Table 2.

Number of events, incidence rates, crude and adjusted HRs, and weighted ARDs for the association between stopping versus continuing RASi and adverse outcomes

NEventsPyIncidence rate per 100 pyCrude HR (95% CI)OW adjusted HRa (95% CI)Absolute risk (95% CI)ARD (95% CI)
Primary outcome: composite of death, MI and stroke
 Overall10 165563325 87221.8 (21.2–22.3)
 Continued RASi5736302015 25719.8 (19.1–20.5)1 (Reference)1 (Reference)62.6 (61.1–64.0)
 Stopped RASi4429261310 61424.6 (23.7–25.6)1.23 (1.17–1.30)1.13 (1.07–1.19)66.3 (64.6–67.9)3.7 (2.6, 4.8)
Secondary outcome: recurrent AKI
 Overall10 165133225 8155.2 (4.9–5.4)
 Continued RASi573678015 1955.1 (4.8–5.5)1 (Reference)1 (Reference)20.7 (19.2–22.1)
 Stopped RASi442955210 6205.2 (4.8–5.7)1.00 (0.90–1.11)0.94 (0.84–1.05)20.4 (18.7–22.2)−0.2 (−1.4, 0.9)
Positive control outcome: moderate hyperkalaemia
 Overall9147153021 7887.0 (6.7–7.4)
 Continued RASi516194312 7037.4 (7.0–7.9)1 (Reference)1 (Reference)27.2 (25.5–28.9)
 Stopped RASi398658790856.5 (5.9–7.0)0.86 (0.77–0.95)0.79 (0.71–0.88)23.6 (21.6–25.6)−3.6 (−5.0, −2.3)
Tertiary outcomes: HHF and progression of CKD
HHF
 Overall10 165424520 62420.6 (20.0–21.2)
 Continued RASi5736247412 09020.5 (19.7–21.3)1 (Reference)1 (Reference)52.5 (50.9–54.2)
 Stopped RASi44291771853320.8 (19.8–21.7)0.98 (0.93–1.05)1.01 (0.94–1.07)53.3 (51.4–55.3)0.8 (−0.5, 2.1)
Progression of CKD
 Overall9147199920 6659.7 (9.3–10.1)
 Continued RASi5161111612 2689.1 (8.6–9.6)1 (Reference)1 (Reference)30.2 (28.5–31.9)
 Stopped RASi3986883839610.5 (9.8–11.2)1.11 (1.02–1.22)1.05 (0.96–1.15)31.4 (29.3–33.4)1.2 (−0.2, 2.5)
NEventsPyIncidence rate per 100 pyCrude HR (95% CI)OW adjusted HRa (95% CI)Absolute risk (95% CI)ARD (95% CI)
Primary outcome: composite of death, MI and stroke
 Overall10 165563325 87221.8 (21.2–22.3)
 Continued RASi5736302015 25719.8 (19.1–20.5)1 (Reference)1 (Reference)62.6 (61.1–64.0)
 Stopped RASi4429261310 61424.6 (23.7–25.6)1.23 (1.17–1.30)1.13 (1.07–1.19)66.3 (64.6–67.9)3.7 (2.6, 4.8)
Secondary outcome: recurrent AKI
 Overall10 165133225 8155.2 (4.9–5.4)
 Continued RASi573678015 1955.1 (4.8–5.5)1 (Reference)1 (Reference)20.7 (19.2–22.1)
 Stopped RASi442955210 6205.2 (4.8–5.7)1.00 (0.90–1.11)0.94 (0.84–1.05)20.4 (18.7–22.2)−0.2 (−1.4, 0.9)
Positive control outcome: moderate hyperkalaemia
 Overall9147153021 7887.0 (6.7–7.4)
 Continued RASi516194312 7037.4 (7.0–7.9)1 (Reference)1 (Reference)27.2 (25.5–28.9)
 Stopped RASi398658790856.5 (5.9–7.0)0.86 (0.77–0.95)0.79 (0.71–0.88)23.6 (21.6–25.6)−3.6 (−5.0, −2.3)
Tertiary outcomes: HHF and progression of CKD
HHF
 Overall10 165424520 62420.6 (20.0–21.2)
 Continued RASi5736247412 09020.5 (19.7–21.3)1 (Reference)1 (Reference)52.5 (50.9–54.2)
 Stopped RASi44291771853320.8 (19.8–21.7)0.98 (0.93–1.05)1.01 (0.94–1.07)53.3 (51.4–55.3)0.8 (−0.5, 2.1)
Progression of CKD
 Overall9147199920 6659.7 (9.3–10.1)
 Continued RASi5161111612 2689.1 (8.6–9.6)1 (Reference)1 (Reference)30.2 (28.5–31.9)
 Stopped RASi3986883839610.5 (9.8–11.2)1.11 (1.02–1.22)1.05 (0.96–1.15)31.4 (29.3–33.4)1.2 (−0.2, 2.5)

