What do systematic reviews say?

C1 esterase inhibitor vs placebo or active control

C1 esterase inhibitor showed no clear difference in adverse events (during compared with placebo or active control (moderate certainty).

• Interventions for the long‐term prevention of hereditary angioedema attacks 2022 · Cochrane Headline outcomes only
  RR 1.03 [0.84, 1.27]
  1 study · 44 participants
  Moderate

Discontinuing cholinesterase inhibitor vs continued cholinesterase inhibitor

Discontinuing cholinesterase inhibitor showed no clear difference in adverse events (any) compared with continued cholinesterase inhibitor (low certainty).

• Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia 2021 · Cochrane Headline outcomes only
  OR 0.85 [0.57, 1.27]
  4 studies · 446 participants
  Low

C1 esterase inhibitor vs placebo or active control

It is very uncertain whether C1 esterase inhibitor changes serious adverse events (during compared with placebo or active control (very low certainty).

• Interventions for the long‐term prevention of hereditary angioedema attacks 2022 · Cochrane Headline outcomes only
  RR 0.34 [0.01, 8.14]
  1 study · 44 participants
  Very low

Discontinuing cholinesterase inhibitor vs continued cholinesterase inhibitor

Discontinuing cholinesterase inhibitor showed no clear difference in serious adverse events (SAEs) compared with continued cholinesterase inhibitor (low certainty).

• Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia 2021 · Cochrane Headline outcomes only
  OR 0.8 [0.46, 1.39]
  4 studies · 390 participants
  Low

Nanofiltered C1 esterase inhibitor vs placebo or active control

The review found no eligible studies for this question.

• Interventions for the long‐term prevention of hereditary angioedema attacks 2022 · Cochrane Headline outcomes only
  no estimate extracted
  Studies not reported
  No studies found

Plasma‐derived C1 esterase inhibitor vs placebo or active control

Plasma‐derived C1 esterase inhibitor showed no clear difference in adverse events(during compared with placebo or active control (low certainty).

• Interventions for the long‐term prevention of hereditary angioedema attacks 2022 · Cochrane Headline outcomes only
  RR 1.05 [0.78, 1.42]
  1 study · 71 participants
  Low

Recombinant human C1 esterase inhibitor vs placebo or active control

Recombinant human C1 esterase inhibitor showed no clear difference in adverse events(during compared with placebo or active control (low certainty).

• Interventions for the long‐term prevention of hereditary angioedema attacks 2022 · Cochrane Headline outcomes only
  RR 1.39 [0.71, 2.7]
  1 study · 29 participants
  Low

Nanofiltered C1 esterase inhibitor vs placebo or active control

The review found no eligible studies for this question.

• Interventions for the long‐term prevention of hereditary angioedema attacks 2022 · Cochrane Headline outcomes only
  no estimate extracted
  Studies not reported
  No studies found

Plasma‐derived C1 esterase inhibitor vs placebo or active control

It is very uncertain whether plasma‐derived C1 esterase inhibitor changes serious adverse events (during compared with placebo or active control (very low certainty).

• Interventions for the long‐term prevention of hereditary angioedema attacks 2022 · Cochrane Headline outcomes only
  RR 0.54 [0.09, 3.1]
  1 study · 71 participants
  Very low

Recombinant human C1 esterase inhibitor vs placebo or active control

It is very uncertain whether recombinant human C1 esterase inhibitor changes serious adverse events (during compared with placebo or active control (very low certainty).

• Interventions for the long‐term prevention of hereditary angioedema attacks 2022 · Cochrane Headline outcomes only
  RR 1.5 [0.06, 34.66]
  1 study · 29 participants
  Very low

Phosphodiesterase 5 inhibitors (PDE5i) vs placebo

• Phosphodiesterase 5 inhibitors (PDE5i) for the treatment of Raynaud's phenomenon 2023 · Cochrane Headline outcomes only
  no estimate extracted
  Studies not reported
  Moderate

Rivastigmine vs placebo

Cholinesterase inhibitors (rivastigmine) showed no clear difference in adverse events nausea compared with placebo (low certainty).

• Cholinesterase inhibitors for the treatment of delirium in non‐ICU settings 2018 · Cochrane Headline outcomes only
  RR 0.3 [0.01, 6.29]
  1 study · 15 participants
  Low

Phosphodiesterase 5 inhibitors (PDE5i) vs placebo

• Phosphodiesterase 5 inhibitors (PDE5i) for the treatment of Raynaud's phenomenon 2023 · Cochrane Headline outcomes only
  no estimate extracted
  Studies not reported
  Moderate

Phosphodiesterase inhibitors vs placebo

• Vasodilators for primary Raynaud's phenomenon 2021 · Cochrane Headline outcomes only
  no estimate extracted
  3 studies · 138 participants
  GRADE not reported

Summary of findings for cholinesterase inhibitors vs placebo

Summary of findings for cholinesterase inhibitors may leads to higher rate of adverse events excluding falls (per person year) compared with placebo (low certainty).

• Interventions for preventing falls in Parkinson's disease 2022 · Cochrane Headline outcomes only
  Rate ratio 1.6 [1.28, 2.01]
  2 studies · 175 participants
  Low

Continuous positive airway pressure (CPAP) vs phosphodiesterase type 5 inhibitors

It is very uncertain whether continuous positive airway pressure (CPAP) changes minor adverse events compared with phosphodiesterase type 5 inhibitors (very low certainty).

• Non‐invasive positive airway pressure therapy for improving erectile dysfunction in men with obstructive sleep apnoea 2021 · Cochrane Headline outcomes only
  RR 1.33 [0.34, 5.21]
  1 study · 40 participants
  Very low

Continuous positive airway pressure (CPAP) vs phosphodiesterase type 5 inhibitors

• Non‐invasive positive airway pressure therapy for improving erectile dysfunction in men with obstructive sleep apnoea 2021 · Cochrane Headline outcomes only
  no estimate extracted
  1 study · 40 participants
  Very low

PDEI plus alpha‐blocker vs PDEI alone

The review found no eligible studies for this question.

• Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia 2018 · Cochrane Headline outcomes only
  no estimate extracted
  Studies not reported
  No studies found

PDEI + 5‐ARI vs 5‐ARI alone

The review found no eligible studies for this question.

• Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia 2018 · Cochrane Headline outcomes only
  no estimate extracted
  Studies not reported
  No studies found
• Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia 2018 · Cochrane Headline outcomes only
  RR 1.07 [0.84, 1.36]
  1 study · 695 participants
  Low

PDEI vs placebo

PDEI may leads to higher adverse events compared with placebo (low certainty).

• Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia 2018 · Cochrane Headline outcomes only
  RR 1.42 [1.21, 1.67]
  11 studies · 4386 participants
  Low