Prognosis after myocardial infarction

INTRODUCTION — Survivors of a first acute myocardial infarction (MI) face a substantial risk of further cardiovascular events, including death, recurrent MI, heart failure, arrhythmias, angina, and stroke. Patients (and family members) often ask what their future holds; thus, information regarding prognosis after MI is necessary for patient care.

This topic discusses prognosis after MI secondary to obstructive coronary artery disease with or without plaque rupture. Prognosis after MI in the setting of less common entities such as MI with no obstructive coronary atherosclerosis, spontaneous coronary artery dissection, or stress (takotsubo) cardiomyopathy are presented separately. (See "Spontaneous coronary artery dissection", section on 'Sequelae' and "Management and prognosis of stress (takotsubo) cardiomyopathy", section on 'Prognosis' and "Myocardial infarction or ischemia with no obstructive coronary atherosclerosis".)

The outcomes discussed in this topic, such as mortality, are presented using pooled data. However, the prognosis may vary widely between individuals, according to the presence or absence of risk factors present before the MI. These risk factors are discussed elsewhere. (See "Risk factors for adverse outcomes after non-ST elevation acute coronary syndromes" and "Risk factors for adverse outcomes after ST-elevation myocardial infarction".)

The prognosis of young patients after MI is discussed separately. (See "Coronary artery disease and myocardial infarction in young people", section on 'Prognosis after MI'.)

The likelihood of subsequent events presented here are rough estimates. For most patients with MI, clinicians should risk stratify them using validated risk prediction models. This process is described in detail separately. (See "Risk stratification after acute ST-elevation myocardial infarction" and "Risk stratification after non-ST elevation acute coronary syndrome".)

The discussion of sudden cardiac death following MI is found elsewhere. (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction" and 'Adverse nonfatal outcomes' below.)

SHORT-TERM OUTCOMES — Reported outcomes, and in particular, mortality, will vary based on the population studied. While many of the reports come from randomized trials, we consider outcomes reported from registries to be a better gauge. Registries usually include broad populations, whereas trial participation is often limited by inclusion/exclusion criteria.

Mortality — Across the broad spectrum of patients with acute MI, short-term (in-hospital or 30-day) mortality has been decreasing over the past 30 years, concomitantly with the increasing use of reperfusion strategies and proven preventative therapies such as beta blockers, aspirin, and statins [1-9]. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

The 30-day mortality after all acute coronary syndromes (ST-elevation myocardial infarction [STEMI], non-ST-elevation myocardial infarction [NSTEMI], and unstable angina) is probably in the 2 to 3 percent range, but likely around 5 percent if patients with unstable angina are not included [10]. (See "Overview of the acute management of ST-elevation myocardial infarction".)

In a report that evaluated the interval 1987 to 2002, the 28-day case fatality fell from 5.3 to 3.8 percent [11]. A similar trend was noted in an analysis of data on 2.5 million patients from the National Registry of Myocardial Infarction in which in-hospital mortality after an acute MI declined from 10.4 percent in 1994 to 6.3 percent in 2006 [7].

Increasing age appears to predict increasing mortality [12].

STEMI — The 30-day mortality rate of patients with STEMI is between 2.5 and 10 percent in reports [10,13-17].

Both in-hospital and 30-day mortality rates after STEMI have been lower in clinical trials compared to registries and reports in patients not in clinical trials. This has been explained by enrollment of a lower risk population and better adherence to proven therapies in the former. Among patients with STEMI enrolled in trials, approximate in-hospital or 30-day mortality rates were 13 percent with medical therapy alone, 6 to 7 percent with optimal fibrinolytic therapy [18,19], and as low as 3 to 5 percent with primary percutaneous coronary intervention (PCI) when performed within two hours of chest pain onset [15,20,21]. (See "Primary percutaneous coronary intervention in acute ST elevation myocardial infarction: Determinants of outcome", section on 'Time from hospital arrival (door-to-balloon time)' and "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy".)

