Key points
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Question: Do renin angiotensin system inhibitors have long term clinical beneficial effect in acute myocardial infarction (AMI) patients with preserved left ventricular systolic function?
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Findings: In this prospective cohort study including 6236 AMI patients who underwent percutaneous coronary intervention, 33% of patients receiving angiotensin converting enzyme inhibitors switched to angiotensin receptor blockers during the first year. Renin angiotensin system inhibitors (RASI) beyond the first year reduced death or recurrent AMI in AMI patients with preserved left ventricular systolic function.
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Meaning: Switching the medication of RASI does not impact on long term major clinical outcomes in AMI patients with preserved left ventricular systolic function. Continuation of treatment is necessary.
Introduction
Methods
Study population
Percutaneous coronary intervention procedure and medical treatment
Study definition and endpoint
Ethics statement
Statistical analysis
Results
Baseline and procedural characteristics
Overall population
Variables, n (%) | Entire population | Matched population | ||||||
---|---|---|---|---|---|---|---|---|
ACEI (n = 2945) | ARB (n = 2197) | No RASI (n = 1094) | P value | ACEI (n = 5854) | ARB (n = 5691) | No RASI (n = 5630) | P value | |
Sex, male | 2315 (78.6%) | 1637 (74.5%) | 869 (79.4%) | < 0.001 | 77.9% | 77.2% | 78.3% | 0.360 |
Age, year | 61.9 ± 12.2 | 63.5 ± 12.1 | 63.2 ± 12.2 | < 0.001 | 62.6 ± 12.2 | 62.9 ± 12.2 | 62.6 ± 12.0 | 0.468 |
LV ejection fraction, % | 58.1 ± 5.8 | 59.4 ± 6.1 | 58.5 ± 6.0 | < 0.001 | 58.5 ± 5.9 | 58.6 ± 5.9 | 58.7 ± 5.9 | 0.313 |
Blood pressure, mmHg | ||||||||
Systolic BP | 135 ± 27 | 132 ± 26 | 127 ± 25 | < 0.001 | 135 ± 27 | 132 ± 26 | 128 ± 25 | < 0.001 |
Diastolic BP | 81 ± 16 | 80 ± 16 | 77 ± 15 | < 0.001 | 81 ± 16 | 80 ± 16 | 78 ± 15 | < 0.001 |
Heart rate, bpm | 74 ± 16 | 76 ± 16 | 74 ± 17 | 0.009 | 74 ± 16 | 75 ± 16 | 74 ± 17 | < 0.001 |
Final diagnosis | ||||||||
STEMI | 1435 (48.7%) | 871 (39.6%) | 514 (46.9%) | < 0.001 | 45.7% | 44.7% | 45.9% | 0.395 |
Non-STEMI | 1510 (51.2%) | 1326 (60.3%) | 580 (53.0%) | < 0.001 | 54.2% | 55.2% | 54.0% | 0.395 |
Risks of patients | ||||||||
Hypertension | 1388 (47.1%) | 1230 (55.9%) | 482 (44.0%) | < 0.001 | 49.3% | 50.3% | 48.7% | 0.249 |
Diabetes mellitus | 660 (22.4%) | 627 (28.5%) | 284 (25.9%) | < 0.001 | 24.3% | 25.9% | 25.7% | 0.104 |
