MedCheck in English No.27

Supplementary appendix
2023-9-15
MedCheck Editorial teamTable. Mortality risk from arrythmia after Pfizer’s SARS-CoV-2 vaccine
compared with general population in England.

*Calculations were shown in Appendix 2-1.

*Arrhythmia mortality rate in the general population is higher in female than that in male and crude mortality rate
ratios in female were far lower than in male. Therefore mortality rate ratios for both sexes were calculated adjusting
sex as a confounding factor. Sex adjusted pooled mortality rate ratios were shown using a random-effects model,
because the I2 values were over 90% (very different mortality rate ratio by sex).

Figure. Sex adjusted arrythmia mortality rate ratio for Pfizer’s SARS-CoV-2 vaccine

7 days
1st dose

2nd dose

Start of vaccine program

1st dose

Vaccinee

2nd dose21days*28daysBlack arrows indicate the observation period for 1st vaccinee; the area enclosed by the black
rectangle indicates the person-times for the entire 1st vaccinee. *According to the Pfizer
Vaccine’s package insert, the interval between the 1st and 2nd dose is approximately 21 days.
Grey arrows indicate the observation period for 2nd vaccinee; the area enclosed by the grey
rectangle indicates the person-times for the entire 2nd vaccinee.

Appendix 1-1:Concept of person-years calculation for Pfizer’s SARS-CoV-2 vaccinee

1st doseStart of vaccine program

28days

2nd doseVaccinee

1st dose

2nd dose28daysBlack arrows indicate the observation period for 1st vaccinee; the area enclosed by the black rectangle
indicates the person-times for the entire 1st vaccinee. *According to the Astra Zeneca Vaccine’s package
insert, the interval between the 1st and 2nd dose is 28 to 84 days.
Grey arrows indicate the observation period for 2nd vaccinee; the area enclosed by the grey rectangle
indicates the person-times for the entire 2nd vaccinee.

Appendix 1-2: Concept of person-years calculation for AstraZeneca’s SARS-CoV-2 vaccinee

Appendix 2-1：Calculations of person-time for Pfizer’s SARS-CoV-2 vaccinee
1 Vaccinated(N)Interval from 1stdose to 2nd dose（days）

AB

Person-timefrom 1st dose to2nd dose
(Person-years)
C(=A×B/365)

Male

5,401,842

21

310,791

1,495,176

7

28,675

339,466

Female7,233,091

21

416,150

1,582,549

730,350

446,501

Total*

16,993,389

21

977,7025,020,656

7

96,287

1,073,988

Sex

First Dose

Sex

Second Dosest

2nd Vaccinated(N)

Vaccinees(Only 1stdose)(N)
D

Person-timeObservation period
Person-time(Only 1st dose)st(Only 1 dose)for 1st dose
（Person(Person-years)（days）
years）
E(=28-B)
F(=D×E/365)
G(=C+F)

Observation period Person-time for(2nd dose)
2nd dose(Person-years)（days）HI

J=H×I/365

Male

3,906,666

28

299,689

Female5,650,542

28

433,466

Total*

11,972,733

28

918,456

Upper row: 1st vaccinated, Bottom row: 2nd vaccinated, * includes sex unspecified

Appendix 2-2：Calculations of person-time for AstraZeneca’s SARS-CoV-2 vaccineeA

Observation
period(1st dose)（days）
BMale

7,191,428

28

551,671

Female8,918,403

28

684,151

Total*

20,615,911

28

1,581,495

2 vaccinated(N)

Observation
period(2nd dose)（days）

Person-time for2nd dose(Person-years)HI

J=H×I/365

Male

6,900,964

28

529,389

Female8,559,325

28

656,606

19,754,224

28

1,515,393

Sex

st1 vaccinated(N)First Dose

Sex

Second Dose

*Totalnd

Person-time for1st dose(Person-years)
C=A×B/365* includes sex unspecified

Appendix 3：Arrhythmia mortality in the general population (2017-2019)
aged 15 years and over in EnglandSex

Age group(years)

15-29
30-39
Male
≥40
Male total
15-29
30-39
Female≥40
Female total
15-29
30-39
Total
≥40TotalArrythmia deathsin 2017-2019（N）

Population total
2017-2019（N）

Arrythmia mortality(/100,000 person-years)

83
78
7,466
7,627
49
44
12,69912,792132
122
20,165
20,41915,995,481
11,172,599
40,237,273
67,405,353
15,287,671
11,274,120
43,531,259
70,093,050
31,283,152
22,446,719
83,768,532
137,498,403

0.52
0.70
18.55
11.32
0.32
0.39
29.17
18.25
0.42
0.54
24.07
14.85

Appendix 4. Mortality risk from arrythmia after AstraZeneca’s SARS-CoV-2
vaccine compared with general population in England.