Somewhat higher in-hospital and 30-day mortality rates after STEMI have been described in patients not enrolled in clinical trials and cared for during a similar time period. The reported in-hospital mortality has been reported between 7 and 9.7 percent and the 30-day mortality between 11.1 and 14 percent for these patients [16,22,23]. A number of factors could contribute to this difference, including patient selection, less frequent use of appropriate therapies, and data collection before trials supporting the value of primary PCI [16,22-24].

More contemporary reports of patients not enrolled in trials have documented a continued decline in mortality in STEMI patients [13,14,25]. For example, outcomes were presented in a 2012 report of 6707 STEMI patients in four French nationwide registries conducted five years apart (1995, 2000, 2005, and 2010) [26]. The following findings were noted:

●There were significant decreases in crude 30-day mortality (from 13.7 to 4.4 percent) and mortality standardized to 2010 population characteristics (from 11.3 to 4.4 percent). These declines were seen irrespective of the type of reperfusion (fibrinolysis or PCI) and in patients who were not reperfused.

●Time from symptom onset to hospital admission decreased, with a shorter time from onset to first call, and broader use of mobile intensive care units.

●During this time, the average age fell and the prevalence of most risk factors increased.

●The use of reperfusion therapy increased from 50 to 75 percent, driven mostly by an increase of the use of PCI, as did the use of recommended preventative medical therapies.

●Within the STEMI population assessed in these registries, the relative proportion of older patients decreased, and the proportion of younger patients increased. These registry data suggest that future strategies aimed at further reducing acute MI incidence and mortality will need to specifically target prevention in younger patients. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

Some patients with acute STEMI present without modifiable cardiovascular risk factors such as smoking, hypertension, diabetes, or dyslipidemia (see "Risk factors for adverse outcomes after ST-elevation myocardial infarction", section on 'Factors present before MI'). The SWEDEHEART registry was used to analyze 30-day survival in adults with and without these traditional risk factors using dichotomous definitions for elevated cholesterol, diabetes mellitus, smoking, and blood pressure. Patients without these risk factors fared worse than persons with at least one risk factor [27]. All-cause mortality at 30 days was 11.3 percent in those without and 7.9 percent in those with at least one traditional risk factor. Key determinants for a worse prognosis were longer time from symptom onset to cardiac intensive care unit or emergency department admission, longer time for symptom onset to angiography, and occurrence of cardiogenic shock during the hospital stay. The authors found that evidence-based interventions at the time of a STEMI hospitalization were the key determinants of 30-day survival. This study has significant limitations. For example, patients without traditional outpatient risk factors using dichotomous definitions experienced greater mortality risk than would be expected. In addition, the authors used dichotomous risk factor definitions that appear to be derived from administrative data information and are probably much less accurate than what is in detailed clinical notes or in the epidemiology literature. The risk factor definitions used in the paper are not optimal or standard; for example, family history was not included. Finally, those individuals without risk factors might have included patients without atherosclerotic plaque rupture as the underlying mechanism (eg, spontaneous coronary artery dissection, microvascular disease, or stress cardiomyopathy). These individuals can represent up to 2 percent of acute STEMI patients, and their prognosis is likely different. Despite its limitations, this paper is important as it highlights limitations to our ability to prognosticate well in the individual patient.

NSTEMI — This category includes a wide spectrum of patients, leading to wide variation in mortality. Among patients with a non-ST-elevation acute coronary syndrome (NSTEACS), in-hospital or 30-day mortality has been about 2 percent in major clinical trials, lower than that seen in STEMI [28,29]. Although an early invasive strategy is now performed in most patients, because of reductions in recurrent MI or rehospitalization for an ACS, mortality rates in randomized trials were not significantly reduced in-hospital (or at six months) by this strategy [28,29].

The following studies include the range of findings for patients not enrolled in randomized controlled clinical trials:

●In the GRACE registry of over 16,000 patients from 14 countries seen between 2001 and 2007, the in-hospital mortality was 3.3 percent with NSTEACS [30].

●In the French registry of 1645 patients with NSTEMI managed with an invasive strategy in 2005, the in-hospital mortality was 2.0 percent [31].

