Losartan vs Candasartan vs Valsartan

Replacement to the List

Peer Feedback:
“candasartan or valsartan - losartan has flat dose response curve, other effective ARB are
available”

Literature Review Question:

What is the most effective ARB of Losartan, Candasartan, and Valsartan?

Literature Search:
eCPS – Hypertension; Cochrane
Pubmed – “angiotensin receptor blockers AND losartan AND (candesartan OR valsartan) AND
(effect OR efficacy) AND meta-analysis/review”

Candesartan and losartan in essential hypertension (2011)

In this systematic review and meta-analysis, we reviewed 12 studies that compared the effects
and safety of candesartan versus losartan. Comparing the common therapeutic dose of the two
agents, candesartan showed a superior lowering of SBP and DBP compared with losartan at
trough after a 24 h dose. When comparing double dosage or titration to double dosage of the two
agents, similar results were found at trough and peak after administration. Nevertheless, the
response and blood pressure-controlling efficacy of candesartan in follow-up was superior to that
of losartan.

The results of this meta-analysis indicate that candesartan is more effective than losartan in
reducing blood pressure. There was no evident difference in their common adverse events
profiles. Candesartan seems to cause fewer serious adverse events than losartan.
Zheng, Zhenfeng, et al. "A systematic review and meta-analysis of candesartan and losartan in the management of
essential hypertension."Journal of Renin-Angiotensin-Aldosterone System (2011): 1470320310391503.

Candesartan compared to other ARBs (2011)

Clinical trials have demonstrated that candesartan cilexetil is an effective agent in reducing the
risk of cardiovascular mortality, stroke, heart failure, arterial stiffness, renal failure, retinopathy,
and migraine in different populations of adult patients including patients with coexisting type 2
diabetes, metabolic syndrome, or kidney impairment. Clinical evidence confirmed that
candesartan cilexetil provides better antihypertensive efficacy than losartan and is at least as
effective as telmisartan and valsartan. Candesartan cilexetil, one of the current market leaders in
BP treatment, is a highly selective compound with high potency, a long duration of action, and a
tolerability profile similar to placebo.
Cernes, Relu, Margarita Mashavi, and Reuven Zimlichman. "Differential clinical profile of candesartan compared to other angiotensin
receptor blockers."Vascular health and risk management 7 (2011): 749.

Valsartan Meta-analysis (2009)

In all, 31 RCTs (n = 13,110 patients) were included in the analysis. This meta-analysis
demonstrates that valsartan at doses of 160 and 320 mg is more effective in reducing BP than
losartan at the 100 mg dose. At comparable doses, valsartan achieves comparable
antihypertensive efficacy to the other ARBs. Findings confirm that valsartan has a strong dose–
response relationship when increasing from 80 to 160 mg and 320 mg and that further head-to-
head trial are warranted. The clinical application of these results should take into consideration
the limitations discussed in this analysis
Nixon, R. M., et al. "Valsartan vs. other angiotensin II receptor blockers in the treatment of hypertension: a meta‐analytical
approach." International journal of clinical practice 63.5 (2009): 766-775.

ARBs Cochrane (2008)

Is there a difference in the magnitude of BP lowering effect between individual drugs in the ARB
class?

This review provides a reasonable amount of data to assess the trough BP lowering effect of 9
different ARBs. When the different ARBs are compared, there is a similarity in their BP lowering
effects at trough. When the best estimate of the near maximal BP lowering efficacy of these 9
drugs is compared, they range from -6/-3 mm Hg to -10/-7 mm Hg. For many of the drugs, there
are insufficient data for a full range of doses. Therefore it remains possible that there could be
differences between some of the drugs. However, the data are most consistent with the near
maximum BP lowering effect of each of the drugs being the same. It would require head-to-head
trials of different ARBs at equivalent BP lowering doses to assess whether or not there are
differences in the BP lowering efficacy between different drugs. This review provides useful dose-
response information for estimating equivalent doses and thus designing trials to compare
different ARBs.
 Heran, Balraj S., et al. "Blood pressure lowering efficacy of angiotensin receptor blockers for
primary hypertension." The Cochrane Library (2008).

eCPS (2015)

Table 6: Drugs Used for Hypertension

Drug
Class Drug Dosage Adverse Effects Interactions Comments Costa

Angiotensin candesartan Initial: 8 $

Receptor mg/day Hyperkalemia.
Blockers Atacand, gen Usual: 8–16
(ARB) erics mg/day Can precipitate renal  Contraindicated in pregnancy—caution when
Once daily po Marked increase
failure in susceptible prescribing to women of child-bearing
in serum K+ in potential.7
patients (bilateral
Angiotensin losartan Initial: 50 renovascular 
patients receiving
$
mg/day disease, those with K+supplements Use lower initial doses in patients who are
Receptor
Cozaar, gener Usual: 25–100 volume depletion or and/or K+-sparing volume depleted or on diuretics (increased risk
Blockers
ics mg/day with concurrent diuretics. of hypotension in hypovolemia).
(ARB)
Maximum:100 NSAID use).
mg/day May elevate Hyperkalemia usually occurs only in those on
Once daily or Angioedema has Li+levels (monitor K+ supplements or drugs that cause K+retention,
divided BID po been reported, but a Li+levels, adjust those with renal impairment or diabetics with
causal association dose). high serum K+ levels. Assess SCr and K+ after a
Angiotensin valsartan Initial: 80 has not been few days, then regularly. $
Receptor mg/day established.
Blockers Diovan, gener Usual: 80–320
mg/day
 Drug
Class Drug Dosage Adverse Effects Interactions Comments Costa

(ARB) ics Once daily po

Legend: $<$20 $-$$ <20–40 $$ 20–40 $$$ 40–60 $$$$ 60–80

Cardiovascular Disorders: Hypertension; Norm R.C. R. C. Campbell, MD, FRCPC, Paul Gibson,
MD, FRCPC, and Ross T. Tsuyuki, PharmD, MSc, FCSHP, FACC; Date of Revision: March 2015

Contraindications (CI), drug Adverse Effects Initial dose; typical

Medication Uses Monitoring
interactions (DI) or cautions (common and severe) dose
losartan hypertension, CI: bilateral artery stenosis or kidney hypotension, cough, headache, 25mg; 25- electrolytes, renal
delay diabetic stenosis if only 1 kidney), dizziness, fatigue, angioedema, 100mg one time a function (SCr, BUN,
nephropathy angioedema, pregnancy(T2 and T3) hyperkalemia day electrolytes)
DI: increases lithium and potassium,
fluconazole, rifampin (decrease
efficacy)