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. 2017 Feb 28;2017(2):CD008996. doi: 10.1002/14651858.CD008996.pub2

Weinberger 2002.

Methods Study design: randomized controlled trial
Study grouping: parallel group
Participants Baseline characteristics
Eplerenone 50 mg daily

  • Female (%): 30

  • White (%): 67

  • African American (%): 19

  • Hispanic (%): 15

  • Asian/other (%): 0

  • Seated SBP (mmHg, mean ±SD): 155.6

  • Seated DBP (mmHg, mean ±SD): 100.8

  • HR (beats/min, mean ±SD): 75.7

  • Standing SBP (mmHg, mean): 154.7

  • Standing DBP (mmHg, mean): 101.6


Placebo

  • Female (%): 4

  • White (%): 58

  • African American (%): 25

  • Hispanic (%): 17

  • Asian/other (%): 0

  • Seated SBP (mmHg, mean ±SD): 153.5

  • Seated DBP (mmHg, mean ±SD): 101.3

  • HR (beats/min, mean ±SD): 76.3

  • Standing SBP (mmHg, mean): 153.1

  • Standing DBP (mmHg, mean): 102.9


Eplerenone 100 mg daily

  • Female (%): 39

  • White (%): 67

  • African American (%): 24

  • Hispanic (%): 8

  • Asian/other (%): 0

  • Seated SBP (mmHg, mean ±SD): 153.0

  • Seated DBP (mmHg, mean ±SD): 100.8

  • HR (beats/min, mean ±SD): 74.5

  • Standing SBP (mmHg, mean): 153.8

  • Standing DBP (mmHg, mean): 102.1


Eplerenone 400 mg daily

  • Female (%): 36

  • White (%): 66

  • African American (%): 25

  • Hispanic (%): 5

  • Asian/other (%): 4

  • Seated SBP (mmHg, mean ±SD): 152.2

  • Seated DBP (mmHg, mean ±SD): 101.7

  • HR (beats/min, mean ±SD): 73.7

  • Standing SBP (mmHg, mean): 151.2

  • Standing DBP (mmHg, mean): 102.5


Eplerenone 25 mg twice daily

  • Female (%): 27

  • White (%): 75

  • African American (%): 15

  • Hispanic (%): 9

  • Asian/other (%): 2

  • Seated SBP (mmHg, mean ±SD): 155.7

  • Seated DBP (mmHg, mean ±SD): 101.0

  • HR (beats/min, mean ±SD): 75.0

  • Standing SBP (mmHg, mean): 154.7

  • Standing DBP (mmHg, mean): 101.9


Eplerenone 50 mg twice daily

  • Female (%): 30

  • White (%): 70

  • African American (%): 19

  • Hispanic (%): 9

  • Asian/other (%): 2

  • Seated SBP (mmHg, mean ±SD): 153.6

  • Seated DBP (mmHg, mean ±SD): 101.2

  • HR (beats/min, mean ±SD): 74.0

  • Standing SBP (mmHg, mean): 153.4

  • Standing DBP (mmHg, mean): 102.1


Eplerenone 200 mg twice daily

  • Female (%): 31

  • White (%): 73

  • African American (%): 15

  • Hispanic (%): 10

  • Asian/other (%): 2

  • Seated SBP (mmHg, mean ±SD): 155.4

  • Seated DBP (mmHg, mean ±SD): 102.0

  • HR (beats/min, mean ±SD): 73.4

  • Male (%): 69

  • Standing SBP (mmHg, mean): 154.7

  • Standing DBP (mmHg, mean): 103.0


Inclusion criteria:

  • 21‐80 years old with both seated, cuff‐assessed diastolic blood pressure (DBP) ≥ 95 mmHg and < 114 mmHg and a 24‐h mean DBP ≥ 85 mmHg determined by a 24‐h ambulatory BP monitoring (ABPM) device

  • Medication compliance (80%) during the single‐blind placebo lead‐in period was required to qualify for randomization


Exclusion criteria:

  • Secondary, severe, or malignant hypertension with or without retinopathy

  • Regular use of systemic medications known to influence BP

  • Regular use of nonsteroidal antiinflammatory drugs

  • Myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, angina pectoris, or intermittent claudication within the previous 6 months

