ACEIs, ARBs, or DRI for Adults With Hypertension

1
ACEIs, ARBs, or DRI for Adults With
Hypertension

• Prepared for
• Agency for Healthcare Research and Quality (AHRQ)
• www.ahrq.gov

2
Background Prevalence

• Approximately 75 million Americans have
  hypertension.
• The prevalence of hypertension increases with
  advancing age.
• More than half of people 55 to 74 years old and
  approximately three-fourths of those 75 years
  are affected.
• Hypertension is the primary attributable risk
  factor for death and results in substantial
  morbidity.
• Hypertension impacts numerous target organs,
  including the brain, eyes, heart, arteries, and
  kidneys.

3
Background Treatment

• Despite the high rates of morbidity and mortality
  attributable to hypertension, control of the
  condition remains suboptimal.
• Effective lifestyle interventions may include
  diet, exercise, and control of body weight.
• Many people also require antihypertensive
  medication to lower blood pressure.

4
Background Pharmacological Blockade of the
Renin-Angiotensin System

• Among the many choices in antihypertensive
  therapy, some of the most common are those aimed
  at affecting the renin-angiotensin-aldosterone
  (renin) system. These include
• Angiotensin Converting Enzyme Inhibitors (ACEIs)
• Angiotensin II Type I Receptor Blockers (ARBs)
• Direct Renin Inhibitor (DRI)

5
Background Drugs Targeting The Renin System May
Not Be Clinically Equivalent

• Although ACEIs and ARBs both target the renin
  system and reduce the downstream effects of
  angiotensin II, it is not clear that these
  medications are in fact clinically equivalent.
• ACEIs only block partial production of
  angiotensin II.
• ACEIs have well-known side effects not shared to
  the same extent by ARBs, including cough and
  angioedema.
• The newer DRI aliskiren may have a side-effect
  profile and efficacy that differ significantly
  from ACEIs or ARBs.
• Given the public health importance and widespread
  use of these agents, it is important to
  understand their comparative effects on clinical
  outcomes.

6
Rationale for Update

• In 2007, AHRQ published its first systematic
  review on the comparative effectiveness of ACEIs
  versus ARBs for adults with hypertension.
• In 2011, this review was updated to include
  comparisons with the DRI aliskiren.
• ACEIs and ARBs are the second and fifth most
  commonly prescribed medications for hypertension,
  and use of DRI is increasing.
• Comparative effectiveness of the DRI versus ACEIs
  or ARBs has not been assessed.

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Agency for Healthcare Research and Quality (AHRQ)
Comparative Effectiveness Review (CER) Development

• Topics are nominated through a public process,
  which includes submissions from health care
  professionals, professional organizations, the
  private sector, policymakers, the public, and
  others.
• A systematic review of all relevant clinical
  studies is conducted by independent researchers,
  funded by AHRQ, to synthesize the evidence in a
  report summarizing what is known and not known
  about the select clinical issue. The research
  questions and the results of the report are
  subject to expert input, peer review, and public
  comment.
• The results of these reviews are summarized into
  Clinician and Consumer Research Summaries for use
  in decisionmaking and in discussions with
  patients. The research reviews and the full
  report, with references for included and excluded
  studies, are available at www.effectivehealthcare
  .ahrq.gov.

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Rating the Strength of Evidence From the CER

• The strength of evidence was classified into four
  broad categories

High Further research is very unlikely to change the confidence in the estimate of effect.
Moderate Further research may change the confidence in the estimate of effect and may change the estimate.
Low Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate.
Insufficient Evidence either is unavailable or does not permit estimation of an effect.
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Number of Studies Evaluating Various Treatment
Options
ARBs ARBs ARBs ARBs ARBs ARBs ARBs ARBs DRI
Unspecified ARBs Candesartan cilexetil Eprosartan Irbesartan Losartan Olmesartan medoxomil Telmisartan Valsartan Aliskiren
ACEIs Unspecified ACEIs 20 1 0 2 2 0 0 0 0
ACEIs Benazepril 0 0 0 0 0 0 0 1 0
ACEIs Captopril 0 0 0 0 2 0 0 0 0
ACEIs Enalapril 0 4 2 4 13 0 5 2 0
ACEIs Fosinopril 0 0 0 2 1 0 0 0 0
ACEIs Lisinopril 0 6 0 0 0 0 3 5 0
ACEIs Moexipril 0 0 0 0 0 0 0 0 0
ACEIs Perindopril 0 1 0 0 2 0 3 0 0
ACEIs Quinapril 0 0 0 2 3 0 0 0 0
ACEIs Ramipril 0 0 0 0 2 1 5 3 2
ACEIs Trandolapril 0 0 0 0 1 0 0 0 0
DRI Aliskiren 0 0 0 0 1 0 0 0 -
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Evidence of Benefits Blood Pressure-Lowering
Effects

