were the 2.5th and 97.5th percentiles of the simulations.
Analyses were conducted in RStudio (version 4.1.1) and Stata (version 15.1, StataCorp LLC, College Station, TX).
Ethics and Approvals
The study was based on de‐identified secondary data sources that were publicly available and therefore not considered human subjects research.
Results
We estimated that >2 million (2 294 336 [95% CI, 2211384–2 385 061]) adults aged 40 years and older in the United States experienced severe chest pain in 2019. Out of this population, 351 493 adults had an AMI, with 158 834 being women (45.2%) and 192 659 being men (54.2%). Under the usual care scenario, we estimated there were 92 372 deaths from AMI in persons with severe chest pain (37 658 women [41.8%] and 54 714 men [59.2%]).
Early self‐administration of 325 mg aspirin was estimated to delay 13 980 (12 602, 15 536) AMI deaths in the United States in 2019 (Table 2 and Figure 2). However, this scenario also led to an estimated 963 (926, 1003) excess bleeding deaths, leading to a net death delayed of 13 016 (11 643, 14 574). Overall, there were more deaths delayed post‐AMI and aspirin‐preventable deaths in men than in women (net deaths delayed: 7922 versus 5093). The absolute net benefit was greatest among older adults.
| Age Group (y) | Annual MI Deaths Delayed† | Annual Excess Bleeding Deaths* | Annual Net Deaths Delayed |
|---|---|---|---|
| Women (N=1 002 012) | |||
| 40–44 | 53 (48–59) | 1 (1–1) | 52 (47–58) |
| 45–49 | 94 (85–105) | 2 (2–2) | 92 (83–103) |
| 50–54 | 162 (147–181) | 4 (4–4) | 158 (143–177) |
| 55–59 | 279 (252–310) | 9 (8–9) | 270 (243–301) |
| 60–64 | 413 (374–460) | 13 (12–13) | 401 (361–447) |
| 65–69 | 479 (433–533) | 17 (16–18) | 462 (416–516) |
| 70–74 | 584 (527–650) | 27 (26–28) | 557 (500–623) |
| 75–79 | 645 (583–718) | 40 (38–41) | 605 (543–678) |
| 80–84 | 696 (628–774) | 62 (59–64) | 634 (567–713) |
| 85 plus | 2073 (1873–2308) | 211 (202–220) | 1862 (1663–2098) |
| Total | 5478 (4950–6098) | 384 (368–400) | 5094 (4566–5715) |
| Men (N = 1 292 324) | |||
| 40–44 | 129 (117–144) | 1 (1–1) | 129 (116–143) |
| 45–49 | 330 (299–367) | 3 (3–3) | 327 (296–364) |
| 50–54 | 438 (396–487) | 5 (5–5) | 433 (391–482) |
| 55–59 | 742 (671–825) | 10 (10–11) | 732 (661–815) |
| 60–64 | 1025 (926–1139) | 17 (17–18) | 1007 (909–1122) |
| 65–69 | 1126 (1018–1252) | 23 (22–24) | 1104 (996–1229) |
| 70–74 | 1119 (1011–1244) | 34 (33–36) | 1084 (977–1209) |
| 75–79 | 1025 (927–1139) | 54 (52–57) | 971 (872–1085) |
| 80–84 | 937 (847–1042) | 88 (85–92) | 849 (757–954) |
| 85 plus | 1634 (1476–1816) | 343 (330–358) | 1290 (1130–1474) |
| Total | 8506 (7689–9455) | 579 (557–604) | 7928 (7106–8874) |
| Overall | 13 983 (12 635–15 545) | 963 (925–1004) | 13 021 (11 661–14 582) |
MI indicates myocardial infarction.
*
Deaths associated with gastrointestinal or intracranial hemorrhage from aspirin use.
†
Deaths delayed post‐acute myocardial infarction.
Figure 2. Net number of annual deaths delayed with early aspirin use after severe chest pain after accounting for excess bleeding deaths among adults ages 40+ years in the United States, 2019.
Across all age groups, there were 166 309 (149 391, 185 505) YOLS in 2019, with an estimated cost of $643 235 ($633 944, $653010) for aspirin pills taken by individuals experiencing chest pain (Table 3). This translated to an average cost‐effectiveness ratio of $3.70 (3.32, 4.12) per YOLS. This ratio was fairly constant across age‐sex groups and ranged from $3.29 to 7.22 per YOLS in women and from $2.56 to 7.38 in men.