  • Severe aortic or mitral valvular disease and cardiac arrhythmia requiring medical treatment or causing haemodynamically relevant disturbances

  • Hypertrophic cardiomyopathy or congestive heart failure requiring digoxin or diuretic therapy

  • Stroke or transient ischemic attack within the previous 6 months

  • Insulin‐dependent diabetes mellitus

  • Acute or chronic hepatic disease

  • Serum creatinine > 1.5 mg/dL or serum potassium > 5.0 mEq/L

  • History of alcohol or drug abuse

  • Known hypersensitivity to spironolactone or steroids

  • Use of any other investigational medication 30 days before this study

  • Night‐shift employment

  • Upper arm circumference > 42 cm


Pretreatment: study notes no differences in baseline characteristics between groups. Groups look well‐balanced
Interventions Intervention characteristics
Eplerenone 50 mg daily
Placebo
Eplerenone 100 mg daily
Eplerenone 400 mg daily
Eplerenone 25 mg twice daily
Eplerenone 50 mg twice daily
Eplerenone 200 mg twice daily
Outcomes Change from baseline in SBP (seated)

  • Outcome type: continuous outcome


Change from baseline in DBP (seated)

  • Outcome type: continuous outcome


Change from baseline in 24 h ambulatory BP monitoring (SBP)

  • Outcome type: continuous outcome

  • Reporting: partially reported

  • Unit of measure: mmHg

  • Direction: lower is better

  • Data value: change from baseline


Change from baseline in 24 h ambulatory BP monitoring (DBP)

  • Outcome type: continuous outcome

  • Reporting: partially reported

  • Unit of measure: mmHg

  • Direction: lower is better

  • Data value: change from baseline


Number of patients with any adverse events (occurring in at least 5% of patients)

  • Outcome type: adverse event

  • Reporting: fully reported

  • Direction: lower is better

  • Data value: endpoint


Number of patients discontinued medication due to AE

  • Outcome type: adverse event

  • Reporting: fully reported

  • Direction: lower is better

  • Data value: endpoint
Identification Sponsorship source: Pharmacia Corporation, Skokie IL
Country: 48 US sites
Author's name: Myron H Weinberger
Institution: Indiana University School of Medicine, Hypertension Research Center
Email: mweinbe@iupui.edu
Address: 541 Clinical Drive #423Indianapolis, IN46202‐5111
Notes —
Risk of bias
Bias Authors' judgement Support for judgement
Sequence Generation Low risk Quote: "Qualified patients in the double‐blind treatment period were randomised by a computer‐generated schedule to 50, 100, or 400 mg of eplerenone administered once daily or in divided doses; 50 mg of spironolactone twice daily; or placebo."
Allocation concealment Low risk Judgement comment: allocation of all patients simultaneously after run‐in via computer randomization.
Blinding of participants and personnel 
 All outcomes Unclear risk Quote: "8‐week double‐blind treatment period."
Judgement comment: unclear, because exactly who was blinded is not known. No mention of matching placebo used to mimic twice daily dosing of eplerenone groups
Blinding of outcome assessors 
 All outcomes Unclear risk Judgement comment: no reference to blinding of assessors made. No mention of double dummy design.
Incomplete outcome data 
 All outcomes Unclear risk Quote: "Overall, 417 patients were randomised to receive at least one dose of study medication and were subsequently included in the safety analyses. Of these, 409 had at least one evaluation after their baseline evaluation and were included in the efficacy analyses. Five patients were excluded because of protocol noncompliance and three were lost to follow‐up. An additional 39 patients did not complete the study because of treatment failure (7), loss to follow‐up (2), protocol noncompliance (16), pre‐existing protocol violation (3), or adverse events (11)."
Judgement comment: not clear how 11.3% patient withdrawals were distributed across groups or how missing data was dealt with.
Selective outcome reporting Unclear risk Judgement comment: no protocol available.
Other sources of bias High risk Quote: "This study was supported by Pharmacia Corporation, Skokie, IL."