SUPPLEMENTARY MATERIAL

Blood Pressure at Six Months after Acute Myocardial Infarction and Outcomes at Two Years:

The Perils Associated with Excessively Low Blood Pressures

Pil Sang Song, MDa,c*, Seung Hun Lee, MDb*, Ki-Hyun Jeon, MDc, Joo-Yong Hahn, MD, PhDb, Seung-Ho Hur, MD, PhDd, Seung-Woon Rha,

MD, PhDe, Chang-Hwan Yoon, MD, PhDf, Myung Ho Jeong, MD, PhDg, Jin-Ok Jeong, MD, PhDa, In-Whan Seong, MD, PhDa, Young Bin

Song, MD, PhDb, Hyeon-Cheol Gwon, MD, PhDb; KAMIR-NIH Investigators

Table of Contents of the Supplementary Appendix

Supplementary Methods

Supplementary Results

Supplementary Discussion

Supplementary Tables

Supplementary Figures

Supplementary Figures Legends

Supplementary References

Supplemental Methods

We sought to conduct a systematic review and meta-analysis of relevant studies to investigate if more intensive (or lower) compared with less

intensive (or higher) blood pressure (BP) control is associated with reduced all-cause mortality risk in patients with acute myocardial

infarction (AMI). PubMed, Cochrane Library, and EMBASE searches were completed up to Oct 31, 2019, with the following keywords:

“acute myocardial infarction”, “blood pressure lowing”, “antihypertensive”, “achievement”, “target”, and “follow up”. The literature search

was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendation.

Study eligibility was individually determined independently by 2 of our authors (SH Lee and YB Song). All relevant studies that compared 2

defined BP targets (either active blood pressure treatment vs. placebo or no treatment, or intensive vs. less intensive blood pressure control)

were included. We identified 813 records, of which 122 duplicates were removed and 691 records screened. Of these, 663 were excluded and

2 were included after manual search, then 29 articles were reviewed for eligibility. Among them, lastly, we excluded 24 records that had

inadequate primary end point (n = 11), were not a full text (n = 2), or had duplicated data (n = 11). We identified a total of 6 reports that met

the inclusion criteria, including the present study, yielding a total of 79,480 patients ( Supplementary Figure S3 ) . We utilized Cochrane

Review Manager (RevMan) 5.3 to perform this meta-analysis with the Mantel-Haenszel method to analyze dichotomous data, measuring the

risk ratio (RR) with a 95% confidence interval (CI). The Cochrane Q test was used to assess heterogeneity between the trials. Heterogeneity

was quantified by I-squared. A random-effects model was used for all outcomes, funnel plots were created to assess for publication bias. The

primary end point varied among these 6 reports, but mortality was virtually always reported. Therefore, the primary outcome of the present

meta-analysis is all-cause mortality. The secondary outcome is myocardial re-infarction (MrI), or re-hospitalization for heart failure (rHHF).

Supplemental Results

An updated systematic review and meta-analysis of relevant studies ( Supplementary Figure S3 ) showed similar results to those of our study;

all-cause mortality tended to occur more frequently with intensive (or lower) blood pressure than less intensive (or higher) blood pressure.

Supplementary Table 5 highlights the characteristics of meta-analysis, and clinical outcomes are described in Supplementary Figure S4 ,

Supplementary Figure S5 , and Supplementary Figure S6 .

Supplemental Discussion

The study by Park et al. also compared the cumulative incidence of adverse events according to mean SBP and DBP, which were measured

during a two-year follow-up, among the groups of patients who underwent PCI and survived acute myocardial infarction (AMI). They showed

similar results to those of our study; the U-shaped curve relationship between blood pressure and clinical outcomes. In many ways, however,

our research is different from Park et al's. We listed the differences between studies as follows:

1. First, the target population of patients was different. Patients who underwent PCI and survived AMI without complications were

finally included in the Park et al's study. However, we analyzed data from 5,503 patients treated with beta-blockers and renin-angiotensin-

aldosterone blockers after AMI. Patients with myocardial re-infarction (MrI), re-hospitalization for heart failure (rHHF), or stroke before 6-

month follow-up were also excluded. Achieved blood pressures at 6-month follow-up were categorized into 10 mmHg increments. After then,

the incidence of clinical outcomes was compared between quartiles.

