Efficacy and safety of twice-vs once-da

dosing of Lisinopril for hypertension

Review and conclusion discussion by
Omar Ayash, Majed , Abdulraza
Presented by Alaa wahoud
 Cohort retrospective study located in Florida, USA. Accepted to
publish in 5/3/2017.
Lisinopril is an ACE inhibitor, with t = 12 hr.
Lisinopril is the 2nd most commonly prescribed Anti-hypertensive
agent in the US.
50% of US adult with hypertension have uncontrolled B.P
Uncontrolled HTN is the major risk factor for cardiovascular
morbidity and mortality.
Then-current recommended B.P goal is US is 140/90.

Introduction
 146
HTN patients treated by 20mg Lisinopril once daily.
Patients

A 101
A- Once-daily 40mg Lisinopril. B 45
B- Twice-daily 20mg Lisinopril.
Patients Patients

Doubled the Lisinopril dose from 20mg to 40mg, either for once-
daily(A) or twice-daily(B).
Measure B.P and safety outcomes before and after Index date.
Medical records were obtained from Ambulatory Electronic Health
Records center from 1/1/2010 to 31/12/2014.
Exclude: If and changes in Smoking, or Medication that might affect
impact B.P during evaluation. If the patient had no documented B.P
6 weeks before or 12 weeks after the Index Date.

Method
They measured:
B.P:
Primary, outcome change in Systolic B.P(first follow-up) comparing to the Bassline
outcome.
Secondary, outcome change in Diastolic B.P(first follow-up) comparing to the
Bassline outcome.

Safety:
- K and Cr serum level changes comparing to the bassline.
- Any other Patient self reported adverse effect.
- Hypotension ( Missing document).

Exclude any Outcome measured by ED or inpatient.

Measurement Of Outcomes
 All patients demographics and bassline characteristics were
summarized using descriptive statistics ( MeanSD, Percentage).

Reported AE and discontinuation of Lisinopril summarized as

percentage.

Statistical Activity
- B.P outcome:
Mean B.P achieved in, Once-daily cohort was 145/84 mm Hg, Twice-
daily cohort was 131/79 mm Hg.
For SBP had 10.2 mm Hg greater reduction in Twice daily ( = 0.015).
For DBP had 4.3 mm Hg greater reduction in Twice daily ( = 0.067 ).

Result
- Safety outcome:
Only 21 patient reported having AE in Once-daily cohort,
16 in Twice-daily cohort.

Dissociation of Lisinopril is due sympathetic AF 3 cases,

( Angioedema (1) , Cough (1) in group A )
(Dizziness (1) in group B).
 The study shows that first time that twice- daily dosing of Lisinopril was associated with greater SBP
lowering and greater achievement of SBP control than once- daily dosing at the same total daily dose.
And that probably related to that Lisinopril has an elimination half-life of approximately 12hours.

Given that twice daily Lisinopril appears to be more effective at reducing BP, and may help in
decrease poly- pharmacy, associated costs, and risk of adverse drug reaction.

According to adherent we couldnt know Because of our study design, adherence could not be
assessed.

Lisinopril is generally well tolerated by most patients and we found that is no significant different
between tow dosing strategies in adverse effect but what interesting that developed AKI incidence in
one daily dose is higher compared with those receiving twice-daily administration.

Several patients was at BP goals at base line and that make us wondering why daily dose was
increased?

Conclusion
 This study observed one heath system and cant be
generalized to other sites.
B.P measurement were taken during outpatient visit, so we
cant determined whether the measurement was taking
during the peak or through of Lisinopril BP lowering
effect.
AE were self reported by the patient according to the
awareness of the patient.
Sample size of patient was small and cant be generalized
on the population.

Study Limitations
To The Check List