Dr Frank T Ruschitzka

Sleight stressed that these observational data have limitations and that the ONTARGET population was not a typical hypertension-trial cohort. The 25 260 patients were elderly and were at high risk, but their blood pressure was not particularly high (high-normal or stage 1 hypertension), and they were already well-treated before they entered the study. "The findings suggest that in high-risk people, the [current] guidelines of 'the lower, the better' may not apply," he noted.

Study discussant Dr Frank T Ruschitzka (University of Zurich, Switzerland) said that the "treasure box" that is ONTARGET has already shown that the combination of the ACE inhibitor ramipril and the angiotensin-receptor blocker (ARB) telmisartan (Micardis, Boehringer Ingelheim)—despite lowering blood pressure more than either drug alone—"fails to translate into clinical benefit." He added that recent findings from the secondary-prevention stroke trial, PROFESS, where telmisartan was pitted against placebo, show that the ARB "does not prevent recurrent strokes." These new findings from the blood-pressure analysis of ONTARGET "show that we should certainly not go too low," he concluded.

The landmark ONTARGET trial showed that telmisartan was "noninferior" to ramipril in 25 260 patients with coronary heart disease or diabetes plus additional risk factors who were over the age of 55 years of age but did not have evidence of heart failure. And the combination of the two drugs was associated with more adverse events without an increase in benefit.

The average BP on study entry was 142/82 mm Hg, and patients were randomized to receive ramipril 10 mg per day, telmisartan 80 mg a day, or the combination of the two. The mean duration of follow-up of the study was 55 months. Results showed that mean blood pressure was lower in the telmisartan (a 0.9/0.6-mm-Hg-greater reduction) and the combination-therapy (a 2.4/1.4-mm-Hg-greater reduction) groups than in the ramipril group.

Dr Peter Sleight

In the new analysis, Sleight said the 25 260 patients were divided into four quartiles based upon blood pressure, regardless of which study arm they had been randomized to.

The analysis showed that only the very highest quartile of BP (systolic BP >154 mm Hg) had a significantly higher risk of the primary end point: cardiovascular death, stroke, MI, or heart-failure hospitalization (p<0.001).

When the end points were considered separately, there were no differences between the four BP quartiles for cardiovascular death or for MI, "which some may say is puzzling, as lowering blood pressure doesn't seem to do anything," Sleight noted.

There was a benefit to lowering blood pressure in terms of stroke, however. Those in the lowest quartile of BP (systolic <130 mm Hg) had significantly less risk of stroke than those in the highest quartile.

But there was also evidence of potential harm among diabetics: although those with diabetes in the highest quartile of blood pressure did have a higher risk of the primary outcome, when it came to cardiovascular death alone, those in the lowest quartile seemed to have an increased risk of death, Sleight said.

Ruschitzka concluded that these findings and others "put a little bit of a cloud over the class of sartans." The overwhelming message from ONTARGET in terms of BP, he said, was that "ACE inhibitors or calcium channel blockers [CCBs] come first, and I'm not so sure about the sartans anymore." Also, "don't go below 140/90 mm Hg in this type of patient," and if more BP lowering is needed on top of ACE inhibitors and CCBs, a beta blocker should be used.