January 11th, 2011
Candesartan Beats Losartan in Swedish HF Registry
Larry Husten, PHD
The Swedish Heart Failure Registry followed more than 5,000 patients treated with the angiotensin II receptor blockers (ARBs) candesartan or losartan between 2000 and 2009. According to a paper published in JAMA, survival at one year was 90% in the candesartan group compared to 83% in the losartan group. Five-year survival was 61% and 44%. After adjustment for clinical differences and propensity scores, the hazard ratio for losartan compared to candesartan was 1.43.
Discussing the large difference between the drugs, the authors acknowledge that “the magnitude of our findings may be due to chance, but RCTs may understate ‘real world’ differences, and it is conceivable that candesartan is better than losartan by a magnitude similar to placebo.” They conclude, however, that “clinical decision making should await supportive evidence” and recommend that differences between ARBs should be tested in randomized trials, though they acknowledge it may be more feasible to confirm the finding in other registries.
11 Responses to “Candesartan Beats Losartan in Swedish HF Registry”
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Retrospective study. Many confounding variables may go unnoticed. Yet to come to firm conclusion about any superiority Candsartan over Losartan. Only neck to neck randomized study can give firm evidence.
I agree with DR. Surs remarks.Also, Losartan is now available in the USA as a generic,which markedly lowers the cost of therapy. Preventing heart failure by treating Hypertension properly is totally different than treating heart failure. Losartan lower cost gives it a significant advantage over other ace receptor blockers if that class of drugs is chosen to treat hypertension.
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For systolic heart failure, I make an analogy with chemotherapy…follow the evidence base data and use candesartan or valsartan. For HTN, many other ARBs are more potent and effective re BP reduction over 24 hours…but this is overall a weaker argument. Nevertheless, I prefer dosing losartan bid. Also, for some insurance plans, cost to patient is minimally if at all lower on this generic.
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This hypothesis generating analysis raises important concerns about within class discordance in efficacy of two individual ARBs and suggests superiority of candesartan over losartan with respect to all-cause mortality at 1 and 5 years in patients with heart failure (HF) with reduced left ventricular ejection fraction.
However, the propensity score driven analysis did not examine dose equivalency with the two agents. For example, would the apparent differences persist with Losartan 150mg vs Candesartan 32mg; Losartan 100mg vs Candesartan 16mg and Losartan 50mg vs Candesartan 8mg.
Even then, we cant be certain that doses in these strata meet equivalency. Overall, the strength of the evidence and whether the findings should affect clinical practice are important considerations. The study has not met both of these criteria due to it retrospective, non-randomized design.
Guidelines on appropriate dosing of Losartan are urgently needed!
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Christopher O. Phillips, MD declares that there are no conflicts of interests to declare with respect to the article, the affiliated institutions and authors.
No matter what is the result of the registry. This is an outrageous example of “trespassing” guidelines. I have been using either valsartan or candesartan. Losaratan use in CHF is off-label. Or have I missed losartan in the guidellines? The price of the two ARBs cannot be compared in case only one of them has been approved for CHF treatment.
I have followed the comparison of these two ARBs for some years (they are the only two available in New Zealand, both are registered for treatment of hypertension and heart failure). Unusually, there have been several published head-to-head comparisons. In 2002 an expert FDA panel unanimously agreed that the manufacturers of candesartan could claim a superior antihypertensive effect over losartan. My reading of the literature supports this – despite my wariness of pro-AstraZeneca drug findings in their “home” country! I do agree that registry data are not conclusive but I am not suprised by the finding in this study.
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I have in the past (>4 years ago) served on advisory panels for both AstraZeneca and Merck Sharp & Dohme (manufacturers of candesartan and losartan respectively).
So what are we to do. Even the investigators of this study suggest that the findings are not strong enough to influence decision making – and yet, even with its weaknesses, the study raises concern – and until more information becomes available, shouldn’t we lean toward candesartan. This study, despite being exploratory and needing validation, makes it at least slightly more likely that candesartan is better than losartan. More importantly it raises the question of whether we should be assuming that intraclass effects are similar. We have enough recent experience to know that is not always true.
I want to share my take on this article for the public…http://tinyurl.com/6hebgez
I think it passed with too little notice.
OK this is a retrospective observational study but….
A study with a much poorer design has all but taken avandia off the market. Why should this study not have us writing for candesartan for all of our CHF patients (or at least for those who cannot tolerate ACE inhibitors?
I cannot understand why JAMA has published this paper on CHF Registry as losartan has no evidence base in guidelines.
(I can see no reason in the discussion where there are flaws in selection criteria. I cannot compare non-comparable items. I could only be interested in comparision of candesartan and valsartan in CHF registry.)
The conclusion in JAMA should read like this:
In the registry losartan was used for CHF pts while there is no support in the guidelines, this use is therefore non lege artis.
Non lege artis use of losartan is accompanied with greater mortality.
Retrospective study, registry based, no measurement of dose equivalency, no measure of dosing frequency, and use of off-label Losratan for CHF management, based on no previous clinical data to support. Not sure if any particular conclusion can be drawn off of this, except for the fact that Candesartan again shows efficacy in HF management as has been proven in the past. If cost effectiveness is a concern, then an appropriate RCT of effectively BID dosed losartan at appropriate target doses should be entailed in comparison to valsartan or candesartan…..
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