Abstract
The present study aimed to investigate temporal trends in myocardial infarction (MI) presentation with or without ST-segment elevation and the association with the use of cardioprotective drugs prior to admission.
Using individual-level linkage of data from Danish nationwide registries, we identified all patients 30 years or older admitted with a first-time MI in the period 2003–2012, and their use of cardioprotective drugs 6 months prior to admission. We calculated incidence rates per 100 000 person-years (IRs) of ST-segment elevation MI (STEMI) and non-STEMI (NSTEMI). We identified 22 247 patients admitted with STEMI and 50 403 with NSTEMI. IRs for NSTEMI decreased by 35% from 194 in 2003 to 126 in 2012, whereas IRs for STEMI peaked in 2007 and subsequently declined from 71 to 65. Preadmission use of cardioprotective drugs increased in both groups from 2003 to 2012. Patients admitted with STEMI had odds ratio (OR) 0.64 [95% confidence interval (CI) 0.61–0.67] for preadmission use of aspirin compared with patients admitted with NSTEMI. Corresponding ORs were 0.82 (CI 0.78–0.87) for statins, 0.87 (CI 0.82–0.91) for beta-blockers, 0.89 (CI 0.85–0.92) for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 0.52 (CI 0.44–0.61) for thienopyridines. Also, 30-day and 1-year mortality declined in patients both admitted with STEMI and NSTEMI.
The IRs of MI declined between 2003 and 2012, primarily driven by a 35% reduction in IRs for NSTEMI whereas IRs for STEMI declined after 2007. Preadmission use of cardioprotective drugs increased markedly and was associated with lower ORs of presenting with STEMI than NSTEMI.
Introduction
Despite improvements in prevention and treatment, myocardial infarction (MI) continues to be a leading cause of death and disability worldwide as well as a major financial burden to society.1,2 Epidemiological studies have documented a significant decline in incidence, severity, and mortality following MI during the past decades,3–11 but only few studies have evaluated changes in incidence of ST-segment elevation MI (STEMI) and non-STEMI (NSTEMI) separately.12–19 Differentiation between these two MI subtypes is essential because of dissimilarities in patient characteristics, management, and outcomes.20 In addition, to our knowledge, the temporal development in the proportion of patients with MI that received cardioprotective drugs prior to admission, and in mortality rates after STEMI and NSTEMI, respectively, has not been reported in a nationwide study of unselected patients with first-time MI.
In view of these uncertainties, the present study investigated temporal trends in use of cardioprotective drugs prior to admission and the association with clinical presentation (STEMI or NSTEMI) in a nationwide population of patients with first-time MI. Also, temporal trends in mortality after MI were examined.
Methods
Study design and data sources
The study was a nationwide retrospective study of patients admitted with first-time MI in the period between 1 January 2003 and 31 December 2012. In Denmark, all 5.6 million citizens are covered by publicly financed national health insurance, guaranteeing free access to healthcare services. All residents hold a unique and permanent personal identification number that allows linkage between the administrative registers. The Danish Civil Registration System holds information on birth, sex, and death status. The Danish National Patient Registry holds information on all admissions since 1978.21 All admissions to hospitals and out-of-hospital contacts are registered by one primary diagnosis, and supplementary secondary diagnoses if appropriate, according to the International Classification of Diseases (ICD) system. Surgical and interventional procedures are defined according to the Nordic Medical Statistics Committees Classification of Surgical Procedures and from the Danish Heart Registry that contains information on >95% of all coronary angiographies (CAGs) and revascularization procedures performed in Denmark.22 Data on CAGs were missing from 3 (out of 13 cardiovascular centres) from 2003 to 2005 in the Danish Heart Registry, but full coverage was obtained on procedures from the Danish National Patient Registry, and information on patients undergoing percutaneous coronary intervention (PCI) was complete in both registries throughout the whole study period.
Study population
With use of the Danish National Patient Registry, we identified all patients aged 30 years or older with a primary first-time discharge diagnosis of MI. Patients with a previous discharge diagnosis of MI were excluded. The MI diagnosis has previously been validated in the registry with a sensitivity and specificity of 90–95%.23
We investigated comorbidity based on discharge- and outpatient- diagnoses 5 years prior to admission date. The comorbidities included in the study were cardiac arrhythmia, heart failure, hypertension, angina pectoris, peripheral artery disease, cerebrovascular disease, diabetes, chronic kidney disease, and chronic obstructive pulmonary disease (see Supplementary material online, Table S1). Since the Danish National Patient Registry data do not allow for differentiation between STEMI and NSTEMI, we used data from the Danish Heart Registry for this purpose. We identified STEMI patients as those that underwent CAG and PCI with the STEMI diagnosis as indication. If data were missing, we used the urgency (acute, sub-acute, and elective) of the PCI or CAG and determined a STEMI diagnosis in subjects referred for acute procedures. We determined PCI procedures performed during index hospitalization and for coronary artery bypass grafting (CABG) within 3 months.
Cardioprotective drugs
Using the Danish Register of Medicinal Product Statistics that holds information on all prescriptions dispensed from pharmacies in Denmark since 1995 we identified prescribed use of cardioprotective drugs within 6 months prior to admission. The registry classifies each drug according to the Anatomic Therapeutical Chemical classification. The Danish health care system provides partial reimbursement of drug expenses which ensures a high validity of the registry.24 We defined cardioprotective drugs as aspirin, statins, beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), and thienopyridines. Furthermore use of vitamin K antagonists, digoxin, thiazides, calcium channel antagonists, loop diuretics, and potassium-sparing diuretics were examined (see Supplementary material online, Table S2).
In order to assess use of cardioprotective drugs 30 days after discharge, we identified redeemed prescription 3 months prior to admission and until 30 days after admission in patients alive at 30 days.
Study outcomes
The study outcomes were (i) annual incidence rates per 100 000 person-years (IRs) of first-time MI separated into STEMI and NSTEMI during the study period, (ii) the temporal trends in use of cardioprotective drugs within 6 months prior to admission, (iii) the association between clinical presentation of MI (STEMI or NSTEMI) and preadmission use of cardioprotective drugs, and (iv) mortality rates 30 days and 1 year after the admission date.
Statistical analysis
The annual IRs of admissions with first-time MI during the study period were calculated. We repeated the analyses, stratified by sex and age groups. The percentage of patients receiving cardioprotective therapy within 6 months prior to admission was calculated. To analyse the association between preadmission use of cardioprotective drugs for STEMI compared with NSTEMI, we applied logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for sex, age, calendar year, socioeconomic status, use of concomitant therapy, comorbidity, and tested for interactions. Age effects were modelled using a linear spline with knots at 50, 60, 70, and 80 years. The cardioprotective drugs were all included in the same model. Lastly, we calculated the crude mortality rates displayed in percentages of patients who died within 30 days and 1 year, respectively. To assess for linearity of the temporal trends in cardioprotective drug consumption and mortality rates we performed Cochran–Armitage testing. Holm–Bonferroni correction was used as a sensitivity analysis to test the adjusted P-values of temporal trends in use of cardioprotective drugs.
Data management and statistical analyses were performed using SAS (version 9.4 for Windows, SAS Institute, NC, USA) and R (version 3.2.2 for Windows, R Foundation for Statistical Computing).
Ethics
This study was approved by the Danish Data Protection Agency (local reference No. 2007-58-0015/GEH-2014-014 I-suite 02732). Ethics approval is not required for retrospective registry-based studies in Denmark.