Dyslipidemia | 364 (12.3%) | 284 (12.9%) | 142 (12.9%) | 0.786 | 12.8% | 12.4% | 13.3% | 0.332 |
Kidney disease | 358 (12.2) | 322 (14.7) | 162 (14.8) | 0.013 | 12.4% | 13.6% | 13.3% | 0.115 |
eGFR-MDRD (mL/min/1.73m2) | 91.6 ± 39.8 | 91.5 ± 31.4 | 91.2 ± 45.9 | 0.959 | 91.6 ± 41.4 | 92.6 ± 30.8 | 91.7 ± 41.6 | 0.304 |
Stroke | 118 (4.0%) | 99 (4.5%) | 51 (4.6%) | 0.551 | 4.1% | 4.1% | 4.2% | 0.937 |
Ischemic | 13 (0.4%) | 14 (0.6%) | 7 (0.6%) | 0.574 | 0.5% | 0.5% | 0.7% | 0.258 |
Hemorrhagic | 108 (3.6%) | 88 (4.0%) | 44 (4.0%) | 0.780 | 3.7% | 3.7% | 3.5% | 0.830 |
Smokers | ||||||||
Current | 1304 (44.2%) | 845 (38.4%) | 447 (40.8%) | < 0.001 | 41.7% | 41.3% | 41.6% | 0.906 |
Ex-smokers | 548 (18.6%) | 487 (22.1%) | 218 (19.9%) | 0.007 | 20.3% | 20.7% | 19.5% | 0.270 |
Laboratory findings | ||||||||
Glucose | 158 ± 67 | 161 ± 70 | 161 ± 77 | 0.543 | 158 ± 66 | 161 ± 71 | 161 ± 80 | 0.074 |
HbA1c | 6.3 ± 1.3 | 6.4 ± 1.4 | 6.4 ± 1.4 | 0.032 | 6.3 ± 1.3 | 6.4 ± 1.4 | 6.4 ± 1.4 | 0.654 |
Angiographic and procedural characteristics | ||||||||
Multi-vessel disease | 1512 (51.3%) | 1004 (45.6%) | 551 (50.3%) | < 0.001 | 49.1% | 48.0% | 49.5% | 0.270 |
Target vessel | ||||||||
LAD | 1928 (65.4) | 1370 (62.3) | 703 (64.2) | 0.071 | 64.2% | 63.6% | 65.3% | 0.191 |
LCX | 1345 (45.6) | 954 (43.4) | 463 (42.3) | 0.097 | 44.4% | 43.9% | 42.2% | 0.051 |
RCA | 1694 (57.5) | 1128 (51.3) | 644 (58.8) | < 0.001 | 55.4% | 54.6% | 55.9% | 0.389 |
Left main | 121 (4.1) | 87 (3.9) | 47 (4.2) | 0.898 | 3.9% | 3.4% | 4.1% | 0.177 |
Drug-eluting stents | ||||||||
Everolimus- | 1501 (50.9%) | 1098 (49.9%) | 525 (47.9%) | 0.240 | 50.0% | 50.9% | 49.2% | 0.220 |
Zotarolimus- | 773 (26.2) | 477 (21.7) | 276 (25.2) | 0.001 | 25.4% | 23.4% | 25.4% | 0.981 |
Biolimus A9 | 558 (18.9%) | 534 (24.3%) | 228 (20.8%) | < 0.001 | 20.4% | 21.5% | 21.2% | 0.280 |
Sirolimus- | 100 (3.3%) | 79 (3.5%) | 59 (5.3%) | 0.010 | 3.7% | 3.6% | 3.6% | 0.851 |
Paclitaxel- | 6 (0.2%) | 1 (0.0%) | 1 (0.0%) | 0.273 | 0.1% | 0.0% | 0.1% | 0.507 |
Number of stents | 1.16 ± 0.40 | 1.17 ± 0.42 | 1.17 ± 0.43 | 0.389 | 1.16 ± 0.41 | 1.16 ± 0.42 | 1.17 ± 0.42 | 0.946 |
Stent diameter, mm | 3.17 ± 0.44 | 3.14 ± 0.44 | 3.14 ± 0.45 | 0.020 | 3.16 ± 0.44 | 3.15 ± 0.44 | 3.16 ± 0.44 | 0.257 |
Total stent length, mm | 29.1 ± 12.7 | 28.1 ± 12.9 | 28.6 ± 12.9 | 0.001 | 29.0 ± 13.0 | 28.7 ± 12.8 | 28.4 ± 12.2 | 0.381 |
Discharge medication | ||||||||
Aspirin | 2931 (99.5%) | 2184 (99.4%) | 1083 (98.9%) | 0.156 | 99.5% | 99.5% | 99.3% | 0.260 |
Clopidogrel | 2073 (70.3%) | 1404 (63.9%) | 693 (63.3%) | < 0.001 | 67.1% | 66.5% | 66.3% | 0.626 |
