The results of the landmark TRANSCEND^® trial show that telmisartan significantly reduces the HOPE primary endpoint (TRANSCEND^® secondary endpoint) of risk of cardiovascular death, myocardial infarction and stroke in a broad cross-section of high risk cardiovascular patients who are intolerant to ACE inhibitors already on best standard care. TRANSCEND^® further demonstrates that telmisartan is well tolerated, even after 5 years of treatment.

The primary composite endpoint (CV death, MI, stroke and hospitalisation for CHF) was reduced by 8% (p=0.22, non-significant). Similar to the HOPE trial with ramipril, there was no impact on hospitalization for CHF, which may be attributed to the high concomitant use of diuretics and ß-blockers in the control group arm.


Efficacy

Fewer patients in the telmisartan group experienced the primary outcome of cardiovascular death, myocardial infarction, stroke or heart failure hospitalization versus the placebo arm (placebo in the meaning of best practice standard care), although the difference was not statistically significant (15.7% vs. 17.0% after 5 years of follow-up; p=0.216) (Figure 1). After the first 18 months, however, fewer events occurred with telmisartan, suggesting that the benefits of telmisartan treatment may be time dependent.

 

Telmisartan was associated with a significant reduction in the HOPE trial primary outcome (TRANSCEND^® secondary outcome) of cardiovascular death, myocardial infarction and stroke as compared to the control group (p<0.05) (Figure 2).

There was a significantly lower rate of newly diagnosed left ventricular hypertrophy (LVH) observed in the telmisartan group (5% for telmisartan vs. 7.9% for placebo, p<0.001), as well as a significantly lower rate of cardiovascular hospitalizations (30.3% for telmisartan vs. 33% for the control group; p=0.025).

There was also a trend towards a lower rate of new-onset diabetes in normo-glycaemic patients treated with telmisartan (11% for telmisartan vs. 12.8% for the control group, p=0.081). Although this result was not significant, it indicates a potential long-term metabolic benefit.


Tolerability and safety

Telmisartan was well tolerated and was associated with a 9% lower rate of discontinuations (p=0.055) than the control group arm. The reasons given for discontinuation were not significantly different in the telmisartan and placebo arms.


Implications of TRANSCEND^®

TRANSCEND^® is part of the ONTARGET^® trial programme, the first ARB programme to demonstrate protective benefits in high cardiovascular risk patients already treated with best practice standard care. TRANSCEND^® is the first placebo-controlled trial to investigate the effect of an ARB on CV outcomes when given on top of best standard care in patients intolerant to ACE inhibitors and was conducted over 5 years with very high quality (only 0.3% of patients lost to follow-up).

The risk reduction of 13% of the HOPE primary endpoint (CV death, MI, stroke) with telmisartan was achieved on top of best standard care. Indeed, patients were better protected than in the HOPE trial, as they received more statins, anti-platelets, beta-blockers and other anti-hypertensives.

Telmisartan was also associated with a significantly lower rate of CV hospitalization and newly diagnosed LVH, suggesting a potential long-term benefit in preventing the development of cardiac complications.

Although the primary outcome of cardiovascular death, myocardial infarction, stroke or heart failure hospitalization was reduced, this result did not achieve significance. Hospitalization for heart failure was not reduced by telmisartan, possibly due to the higher concomitant use of other anti-hypertensive agents in the control group arm.

TRANSCEND^® confirmed that telmisartan is well tolerated and associated with higher compliance rates than placebo.

TRANSCEND^® and the stroke prevention trial, PRoFESS™, suggest that the benefits of telmisartan cannot be detected until 6-12 months after treatment initiation, with full benefits emerging later. Considering that many high-risk patients require blood pressure and cardiovascular risk interventions throughout their lives, the long-term effect of treatment is particularly relevant.

Together with the ONTARGET^® trial, TRANSCEND^® shows that telmisartan has sustained tolerability and provides significant beneficial effects on cardiovascular outcomes. Telmisartan thus serves as an important treatment option for both ACE inhibitor-tolerant and intolerant patients at high cardiovascular risk.

Indication
Pritor^®/Kinzalmono^® is indicated for the treatment of essential hypertension. PritorPlus^®/Kinzalkomb^® is indicated in patients whose blood pressure is not adequately controlled on telmisartan alone.

Reference
The Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND^®) Investigators. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008;372(9644):1174-83.


The sponsor of TRANSCEND^® is Boehringer Ingelheim, the co-funders in selected countries are Bayer Schering Pharma and GlaxoSmithKline