Results
We identified 72 650 patients hospitalized with first-time MI in Denmark between 2003 and 2012 (Figure 1). Of these, 22 247 (30.6%) were admitted with STEMI and 50 403 (69.4%) were admitted with NSTEMI.
Flowchart of study population. STEMI, ST-segment elevation myocardial infarction; NSTEMI, non-STEMI.
Patient characteristics
The baseline characteristics of the study population are displayed in Table 1. Women were older than men, both when admitted with STEMI (median age 69 vs. 62 years, P < 0.01) and NSTEMI (77 vs. 69 years, P < 0.01). In general, patients hospitalized with STEMI had less comorbidity than patients with NSTEMI and the burden of comorbidity increased markedly in NSTEMI subjects during the study period (Table 1).
Baseline characteristics of study population
| 2003–2004 | 2005–2006 | 2007–2008 | 2009–2010 | 2011–2012 | P-valuea | |
|---|---|---|---|---|---|---|
| STEMI | ||||||
| n | 4019 | 4572 | 4681 | 4533 | 4442 | |
| Age, men (median [IQR]) | 61 [53,70] | 62 [53,71] | 62 [53,70] | 62 [54,71] | 62 [53,71] | 0.05 |
| Age, women (median [IQR]) | 68 [58,77] | 70 [60,79] | 69 [57,77] | 68 [57,78] | 68 [56,78] | 0.34 |
| Male (%) | 2801 (69.7) | 3255 (71.2) | 3329 (71.1) | 3262 (72.0) | 3193 (71.9) | 0.02 |
| Arrhythmia (%) | 149 (3.7) | 185 (4.0) | 195 (4.2) | 165 (3.6) | 171 (3.8) | 0.85 |
| Heart failure (%) | 77 (1.9) | 95 (2.1) | 92 (2.0) | 67 (1.5) | 57 (1.3) | <0.01 |
| Hypertension (%) | 312 (7.8) | 483 (10.6) | 522 (11.2) | 503 (11.1) | 481 (10.8) | <0.01 |
| Angina pectoris (%) | 222 (5.5) | 262 (5.7) | 280 (6.0) | 211 (4.7) | 206 (4.6) | <0.01 |
| Peripheral vascular disease (%) | 143 (3.6) | 157 (3.4) | 162 (3.5) | 178 (3.9) | 173 (3.9) | 0.18 |
| Cerebrovascular disease (%) | 138 (3.4) | 173 (3.8) | 174 (3.7) | 149 (3.3) | 138 (3.1) | 0.17 |
| Diabetes (%) | 268 (6.7) | 325 (7.1) | 336 (7.2) | 341 (7.5) | 367 (8.3) | <0.01 |
| Chronic kidney disease (%) | 36 (0.9) | 64 (1.4) | 59 (1.3) | 60 (1.3) | 72 (1.6) | 0.01 |
| COPD (%) | 122 (3.0) | 155 (3.4) | 164 (3.5) | 167 (3.7) | 165 (3.7) | 0.07 |
| Cancer | 170 (4.2) | 210 (4.6) | 234 (5.0) | 256 (5.7) | 294 (6.6) | <0.01 |
| Prior PCI (%) | 55 (1.4) | 102 (2.2) | 110 (2.4) | 138 (3.0) | 119 (2.7) | <0.01 |
| Prior CABG (%) | 35 (0.9) | 27 (0.6) | 27 (0.6) | 41 (0.9) | 24 (0.5) | 0.43 |
| SES (mean [SD])b | 2.22 (1.42) | 2.27 (1.41) | 2.38 (1.36) | 2.46 (1.35) | 2.51 (1.34) | <0.01 |
| NSTEMI | ||||||
| n | 12260 | 10202 | 9433 | 9523 | 8985 | |
| Age, men (median [IQR]) | 69 [59,79] | 68 [59,78] | 69 [59,79] | 68 [59,78] | 68 [59,78] | 0.11 |
| Age, women (median [IQR]) | 78 [68,84] | 78 [68,85] | 77 [67,85] | 77 [66,85] | 76 [65,85] | <0.01 |
| Male (%) | 7267 (59.3) | 6003 (58.8) | 5608 (59.5) | 5614 (59.0) | 5340 (59.4) | 0.82 |
| Arrhythmia (%) | 1231 (10.0) | 1148 (11.3) | 1058 (11.2) | 1233 (12.9) | 1167 (13.0) | <0.01 |
| Heart failure (%) | 1118 (9.1) | 958 (9.4) | 850 (9.0) | 855 (9.0) | 715 (8.0) | <0.01 |
| Hypertension (%) | 1864 (15.2) | 1926 (18.9) | 1993 (21.1) | 2222 (23.3) | 2292 (25.5) | <0.01 |
| Angina pectoris (%) | 1618 (13.2) | 1465 (14.4) | 1280 (13.6) | 1361 (14.3) | 1324 (14.7) | <0.01 |
| Peripheral vascular disease (%) | 885 (7.2) | 831 (8.1) | 675 (7.2) | 784 (8.2) | 794 (8.8) | <0.01 |
| Cerebrovascular disease (%) | 1028 (8.4) | 919 (9.0) | 793 (8.4) | 860 (9.0) | 740 (8.2) | 0.89 |
| Diabetes (%) | 1516 (12.4) | 1290 (12.6) | 1229 (13.0) | 1326 (13.9) | 1380 (15.4) | <0.01 |
| Chronic kidney disease (%) | 350 (2.9) | 333 (3.3) | 365 (3.9) | 408 (4.3) | 414 (4.6) | <0.01 |
| COPD (%) | 934 (7.6) | 828 (8.1) | 798 (8.5) | 859 (9.0) | 859 (9.6) | <0.01 |
| Cancer | 938 (7.7) | 736 (7.5) | 786 (8.3) | 867 (9.1) | 896 (10.0) | <0.01 |
| Prior PCI (%) | 263 (2.2) | 357 (3.5) | 413 (4.4) | 550 (5.8) | 602 (6.7) | <0.01 |
| Prior CABG (%) | 259 (2.1) | 200 (2.0) | 254 (2.7) | 292 (3.1) | 313 (3.5) | <0.01 |
| SES (mean [SD])b | 1.63 (1.43) | 1.73 (1.42) | 1.88 (1.39) | 1.97 (1.36) | 2.05 (1.34) | <0.01 |
| 2003–2004 | 2005–2006 | 2007–2008 | 2009–2010 | 2011–2012 | P-valuea | |
|---|---|---|---|---|---|---|
| STEMI | ||||||
| n | 4019 | 4572 | 4681 | 4533 | 4442 | |
| Age, men (median [IQR]) | 61 [53,70] | 62 [53,71] | 62 [53,70] | 62 [54,71] | 62 [53,71] | 0.05 |
| Age, women (median [IQR]) | 68 [58,77] | 70 [60,79] | 69 [57,77] | 68 [57,78] | 68 [56,78] | 0.34 |
| Male (%) | 2801 (69.7) | 3255 (71.2) | 3329 (71.1) | 3262 (72.0) | 3193 (71.9) | 0.02 |
| Arrhythmia (%) | 149 (3.7) | 185 (4.0) | 195 (4.2) | 165 (3.6) | 171 (3.8) | 0.85 |
| Heart failure (%) | 77 (1.9) | 95 (2.1) | 92 (2.0) | 67 (1.5) | 57 (1.3) | <0.01 |
| Hypertension (%) | 312 (7.8) | 483 (10.6) | 522 (11.2) | 503 (11.1) | 481 (10.8) | <0.01 |
| Angina pectoris (%) | 222 (5.5) | 262 (5.7) | 280 (6.0) | 211 (4.7) | 206 (4.6) | <0.01 |