*a: Culculations were shown in Appendix 2-2.
*b: Arrhythmia mortality rate in the general population is higher in female than that in male and crude mortality rate ratios infemale were far lower than in male. Therefore mortality rate ratios for both sexes were calculated adjusting sex as aconfounding factor. Sex adjusted pooled mortality rate ratios were shown using a random-effects model, because theI2 values were over 90% (very different mortality rate ratio by sex).

Appendix 5-1: Percent coverage of Pfizer’s SARS-CoV-2 vaccine
by age group.
Age group(years)Populationin 2021
(N)

1st dose(N)

1st dosecoverage(%)

2nd dose(N)

2nd dosecoverage
(%)

16-29

10,324,377

4,285,600

41.5%

1,244,710

12.1%

30-39

7,753,274

3,945,405

50.9%

2,475,091

31.9%

≥40

28,640,319

8,762,384

30.6%

8,252,932

28.8%

Total

46,717,970

16,993,389

36.4%

11,972,733

25.6%

Appendix 5-2: Percent coverage of AstraZeneca’s SARS-CoV-2 vaccine by age group.

Age group Population in 2021
(years)(N)

1st dose(N)1st dosecoverage(%)

2nd dose(N)

2nd dosecoverage(%)

16-29

10,324,377

1,064,443

10.3%

988,291

9.6%

30-39

7,753,274

1,598,406

20.6%

1,494,285

19.3%

≥40

28,640,319

17,953,062

62.7%

1,494,285

5.2%

Total

46,717,970

20,615,911

44.1%

19,754,224

42.3%

Appendix 6-1: Person-time calculations for Pfizer’s SARS-CoV-2
vaccinee by age group.

First Dose

Second Dose

Person-time
AgeInterval from 1stst1 vaccinatedfrom 1st dose togroupdose to 2nd dose(N)
2nd dose(years)（days）(Person-years)

Vaccinee(Only 1stdose)(N)

Observationperiod(Only 1st dose)（days）

Person-time
Person-time(Only 1st dose)for 1st dose
（Person(Person-years)
years）AB

C(=A×B/365)

DE(=28-B)

F(=D×E/365)

G(=C+F)

16-29

4,285,600

21

246,5693,040,890

7

58,318304,88730-39

3,945,405

21

226,996

1,470,314

7

28,198255,194≥ 40

8,762,384

21

504,137

509,4527

9,770

513,907

Age group 2nd vaccinated(years(N)H

Observation period
Person-time for 2nd dose
(2nd dose)(Person-years)（days）I
J=H×I/365

16-29

1,244,710

28

95,48530-39

2,475,091

28

189,870≥ 40

8,252,932

28

633,102

Appendix 6-2: Person-time calculations for AstraZeneca’s SARS-CoV-2 vaccineeby age group.

First DoseAge group(years)

1st vaccinated(N)

Observation period(1st dose)（days）

Person-time for 1st dose
(Person-years)

16-29
30-39
≥ 40

A
1,064,443
1,064,443
17,953,062

B
28
28
28

C=A×B/365
81,65681,656
1,377,221

Age group(years)

2nd vaccinated(N)

Observation period(2nd dose)（days）

Person-time for 2nd dose
(Person-years)

16-29
30-39
≥ 40

H
988,291
1,494,285
17,271,648

I28
28
28

J=H×I/365
75,814
114,630
1,324,948

Second Dose

Appendix 7a: Sensitivity analysis-1
Age group(years)

16-29
30-39
≥ 40
Total

Arrhythmia cases
after vaccination*1（N）

Expected arrhythmia
deaths*2（N）

a1
b1
c1
t1=(a1+b1+c1)

A1=T×a1/t1
B1=T×b1/t1
C1=T×c1/t1
T*1

a1,b1,and c1 were listed in Supplementary table 3b in reference [4].

*2T was listed in Supplementary table1 in reference [4].

Appendix 7b-1: Sensitivity anlysis-1 for Pfizer’s SARS-CoV-2 vaccine

Age group Vaccine(years)dose

Arrhythmia
cases aftervaccination(N)

Proportion ofarrhythmia cases
to total (all ages)(%)

Expected arrhythmia
deaths by age groups*（N）

1st810
4.4%
33
16-29
2nd3151.5%
8
1st829
4.5%
34
30-39
2nd4872.3%
12
1st16,720
91.1%
688
≥ 40
2nd20,145
96.2%
504
1st18,359
100%
755
Total
2nd20,947
100%
524*Assuming a proportional relationship between post-vaccination arrhythmia incidence andarrythmia mortality by age groupAppendix 7b-2: Sensitivity anlysis-1 for AstraZeneca’s SARS-CoV-2 vaccine

Age group Vaccine(years)
dose

16-29
30-39
≥ 40Total
*

1st
2nd
1st
2nd
1st
2nd
1st
2nd

Arrhythmia
cases aftervaccination(N)

Proportion ofarrhythmia cases
to total (all ages)(%)

