Renal safety profile of Losartan and Enalapril Optimizing medicine use to improve patient outcomes

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Renal safety profile of Losartan and
EnalaprilOptimizing medicine use to improve
patient outcomes

• Mugendi AG,
• BPharm, MPharm (Clin Pharm)

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• Comparison of the effects of losartan and
  enalapril on renal function in adults with
  chronic kidney disease at Kenyatta National
  Hospital

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Introduction

• Chronic kidney disease (CKD) is a growing health
  concern
• Its prevalence is increasing at a rate of 8 per
  year worldwide
• The renin angiotensin aldosterone system is
  strongly implicated in the progression of kidney
  failure

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Introduction

• Angiotensin II converting enzyme inhibitors and
  angiotensin II receptor blockers inhibit this
  system
• They control blood pressure and retard the
  progression to end stage renal failure
• Enalapril and losartan are commonly used at the
  renal and diabetic clinics in Kenyatta National
  Hospital

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Study problem

• Previous studies evaluated the adequacy of blood
  pressure control in patients with CKD and
  hypertension
• They did not investigate the state of renal
  function in patients who were on ACE inhibitors
  or ARBs
• No comparisons were done between ACEi and ARBs
• Paucity of local and regional data regarding the
  use of these drugs and renal outcomes

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Objectives

• Broad objective
• To compare the effects of enalapril and losartan
  on renal function in adults with chronic kidney
  disease at KNH
• Specific objectives
• To compare the incidence of doubling of baseline
  serum creatinine concentrations in patients using
  enalapril and losartan based regimens

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Objectives

• Specific objectives
• To compare the change in the level of proteinuria
  in patients using enalapril and losartan based
  regimens
• To compare the change in estimated glomerular
  filtration rate in patients using enalapril and
  losartan based regimens

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Methodology

• Ethical approval was granted by the KNH UoN ERC
• Retrospective analytic cohort at the Kenyatta
  National Hospital from January 2006-December 2012
• Data collection was done between June and August
  2013
• Two arm study enalapril and losartan
• Male and female patients 18 years of age or older
  with hypertension and diabetic nephropathy were
  recruited

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Results doubling of serum creatinine

• Patients on losartan had a higher risk of
  doubling of serum creatinine (Adjusted HR1.572
  95 CI (1.015-2.434) p0.043) than those on
  enalapril
• A significant difference in survival
  probabilities between the two arms losartan 18
  months, enalapril 36 month (p0.046)- was noted

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Results doubling of serum creatinine
P0.046 Log Rank Test
Figure 1 Kaplan Meir survival probability curve
to first doubling of serum creatinine
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Results changes in eGFR

• Significant differences in the means of the
  estimated glomerular filtration (eGFR) rates
  between the two arms were observed at months 3
  (p0.045) and month 6 (p0.046) of follow up
• Univariate analysis of variance revealed that
  increased length of therapy with either agent was
  protective (p0.007)

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Results changes in eGFR
Figure 4 Plot of the mean eGFR from baseline at
different time points between the two arms.
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Discussion

• Both drugs inhibit the renin angiotensin
  aldosterone system
• However, there is differential stimulation of the
  kallikrein kinin system (KKS)
• KKS activation causes inhibition of the
  progression of diabetic nephropathy
• Postulated to be the main reason for the
  difference of effect

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Conclusion

• Patients on enalapril are less likely to
  experience a doubling of baseline serum
  creatinine
• Renal function is better preserved in patients on
  enalapril
• Prolonged duration of therapy is also
  renoprotective

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Recommendation

• Enalapril should be first line therapy in
  hypertensive patients with diabetic nephropathy
• RAAS blockers should be initiated as soon as
  possible after diagnosis
• Larger studies- prospective cohort or randomised
  clinical studies- are required

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Challenges

1. Incomplete records was the biggest challenge