| Peripheral vascular disease (%) | 143 (3.6) | 157 (3.4) | 162 (3.5) | 178 (3.9) | 173 (3.9) | 0.18 |
| Cerebrovascular disease (%) | 138 (3.4) | 173 (3.8) | 174 (3.7) | 149 (3.3) | 138 (3.1) | 0.17 |
| Diabetes (%) | 268 (6.7) | 325 (7.1) | 336 (7.2) | 341 (7.5) | 367 (8.3) | <0.01 |
| Chronic kidney disease (%) | 36 (0.9) | 64 (1.4) | 59 (1.3) | 60 (1.3) | 72 (1.6) | 0.01 |
| COPD (%) | 122 (3.0) | 155 (3.4) | 164 (3.5) | 167 (3.7) | 165 (3.7) | 0.07 |
| Cancer | 170 (4.2) | 210 (4.6) | 234 (5.0) | 256 (5.7) | 294 (6.6) | <0.01 |
| Prior PCI (%) | 55 (1.4) | 102 (2.2) | 110 (2.4) | 138 (3.0) | 119 (2.7) | <0.01 |
| Prior CABG (%) | 35 (0.9) | 27 (0.6) | 27 (0.6) | 41 (0.9) | 24 (0.5) | 0.43 |
| SES (mean [SD])b | 2.22 (1.42) | 2.27 (1.41) | 2.38 (1.36) | 2.46 (1.35) | 2.51 (1.34) | <0.01 |
| NSTEMI | ||||||
| n | 12260 | 10202 | 9433 | 9523 | 8985 | |
| Age, men (median [IQR]) | 69 [59,79] | 68 [59,78] | 69 [59,79] | 68 [59,78] | 68 [59,78] | 0.11 |
| Age, women (median [IQR]) | 78 [68,84] | 78 [68,85] | 77 [67,85] | 77 [66,85] | 76 [65,85] | <0.01 |
| Male (%) | 7267 (59.3) | 6003 (58.8) | 5608 (59.5) | 5614 (59.0) | 5340 (59.4) | 0.82 |
| Arrhythmia (%) | 1231 (10.0) | 1148 (11.3) | 1058 (11.2) | 1233 (12.9) | 1167 (13.0) | <0.01 |
| Heart failure (%) | 1118 (9.1) | 958 (9.4) | 850 (9.0) | 855 (9.0) | 715 (8.0) | <0.01 |
| Hypertension (%) | 1864 (15.2) | 1926 (18.9) | 1993 (21.1) | 2222 (23.3) | 2292 (25.5) | <0.01 |
| Angina pectoris (%) | 1618 (13.2) | 1465 (14.4) | 1280 (13.6) | 1361 (14.3) | 1324 (14.7) | <0.01 |
| Peripheral vascular disease (%) | 885 (7.2) | 831 (8.1) | 675 (7.2) | 784 (8.2) | 794 (8.8) | <0.01 |
| Cerebrovascular disease (%) | 1028 (8.4) | 919 (9.0) | 793 (8.4) | 860 (9.0) | 740 (8.2) | 0.89 |
| Diabetes (%) | 1516 (12.4) | 1290 (12.6) | 1229 (13.0) | 1326 (13.9) | 1380 (15.4) | <0.01 |
| Chronic kidney disease (%) | 350 (2.9) | 333 (3.3) | 365 (3.9) | 408 (4.3) | 414 (4.6) | <0.01 |
| COPD (%) | 934 (7.6) | 828 (8.1) | 798 (8.5) | 859 (9.0) | 859 (9.6) | <0.01 |
| Cancer | 938 (7.7) | 736 (7.5) | 786 (8.3) | 867 (9.1) | 896 (10.0) | <0.01 |
| Prior PCI (%) | 263 (2.2) | 357 (3.5) | 413 (4.4) | 550 (5.8) | 602 (6.7) | <0.01 |
| Prior CABG (%) | 259 (2.1) | 200 (2.0) | 254 (2.7) | 292 (3.1) | 313 (3.5) | <0.01 |
| SES (mean [SD])b | 1.63 (1.43) | 1.73 (1.42) | 1.88 (1.39) | 1.97 (1.36) | 2.05 (1.34) | <0.01 |
STEMI, ST-segment elevation myocardial infarction; NSTEMI, non-STEMI; IQR, interquartile range; COPD, chronic obstructive pulmonary disease; PCI, percutaneous coronary intervention; CABG, coronary artery by pass grafting; SD, standard deviation; SES, socioeconomic status.
P-values for trend were calculated using simple linear regression for age and SES and Cochrane–Armitage trend test for the categorical variables.
SES in 5 groups from 0 to 4, with increasing household income.
Baseline characteristics of study population
| 2003–2004 | 2005–2006 | 2007–2008 | 2009–2010 | 2011–2012 | P-valuea | |
|---|---|---|---|---|---|---|
| STEMI | ||||||
| n | 4019 | 4572 | 4681 | 4533 | 4442 | |
| Age, men (median [IQR]) | 61 [53,70] | 62 [53,71] | 62 [53,70] | 62 [54,71] | 62 [53,71] | 0.05 |
| Age, women (median [IQR]) | 68 [58,77] | 70 [60,79] | 69 [57,77] | 68 [57,78] | 68 [56,78] | 0.34 |
| Male (%) | 2801 (69.7) | 3255 (71.2) | 3329 (71.1) | 3262 (72.0) | 3193 (71.9) | 0.02 |
| Arrhythmia (%) | 149 (3.7) | 185 (4.0) | 195 (4.2) | 165 (3.6) | 171 (3.8) | 0.85 |
| Heart failure (%) | 77 (1.9) | 95 (2.1) | 92 (2.0) | 67 (1.5) | 57 (1.3) | <0.01 |
| Hypertension (%) | 312 (7.8) | 483 (10.6) | 522 (11.2) | 503 (11.1) | 481 (10.8) | <0.01 |
| Angina pectoris (%) | 222 (5.5) | 262 (5.7) | 280 (6.0) | 211 (4.7) | 206 (4.6) | <0.01 |
| Peripheral vascular disease (%) | 143 (3.6) | 157 (3.4) | 162 (3.5) | 178 (3.9) | 173 (3.9) | 0.18 |
| Cerebrovascular disease (%) | 138 (3.4) | 173 (3.8) | 174 (3.7) | 149 (3.3) | 138 (3.1) | 0.17 |
| Diabetes (%) | 268 (6.7) | 325 (7.1) | 336 (7.2) | 341 (7.5) | 367 (8.3) | <0.01 |
| Chronic kidney disease (%) | 36 (0.9) | 64 (1.4) | 59 (1.3) | 60 (1.3) | 72 (1.6) | 0.01 |
| COPD (%) | 122 (3.0) | 155 (3.4) | 164 (3.5) | 167 (3.7) | 165 (3.7) | 0.07 |
| Cancer | 170 (4.2) | 210 (4.6) | 234 (5.0) | 256 (5.7) | 294 (6.6) | <0.01 |
| Prior PCI (%) | 55 (1.4) | 102 (2.2) | 110 (2.4) | 138 (3.0) | 119 (2.7) | <0.01 |
| Prior CABG (%) | 35 (0.9) | 27 (0.6) | 27 (0.6) | 41 (0.9) | 24 (0.5) | 0.43 |
| SES (mean [SD])b | 2.22 (1.42) | 2.27 (1.41) | 2.38 (1.36) | 2.46 (1.35) | 2.51 (1.34) | <0.01 |
| NSTEMI | ||||||
| n | 12260 | 10202 | 9433 | 9523 | 8985 | |
| Age, men (median [IQR]) | 69 [59,79] | 68 [59,78] | 69 [59,79] | 68 [59,78] | 68 [59,78] | 0.11 |
| Age, women (median [IQR]) | 78 [68,84] | 78 [68,85] | 77 [67,85] | 77 [66,85] | 76 [65,85] | <0.01 |
