Table 2.

Main characteristics of cohort studies included in meta-analysis of acetazolamide therapy in heart failure patients.

	Study (Author, Year)	Schwartz, 1955 [23]	Mauck, 1957 [24]	Khan, 1980 [25]	Fontana, 2011 [26]	Apostolo, 2014 [27]	Verbrugge, 2015 [28]
Method	Study design	Cohort, time series	Cohort, time series	Cohort, time series	Cohort	Cohort	Cohort
	Total number	17	14	74	12	20	54
	Patient sample	Severe CHF with cor pulmonale	Stable CHF	Hospitalized decompensated CHF	CHF with periodic breathing	CHF with periodic breathing	Hospitalized decompensated CHF
	CHF definition	Clinical diagnosis with severe pulmonary disease, with ECG or Xray change of right heart enlargement or strain	Fully digitalized ambulatory CHF on 1 gm diet, mostly edema free. Wash out from other diuretics for two weeks	Patients diagnosed with CHF that failed treatment with furosemide, spironolactone and salt restriction	EF < 50%, with AHI > 15	EF < 40%, with periodic breathing during exercise	At least three signs of volume overload, EF < 45%
	Acetazolamide dosing	1–1.5 gm over 24 h	250 mg qday	250 mg qid (1 g per day), used as a replacement of furosemide	250 mg po bid for 4 days	500 mg IV and prolonged 2 gm over 24 h	250 mg qday
	Description	Using acetazolamide to treat patient with cor pulmonale and respiratory acidosis	Studying effect of acetazolamide in ambulatory CHF, aiming at electrolyte values during therapy	Using acetazolamide instead of furosemide for diuresis	Measure breathing parameters with ABG analysis before and after acetazolamide treatment	Measured respiratory pattern before and after acetazolamide treatment	Cohort finding predictor of natriuresis
Quality assessment (Newcastle-Ottawa scale)	Selection	2	2	2 - Independent validation - Obvious series of cases	3 - Using cohort of CHF - Non-exposed cohort is self prior to acetazolamide - Secure record	3 - Using cohort of CHF - Non-exposed cohort is self prior to acetazolamide - secure record	3 - True representation of CHF - Same community of control - Secure record
	Comparability	1	1	1 - Study controls by using prior-self prior to treatment with acetazolamide	1 - Study controls by using prior-self prior to treatment with acetazolamide	1 - Study controls by using prior-self prior to treatment with acetazolamide	2 - Using multivariate analysis and still showed acetazolamide as important factor
	Outcome	1	1	1 -Secure record (hospital)	NA	NA	NA
	Exposure	NA	NA	NA	2 - Record linkage - Long follow up	2 - Record linkage - Long follow up	3 -Record linkage - Long follow up - Complete follow up of all subjects

Abbreviations: CHF, congestive heart failure; EF, ejection fraction; AHI, apnea–hypopnea index; ECG, electrocardiogram; IV, intravenous; ABG, arterial blood gas; NA, not applicable.