Telmisartan, Valsartan Lower Risk of CVD Complications in Diabetics

July 08, 2013

TORONTO, Ontario — For patients with diabetes, the use of the angiotensin-receptor blockers (ARBs) telmisartan (Micardis, Boehringer Ingelheim) and valsartan are both associated with a significantly lower risk of macrovascular disease compared with irbesartan, a large, retrospective study suggests [1]. In the analysis, the use of telmisartan and valsartan lowered the risk of hospital admission for MI, stroke, or heart failure by 15% and 14%, respectively.

In contrast, the use of losartan or candesartan did not significantly reduce the risk of cardiovascular events in the diabetic patients.

”Our findings suggest that statistically important differences exist in the effectiveness of angiotensin-receptor blockers when used for the prevention of diabetes-related macrovascular disease and that a class effect for these agents may not be assumed when used for this purpose in clinical practice," say Dr Tony Antoniou (St Michael's Hospital, Toronto, ON) and colleagues in their report, published online July 8, 2013 in CMAJ.

Given their findings, the group states that telmisartan and valsartan "may therefore be the preferred ARBs for use in these patients."

In their paper, the researchers explain that telmisartan has several pleiotropic properties that distinguish the drug from other ARBs. Specifically, they note that it is a partial agonist of peroxisome proliferator-activated receptor-{:gamma:} (PPAR-{:gamma:}). PPAR-{:gamma:} is a ligand-activated transcription factor that regulates lipid metabolism and insulin sensitivity. Because telmisartan is only a partial agonist of PPAR-{:gamma:}, it is not associated with adverse effects associated with full agonists, those being sodium and water retention, edema, and heart failure.

To heartwire , Dr Sripal Bangalore (New York University School of Medicine), who was not involved in the study, said the results were thought provoking.

"In clinical practice, most of us assume that the effect of ARBs as a class is similar," said Bangalore. "However, intergroup differences have long been debated. We have shown that of all the ARBs the antihypertensive efficacy of losartan is the lowest. It is therefore interesting to see these data from a large observational study showing probable superiority of telmisartan and valsartan."

More Than 54,000 Patients Analyzed

The population-based retrospective study included an analysis of 54 186 Canadian patients with diabetes who started taking an ARB between 2001 and 2011. All patients were 66 years of age or older, the average age being 73 years, and the average duration of diabetes was approximately six years. Overall, 20.2% of patients were treated with candesartan, 23.4% with irbesartan, 15.5% with losartan, 15.1% with telmisartan, and 25.8% with valsartan.

The primary end point, a composite of admission to the hospital for MI, heart failure, or stroke, occurred in 2712 patients taking an ARB. In an adjusted risk model, telmisartan was associated with a 15% lower risk of the primary end point, while valsartan was associated with a 14% lower risk, when compared with irbesartan. In a dose-response analysis, the group found no difference in the risk of the primary outcome with moderate or high doses of ARBs, although the effectiveness of valsartan was "somewhat attenuated" when adjusted for dose.

Risk of the Composite Outcome of Hospitalization for MI, Stroke, or Heart Failure

Drug Adjusted hazard ratio (95% CI)
Irbesartan 1.00 (reference)
Telmisartan 0.85 (0.74–0.97)
Candesartan 0.99 (0.89–1.11)
Losartan 0.93 (0.83–1.05)
Valsartan 0.86 (0.77–0.96)

The reduction in the primary end point, however, was driven primarily by a reduction in the risk of heart-failure hospitalizations. Analyzed separately, telmisartan was associated with a 20% lower risk of heart-failure hospitalizations, while valsartan was associated with a borderline 13% nonsignificant reduction (hazard ratio 0.87; 95% CI 0.75–1.00).

To heartwire , Bangalore said the advantage of the analysis is the large number of patients. Such large numbers are unlikely to be replicated in a large-scale randomized, clinical trial comparing the different ARBs head-to-head. The disadvantages, however, are those typical for such observational analyses, that being the potential for confounding and selection ascertainment bias. He pointed out that the primary outcome was driven by a reduction in hospitalization for heart failure and that just 6.3% of telmisartan-treated patients and 7.1% of valsartan-treated patients had congestive heart failure at baseline compared with 9.0% of losartan-treated patients.

"Nevertheless, the results are provocative," said Bangalore. 

Antoniou has received unrestricted research grants from Merck and Pfizer. Disclosures for the coauthors are listed in the paper.

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