| Male (%) | 7267 (59.3) | 6003 (58.8) | 5608 (59.5) | 5614 (59.0) | 5340 (59.4) | 0.82 |
| Arrhythmia (%) | 1231 (10.0) | 1148 (11.3) | 1058 (11.2) | 1233 (12.9) | 1167 (13.0) | <0.01 |
| Heart failure (%) | 1118 (9.1) | 958 (9.4) | 850 (9.0) | 855 (9.0) | 715 (8.0) | <0.01 |
| Hypertension (%) | 1864 (15.2) | 1926 (18.9) | 1993 (21.1) | 2222 (23.3) | 2292 (25.5) | <0.01 |
| Angina pectoris (%) | 1618 (13.2) | 1465 (14.4) | 1280 (13.6) | 1361 (14.3) | 1324 (14.7) | <0.01 |
| Peripheral vascular disease (%) | 885 (7.2) | 831 (8.1) | 675 (7.2) | 784 (8.2) | 794 (8.8) | <0.01 |
| Cerebrovascular disease (%) | 1028 (8.4) | 919 (9.0) | 793 (8.4) | 860 (9.0) | 740 (8.2) | 0.89 |
| Diabetes (%) | 1516 (12.4) | 1290 (12.6) | 1229 (13.0) | 1326 (13.9) | 1380 (15.4) | <0.01 |
| Chronic kidney disease (%) | 350 (2.9) | 333 (3.3) | 365 (3.9) | 408 (4.3) | 414 (4.6) | <0.01 |
| COPD (%) | 934 (7.6) | 828 (8.1) | 798 (8.5) | 859 (9.0) | 859 (9.6) | <0.01 |
| Cancer | 938 (7.7) | 736 (7.5) | 786 (8.3) | 867 (9.1) | 896 (10.0) | <0.01 |
| Prior PCI (%) | 263 (2.2) | 357 (3.5) | 413 (4.4) | 550 (5.8) | 602 (6.7) | <0.01 |
| Prior CABG (%) | 259 (2.1) | 200 (2.0) | 254 (2.7) | 292 (3.1) | 313 (3.5) | <0.01 |
| SES (mean [SD])b | 1.63 (1.43) | 1.73 (1.42) | 1.88 (1.39) | 1.97 (1.36) | 2.05 (1.34) | <0.01 |
| 2003–2004 | 2005–2006 | 2007–2008 | 2009–2010 | 2011–2012 | P-valuea | |
|---|---|---|---|---|---|---|
| STEMI | ||||||
| n | 4019 | 4572 | 4681 | 4533 | 4442 | |
| Age, men (median [IQR]) | 61 [53,70] | 62 [53,71] | 62 [53,70] | 62 [54,71] | 62 [53,71] | 0.05 |
| Age, women (median [IQR]) | 68 [58,77] | 70 [60,79] | 69 [57,77] | 68 [57,78] | 68 [56,78] | 0.34 |
| Male (%) | 2801 (69.7) | 3255 (71.2) | 3329 (71.1) | 3262 (72.0) | 3193 (71.9) | 0.02 |
| Arrhythmia (%) | 149 (3.7) | 185 (4.0) | 195 (4.2) | 165 (3.6) | 171 (3.8) | 0.85 |
| Heart failure (%) | 77 (1.9) | 95 (2.1) | 92 (2.0) | 67 (1.5) | 57 (1.3) | <0.01 |
| Hypertension (%) | 312 (7.8) | 483 (10.6) | 522 (11.2) | 503 (11.1) | 481 (10.8) | <0.01 |
| Angina pectoris (%) | 222 (5.5) | 262 (5.7) | 280 (6.0) | 211 (4.7) | 206 (4.6) | <0.01 |
| Peripheral vascular disease (%) | 143 (3.6) | 157 (3.4) | 162 (3.5) | 178 (3.9) | 173 (3.9) | 0.18 |
| Cerebrovascular disease (%) | 138 (3.4) | 173 (3.8) | 174 (3.7) | 149 (3.3) | 138 (3.1) | 0.17 |
| Diabetes (%) | 268 (6.7) | 325 (7.1) | 336 (7.2) | 341 (7.5) | 367 (8.3) | <0.01 |
| Chronic kidney disease (%) | 36 (0.9) | 64 (1.4) | 59 (1.3) | 60 (1.3) | 72 (1.6) | 0.01 |
| COPD (%) | 122 (3.0) | 155 (3.4) | 164 (3.5) | 167 (3.7) | 165 (3.7) | 0.07 |
| Cancer | 170 (4.2) | 210 (4.6) | 234 (5.0) | 256 (5.7) | 294 (6.6) | <0.01 |
| Prior PCI (%) | 55 (1.4) | 102 (2.2) | 110 (2.4) | 138 (3.0) | 119 (2.7) | <0.01 |
| Prior CABG (%) | 35 (0.9) | 27 (0.6) | 27 (0.6) | 41 (0.9) | 24 (0.5) | 0.43 |
| SES (mean [SD])b | 2.22 (1.42) | 2.27 (1.41) | 2.38 (1.36) | 2.46 (1.35) | 2.51 (1.34) | <0.01 |
| NSTEMI | ||||||
| n | 12260 | 10202 | 9433 | 9523 | 8985 | |
| Age, men (median [IQR]) | 69 [59,79] | 68 [59,78] | 69 [59,79] | 68 [59,78] | 68 [59,78] | 0.11 |
| Age, women (median [IQR]) | 78 [68,84] | 78 [68,85] | 77 [67,85] | 77 [66,85] | 76 [65,85] | <0.01 |
| Male (%) | 7267 (59.3) | 6003 (58.8) | 5608 (59.5) | 5614 (59.0) | 5340 (59.4) | 0.82 |
| Arrhythmia (%) | 1231 (10.0) | 1148 (11.3) | 1058 (11.2) | 1233 (12.9) | 1167 (13.0) | <0.01 |
| Heart failure (%) | 1118 (9.1) | 958 (9.4) | 850 (9.0) | 855 (9.0) | 715 (8.0) | <0.01 |
| Hypertension (%) | 1864 (15.2) | 1926 (18.9) | 1993 (21.1) | 2222 (23.3) | 2292 (25.5) | <0.01 |
| Angina pectoris (%) | 1618 (13.2) | 1465 (14.4) | 1280 (13.6) | 1361 (14.3) | 1324 (14.7) | <0.01 |
| Peripheral vascular disease (%) | 885 (7.2) | 831 (8.1) | 675 (7.2) | 784 (8.2) | 794 (8.8) | <0.01 |
| Cerebrovascular disease (%) | 1028 (8.4) | 919 (9.0) | 793 (8.4) | 860 (9.0) | 740 (8.2) | 0.89 |
| Diabetes (%) | 1516 (12.4) | 1290 (12.6) | 1229 (13.0) | 1326 (13.9) | 1380 (15.4) | <0.01 |
| Chronic kidney disease (%) | 350 (2.9) | 333 (3.3) | 365 (3.9) | 408 (4.3) | 414 (4.6) | <0.01 |
| COPD (%) | 934 (7.6) | 828 (8.1) | 798 (8.5) | 859 (9.0) | 859 (9.6) | <0.01 |
| Cancer | 938 (7.7) | 736 (7.5) | 786 (8.3) | 867 (9.1) | 896 (10.0) | <0.01 |
| Prior PCI (%) | 263 (2.2) | 357 (3.5) | 413 (4.4) | 550 (5.8) | 602 (6.7) | <0.01 |
| Prior CABG (%) | 259 (2.1) | 200 (2.0) | 254 (2.7) | 292 (3.1) | 313 (3.5) | <0.01 |
| SES (mean [SD])b | 1.63 (1.43) | 1.73 (1.42) | 1.88 (1.39) | 1.97 (1.36) | 2.05 (1.34) | <0.01 |
STEMI, ST-segment elevation myocardial infarction; NSTEMI, non-STEMI; IQR, interquartile range; COPD, chronic obstructive pulmonary disease; PCI, percutaneous coronary intervention; CABG, coronary artery by pass grafting; SD, standard deviation; SES, socioeconomic status.