●In the Worcester (Massachusetts, United States) Heart Attack Study, the hospital and 30-day post-admission case fatality rates for 2005 were 9.5 and 14.0 percent, respectively [32].

STEMI versus NSTEMI — While initial studies suggested that short-term mortality is lower in patients with NSTEMI (2 to 4 percent) compared with patients with STEMI (2.5 to 10 percent) treated with primary PCI within two hours of hospital arrival [10,20,21,23,28,29,33], other studies show no significant differences. An analysis of 5420 patients in the Kyoto registry showed no differences in both short- and long-term mortality in STEMI compared with NSTEMI patients [34]. Similarly, no differences were observed in a prospective study of 2151 patients in 56 medical centers in France [35].

Better short-term outcomes for patients with NSTEMI have also been noted in other studies (eg, in-hospital mortality 5 to 7 percent compared with 7.0 to 9.3 percent with STEMI in the GRACE and Euro Heart registries) [22,23,28].

Adverse nonfatal outcomes — Besides death, other patient-important outcomes include stroke, recurrent MI, heart failure, and major bleeding. In the GRACE registry of patients with NSTEACS discussed above, the rates of in-hospital heart failure or shock, MI, major bleeding, or stroke were 10, 2.4, 1.8, and 0.5 percent, respectively [30]. In the HORIZONS AMI randomized trial, the rate of stroke was around 1 percent and the rate of reinfarction was about 2 percent at 30 days [15].

Early rehospitalization — The rate of rehospitalization within 30 days after acute MI is reported to range between 17 and 25 percent [36,37]. In a single-community (Olmsted County, Minnesota, United States) study of 3010 patients who were hospitalized for a first-ever MI (31 percent STEMI) between 1987 and 2010, rehospitalization within 30 days occurred in about 19 percent [38]. Of these, 30 percent were and 43 percent were not related to the incident event. Diabetes, chronic obstructive pulmonary disease, anemia, higher Killip class (table 1), longer length of stay during the index hospitalization, and a complication of angiography or reperfusion or revascularization were associated with increased rehospitalization risk.

Additionally, the rate of rehospitalization at 30 days appears to be higher in females. (See "Risk factors for adverse outcomes after non-ST elevation acute coronary syndromes", section on 'Sex'.) In a study of 42,518 individuals aged 18 to 64 years, the 30-day all-cause readmission rate was higher for females (15.5 versus 9.7 percent; p = 0.01) [39]. This increase in risk persisted after adjustment but was of a smaller magnitude (hazard ratio, 1.22; 95% CI 1.15-1.3).

COVID-19 patients — Acute myocardial injury with troponin elevation occurs in approximately 20 percent of adults hospitalized with coronavirus disease 2019 (COVID-19) infection [40]. Higher troponin levels during hospitalization have been reported to adversely affect survival in COVID-19-infected patients [41,42]. Additional determinants of mortality following acute myocardial injury include diabetes, hypertension, and underlying cardiovascular disease (CVD) [43]. This issue is discussed in greater detail elsewhere. (See "COVID-19: Myocardial infarction and other coronary artery disease issues", section on 'Prognosis'.)

LONG-TERM OUTCOMES

Mortality — − Similar to short-term outcomes, long-term mortality rates after MI have declined over time, which correlates with improvements in reperfusion and preventative strategies. In an analysis of 23 published studies in which follow-up was completed prior to 1980, the death rate was about 28 percent at five years [44]. A report had a five-year death rate of about 21 percent in patients treated between 1989 and 1993 [45].

A 2022 report described the post-MI prognosis for 100,601 patients who survived an MI between 2005 to 2012 and had an outpatient risk factor assessment after hospital discharge [46]. Over a mean of 4.0 years of follow-up there were 31,622 all-cause deaths and 12,901 CVD deaths. At the postdischarge visit, older age, current smoking, atrial fibrillation, heart failure, peripheral artery disease, and lower body mass index were associated with worse prognosis, while statin therapy, hypertension medication, higher estimated glomerular filtration rate, and higher body mass index were associated with a lower risk of fatal outcomes.