2. Second, the biggest difference is the timing of the blood pressure measurement. In the Park et al's study, blood pressure was

recorded at each clinical visit at specified time points (6, 12, and 24 months after discharge), and the mean of these values were used in the

analyses. Then, the entire target population was divided into quintiles according to average BP (SBP and DBP). In our study, however, based

on the achieved official blood pressure at the landmark point of 6 months follow-up, patients were categorized into four groups: SBP of less

than 115 mmHg, 115 to 124 mmHg, 125 to 134 mmHg (reference) and equal to or greater than 135 mmHg; and diastolic blood pressure

(DBP) of less than 65 mmHg, 65 to 74 mmHg, 75 to 84 mmHg (reference) and equal to or greater than 85 mmHg, respectively.

3. Third, the end points of interest are different. They analyzed two-year cumulative incidence of major adverse cardiac events

(MACE) among the groups. MACE was defined as a composite of cardiac death, need for recurrent revascularization, ischemic

cerebrovascular accident, and need for hospitalization due to heart failure. However, the primary outcome of interest was all-cause death in

our study. Also, secondary outcomes were MrI, rHHF and a composite outcome of all-cause death, MrI and rHHF at 24 months after the index

hospitalization.

4. Finally, for sensitivity analyses, we tested interactions between achieved systolic blood pressure or diastolic blood pressure and

covariates (such as elderly patients aged ≥ 75 years, pulse pressure < 60 vs. ≥ 60 mmHg, patients with estimated glomerular filtration rate <

60 mL/min/1.73m2 at baseline and patients with left ventricular ejection fraction of less than 45% on the primary outcome and a composite

outcome) to ensure that results were not due to reverse causality. Furthermore, to address non-detected background comorbidities acting on

blood pressure, we excluded patients with an achieved SBP less than 100 mmHg or an achieved DBP less than 60 mmHg at follow-up of 6

months and analyzed the association between achieved blood pressure and clinical outcomes in the restricted population.

Supplemental Tables

Supplemental Table S1. Demographic and baseline characteristics of the patients for achieved systolic blood pressure subgroup

< 115 mmHg

(n = 1,584)

115-124 mmHg

(n = 1,245)

125-134 mmHg

(n = 1,225)

≥ 135 mmHg

(n = 1,449)