P-values for trend were calculated using simple linear regression for age and SES and Cochrane–Armitage trend test for the categorical variables.
SES in 5 groups from 0 to 4, with increasing household income.
Incidence rates of first-time MI
The annual IRs of MI decreased by 24% (from 252 to 192) during the study period, mainly driven by a 35% decline in annual IRs of NSTEMI from 194 to 126 (Figure 2). This decline was most notable in the oldest (70–79 and ≥80 years) age groups for both men and women, where the IRs were almost halved. The IRs of STEMI did not display the same clear trend and remained relatively stable, but they peaked in 2007, and thereafter declined by 8% from 71 to 65. In general, the IRs were higher for men than women, but the temporal trends were similar.
Temporal trends in incidence rates (IRs) of first-time myocardial infarction (MI), ST-segment elevation MI (STEMI), and non-STEMI (NSTEMI). (A) Overall IRs of MI, STEMI, and NSTEMI, (B and D) Age-stratified IRs of STEMI and NSTEMI, respectively, for women, (C and E) Age-stratified IRs of STEMI and NSTEMI, respectively, for men.
Cardioprotective drugs and association with MI presentation
Preadmission use of cardioprotective drugs was generally lower for the STEMI group compared with the NSTEMI group (Figure 3, Table 2). In the STEMI population, a relatively constant preadmission use of aspirin (13.8% in 2003 to 13.1% in 2012, P-value for trend = 0.51) and beta-blockers (12.9–11.8%, P-value for trend = 0.71) was observed, while preadmission use of statins increased from 6.9 to 16.9%, ACEIs/ARBs from 16.0 to 23.6%, and thienopyridines from 0.3 to 1.5% (P-value for trend all <0.05). In the NSTEMI population, an increase was seen in preadmission use of all cardioprotective drugs during the study period, i.e. for aspirin from 29.2 to 32.0%, statins from 11.2 to 31.1%, beta-blockers from 19.1 to 25.6%, ACEIs/ARBs from 24.3 to 38.6%, and thienopyridines from 1.6 to 5.7% (P-value for trend all <0.01). The pattern was similar when Holm–Bonferroni adjustments were applied. In addition, preadmission use of cardioprotective drugs was generally higher among women than men (see Supplementary material online, Figure S1).
Preadmission (≤6 months) medication for subjects admitted with first-time acute myocardial infarction during the study period
| 2003–2004 | 2005–2006 | 2007–2008 | 2009–2010 | 2011–2012 | P-valuea | |
|---|---|---|---|---|---|---|
| STEMI | ||||||
| Vitamin K antagonists (%) | 67 (1.7) | 93 (2.0) | 101 (2.2) | 102 (2.3) | 88 (2.0) | 0.24 |
| Digoxin (%) | 79 (2.0) | 75 (1.6) | 66 (1.4) | 56 (1.2) | 51 (1.1) | <0.01 |
| Thiazides (%) | 456 (11.3) | 583 (12.8) | 548 (11.7) | 523 (11.5) | 479 (10.8) | 0.1 |
| Calcium channel antagonists (%) | 490 (12.2) | 633 (13.8) | 717 (15.3) | 703 (15.5) | 707 (15.9) | <0.01 |
| Loop-diuretics (%) | 211 (5.3) | 261 (5.7) | 272 (5.8) | 222 (4.9) | 219 (4.9) | 0.16 |
| Potassium-sparing diuretics (%) | 38 (1.0) | 57 (1.3) | 51 (1.1) | 61 (1.4) | 58 (1.3) | 0.13 |
| Number of cardioprotective drugs (%)b | ||||||
| 0 | 2713 (67.5) | 2935 (64.2) | 2864 (61.2) | 2709 (59.8) | 2691 (60.6) | |
| 1 | 770 (19.2) | 888 (19.4) | 947 (20.2) | 938 (20.7) | 896 (20.2) | |
| 2 | 368 (9.2) | 461 (10.1) | 509 (10.9) | 497 (11.0) | 523 (11.8) | |
| 3 | 138 (3.4) | 214 (4.7) | 270 (5.8) | 283 (6.2) | 242 (5.4) | |
| 4 | 27 (0.7) | 64 (1.4) | 84 (1.8) | 100 (2.2) | 81 (1.8) | |
| 5 | 3 (0.1) | 10 (0.2) | 7 (0.1) | 6 (0.1) | 9 (0.2) | |
| NSTEMI | ||||||
| Vitamin K antagonists (%) | 507 (4.1) | 484 (4.7) | 494 (5.2) | 580 (6.1) | 546 (6.1) | <0.01 |
| Digoxin (%) | 951 (7.8) | 723 (7.1) | 555 (5.9) | 551 (5.8) | 407 (4.5) | <0.01 |
| Thiazides (%) | 2026 (16.5) | 1849 (18.1) | 1681 (17.8) | 1646 (17.3) | 1394 (15.5) | 0.05 |
| Calcium channel antagonists (%) | 2296 (18.7) | 2091 (20.5) | 2144 (22.7) | 2146 (22.5) | 2268 (25.2) | <0.01 |
| Loop-diuretics (%) | 2418 (19.7) | 2006 (19.7) | 1878 (19.9) | 1883 (19.8) | 1624 (18.1) | 0.17 |
| Potassium-sparing diuretics (%) | 566 (4.6) | 474 (4.5) | 396 (4.2) | 372 (3.9) | 354 (3.9) | <0.01 |
| Number of cardioprotective drugs (%)b | ||||||
| 0 | 5966 (48.7) | 4473 (43.8) | 3869 (41.0) | 3604 (37.8) | 3314 (36.9) | |
| 1 | 3193 (26.0) | 2511 (24.6) | 2227 (23.6) | 2181 (22.9) | 1948 (21.7) | |
| 2 | 1908 (15.6) | 1818 (17.8) | 1670 (17.7) | 1837 (19.3) | 1766 (19.7) | |
| 3 | 857 (7.0) | 985 (9.7) | 1129 (12.0) | 1268 (13.3) | 1258 (14.0) | |
| 4 | 300 (2.4) | 373 (3.7) | 484 (5.1) | 565 (5.9) | 612 (6.8) | |
| 5 | 36 (0.3) | 42 (0.4) | 54 (0.6) | 68 (0.7) | 87 (1.0) | |
| 2003–2004 | 2005–2006 | 2007–2008 | 2009–2010 | 2011–2012 | P-valuea | |
|---|---|---|---|---|---|---|
| STEMI | ||||||
| Vitamin K antagonists (%) | 67 (1.7) | 93 (2.0) | 101 (2.2) | 102 (2.3) | 88 (2.0) | 0.24 |
| Digoxin (%) | 79 (2.0) | 75 (1.6) | 66 (1.4) | 56 (1.2) | 51 (1.1) | <0.01 |