Prasugrel | 302 (10.2%) | 285 (12.9%) | 118 (10.7%) | 0.008 | 11.1% | 11.5% | 10.9% | 0.593 |
Ticargrelor | 554 (18.8%) | 497 (22.6%) | 268 (24.4%) | < 0.001 | 21% | 21.3% | 21.7% | 0.623 |
Ca-channel blockers | 136 (4.6%) | 180 (8.1%) | 117 (10.6%) | < 0.001 | 6.7% | 7.0% | 7.3% | 0.485 |
Beta-blockers | 2741 (93.0%) | 1921 (87.4%) | 757 (69.1%) | < 0.001 | 87.8% | 86.9% | 86.3% | 0.053 |
Statin | 2848 (96.7%) | 2114 (96.2%) | 1028 (93.9%) | < 0.001 | 96.5% | 96.5% | 95.7% | 0.057 |
Major clinical outcomes
Overall population at 1 year and 3 years after AMI
Variables, n (%) | ACEI | ARB | No RASI | P value | |||
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All groups | ACE vs. ARB | ACE vs. No RASI | ARB vs. No RASI | ||||
Entire population | (n = 2945) | (n = 2197) | (n = 1094) | ||||
Primary endpoint at 1 year | 175 (5.9%) | 164 (7.4%) | 93 (8.5%) | 0.008 | 0.030 | 0.004 | 0.297 |
Total death | 110 (3.7%) | 104 (4.7%) | 67 (6.1%) | 0.004 | 0.076 | 0.001 | 0.090 |
Myocardial infarction | 71 (2.4%) | 70 (3.1%) | 30 (2.7%) | 0.242 | 0.092 | 0.549 | 0.485 |
Secondary endpoints | |||||||
MACE | 377 (12.8%) | 289 (13.1%) | 169 (15.4%) | 0.083 | 0.709 | 0.029 | 0.073 |
Revascularization | 268 (9.1%) | 171 (7.7%) | 103 (9.4%) | 0.163 | 0.095 | 0.758 | 0.110 |
Target lesion: TLR | 72 (2.4%) | 59 (2.6%) | 35 (3.1%) | 0.415 | 0.588 | 0.185 | 0.405 |
Target vessel: TVR | 137 (4.6%) | 102 (4.6%) | 64 (5.8%) | 0.244 | 0.988 | 0.120 | 0.136 |
Non-TVR | 139 (4.7%) | 73 (3.3%) | 40 (3.6%) | 0.033 | 0.013 | 0.144 | 0.621 |
Stroke | 44 (1.4%) | 57 (2.5%) | 19 (1.7%) | 0.016 | 0.005 | 0.580 | 0.123 |
Hemorrhagic | 11 (0.3%) | 21 (0.9%) | 4 (0.3%) | 0.014 | 0.009 | > 0.999 | 0.066 |
Ischemic | 31 (1.0%) | 34 (1.5%) | 13 (1.1%) | 0.281 | 0.116 | 0.712 | 0.413 |
TIA | 3 (0.1%) | 2 (0.0%) | 2 (0.1%) | 0.740 | > 0.999 | 0.617 | 0.604 |
Variables, n (%) | ACEI | ARB | No RASI | P value | |||
---|---|---|---|---|---|---|---|
All groups | ACE vs. ARB | ACE vs. No RASI | ARB vs. No RASI | ||||
IPTW weighted population | (n = 5854) | (n = 5691) | (n = 5630) | ||||
Primary endpoint at 3 years | 6.0% | 7.0% | 7.3% | 0.018 | 0.033 | 0.007 | 0.553 |
Total death | 3.9% | 4.4% | 5.2% | 0.005 | 0.213 | 0.001 | 0.048 |
Myocardial infarction | 2.3% | 3.0% | 2.5% | 0.036 | 0.012 | 0.416 | 0.095 |
Secondary endpoints | |||||||
MACE | 12.7% | 13.2% | 13.8% | 0.244 | 0.503 | 0.095 | 0.321 |
Revascularization | 8.9% | 8.2% | 8.8% | 0.382 | 0.207 | 0.917 | 0.251 |
Target lesion: TLR | 2.5% | 2.6% | 2.6% | 0.955 | 0.806 | 0.780 | 0.973 |
Target vessel: TVR | 4.8% | 4.6% | 4.9% | 0.750 | 0.620 | 0.797 | 0.455 |