P Value

Age 60.6±11.4 60.5±11.8 60.7±12.1 63.3±12.2 <0.001

Age ≥ 75 years 193 (12.2) 163 (13.1) 170 (13.9) 298 (20.6) <0.001

Sex (Female) 313 (19.8) 223 (17.9) 260 (21.2) 414 (28.6) <0.001

Body mass index (kg/m2) 23.9±3.1 24.3±3.0 24.6±3.2 24.9±3.5 <0.001

Diabetes mellitus 365 (37.6) 290 (34.6) 325 (36.6) 481 (41.0) 0.025

Hypertension 524 (54.0) 563 (67.1) 644 (72.6) 1005 (85.7) <0.001

Dyslipidemia 635 (40.1) 504 (40.5) 477 (38.9) 562 (38.8) 0.756

Current smoker 701 (45.5) 577 (47.5) 519 (43.2) 541 (38.4) <0.001

History of myocardial infarction 105 (10.8) 77 (9.2) 76 (8.6) 91 (7.8) 0.095

History of cerebrovascular accident 74 (7.7) 56 (6.7) 77 (8.7) 92 (7.9) 0.504

Vital sign at presentation

SBP

DBP

Pulse rate

132.3±23.9

81.2±15.1

77.7±16.2

134.5±23.8

81.6±14.9

77.9±16.3

139.2±25.8

84.3±15.4

78.6±16.6

140.4±27.0

83.9±16.1

79.3±16.8

<0.001

<0.001

0.033

Killip class ≥ II 233 (14.7) 173 (13.9) 154 (12.6) 203 (14.0) 0.442

White blood cell (×103/μl) 10360±3646 10410±3606 10240±3778 9950±3687 <0.001

Hemoglobin (g/dl) 14.3±1.9 14.4±1.8 14.3±2.0 13.9±2.1 <0.001

Anemia 216 (13.6) 172 (13.8) 191 (15.6) 312 (21.5) <0.001

Glucose (mg/dl) 157.8±66.1 159.0±64.8 162.6±72.9 167.5±76.6 0.024

GFR (mL/min/1.73m2) 88.3±39.4 89.7±30.3 85.8±30.8 83.9±44.8 <0.001

Chronic kidney disease 213 (13.5) 150 (12.1) 200 (16.4) 295 (20.4) <0.001

Troponin I (pg/ml) 23.0 (4.0-60.0) 21.0 (4.0-53.0) 15.0 (2.0-50.0) 11.0 (2.0-36.0) <0.001

Total cholesterol (mg/dl) 184.9±43.3 184.5±45.1 185.1±45.5 182.3±45.2 0.329

LDL-C (mg/dl) 116.3±37.5 117.2±38.6 116.2±38.1 114.0±38.1 0.259

LVEF (%) 51.9±10.8 53.1±9.6 53.4±9.6 54.0±10.2 <0.001

LVEF <45 % 347 (22.4) 197 (16.2) 198 (16.5) 230 (16.2) <0.001

Type of AMI <0.001

STE-AMI

NSTE-AMI

861 (54.4)

723 (45.6)

671 (53.9)

574 (46.1)

575 (46.9)

650 (53.1)

614 (42.4)

835 (57.6)

Coronary angiography 1582 (99.9) 1238 (99.4) 1225 (100.0) 1444 (99.7) 0.026

Extent of diseased vessel

1 VD

2 VD

3 VD

856 (54.1)

451 (28.5)

275 (17.4)

680 (54.9)

335 (27.1)

223 (18.0)

613 (50.0)

383 (31.3)

229 (18.7)

709 (49.1)

418 (28.9)

317 (22.0)

0.003

Multi-vessel disease 728 (46.0) 565 (45.4) 612 (50.0) 740 (51.1) 0.004

Culprit

LAD

LCx

RCA

LM

792 (51.8)

278 (18.2)

440 (28.8)

20 (1.3)

595 (49.6)

222 (18.5)

363 (30.2)

20 (1.7)

554 (47.0)

228 (19.3)

381 (32.3)

16 (1.4)

604 (44.0)

272 (19.8)

470 (34.3)

26 (1.9)

0.013

Anterior AMI 812 (53.1) 615 (51.2) 570 (48.3) 630 (45.9) 0.001

Type B2/C 1307 (85.4) 1041 (86.8) 994 (84.3) 1167 (85.1) 0.391

Pre-TIMI 2 or 3 587 (38.4) 477 (39.8) 491 (41.6) 680 (49.6) <0.001

Percutaneous coronary intervention 1525 (96.3) 1194 (95.9) 1175 (95.9) 1370 (94.5) 0.105

PCI for

LAD

LCx

RCA

LM

1084 (70.9)

638 (41.7)

736 (48.1)

45 (2.9)

841 (70.3)

482 (40.3)

575 (48.0)

45 (3.8)

803 (68.1)

540 (45.8)

601 (51.0)

38 (3.2)

934 (68.1)

649 (47.3)

732 (53.4)

56 (4.1)

0.252

0.001

0.014

0.349

Stenting 1445 (91.2) 1125 (90.4) 1099 (89.7) 1285 (88.7) 0.125

Intravascular ultrasound 307 (20.1) 248 (20.7) 219 (18.6) 226 (16.5) 0.025

GP IIb/IIIa inhibitor 232 (15.2) 201 (16.8) 162 (13.8) 138 (10.1) <0.001

Successful PCI 1512 (99.0) 1190 (99.5) 1168 (99.2) 1361 (99.3) 0.449

Complete revascularization 1095 (71.7) 895 (74.8) 837 (71.1) 979 (71.4) 0.136

Major bleeding during hospitalization 13 (0.8) 15 (1.2) 14 (1.1) 17 (1.2) 0.718

Atrial fibrillation during hospitalization 22 (1.4) 16 (1.3) 21 (1.7) 22 (1.5) 0.827