Expected arrhythmia
deaths by age groups*
（N）

498
416
674
574
23,05322,02924,22523,019

2.1%
1.8%
2.8%
2.5%
95.2%
95.7%
100%100%19925
12860
457904478

Assuming a proportional relationship between post-vaccination arrhythmia incidence andarrhythmia mortality by age groupAppendix7c：Results for sensitivity analysis-1
Age group(years)
16-29
30-39
≥ 40
SMR

Age group(years)
16-29
30-39
≥ 40
SMR

Arrhythmia MRR (95% CI), for Pfizer’s SARS-CoV-2 vaccine
1st dose
25.89(16.54-39.85)
24.58(15.67-37.98)
5.56(5.14-6.01)
5.80(5.39-6.25)

2nd dose
19.56(8.05-41.02)
11.81(5.82-22.06)
3.31(3.02-3.62)
3.46(3.17-3.79)

Overall
24.38(16.75-34.83)
19.13(13.33-27.04)
4.32(4.07-4.58)
4.53(4.28-4.80)

Arrhythmia MRR (95% CI), for AstraZeneca’s SARS-CoV-2 vaccine
1st dose

2nd dose

Overall

55.14(31.25-93.01)
56.33(33.88-91.08)
2.59(2.42-2.78)
3.25(2.99-3.54)

28.13(12.32-56.71)
19.26(9.44-36.13)
1.43(1.30-1.57)
1.71(1.53-1.91)

42.14(26.97-63.73)
34.68(23.33-50.47)
2.02(1.91-2.14)
2.48(2.32-2.65)

MRR: mortality rate ratio

Appendix 8a: Sensitivity analysis-2
Age group(years)15-2930-39
≥ 40
Total

Arrhythmia death ingeneral population*1（N）

Expected arrhythmia
deaths in vaccinatedPopulation *2 （N）

a2b2
c2
t2=(a2+b2+c2)

A2=T×a2/t2
B2=T×b2/t2
C2=T×c2/t2
T*1

a2,b2,and c2 were calculated from data in the Mortality Statistics for England [24].

*2T (total arrythmia death in vaccinated population) was listed in Supplementary table 1 in ref. [4].

Appendix 8b-1: Sensitivity analysis-2 for Pfizer’s SARS-CoV-2 vaccine
Arrhythmia
Proportion of arrhythmia
VaccineAge group
deaths in generaldeaths in general
dose
population
population by age group(years)
(N)
(%)

16-29
30-39
≥ 40Total

1st
2nd
1st
2nd
1st
2nd
1st
2nd132132
122
122
20,165
20,165
20,41920,419

0.6%
0.6%
0.6%
0.6%
98.8%
98.8%
100%
100%

*Assumed to be proportional to the proportion of arrhythmia deaths in the general population

Expected arrhythmia
deaths in vaccinated
Population*
(N)

53
53746
517
755
524

Appendix 8b-2: Sensitivity anlysis-2 for AstraZeneca’s SARS-CoV-2 vaccine

Age group(years)

16-29
30-39
≥ 40
Total

Vaccine
dose

1st
2nd
1st
2nd
1st
2nd
1st
2nd

Expected
Arrhythmia
Proportion of arrhythmia
arrhythmia deaths
deaths in generaldeaths in generalin vaccinatedpopulation
population by age group
Population *(N)
(%)
(N)

132
132
122
122
20,165
20,165
20,41920,419

0.6%
0.6%
0.6%
0.6%
98.8%
98.8%
100%
100%

63
53893
472
904
478

*Assumed to be proportional to the proportion of arrhythmia deaths in the general population

Appendix 8c：Results of sensitivity analysis-2
Age group(years)
16-2930-39≥ 40
SMR
Age group(years)
16-2930-39
≥ 40
SMR

Arrhythmia MRR (95% CI) for Pfizer’s SARS-CoV-2 vaccine
1st dose

2nd dose

Overall

3.79(1.17-9.40)
3.25(0.95-8.34)
6.03(5.59-6.49)
6.00(5.57-6.46)

8.41(1.91-24.26)
3.03(0.64-9.11)
3.40(3.10-3.71)
3.43(3.14-3.74)

4.89(2.10-9.83)
3.16(1.30-6.52)
4.57(4.32-4.84)
4.57(4.32-4.83)

Arrhythmia MRR (95% CI), for AstraZeneca’s SARS-CoV-2 vaccine
1st dose
17.41(6.17-39.96)
11.27(3.53-27.76)
2.69(2.51-2.88)
2.84(2.64-3.06)

MRR: mortality rate ratio

2nd dose
9.38(1.89-28.63)
4.82(0.97-14.75)
1.48(1.35-1.62)
1.55(1.40-1.71)

Overall
13.55(6.06-26.50)
7.50(3.17-15.25)
2.10(1.99-2.22)
2.20(2.08-2.34)