py, person-years; HR, hazard ratio; CI, confidence interval; OW, overlap weights; ARD, absolute risk difference; RASi, renin–angiotensin system inhibitors; AKI, acute kidney injury; CKD, chronic kidney disease.

a

Adjusted for age, age categories, sex, education, eGFR at admission, eGFR category at admission, medical history of diabetes, hypertension, MI, arrhythmia, cerebrovascular disease, peripheral vascular disease, ischaemic heart disease, chronic obstructive pulmonary disease, cancer, liver disease, chronic heart failure, dyslipidaemia, hypothyroidism, extracranial haemorrhage, and valvular heart disease, use in the year prior to admission of beta blockers, calcium channel blockers, loop diuretics, thiazide diuretics, potassium-sparing diuretics, NSAIDs, antilipids, alpha blockers, nitrate, mineralocorticoid receptor antagonists, hydralazine, antiarrhythmics, digoxin, anticoagulants, diabetes medication and opioids, health care access in the year prior in primary care context, specialist care context and hospitalizations, primary cause of admission, complications during admission (i.e. sepsis, cardiac surgery, cardiac catheterization, abdominal aortic aneurysm repair, pneumonia, liver failure, acute MI and non-cardiac surgery) and characteristics of admission including duration of stay, AKI as cause of admission, stage of AKI according to KDIGO and average and peak creatinine during hospitalization.

Table 2.

Number of events, incidence rates, crude and adjusted HRs, and weighted ARDs for the association between stopping versus continuing RASi and adverse outcomes