Vital sign at discharge

SBP

DBP

109.1±12.8

66.6±9.0

112.6±14.1

68.1±9.5

114.7±14.0

69.4±10.0

118.6±15.4

71.0±10.4

<0.001

<0.001

Pulse rate 70.5±9.6 70.0±9.7 70.2±9.5 70.0±9.3 0.828

Discharge medication

Aspirin

P2Y12 inhibitor

Calcium channel blocker

Statin

1583 (99.9)

1579 (99.7)

40 (2.5)

1524 (96.2)

1242 (99.8)

1244 (99.9)

59 (4.7)

1187 (95.3)

1224 (99.9)

1221 (99.7)

82 (6.7)

1176 (96.0)

1449 (100.0)

1445 (99.7)

108 (7.5)

1391 (96.0)

0.208

0.573

<0.001

0.694

Vital sign at 6-months follow-up

SBP

DBP

Pulse rate

105.0±7.3

64.4±8.2

68.1±18.2

119.8±2.7

72.4±7.7

67.5±20.0

129.5±2.7

77.2±8.2

68.4±19.8

146.4±10.7

83.6±10.9

69.7±19.3

<0.001

<0.001

0.001

AMI: acute myocardial infarction, DBP: diastolic blood pressure, GFR: glomerular filtration rate, GP: glycoprotein, LAD: left anterior

descending, LCx: left circumflex, LDL-C: low density lipoprotein-cholesterol, LM: left main, LVEF: left ventricular ejection fraction, NSTE-

AMI: non ST segment elevation-acute myocardial infarction, PCI: percutaneous coronary intervention, RCA: right coronary artery, SBP:

systolic blood pressure, STE-AMI: ST segment elevation-acute myocardial infarction, TIMI: thrombolysis in myocardial infarction, VD:

vessel disease

Chronic kidney disease defined as estimated GFR < 60 mL/min/1.73m2

Successful PCI defined as the final residual stenosis <30% with Thrombolysis In Myocardial Infarction grade 3 flow after PCI

Complete revascularization defined as no residual stenosis ≥50% in a coronary artery after PCI

Supplemental Table S2. Demographic and baseline characteristics of the patients for achieved diastolic blood pressure subgroup

< 65 mmHg

(n = 1,115)

65-74 mmHg

(n = 1,805)

75-84 mmHg

(n = 1,627)

≥ 85 mmHg

(n = 956)