Non-TVR | 4.3% | 3.7% | 3.9% | 0.301 | 0.126 | 0.356 | 0.548 |
Stroke | 1.6% | 2.5% | 1.7% | 0.002 | 0.001 | 0.675 | 0.006 |
Hemorrhagic | 0.3% | 0.9% | 0.4% | < 0.001 | 0.000 | 0.323 | 0.003 |
Ischemic | 1.2% | 1.4% | 1.0% | 0.106 | 0.290 | 0.279 | 0.034 |
TIA | 0.0% | 0.0% | 0.2% | 0.028 | > 0.999 | 0.031 | 0.037 |
Unadjusted | Matched Population | |||
---|---|---|---|---|
HR (95% CI) | P value | HR (95% CI) | P value | |
One year clinical outcomes | ||||
Primary endpoint (Death or MI) | ||||
ACEI vs. ARB | 1.449 (1.045–2.008) | 0.026 | 1.384 (1.115–1.717) | 0.003 |
ACEI vs. No RASI | 1.991 (1.384–2.864) | < 0.001 | 1.637 (1.328–2.019) | < 0.001 |
ARB vs. No RASI | 1.373 (0.959–1.968) | 0.083 | 1.182 (0.974–1.435) | 0.089 |
All-cause death | ||||
ACEI vs. ARB | 1.408 (0.932–2.128) | 0.103 | 1.308 (0.999–1.714) | 0.051 |
ACEI vs. No RASI | 2.509 (1.633–3.853) | < 0.001 | 1.895 (1.473—2.439) | < 0.001 |
ARB vs. No RASI | 1.781 (1.164–2.725) | 0.008 | 1.448 (1.145–1.831) | 0.002 |
Myocardial infarction: MI | ||||
ACEI vs. ARB | 1.573 (0.962–2.569) | 0.070 | 1.577 (1.127–2.205) | 0.008 |
ACEI vs. No RASI | 1.259 (0.665–2.384) | 0.479 | 1.351 (0.955–1.911) | 0.089 |
ARB vs. No RASI | 0.800 (0.428–1.494) | 0.485 | 0.856 (0.627–1.169) | 0.331 |
Stroke | ||||
ACEI vs. ARB | 2.254 (1.308–3.882) | 0.003 | 2.015 (1.391–2.917) | < 0.001 |
ACEI vs. No RASI | 1.284 (0.602–2.736) | 0.516 | 1.307 (0.873–1.955) | 0.192 |
ARB vs. No RASI | 0.569 (0.281–1.155) | 0.119 | 0.648 (0.459–0.915) | 0.014 |
Three year clinical outcomes | ||||
Primary endpoint (Death or MI) | ||||
ACEI vs. ARB | 1.276 (1.024–1.591) | 0.030 | 1.174 (1.013–1.361) | 0.032 |
ACEI vs. No RASI | 1.470 (1.131–1.910) | 0.004 | 1.225 (1.058–1.419) | 0.006 |
ARB vs. No RASI | 1.151 (0.883–1.501) | 0.297 | 1.043 (0.904–1.202) | 0.560 |
All-cause death | ||||
ACEI vs. ARB | 1.280 (0.973–1.684) | 0.077 | 1.122 (0.935–1.347) | 0.214 |
ACEI vs. No RASI | 1.681 (1.230–2.297) | 0.001 | 1.335 (1.119–1.593) | 0.001 |
ARB vs. No RASI | 1.312 (0.957–1.800) | 0.091 | 1.189 (1.001–1.414) | 0.049 |
Myocardial infarction: MI | ||||
ACEI vs. ARB | 1.332 (0.953–1.862) | 0.093 | 1.333 (1.061–1.674) | 0.013 |
ACEI vs. No RASI | 1.141 (0.740–1.758) | 0.549 | 1.099 (0.866–1.394) | 0.437 |
ARB vs. No RASI | 0.856 (0.555–1.322) | 0.485 | 0.824 (0.658–1.031) | 0.091 |
Stroke | ||||
ACEI vs. ARB | 1.756 (1.180–2.612) | 0.005 | 1.521 (1.175–1.969) | 0.001 |
ACEI vs. No RASI | 1.165 (0.677–2.004) | 0.581 | 1.056 (0.798–1.397) | 0.701 |
ARB vs. No RASI | 0.663 (0.392–1.121) | 0.125 | 0.694 (0.536–0.897) | 0.005 |