| Age Group (y) | Years of Life Saved | Cost of Aspirin Pills ($) | Cost of Saving 1Year of Life ($/Year) |
|---|---|---|---|
| Women (N=1 002 012) | |||
| 40–44 | 2083 (1889–2311) | 6609 (6495–6726) | 3.17 (2.86–3.50) |
| 45–49 | 3181 (2876–3539) | 11 660 (11 465–11 862) | 3.67 (3.30–4.06) |
| 50–54 | 4664 (4210–5195) | 17 597 (17 309–17 893) | 3.77 (3.39–4.18) |
| 55–59 | 6756 (6090–7536) | 26 074 (25 642–26 521) | 3.86 (3.46–4.28) |
| 60– 64 | 8342 (7517–9308) | 31 312 (30 791–31 852) | 3.75 (3.37–4.17) |
| 65–69 | 7801 (7026– 8711) | 28 892 (28 399–29 403) | 3.70 (3.32–4.12) |
| 70–74 | 7327 (6589–8193) | 30 041 (29 519–30 580) | 4.10 (3.67–4.56) |
| 75–79 | 5957 (5347–6674) | 28 330 (27 830–28 847) | 4.76 (4.25–5.30) |
| 80–84 | 4455 (3989–5009) | 26 772 (26 288–27 269) | 6.01 (5.35–6.72) |
| 85 plus | 8951 (7997–10 082) | 66 107 (64 910–67 336) | 7.38 (6.56–8.28) |
| Total | 59 516 (53 522–66 562) | 273 391 (268 659–278 275) | 4.06 (3.64–4.52) |
| Men (N=1 292 324) | |||
| 40–44 | 4487 (4062–4979) | 11 464 (11 289–11 643) | 2.56 (2.30–2.83) |
| 45–49 | 9865 (8918–10 965) | 29 511 (29 051–29 981) | 2.99 (2.69–3.31) |
| 50–54 | 11 188 (10 106–12 441) | 35 509 (34 970–36 059) | 3.17 (2.85–3.52) |
| 55–59 | 16 017 (14 461–17 821) | 49 733 (48 980–50 498) | 3.11 (2.79–3.44) |
| 60–64 | 18 281 (16 501–20 349) | 55 277 (54 441–56 125) | 3.02 (2.72–3.36) |
| 65– 69 | 16 150 (14 572–17 985) | 49 891 (49 129–50 668) | 3.09 (2.77–3.43) |
| 70–74 | 12 281 (11 067–13 690) | 41 641 (40 985–42 310) | 3.39 (3.04–3.77) |
| 75– 79 | 8176 (7346–9136) | 32 405 (31 886–32 937) | 3.97 (3.55–4.42) |
| 80–84 | 5108 (4560–5737) | 26 137 (25 708–26 577) | 5.12 (4.56–5.73) |
| 85 plus | 5298 (4644–6052) | 38 224 (37 593–38 872) | 7.22 (6.31–8.24) |
| Total | 106 849 (96 259–119 141) | 369 797 (364 043–375 671) | 3.29 (2.95–3.66) |
| Overall | 166 363 (149 677–185 630) | 643 177 (633 465–652 990) | 3.70 (3.32–4.11) |
Sensitivity Analysis
The more conservative definition of AMI‐related deaths resulted in 10 169 (9053, 11 388) net annual deaths delayed, which were associated with a total cost of aspirin pills of $3.71 per YOLS while the less conservative definition of AMI‐related deaths resulted in 15 327 (13 637, 17 174) net annual deaths delayed, which were associated with a total cost of aspirin pills of $3.70 per YOLS. (Tables S9 and S10). When using the alternative estimate of PPV from US studies only, bleeding deaths were slightly lower than the main analysis, leading to 13 142 (11 766, 14 708) net deaths delayed, associated with a cost of aspirin pills per YOLS of $3.54 (3.18, 3.94).
Discussion
We estimated significant population‐level benefits to self‐administering aspirin within 4 hours of onset of severe chest pain, resulting in >10 000 net annual deaths delayed in adults aged 40 years and older in the United States in 2019. Bleeding deaths due to aspirin use were small and did not outweigh the substantial benefits of deaths delayed post‐AMI. The use of aspirin was cost‐effective overall and within age‐sex groups, with an average estimated cost per YOLS <$4 US dollar. The costs are orders of magnitude lower than the thresholds of $50 000 per quality‐adjusted life year used in many cost‐effectiveness analyses.
Several studies have recommended the need for more research quantifying the effect of aspirin self‐administration given the potential for significant population‐level benefits.3, 22 Low self‐administration (8%–24%) has been reported in a few studies examining prehospital aspirin use among patients with AMI admitted to the hospital with suspected cardiac chest pain.23, 24 A randomized trial was conducted in the late 1990s aimed at increasing the use of emergency medical services and aspirin among adults over the age of 65 experiencing symptoms of AMI.25 The intervention involved a door‐to‐door campaign by firefighters who provided a Heart Attack Survival kit that included educational resources and a packet of high‐dose, 325 mg aspirin. The intervention was moderately successful, increasing health care–seeking behavior, including 911 calls, as well as reports of aspirin use during chest pain. Longer‐term health impacts were not evaluated, similar to other research on prehospital aspirin use that focuses predominantly on health care utilization and aspirin administration by health care professionals.22, 26, 27 The Noncomunicable Diseases Countdown (NCD) 2030 Health Policy Report, which evaluated 15 interventions to reduce AMI‐related mortality at the population‐level, found that nurse‐administered aspirin for patients seeking care with reports of chest pain was the most cost‐effective, at $0.075 per disability‐adjusted‐life‐years averted.28
Self‐administration of aspirin would have immediate population‐level effects on AMI mortality. In contrast, other effective secondary prevention strategies rely on longer‐term daily adherence and maintained changes. These include early statin treatment post AMI, which was estimated to avert 7450 AMI deaths annually and cost $16 000 to $210 000 per YOLS.29 The reach and effectiveness of these strategies is contingent upon individual income, education, and other sociodemographic factors, which in turn influence health care insurance coverage and medical literacy. While efforts should continue to scale up access to other pharmaceutical therapies such as statins, as well as encourage dietary improvements, self‐administration of aspirin alone can drastically reduce AMI mortality without imposing financial strains or requiring long‐term behavioral change.