P Value

Age 64.9±11.6 62.5±11.6 60.0±11.6 57.3±11.7 <0.001

Age ≥ 75 years 251 (22.5) 300 (16.6) 187 (11.5) 86 (9.0) <0.001

Sex (Female) 312 (28.0) 409 (22.7) 312 (19.2) 117 (18.5) <0.001

Body mass index (kg/m2) 23.5±3.0 24.2±3.1 24.8±3.2 25.3±3.4 <0.001

Diabetes mellitus 325 (44.2) 474 (38.8) 418 (34.9) 244 (34.1) <0.001

Hypertension 452 (61.5) 830 (67.9) 876 (73.2) 578 (80.8) <0.001

Dyslipidemia 389 (34.9) 718 (39.8) 671 (41.2) 400 (41.8) 0.003

Current smoker 395 (36.3) 755 (42.8) 715 (45.3) 473 (50.7) <0.001

History of myocardial infarction 94 (12.8) 99 (8.1) 104 (8.7) 52 (7.3) 0.001

History of cerebrovascular accident 74 (10.1) 101 (8.3) 77 (6.5) 47 (6.6) 0.017

Vital sign at presentation

SBP 133.8±24.8 135.0±24.5 137.6±26.0 140.3±26.1 <0.001

<0.001

DBP

Pulse rate

80.3±15.0

79.0±17.4

81.6±14.4

77.3±16.0

83.6±16.0

78.2±16.7

85.8±16.3

79.8±15.7

<0.001

Killip class ≥ II 219 (19.6) 282 (15.6) 171 (10.5) 91 (9.5) <0.001

White blood cell (×103/μl) 10060±3547 10200±3671 10330±3736 10360±3754 0.229

Hemoglobin (g/dl) 13.7±2.0 14.2±1.9 14.5±1.9 14.6±1.9 <0.001

Anemia 249 (22.4) 308 (17.1) 208 (12.8) 126 (13.2) <0.001

Glucose (mg/dl) 161.1±71.9 162.2±67.6 161.5±70.8 161.8±72.8 0.401

GFR (mL/min/1.73m2) 84.1±32.9 86.3±38.5 87.8±29.9 89.9±49.5 <0.001

Chronic kidney disease 222 (19.9) 286 (15.9) 216 (13.3) 134 (14.0) <0.001

Troponin I (pg/ml) 16.0 (3.0-48.0) 20.0 (3.0-51.5) 17.0 (3.0-50.0) 15.0 (2.0-46.8) 0.032

Total cholesterol (mg/dl) 179.6±45.0 183.7±43.8 185.2±44.0 188.7±46.5 <0.001

LDL-C (mg/dl) 112.5±39.0 115.9±37.4 116.8±37.5 117.8±38.9 0.005

LVEF (%) 51.7±11.4 53.2±9.8 53.5±9.8 53.7±9.8 <0.001

LVEF <45 % 259 (23.7) 294 (16.6) 255 (16.1) 164 (17.4) <0.001

Type of AMI

STE-AMI 533 (47.8) 939 (52.0) 787 (48.4) 462 (48.3)

0.065

NSTE-AMI 582 (52.2) 866 (48.0) 840 (51.6) 494 (51.7)

Coronary angiography 1111 (99.6) 1798 (99.6) 1624 (99.8) 956 (100.0) 0.213

Extent of diseased vessel

1 VD

2 VD

3 VD

578 (52.0)

301 (27.1)

232 (20.9)

936 (52.1)

527 (29.3)

335 (18.6)

851 (52.4)

483 (29.7)

290 (17.9)

493 (51.6)

276 (28.9)

187 (19.6)

0.505

Multi-vessel disease 537 (48.2) 869 (48.1) 776 (47.7) 463 (48.4) 0.985

Culprit

LAD

LCx

RCA

LM

549 (51.5)

188 (17.7)

312 (29.3)

16 (1.5)

835 (48.0)

318 (18.3)

552 (31.7)

36 (2.1)

745 (48.2)

296 (19.1)

488 (31.5)

18 (1.2)

416 (44.8)

198 (21.3)

302 (32.5)

12 (1.3)

0.073

Anterior AMI 565 (53.1) 871 (50.0) 763 (49.3) 428 (46.1) 0.021

Type B2/C 904 (84.9) 1492 (85.7) 1333 (86.2) 780 (84.1) 0.488

Pre-TIMI 2 or 3 441 (41.4) 704 (40.4) 673 (43.5) 417 (44.9) 0.094

Percutaneous coronary intervention 1063 (95.3) 1738 (96.3) 1540 (94.7) 923 (96.5) 0.051

PCI for

LAD

LCx

RCA

LM

774 (72.7)

449 (42.2)

540 (50.7)

37 (3.5)

1196 (68.7)

762 (43.8)

884 (50.8)

63 (3.6)

1076 (69.7)

671 (43.5)

750 (48.6)

51 (3.3)

616 (66.5)

427 (46.1)

470 (50.7)

33 (3.6)

0.022

0.367

0.563

0.967

Stenting 993 (89.1) 1638 (90.7) 1452 (89.2) 871 (91.1) 0.206

Intravascular ultrasound 202 (19.0) 350 (20.1) 281 (18.2) 167 (18.0) 0.464

GP IIb/IIIa inhibitor 133 (12.5) 265 (15.2) 207 (13.4) 128 (13.8) 0.204

Successful PCI 1052 (98.9) 1726 (99.1) 1535 (99.5) 918 (99.1) 0.271

Complete revascularization 755 (71.0) 1249 (71.7) 1123 (72.8) 679 (73.3) 0.596

Major bleeding during hospitalization 16 (1.4) 19 (1.1) 14 (0.9) 10 (1.0) 0.555

Atrial fibrillation during hospitalization 14 (1.3) 26 (1.4) 28 (1.7) 13 (1.4) 0.765