| Thiazides (%) | 456 (11.3) | 583 (12.8) | 548 (11.7) | 523 (11.5) | 479 (10.8) | 0.1 |
| Calcium channel antagonists (%) | 490 (12.2) | 633 (13.8) | 717 (15.3) | 703 (15.5) | 707 (15.9) | <0.01 |
| Loop-diuretics (%) | 211 (5.3) | 261 (5.7) | 272 (5.8) | 222 (4.9) | 219 (4.9) | 0.16 |
| Potassium-sparing diuretics (%) | 38 (1.0) | 57 (1.3) | 51 (1.1) | 61 (1.4) | 58 (1.3) | 0.13 |
| Number of cardioprotective drugs (%)b | ||||||
| 0 | 2713 (67.5) | 2935 (64.2) | 2864 (61.2) | 2709 (59.8) | 2691 (60.6) | |
| 1 | 770 (19.2) | 888 (19.4) | 947 (20.2) | 938 (20.7) | 896 (20.2) | |
| 2 | 368 (9.2) | 461 (10.1) | 509 (10.9) | 497 (11.0) | 523 (11.8) | |
| 3 | 138 (3.4) | 214 (4.7) | 270 (5.8) | 283 (6.2) | 242 (5.4) | |
| 4 | 27 (0.7) | 64 (1.4) | 84 (1.8) | 100 (2.2) | 81 (1.8) | |
| 5 | 3 (0.1) | 10 (0.2) | 7 (0.1) | 6 (0.1) | 9 (0.2) | |
| NSTEMI | ||||||
| Vitamin K antagonists (%) | 507 (4.1) | 484 (4.7) | 494 (5.2) | 580 (6.1) | 546 (6.1) | <0.01 |
| Digoxin (%) | 951 (7.8) | 723 (7.1) | 555 (5.9) | 551 (5.8) | 407 (4.5) | <0.01 |
| Thiazides (%) | 2026 (16.5) | 1849 (18.1) | 1681 (17.8) | 1646 (17.3) | 1394 (15.5) | 0.05 |
| Calcium channel antagonists (%) | 2296 (18.7) | 2091 (20.5) | 2144 (22.7) | 2146 (22.5) | 2268 (25.2) | <0.01 |
| Loop-diuretics (%) | 2418 (19.7) | 2006 (19.7) | 1878 (19.9) | 1883 (19.8) | 1624 (18.1) | 0.17 |
| Potassium-sparing diuretics (%) | 566 (4.6) | 474 (4.5) | 396 (4.2) | 372 (3.9) | 354 (3.9) | <0.01 |
| Number of cardioprotective drugs (%)b | ||||||
| 0 | 5966 (48.7) | 4473 (43.8) | 3869 (41.0) | 3604 (37.8) | 3314 (36.9) | |
| 1 | 3193 (26.0) | 2511 (24.6) | 2227 (23.6) | 2181 (22.9) | 1948 (21.7) | |
| 2 | 1908 (15.6) | 1818 (17.8) | 1670 (17.7) | 1837 (19.3) | 1766 (19.7) | |
| 3 | 857 (7.0) | 985 (9.7) | 1129 (12.0) | 1268 (13.3) | 1258 (14.0) | |
| 4 | 300 (2.4) | 373 (3.7) | 484 (5.1) | 565 (5.9) | 612 (6.8) | |
| 5 | 36 (0.3) | 42 (0.4) | 54 (0.6) | 68 (0.7) | 87 (1.0) | |
STEMI, ST segment elevation myocardial infarction; NSTEMI, non-STEMI.
P-values for trend were calculated using Cochrane–Armitage trend test.
Aspirin, statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and/or thienopyridines.
Preadmission (≤6 months) medication for subjects admitted with first-time acute myocardial infarction during the study period
| 2003–2004 | 2005–2006 | 2007–2008 | 2009–2010 | 2011–2012 | P-valuea | |
|---|---|---|---|---|---|---|
| STEMI | ||||||
| Vitamin K antagonists (%) | 67 (1.7) | 93 (2.0) | 101 (2.2) | 102 (2.3) | 88 (2.0) | 0.24 |
| Digoxin (%) | 79 (2.0) | 75 (1.6) | 66 (1.4) | 56 (1.2) | 51 (1.1) | <0.01 |
| Thiazides (%) | 456 (11.3) | 583 (12.8) | 548 (11.7) | 523 (11.5) | 479 (10.8) | 0.1 |
| Calcium channel antagonists (%) | 490 (12.2) | 633 (13.8) | 717 (15.3) | 703 (15.5) | 707 (15.9) | <0.01 |
| Loop-diuretics (%) | 211 (5.3) | 261 (5.7) | 272 (5.8) | 222 (4.9) | 219 (4.9) | 0.16 |
| Potassium-sparing diuretics (%) | 38 (1.0) | 57 (1.3) | 51 (1.1) | 61 (1.4) | 58 (1.3) | 0.13 |
| Number of cardioprotective drugs (%)b | ||||||
| 0 | 2713 (67.5) | 2935 (64.2) | 2864 (61.2) | 2709 (59.8) | 2691 (60.6) | |
| 1 | 770 (19.2) | 888 (19.4) | 947 (20.2) | 938 (20.7) | 896 (20.2) | |
| 2 | 368 (9.2) | 461 (10.1) | 509 (10.9) | 497 (11.0) | 523 (11.8) | |
| 3 | 138 (3.4) | 214 (4.7) | 270 (5.8) | 283 (6.2) | 242 (5.4) | |
| 4 | 27 (0.7) | 64 (1.4) | 84 (1.8) | 100 (2.2) | 81 (1.8) | |
| 5 | 3 (0.1) | 10 (0.2) | 7 (0.1) | 6 (0.1) | 9 (0.2) | |
| NSTEMI | ||||||
| Vitamin K antagonists (%) | 507 (4.1) | 484 (4.7) | 494 (5.2) | 580 (6.1) | 546 (6.1) | <0.01 |
| Digoxin (%) | 951 (7.8) | 723 (7.1) | 555 (5.9) | 551 (5.8) | 407 (4.5) | <0.01 |
| Thiazides (%) | 2026 (16.5) | 1849 (18.1) | 1681 (17.8) | 1646 (17.3) | 1394 (15.5) | 0.05 |
| Calcium channel antagonists (%) | 2296 (18.7) | 2091 (20.5) | 2144 (22.7) | 2146 (22.5) | 2268 (25.2) | <0.01 |
| Loop-diuretics (%) | 2418 (19.7) | 2006 (19.7) | 1878 (19.9) | 1883 (19.8) | 1624 (18.1) | 0.17 |
| Potassium-sparing diuretics (%) | 566 (4.6) | 474 (4.5) | 396 (4.2) | 372 (3.9) | 354 (3.9) | <0.01 |
| Number of cardioprotective drugs (%)b | ||||||
| 0 | 5966 (48.7) | 4473 (43.8) | 3869 (41.0) | 3604 (37.8) | 3314 (36.9) | |
| 1 | 3193 (26.0) | 2511 (24.6) | 2227 (23.6) | 2181 (22.9) | 1948 (21.7) | |
| 2 | 1908 (15.6) | 1818 (17.8) | 1670 (17.7) | 1837 (19.3) | 1766 (19.7) | |
| 3 | 857 (7.0) | 985 (9.7) | 1129 (12.0) | 1268 (13.3) | 1258 (14.0) | |
| 4 | 300 (2.4) | 373 (3.7) | 484 (5.1) | 565 (5.9) | 612 (6.8) | |
| 5 | 36 (0.3) | 42 (0.4) | 54 (0.6) | 68 (0.7) | 87 (1.0) | |
| 2003–2004 | 2005–2006 | 2007–2008 | 2009–2010 | 2011–2012 | P-valuea | |
|---|---|---|---|---|---|---|
| STEMI | ||||||
| Vitamin K antagonists (%) | 67 (1.7) | 93 (2.0) | 101 (2.2) | 102 (2.3) | 88 (2.0) | 0.24 |
| Digoxin (%) | 79 (2.0) | 75 (1.6) | 66 (1.4) | 56 (1.2) | 51 (1.1) | <0.01 |
| Thiazides (%) | 456 (11.3) | 583 (12.8) | 548 (11.7) | 523 (11.5) | 479 (10.8) | 0.1 |