The PEGASUS-TIMI 54 trial evaluated effects over three-year follow-up for ticagrelor added to aspirin therapy in persons who had survived an MI that occurred one to three years earlier (see "Long-term antiplatelet therapy after coronary artery stenting in stable patients", section on 'Treatment for longer than 12 months'). There was a 15 percent reduction in CVD death (2.9 versus 3.4 percent) [47]. Approximately 1 percent of the aspirin-only participants experienced TIMI major bleeding, and ticagrelor increased that risk more than twofold. Benefit for ticagrelor was observed in both diabetic and nondiabetic trial participants [48].

In contrast to the short-term outcomes, which are worse with STEMI, long-term outcomes have been similar or worse with NSTEMI [2,28,49-53]. The largest direct comparison comes from the GUSTO-IIb trial performed in the early 1990s of 12,142 patients with STEMI, NSTEMI (using only creatine kinase MB fraction, not troponins, for diagnosis), or unstable angina [49]. The mortality rate at 30 days was lower with NSTEMI than STEMI (3.8 versus 6.1 percent). In contrast, the mortality at one year was similar (8.8 for NSTEMI versus 9.6 percent for STEMI). However, outcomes from patients with NSTEMI managed more recently were lower in the ISAR REACT 4 trial, in which mortality at one year was about 4.4 percent. (See "Anticoagulant therapy in non-ST elevation acute coronary syndromes", section on 'Unfractionated heparin compared with bivalirudin'.)

In a community-based observational study of almost 6000 first MIs over a 23-year period, patients with an NSTEMI (compared to those with STEMI) had higher two-year mortality (20 versus 11 percent) [2]. Other registry reports suggest that, at one and two years, the cumulative mortality for NSTEMI exceeds that of STEMI patients. In the OPERA registry, cardiovascular outcomes were evaluated in 2151 consecutive patients (71 percent STEMI) with confirmed MI during 2002 and 2003 [35]. The STEMI patients were treated with primary percutaneous coronary intervention (PCI) (71 percent) or fibrinolytic therapy (29 percent), while PCI was performed in 52 percent of NSTEMI patients. In-hospital mortality was not different for both groups (4.6 versus 4.3 percent), while the one-year post-discharge mortality was higher with NSTEMI (8.2 versus 5.0 percent). In a report for the Worcester (Massachusetts, United States) Heart Attack Study, the one-year post-discharge case fatality rates in 2005 for patients with STEMI and NSTEMI were 8.4 and 18.7 percent, respectively [16].

Further evidence suggesting worse long-term outcomes with NSTEMI comes from a comparison of two studies that evaluated outcomes separately. A French registry evaluated outcomes in 1645 patients with NSTEMI managed with an invasive strategy during 2005 and found that mortality at three years was approximately 20 percent, with about half the deaths due to cardiovascular causes [31]. However, mortality at three years was around 6 to 7 percent in the HORIZONS AMI trial of patients with STEMI who underwent primary PCI [54].

The similar or worse long-term prognosis in NSTEMI is in part related to more than a 50 percent prevalence of multivessel disease in affected patients and to a greater likelihood of residual ischemia [49,55,56], indicating that in these patients, a significant amount of myocardium often remains at risk.

Sudden cardiac death — The broad discussion of sudden cardiac death (SCD) and sudden cardiac arrest is found elsewhere. (See "Overview of sudden cardiac arrest and sudden cardiac death" and "Pathophysiology and etiology of sudden cardiac arrest" and "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".)

The incidence of SCD after acute MI is the same with STEMI and NSTEMI [1,57]. Among patients who have had an MI and are followed for about four years, approximately one-half of sudden deaths occur in the first year and one-quarter in the first three months [58,59]. The risk is markedly increased in patients with a left ventricular ejection fraction ≤35 percent. (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction", section on 'Incidence of SCD'.)