Prior research has investigated methods to increase utilization of aspirin. Adults over the age of 65 who received an educational campaign from local firefighters and the Heart Attack Survival kit reported a 4.3 percentage point increase in self‐administration of aspirin during chest pain.22 Additional strategies could include encouraging all individuals to keep 325 mg aspirin tablets on hand, advocating for self‐administration of aspirin during severe chest pain in media campaigns, and educational materials focused on heart attack symptoms and overall heart health, which would result in little additional costs but could vastly improve knowledge.30
Encouraging patients to carry and self‐administer a therapeutic is not a novel prevention strategy. Individuals with severe allergies are told to carry epinephrine to reduce the risk of death from anaphylaxis. A recent advisory from the US Surgeon General calls for individuals taking opioids to keep naloxone on hand to prevent overdose deaths. Even within the field of cardiovascular disease, a new injectable antiplatelet is in development, intended for patients with a history of AMI to self‐administer at the onset of AMI symptoms. Efforts needed to scale‐up the use and advertise benefits of aspirin could draw from previous work encouraging self‐administration of these other therapeutics. We anticipate that uptake of aspirin self‐administration may be high given the low‐cost and oral route of administration.
There are a few assumptions and limitations to note. We assumed that the benefits of early aspirin use would also apply to individuals taking daily low‐dose aspirin for primary prevention. This is supported by pharmacodynamic studies examining different dosing regimens, which found that high‐risk patients with cardiovascular disease had greater inhibition of platelet reactivity when given higher doses of aspirin.31 Limited data availability prevented us from calculating age‐ and sex‐specific PPV of severe chest pain for AMI as well as mortality RR reduction for aspirin; thus, we assumed these parameters apply to all age‐sex groups. Moreover, we focused on chest pain alone, rather than considering shortness of breath, diaphoresis or other pain, because this is the most reliable sign of an AMI. We only examined the net benefits of aspirin on mortality, ignoring nonfatal bleeding risks, which may similarly be negligible in comparison to nonfatal benefits. Lastly, we did not include the cost of an education dissemination campaign to encourage aspirin use at severe chest pain onset in our cost‐effectiveness analysis, though we expect additional costs of such campaign would be unlikely to exceed the threshold for cost‐effectiveness based on past research (ie, $50 000/YOLS).22
Our analyses had many strengths. We used a population‐based simulation model. Data inputs from this model were derived from meta‐analyses and randomized control trials, when possible, and counts from death certificates. We propagated statistical uncertainty for model parameters for which uncertainty data were available. Overall, our findings are conservative. All 3 definitions of AMI‐related deaths resulted in estimates of annual AMI incident cases that were substantially lower than those reported by the American Heart Association, which had applied the incidence of AMI in the Atherosclerosis Risk in Communities Study to the US population.1
Using the United States as a case study, we estimated that self‐administration of aspirin after experiencing nonspecific, severe chest pain has enormous potential to save lives, without imposing significant costs or harms. These findings may also be applicable to other countries, especially high‐income countries with a similar cardiovascular disease burden. Self‐administration of aspirin at onset of severe chest pain differs from other secondary prevention efforts in that the benefits are largely independent of personal resources or health care access. Scaling up self‐administration of aspirin will still be a challenge, because this requires increased access and knowledge of patients. Many adults remain unaware of the symptoms of and appropriate response to AMI, with knowledge levels varying with sociodemographic characteristics.32 Because case fatality rates for AMI tend to be higher among disadvantaged subgroups,33 self‐administration of aspirin may also reduce racial/ethnic and social disparities in AMI mortality.
Sources of Funding
R.G.R. reports support from NIH Pre‐Doctoral Training Grant T32 HL098048. The funders had no role in considering the study design, in the collection, analysis, or in the interpretation of data, in the writing of the report, or in the decision to submit the article for publication.
Disclosures
None.
Acknowledgments
Author contributions: G.D. and D.W. conceived the study. G.D., D.W., and K.R. provided expert opinions on intervention design and implementation. R.G.R. and G.D. designed the model and R.G.R. performed the analyses. R.G.R. wrote the manuscript with input and feedback from all authors.
Footnotes
This manuscript was sent to Mahasin S. Mujahid, PhD, MS, Associate Editor, for review by expert referees, editorial decision, and final disposition.
Supplemental Material is available at Supplemental Material
For Sources of Funding and Disclosures, see page 8.
Supplemental Material
Data S1
References 34–44
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Received: 15 December 2023
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