NEventsPyIncidence rate per 100 pyCrude HR (95% CI)OW adjusted HRa (95% CI)Absolute risk (95% CI)ARD (95% CI)
Primary outcome: composite of death, MI and stroke
 Overall10 165563325 87221.8 (21.2–22.3)
 Continued RASi5736302015 25719.8 (19.1–20.5)1 (Reference)1 (Reference)62.6 (61.1–64.0)
 Stopped RASi4429261310 61424.6 (23.7–25.6)1.23 (1.17–1.30)1.13 (1.07–1.19)66.3 (64.6–67.9)3.7 (2.6, 4.8)
Secondary outcome: recurrent AKI
 Overall10 165133225 8155.2 (4.9–5.4)
 Continued RASi573678015 1955.1 (4.8–5.5)1 (Reference)1 (Reference)20.7 (19.2–22.1)
 Stopped RASi442955210 6205.2 (4.8–5.7)1.00 (0.90–1.11)0.94 (0.84–1.05)20.4 (18.7–22.2)−0.2 (−1.4, 0.9)
Positive control outcome: moderate hyperkalaemia
 Overall9147153021 7887.0 (6.7–7.4)
 Continued RASi516194312 7037.4 (7.0–7.9)1 (Reference)1 (Reference)27.2 (25.5–28.9)
 Stopped RASi398658790856.5 (5.9–7.0)0.86 (0.77–0.95)0.79 (0.71–0.88)23.6 (21.6–25.6)−3.6 (−5.0, −2.3)
Tertiary outcomes: HHF and progression of CKD
HHF
 Overall10 165424520 62420.6 (20.0–21.2)
 Continued RASi5736247412 09020.5 (19.7–21.3)1 (Reference)1 (Reference)52.5 (50.9–54.2)
 Stopped RASi44291771853320.8 (19.8–21.7)0.98 (0.93–1.05)1.01 (0.94–1.07)53.3 (51.4–55.3)0.8 (−0.5, 2.1)
Progression of CKD
 Overall9147199920 6659.7 (9.3–10.1)
 Continued RASi5161111612 2689.1 (8.6–9.6)1 (Reference)1 (Reference)30.2 (28.5–31.9)
 Stopped RASi3986883839610.5 (9.8–11.2)1.11 (1.02–1.22)1.05 (0.96–1.15)31.4 (29.3–33.4)1.2 (−0.2, 2.5)
NEventsPyIncidence rate per 100 pyCrude HR (95% CI)OW adjusted HRa (95% CI)Absolute risk (95% CI)ARD (95% CI)
Primary outcome: composite of death, MI and stroke
 Overall10 165563325 87221.8 (21.2–22.3)
 Continued RASi5736302015 25719.8 (19.1–20.5)1 (Reference)1 (Reference)62.6 (61.1–64.0)
 Stopped RASi4429261310 61424.6 (23.7–25.6)1.23 (1.17–1.30)1.13 (1.07–1.19)66.3 (64.6–67.9)3.7 (2.6, 4.8)
Secondary outcome: recurrent AKI
 Overall10 165133225 8155.2 (4.9–5.4)
 Continued RASi573678015 1955.1 (4.8–5.5)1 (Reference)1 (Reference)20.7 (19.2–22.1)
 Stopped RASi442955210 6205.2 (4.8–5.7)1.00 (0.90–1.11)0.94 (0.84–1.05)20.4 (18.7–22.2)−0.2 (−1.4, 0.9)
Positive control outcome: moderate hyperkalaemia
 Overall9147153021 7887.0 (6.7–7.4)
 Continued RASi516194312 7037.4 (7.0–7.9)1 (Reference)1 (Reference)27.2 (25.5–28.9)
 Stopped RASi398658790856.5 (5.9–7.0)0.86 (0.77–0.95)0.79 (0.71–0.88)23.6 (21.6–25.6)−3.6 (−5.0, −2.3)
Tertiary outcomes: HHF and progression of CKD
HHF
 Overall10 165424520 62420.6 (20.0–21.2)
 Continued RASi5736247412 09020.5 (19.7–21.3)1 (Reference)1 (Reference)52.5 (50.9–54.2)
 Stopped RASi44291771853320.8 (19.8–21.7)0.98 (0.93–1.05)1.01 (0.94–1.07)53.3 (51.4–55.3)0.8 (−0.5, 2.1)
Progression of CKD
 Overall9147199920 6659.7 (9.3–10.1)
 Continued RASi5161111612 2689.1 (8.6–9.6)1 (Reference)1 (Reference)30.2 (28.5–31.9)
 Stopped RASi3986883839610.5 (9.8–11.2)1.11 (1.02–1.22)1.05 (0.96–1.15)31.4 (29.3–33.4)1.2 (−0.2, 2.5)

py, person-years; HR, hazard ratio; CI, confidence interval; OW, overlap weights; ARD, absolute risk difference; RASi, renin–angiotensin system inhibitors; AKI, acute kidney injury; CKD, chronic kidney disease.

a

Adjusted for age, age categories, sex, education, eGFR at admission, eGFR category at admission, medical history of diabetes, hypertension, MI, arrhythmia, cerebrovascular disease, peripheral vascular disease, ischaemic heart disease, chronic obstructive pulmonary disease, cancer, liver disease, chronic heart failure, dyslipidaemia, hypothyroidism, extracranial haemorrhage, and valvular heart disease, use in the year prior to admission of beta blockers, calcium channel blockers, loop diuretics, thiazide diuretics, potassium-sparing diuretics, NSAIDs, antilipids, alpha blockers, nitrate, mineralocorticoid receptor antagonists, hydralazine, antiarrhythmics, digoxin, anticoagulants, diabetes medication and opioids, health care access in the year prior in primary care context, specialist care context and hospitalizations, primary cause of admission, complications during admission (i.e. sepsis, cardiac surgery, cardiac catheterization, abdominal aortic aneurysm repair, pneumonia, liver failure, acute MI and non-cardiac surgery) and characteristics of admission including duration of stay, AKI as cause of admission, stage of AKI according to KDIGO and average and peak creatinine during hospitalization.

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