Adverse nonfatal outcomes — While most patients are concerned about survival, many ask questions about other clinically important outcomes:

●Angina − A study of nearly 2000 patients who sustained an MI in 2003 or 2004 found that angina occurred in nearly 20 percent as early as one year and the determinants were younger age, male sex, not being a White person, prior angina, angina during the hospital stay, smoking continuation, depression, and coronary artery bypass graft surgery history [60].

●Recurrent MI and stroke – In the HORIZONS AMI trial, the risk of reinfarction or stroke at three years was approximately 6 to 7 and 1.5 to 2 percent, respectively [54].

Risk after an MI is not the same for all patients and prognosis can be estimated in the outpatient setting for survivors. The GRACE Study investigated subjects at the time of an acute coronary syndrome event and the key variables were age, heart rate, systolic pressure, creatinine, congestive heart failure, cardiac arrest at admission, ST segment deviation, and cardiac enzymes [61]. Other investigators have evaluated prognosis when the baseline evaluation is more than several months after a vascular disease event. For example, a report based on the two-year post-MI experience of 49,689 REACH Registry participants from around the world has shown that recurrent cardiovascular (CVD) disease and CVD death can be predicted with a simple algorithm. The core variables in the REACH prediction model were age, male sex, presence of peripheral vascular disease or cerebrovascular disease, diabetes, smoking, low body mass index, history of atrial fibrillation, heart failure, history of a CVD event in the past year, and favorable effects on risk were seen for statins and aspirin [62].

Similarly, in the SMART Study, after 4.7 years of follow-up for 5788 Dutch adults with coronary disease, peripheral arterial disease, or cerebrovascular disease at baseline, the key predictor variables for recurrent vascular disease were age, male sex, smoking, systolic pressure, total cholesterol, high density lipoprotein-cholesterol, high sensitivity C-reactive protein, estimated glomerular filtration rate, and years since first vascular event [63].

SOCIAL AND ENVIRONMENTAL FACTORS AND PROGNOSIS AFTER MYOCARDIAL INFARCTION — Prognosis following an MI is affected by social and environmental factors:

●Environmental factors – In an analysis across 567 cities in 27 countries, extreme ambient temperatures, either very hot (99^th percentile) or very cold (1^st percentile), were associated with a greater risk of mortality in persons known to have ischemic heart disease [64]. In a meta-analysis of 42 studies, greater exposure to air particles <2.5 micrometers in diameter was associated with increased risk of death and recurrent acute MI in persons with ischemic heart disease [65].

●Socioeconomic factors – Socioeconomic disadvantage has also been associated with greater long-term mortality for persons experiencing an MI prior to age 50 years, and the impact of social disadvantage was an independent risk factor for adverse outcomes [66].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Heart attack recovery (The Basics)")

●Beyond the Basics topics (see "Patient education: Heart attack recovery (Beyond the Basics)")

SUMMARY

●Survivors of a myocardial infarction (MI) face a substantial excess risk of further cardiovascular events, including an increase in mortality. However, the prognosis for an individual varies markedly according to the presence or absence of adverse risk factors. (See 'Introduction' above.)

●Short- and long-term death rates following MI have fallen substantially in the past few decades with improvements in medical care, particularly the widespread use of reperfusion techniques and the adjunctive use of multiple medical therapies. (See 'Short-term outcomes' above and 'Mortality' above.)

●The current 30-day mortality after all acute coronary syndromes (ST-elevation myocardial infarction [STEMI], non-ST-elevation myocardial infarction [NSTEMI], and unstable angina) is probably in the 2 to 3 percent range, but likely around 5 percent if patients with unstable angina are not included. (See 'Mortality' above.)

●Short-term mortality is lower in patients with NSTEMI (2 to 4 percent) compared to patients with STEMI (3 to 8 percent) treated with primary percutaneous coronary intervention within two hours of hospital arrival. (See 'STEMI versus NSTEMI' above.) Long-term mortality is similar or worse with NSTEMI. At one year, mortality is around 5 to 9 percent. (See 'Mortality' above.)