| Calcium channel antagonists (%) | 490 (12.2) | 633 (13.8) | 717 (15.3) | 703 (15.5) | 707 (15.9) | <0.01 |
| Loop-diuretics (%) | 211 (5.3) | 261 (5.7) | 272 (5.8) | 222 (4.9) | 219 (4.9) | 0.16 |
| Potassium-sparing diuretics (%) | 38 (1.0) | 57 (1.3) | 51 (1.1) | 61 (1.4) | 58 (1.3) | 0.13 |
| Number of cardioprotective drugs (%)b | ||||||
| 0 | 2713 (67.5) | 2935 (64.2) | 2864 (61.2) | 2709 (59.8) | 2691 (60.6) | |
| 1 | 770 (19.2) | 888 (19.4) | 947 (20.2) | 938 (20.7) | 896 (20.2) | |
| 2 | 368 (9.2) | 461 (10.1) | 509 (10.9) | 497 (11.0) | 523 (11.8) | |
| 3 | 138 (3.4) | 214 (4.7) | 270 (5.8) | 283 (6.2) | 242 (5.4) | |
| 4 | 27 (0.7) | 64 (1.4) | 84 (1.8) | 100 (2.2) | 81 (1.8) | |
| 5 | 3 (0.1) | 10 (0.2) | 7 (0.1) | 6 (0.1) | 9 (0.2) | |
| NSTEMI | ||||||
| Vitamin K antagonists (%) | 507 (4.1) | 484 (4.7) | 494 (5.2) | 580 (6.1) | 546 (6.1) | <0.01 |
| Digoxin (%) | 951 (7.8) | 723 (7.1) | 555 (5.9) | 551 (5.8) | 407 (4.5) | <0.01 |
| Thiazides (%) | 2026 (16.5) | 1849 (18.1) | 1681 (17.8) | 1646 (17.3) | 1394 (15.5) | 0.05 |
| Calcium channel antagonists (%) | 2296 (18.7) | 2091 (20.5) | 2144 (22.7) | 2146 (22.5) | 2268 (25.2) | <0.01 |
| Loop-diuretics (%) | 2418 (19.7) | 2006 (19.7) | 1878 (19.9) | 1883 (19.8) | 1624 (18.1) | 0.17 |
| Potassium-sparing diuretics (%) | 566 (4.6) | 474 (4.5) | 396 (4.2) | 372 (3.9) | 354 (3.9) | <0.01 |
| Number of cardioprotective drugs (%)b | ||||||
| 0 | 5966 (48.7) | 4473 (43.8) | 3869 (41.0) | 3604 (37.8) | 3314 (36.9) | |
| 1 | 3193 (26.0) | 2511 (24.6) | 2227 (23.6) | 2181 (22.9) | 1948 (21.7) | |
| 2 | 1908 (15.6) | 1818 (17.8) | 1670 (17.7) | 1837 (19.3) | 1766 (19.7) | |
| 3 | 857 (7.0) | 985 (9.7) | 1129 (12.0) | 1268 (13.3) | 1258 (14.0) | |
| 4 | 300 (2.4) | 373 (3.7) | 484 (5.1) | 565 (5.9) | 612 (6.8) | |
| 5 | 36 (0.3) | 42 (0.4) | 54 (0.6) | 68 (0.7) | 87 (1.0) | |
STEMI, ST segment elevation myocardial infarction; NSTEMI, non-STEMI.
P-values for trend were calculated using Cochrane–Armitage trend test.
Aspirin, statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and/or thienopyridines.
Temporal trends in preadmission (≤6 months) use of cardioprotective drugs in patients admitted with first-time ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). (A) STEMI. (B) NSTEMI. ACEIs/ARBs, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.
Presentation with STEMI was associated with a lower likelihood of preadmission use of cardioprotective drugs compared with patients presenting with NSTEMI (all P < 0.05) (Figure 4), but more STEMI patients used cardioprotective drugs after discharge (see Supplementary material online, Table S3).
Odds ratios (ORs) and 95% confidence intervals (CIs) for preadmission (≤6 months) use of cardioprotective drugs in patients admitted with first-time ST-segment elevation myocardial infarction (STEMI) compared with non-STEMI (NSTEMI). The ORs and 95% CIs are displayed on a logarithmic scale. The model was adjusted for sex, age and calendar year, socioeconomic status, thiazides, warfarin, digoxin, calcium channel antagonists, diabetes, heart failure, cardiac arrhythmias, chronic kidney disease, cerebrovascular disease, peripheral vascular disease, and the other exposure variables. ACEIs/ARBs, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.
Revascularization and mortality rates
Revascularization rates in patients admitted with STEMI were fairly constant throughout the study period with a modest reduction in patients undergoing PCI during hospitalization from 93.3% in 2003 to 92.1% in 2012 (P-value for trend <0.05), and respective rates of CABG performed within 3 months from admission were 5.5% and 4.2%, respectively, (P-value for trend = 0.20) (Figure 5). A considerable increase was observed in patients with NSTEMI treated with PCI, from 16.7% to 36.8% (P-value for trend < 0.05), while the rate of patients undergoing CABG after NSTEMI remained stable from 9.7% to 9.9% (P-value for trend = 0.21).
Temporal trends in percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for patients with first-time ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) during the study period. The figure displays PCI performed during the index hospitalization and CABG performed within 3 months from admission, respectively.
The 30-day mortality for patients with first-time MI was reduced from 13.2% in 2003 to 8.4% in 2012 (P-value for trend < 0.05) (Figure 6). For patients admitted with STEMI, the 30-day mortality decreased from 6.3% to 4.9% (P-value for trend = 0.05), while 30-day mortality declined for NSTEMI patients from 15.3% to 10.5% during the study period (P-value for trend < 0.05). The 1-year mortality for patients with first-time MI decreased continuously from 22.2% in 2003 to 15.7% in 2012 (P-value for trend < 0.05). This decline was observed both in patients admitted with STEMI (from 9.7% to 8.0%) and NSTEMI (from 26.0% to 19.7%) (both P-values for trend < 0.05).