• Similar long-term blood pressure-lowering effects
  were seen with ACEIs and ARBs. (high strength of
  evidence)
• The DRI aliskiren may be slightly more effective
  at reducing blood pressure than an ACEI
  (ramipril) however, no differences were detected
  between aliskiren and an ARB (losartan). (low
  strength of evidence)

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Evidence of Benefits Clinical Outcomes

• There were no significant differences between
  ACEIs and ARBs for these outcomes
• Mortality and major cardiovascular events (low
  strength of evidence)
• Rate of monotherapy success (high strength of
  evidence)
• Quality of life measures (low strength of
  evidence)
• Progression of renal disease (moderate strength
  of evidence)
• Effects on LVMI or LVEF (low strength of
  evidence)
• ACEI and ARBs are similar in their lack of effect
  on serum lipid levels, blood glucose levels, and
  HbA1c. (moderate strength of evidence)
• There was insufficient evidence for all other
  outcomes beyond blood pressure reduction on the
  comparative effectiveness of the DRI aliskiren.

12
Evidence on Adverse Effects

• Cough is more prevalent in patients on ACEIs than
  ARBs (About 9 of patients treated with an ACEI
  and about 2 of patients treated with an ARB
  report a cough).
• (high strength of evidence)
• ACEIs were associated with lower rates of
  persistence and higher rates of withdrawals due
  to adverse events when compared with ARBs.
  (moderate strength of evidence)
• Lower persistence with ACEIs versus ARBs may be
  explained largely by the differential rates of
  cough.
• Excluding cough, there were no significant
  between-class differences in any other specific
  adverse events.

13
Evidence on Adverse Effects Angioedema

• Angioedema was uncommon and most frequently
  associated with ACEIs.
• In one study, the DRI was associated with
  angioedema in one patient, but overall the
  evidence was insufficient.

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Gaps in Knowledge

• Long-term comparisons of a DRI with ACEIs and
  ARBs.
• The impact of cough on quality of life, care
  patterns (e.g., use of therapeutic agents for
  cough symptoms or conditions associated with
  cough), and health outcomes, particularly for
  individuals who continue to use ACEIs.
• Subgroups of special importance such as
  individuals with hypertension and diabetes
  mellitus, congestive heart failure, chronic
  kidney disease, and dyslipidemia.
• Broader representation of groups such as the
  elderly and ethnic and racial minorities.
• Clinical trials with long-term followup that
  report on the incidence of new cancer diagnoses
  and cancer deaths in patients on ACEIs, ARBs, or
  a DRI.

15
Patient Cost Information

• Medication costs may contribute to decreased
  adherence among patients.
• Average wholesale prices for these
  antihypertensive agents range from 30 to 160
  per month, depending on dosage.
• On average, ACEIs are less expensive for patients
  than ARBs and the DRI aliskiren.
• The most inexpensive ACEIs for patients are the
  generic forms of benazepril, enalapril,
  lisinopril, and quinapril.
• The majority of ARBs are not available in generic
  form. The average cost of most brand-name ARBs is
  between 80 and 195 per month, depending on
  dosage.
• The DRI aliskiren is also not available in a
  generic form. The average wholesale cost of
  aliskiren is 100 or 120 per month, depending on
  dosage.

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What To Discuss With Your Patients

• The importance of taking blood pressure
  medication as prescribed.
• The tradeoffs between the benefits and adverse
  effects when taking an ACEI, ARB, or DRI.
• How to identify and when to report serious side
  effects.
• Barriers that may affect adherence to their
  specific treatment regimen.
• All other medications they may be taking and
  their possible interactions.