Vital sign at discharge

SBP

DBP

Pulse rate

111.2±14.2

66.2±9.4

70.3±9.9

112.0±14.3

67.4±9.4

69.7±9.2

115.0±14.3

69.8±9.6

70.4±9.6

117.2±14.7

72.1±10.6

70.6±9.4

<0.001

<0.001

0.053

Discharge medication

Aspirin

P2Y12 inhibitor

Calcium channel blocker

Statin

1114 (99.9)

1109 (99.5)

50 (4.5)

1063 (95.3)

1803 (99.9)

1803 (99.9)

103 (5.7)

1731 (95.9)

1625 (99.9)

1624 (99.8)

87 (5.3)

1558 (95.8)

956 (100.0)

953 (99.7)

49 (5.1)

926 (96.9)

0.769

0.142

0.546

0.356

Vital sign at 6-months follow-up

SBP

DBP

Pulse rate

108.9±14.5

58.6±4.7

66.5±18.2

120.3±12.5

69.7±2.7

68.0±18.5

130.1±12.4

79.3±2.7

68.4±21.0

142.4±14.3

91.7±6.4

71.8±18.4

<0.001

<0.001

<0.001

AMI: acute myocardial infarction, DBP: diastolic blood pressure, GFR: glomerular filtration rate, GP: glycoprotein, LAD: left anterior

descending, LCx: left circumflex, LDL-C: low density lipoprotein-cholesterol, LM: left main, LVEF: left ventricular ejection fraction, NSTE-

AMI: non ST segment elevation-acute myocardial infarction, PCI: percutaneous coronary intervention, RCA: right coronary artery, SBP:

systolic blood pressure, STE-AMI: ST segment elevation-acute myocardial infarction, TIMI: thrombolysis in myocardial infarction, VD:

vessel disease

Chronic kidney disease defined as estimated GFR < 60 mL/min/1.73m2

Successful PCI defined as the final residual stenosis <30% with Thrombolysis In Myocardial Infarction grade 3 flow after PCI

Complete revascularization defined as no residual stenosis ≥50% in a coronary artery after PCI

Supplemental Table S3. Interaction analyses

Outcome Category Covariate P for interaction

All-cause death SBP Age < 75 vs. ≥ 75 years 0.119

Estimated GFR < 60 vs. ≥ 60 0.752

LVEF < 45 vs. ≥ 45 % 0.654

Pulse pressure < 60 vs. ≥ 60 mmHg 0.970

DBP Age < 75 vs. ≥ 75 years 0.790

Estimated GFR < 60 vs. ≥ 60 0.564

LVEF < 45 vs. ≥ 45 % 0.783

Pulse pressure < 60 vs. ≥ 60 mmHg 0.506

Composite outcome SBP Age < 75 vs. ≥ 75 years 0.271

Estimated GFR < 60 vs. ≥ 60 0.280

LVEF < 45 vs. ≥ 45 % 0.281

Pulse pressure < 60 vs. ≥ 60 mmHg 0.956

DBP Age < 75 vs. ≥ 75 years 0.005

Estimated GFR < 60 vs. ≥ 60 0.508

LVEF < 45 vs. ≥ 45 % 0.302

Pulse pressure < 60 vs. ≥ 60 mmHg 0.669

Unit of estimated GFR = mL/min/1.73m2

DBP: diastolic blood pressure, GFR: glomerular filtration rate, LVEF: left ventricular ejection fraction, SBP: systolic blood pressure

Composite outcome: all-cause death, myocardial re-infarction, or re-hospitalization for heart failure

Supplemental Table S4. Subgroup analysis for composite outcome

Adjusted HR (95% CI) P Value P Value

Age < 75 years 0.010

Diastolic blood pressure

< 65 mmHg 2.492 (1.401-4.434) 0.002

65-74 mmHg 1.322 (0.726-2.405) 0.361

75-84 mmHg Reference

≥ 85 mmHg 1.883 (0.984-3.605) 0.056

Age ≥ 75 years 0.574

Diastolic blood pressure

< 65 mmHg 0.731 (0.370-1.444) 0.367

65-74 mmHg 1.071 (0.585-1.962) 0.824

75-84 mmHg Reference

≥ 85 mmHg 0.717 (0.281-1.831) 0.487

CI: confidence interval, HR: hazard ratio

Composite outcome: all-cause death, myocardial re-infarction, or re-hospitalization for heart failure

Supplemental Table S5. Characteristics of Studies Included in Meta-Analysis

Source (Year)Study

Acronym

Study

PeriodStudy Design

Intensive

control

Standard

Control

Follow-up

Duration

Wright, J. T. et al.

