MOSES: Eprosartan vs nitrendipine to reduce risk of subsequent events after stroke

Shelley Wood

September 16, 2004

Munich, Germany - A new study suggests that the angiotensin II receptor antagonist eprosartan (Teveten® HCT, Solvay) may be better than the calcium-channel blocker nitrendipine in protecting against cardiovascular and cerebrovascular events in hypertensive patients who have had a previous stroke. One expert, however, says it is difficult to accept the study's conclusions at face value.

Dr Joachim Schrader (St Josefs-Hospital, Cloppenburg, Germany) presented the results of the Morbidity and Mortality After Stroke: Eprosartan versus Nitrendipine in Secondary Prevention (MOSES) trial during a satellite session held during the European Society of Cardiology Congress 2004. As Schrader explained, the study was testing the hypothesis that eprosartan would be better than nitrendipine in reducing mortality and cardiovascular (CV) and cerebrovascular (CE) events while achieving the same degree of blood-pressure control.

According to Schrader, the MOSES results show eprosartan to have "significant advantages" over nitrendipine in the prevention of future events.

MOSES findings

MOSES randomized more than 1400 patients in Germany and Austria to either 600-mg eprosartan or 10-mg nitrendipine daily to achieve normotension. Additional BP-lowering drugs could be added if necessary, starting with a diuretic, then a beta blocker, than an alpha blocker. Mean follow-up was 2.5 years; most patients had their "qualifying event" nearly one year before being enrolled in the study.

The investigators report that while blood-pressure lowering was similar for both arms, the primary end pointa combination of total mortality plus total CV and CE eventswas higher in the nitrendipine-treated patients when recurrent events were included. Likewise, for recurrent CE events alone, the eprosartan-treated patients had fewer events. For CV events, including recurrent events, eprosartan patients showed a nonsignificant trend toward reduced events.

When the data were examined considering only first events, the only significant difference was seen in cardiovascular events alone, with fewer eprosartan patients having a first CV event over the study period. No differences in mortality occurred between the first two groups

MOSES: Primary and secondary outcomes

Outcome

Eprosartan (n)

Nitrendipine (n)

p

All deaths and CV and CE events, recurrent (n=461)

205 255 0.014

All CE events, recurrent (n=236)

102 134 0.02

All CV events, recurrent (n=178)

77 101 0.06

First event, all (n=320)

149 171 0.15

First event, CE (n=169)

80 89 0.42

First event, CV (n=149)

60 84 0.03

"Eprosartan had significant advantages with regard to the primary end point and with regard to cerebrovascular and cardiovascular events when recurrent events were included and with regard to first cardiovascular events," Schrader concluded.

Dissociating outcomes from BP lowering

Asked to comment on the MOSES trial for heartwire , Prof Anthony Heagerty (University of Manchester, UK) pointed out that the systolic blood pressures at baseline were slightly lower in the eprosartan-treated patients, compared with nitrendipine-treated patients, 150.7 mm Hg vs 152 mm Hg.

"Eprosartan patients start off with slightly lower blood pressure, which would mean that their risk of having a stroke is slightly less than the nitrendipine patients from the outset," Heagerty observed. "Then if they lowered blood pressure to about the same degree, there will be fewer events in the eprosartan group because they will always have a slightly lower risk than the nitrendipine-treated patients."

Heagerty said he could not say whether this difference accounted for all of the benefit seen in the eprosartan-treated patients but noted that the data that would help clarify the results were not presented. For example, the MOSES investigators provided pie charts showing the number of patients in each group who reached target blood-pressure levels, but they did not provide final blood-pressure values for both groups.

 

This is absolutely fraught with danger.

 

What the study does reconfirm is the benefit of lowering blood pressure in these patients. "It demonstrates that if you actually treat hypertension you can ameliorate the risk of stroke and heart disease, but there's nothing new there....There's no question that eprosartan is a good drug, but only a minority of patients in this trial were on monotherapy," he added, so it is impossible to attribute any benefits to any one drug.

In some ways, Heagerty noted, MOSES suffers from the same problems that have plagued other major trials trying to link morbidity and mortality outcomes to blood-pressure reductions in head-to-head studies. These depend on having mean blood pressures at baseline that are identical between the two groups that then are reduced to the same degree. "This is absolutely fraught with danger," he said. "There are very few of these major studies that start off with identical blood pressures at baseline and have the same blood pressures at close."

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