Definitions for the level of evidence, strength of recommendation, and net benefit follow the "Major Recommendations."
- In patients presenting with chronic cough, in order to determine that the angiotensin-converting enzyme (ACE) inhibitor is the cause of the cough, therapy with ACE inhibitors should be discontinued regardless of the temporal relation between the onset of cough and the initiation of ACE inhibitor therapy. The diagnosis is confirmed by the resolution of cough, usually within 1 to 4 weeks of the cessation of the offending agent; however, the resolution of cough may be delayed in a subgroup of patients for up to 3 months. Quality of evidence, low; net benefit, substantial; grade of recommendation, B
- In patients presenting with chronic ACE inhibitor-induced cough, discontinue therapy with the drug because it is the only uniformly effective treatment. Quality of evidence, low; net benefit, substantial; grade of recommendation, B
- In patients whose cough resolves after the cessation of therapy with ACE inhibitors, and for whom there is a compelling reason to treat with these agents, a repeat trial of ACE inhibitor therapy may be attempted. Quality of evidence, fair; net benefit, substantial; grade of recommendation, A
- In patients for whom the cessation of ACE inhibitor therapy is not an option, pharmacologic therapy, including that with sodium cromoglycate, theophylline, sulindac, indomethacin, amlodipine, nifedipine, ferrous sulfate, and picotamide that is aimed at suppressing cough should be attempted. Quality of evidence, fair; net benefit, intermediate; grade of recommendation, B
- In patients in whom persistent or intolerable ACE inhibitor-induced cough occurs, therapy should be switched, when indicated, to an angiotensin receptor blockers (ARB), with which the incidence of associated cough appears to be similar to that for the control drug, or to an appropriate agent of another drug class. Quality of evidence, good; net benefit, substantial; grade of recommendation, A
Definitions:
Quality of the Evidence
Good = evidence is based on good randomized controlled trials (RCTs) or meta-analyses
Fair = evidence is based on other controlled trials or RCTs with minor flaws
Low = evidence is based on nonrandomized, case-control, or other observational studies
Expert opinion = evidence is based on the consensus of the carefully selected panel of experts in the topic field. There are no studies that meet the criteria for inclusion in the literature review.
Strength of Recommendations
A = strong recommendation
B = moderate recommendation
C = weak recommendation
D = negative recommendation
I = no recommendation possible (inconclusive)
E/A = strong recommendation based on expert opinion only
E/B = moderate recommendation based on expert opinion only
E/C = weak recommendation based on expert opinion only
E/D = negative recommendation based on expert opinion only
Net Benefit
Substantial = There is evidence of benefit that clearly exceeds the minimum clinically significant benefit and evidence of little harm
Intermediate = Clear evidence of benefit but with some evidence of harms, with a net benefit between that defined for "substantial" and "small/weak"
Small/weak = There is evidence of a benefit that may not clearly exceed the minimum clinically significant benefit, or there is evidence of harms that substantially reduce (but do not eliminate) the benefit such that it may not clearly exceed the minimum clinically significant benefit
None = Evidence shows that either there is no benefit or the benefits equal the harms
Conflicting = Evidence is inconsistent with regard to benefits and/or harms such that the net benefit is uncertain
Negative = Expected harms exceed the expected benefits to the population
Table: Relationship of Strength of the Recommendations Scale to Quality of Evidence and Net Benefits
|
Net Benefit |
Quality of Evidence |
Substantial |
Intermediate |
Small/Weak |
None |
Conflicting |
Negative |
Good |
A |
A |
B |
D |
I |
D |
Fair |
A |
B |
C |
D |
I |
D |
Low |
B |
B |
C |
I |
I |
D |
Expert Opinion |
E/A |
E/B |
E/C |
I |
I |
E/D |