Temporal trends in 30-day and 1-year mortality rates for first-time myocardial infarction (MI), ST-segment elevation MI (STEMI), and non-STEMI (NSTEMI), respectively.
Discussion
In this nationwide register-based study, we found a continuous reduction in IRs of first-time MI between 2003 and 2012. Furthermore, preadmission use of cardioprotective drugs increased and the likelihood of preadmission use of cardioprotective drugs was lower in patients admitted with STEMI compared with NSTEMI. Mortality rates declined both in patients admitted with STEMI and NSTEMI.
STEMI and NSTEMI incidence rates
During the study period, a continuous reduction was observed in IRs of MI, most notably in patients admitted with NSTEMI. Furthermore, this decline was most evident in patients older than 70 years. In the modern era of sensitive cardiac troponin measurements, NSTEMI accounts for the vast majority of MIs and our findings support and extend results of previous studies indicating a temporal decline in the proportion of STEMI, e.g., the Atherosclerosis Risk in Communities (ARIC) Study, the Worcester Heart Attack Study, the Olmsted Country Study, and a study from Kaiser Permanente.12–14,16 The current predominance of NSTEMI has been hypothesized to be caused, in part, by an ageing population with increased comorbidity, e.g. leading to more type 2 MI.15
Our findings of a reduction in IRs of MI are in line with results of several other studies.3,6,8–12 Only one other study, however, reported a temporal decline in incidences of both STEMI and NSTEMI, where the reduction in NSTEMI was observed after 2004.12 Although other research groups have found temporal decreases in IRs of STEMI, they also found increased IRs of NSTEMI.16–19 These dissimilarities probably reflect the differences in respective study designs. Whereas first-time MI was the subject in our investigation, others have not discriminated between first-time MI and repeat MI. Furthermore, the nationwide study population and the access to free health care for all citizens in our study are essential because socioeconomic and health care insurance factors obviously play a role for both health status and health care utilization.
Preadmission cardioprotective drug therapy and MI presentation
Limited studies have indicated a considerable increase in preadmission use of cardioprotective drugs in patients referred for CAG, and subjects admitted with MI, respectively.12,25 Along this line, our study showed that preadmission use of statins, ACEIs/ARBs, and thienopyridines significantly increased in patients presenting with first-time MI during the study period, and use of beta-blockers and aspirin increased in subjects with NSTEMI but not in those with STEMI. While higher preadmission use of cardioprotective drugs in patients with NSTEMI is compatible with their increased comorbidity compared with the STEMI population, increased preadmission use of cardioprotective drugs in patients with both types of MI clearly suggest that in general, high-risk patients are increasingly being identified and treated according to the current guidelines.
Importantly, our results showed that patients presenting with STEMI were less often treated with cardioprotective drugs prior to admission compared with those presenting with NSTEMI. These data suggest that cardioprotective treatment may diminish the acute severity of MI and they are in line with limited evidence that these drugs can contribute to a shift from STEMI to NSTEMI.26 Moreover, previous findings showed that preadmission use of aspirin is associated with lower risk of presenting with STEMI in patients with acute coronary syndromes, and that patients using beta-blockers are more likely to initially present with stable angina rather than MI.27,28 Furthermore, patients using statins are more likely to present with stable angina rather than MI and NSTEMI rather than STEMI.27,29 Indeed, it is possible that cardioprotective drugs can have beneficial actions that can contribute to STEMI vs. NSTEMI presentation, e.g. by modulation of inflammatory mechanisms and improvement of endothelial function.30–32
STEMI and NSTEMI mortality rates
During the 10-year study, our results demonstrated improved 30-day and 1-year survival rates in patients with MI for patients admitted with STEMI and NSTEMI. Other research groups have also found improvements of in-hospital, 30-day, and 1-year survival rates in patients with NSTEMI, whereas reported temporal trends in survival for STEMI patients have shown greater differences.8,12,14–16,18,33,34 The mortality rates were higher for patients with NSTEMI than STEMI in accordance with the previous findings.14,35 Increased identification of less severe NSTEMIs by expanded use of sensitive troponin testing is likely to have contributed to improved overall MI mortality rates. Also, improved treatment algorithms probably played a role and it is notable that there was a continuous increase of PCI rates in patients with NSTEMI, whereas rates of primary PCI in patients with STEMI remained constant. The latter observation is compatible with the full national implementation of primary PCI in Denmark being in place at study start after the treatment benefits had been validated in a nationwide trial.36
Strengths and limitations of the study
The nationwide study design in a country with equal access to healthcare for all citizens prevented selection bias and provided optimal circumstances for obtaining a real-life picture of the temporal trends in MI. The high validity of the MI diagnosis in the Danish National Patient Registry ensured a high accuracy and the registry-based information on comorbidities and pharmaceutical drugs prevented recall bias. However, only data on prescribed pharmaceutical drugs were available which may have underestimated the use of aspirin in this study since aspirin can be brought over-the-counter. However, in 2012, 92% of subjects in Denmark who bought low-lose aspirin used prescriptions for the drug which is required for patients to receive partial reimbursement of drug expenses from the government.24,37 Furthermore, observed rates of hypertension were probably underestimated since most patients are diagnosed by their general practitioner.
Our study was limited by its observational design and the lack of clinical data that potentially contributed to residual confounding, e.g. information on smoking, blood pressure, cholesterol levels, body mass index, umbilical circumference, and left ventricular ejection fraction.
Also, other data important to the prognosis including MI size, and in-hospital complications and medication, respectively, were missing. Another limitation of the study is the lack of data to discriminate between type I and II MI, where type II MI may contributed to a worse prognosis.38 Also, data on CAGs were missing in the Danish Heart Registry from 3 of 13 invasive cardiovascular centres in 2003 and 2004. The importance of this limitation is restricted because patients with STEMI were transported directly to tertiary centres performing acute PCI and data on patients undergoing PCI had national coverage throughout the whole period.22
Conclusion
In an unselected Danish population, IRs of first-time MI declined considerably after 2003 for NSTEMI and less so after 2007 for STEMI. Preadmission use of cardioprotective drugs including aspirin, statins, ACEIs/ARBs, beta-blockers, and thienopyridines increased markedly and was associated with a lower likelihood of presentation with STEMI compared with NSTEMI. Significant improvements in mortality rates up to 1 year were found for both MI groups.
Supplementary material
Supplementary material is available at European Heart Journal—Cardiovascular Pharmacotherapy online.
Funding
This work was supported by the Danish Agency for Science, Technology and Innovation and by the Danish Council for Strategic Research (EDITORS: Eastern Denmark Initiative to Improve Revascularisation Strategies, grant 09-066994).
P.R.H. is recipient of an unrestricted research grant from the LEO Foundation, outside the submitted work. G.H.G. is supported by an unrestricted clinical research scholarship from the Novo Nordisk Foundation and has received research grants from Bayer, Pfizer, AstraZeneca, Boehringer-Ingelheim, and Bristol Meyer Squibb (BMS) and speaker honoraria from Pfizer, AstraZeneca, and BMS, outside the submitted work.
Conflicts of interest: none declared.