(2015)1SPRINT 2010-2013 RCT

SBP <120

mmHg

SBP 135-140

mmHg5 Years

Ko, M. J. et al. (2016)2 2008-2013Prospective

registry

SBP <120

mmHg

SBP 120-140

mmHg7.8 Years

Manica, G. et al. (2016)3 VALUE 1997-1999 RCTSBP <130

mmHg

SBP 130-140

mmHg6 Years

Weber, M. A. et al.

(2016)4

ACCOMPLIS

H2003-2005 RCT

SBP 110-120

mmHg

SBP 120-130

mmHg3 Years

O. Hartaigh B. et al.

(2018)5ACCORD BP 2001-2005 RCT

SBP <120

mmHg

SBP 120-140

mmHg7 Years

Song P. S. et al. (2019) 2011-2015Prospective

registry

SBP <115

mmHg

SBP 125-135

mmHg2 Years

RCT: randomized control trial, SBP: systolic blood pressure

Supplemental Figures

Supplemental Figure S1. Study Flow of Patient Selection and Follow-up

DBP: diastolic blood pressure, MrI: myocardial re-infarction, RAAS: renin-angiotensin-aldosterone system, rHHF: re-hospitalization for heart

failure, SBP: systolic blood pressure.

Supplemental Figure S2. Forest plot of adjusted hazard ratio (HR) of the primary outcome

Adjusted HR with 95% confidence interval (CI) for achieved systolic blood pressure (SBP) and diastolic blood pressure (DBP) with all-cause

death after excluding patients with a SBP less than 100 mmHg or a DBP less than 60 mmHg at 6 months follow-up.

Supplemental Figure S3 . Flow Diagram of Study Selection for Meta-Analysis

Supplemental Figure S4 . Forest Plot Comparing All-Cause Mortality According to Intensive vs. Standard Blood Pressure Lowering

Strategies

Individual and summary risk ratios with 95% confidence intervals (CIs). M-H, Mantel-Haenszel

Supplemental Figure S5 . Forest Plot Comparing Myocardial Infarction According to Intensive vs. Standard Blood Pressure Lowering

Strategies

Individual and summary risk ratios with 95% confidence intervals (CIs). M-H, Mantel-Haenszel

Supplemental Figure S6 . Forest Plot Comparing re-Hospitalisation for Heart Failure According to Intensive vs. Standard Blood Pressure

Lowering Strategies

Individual and summary risk ratios with 95% confidence intervals (CIs). M-H, Mantel-Haenszel

Supplementary Figures Legends

Supplementary Figure S1 . Study Flow of Patient Selection and Follow-up

DBP: diastolic blood pressure, MrI: myocardial re-infarction, RAAS: renin-angiotensin-aldosterone system, rHHF: re-hospitalization for heart

failure, SBP: systolic blood pressure.

Supplementary Figure S2 . Forest plot of adjusted hazard ratio (HR) of the primary outcome

Adjusted HR with 95% confidence interval (CI) for achieved systolic blood pressure (SBP) and diastolic blood pressure (DBP) with all-cause

death after excluding patients with a SBP less than 100 mmHg or a DBP less than 60 mmHg at 6 months follow-up .

Supplementary Figure S3 . Flow Diagram of Study Selection for Meta-Analysis

Supplementary Figure S4 . Forest Plot Comparing All-Cause Mortality According to Intensive vs. Standard Blood Pressure Lowering

Strategies

Supplementary Figure S5 . Forest Plot Comparing Myocardial Infarction According to Intensive vs. Standard Blood Pressure Lowering

Strategies

Supplementary Figure S6 . Forest Plot Comparing re- Hospitalisation for Heart Failure According to Intensive vs. Standard Blood Pressure

Lowering Strategies

Supplementary References

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