<International Circulation>: The findings of the FEVER study have been of interest to specialists in hypertension and even been referred to by ESH guideline. Professor Zhang from China has presented some new data for subgroup analysis here at the ESH meeting. Would you like to give us your views or comments on the FEVER study?
    Professor Zanchetti: The FEVER study is a Chinese study done on Chinese patients and run by Chinese investigators lead by Professor Lisheng Liu in Beijing， but I had the privilege of being associated with them at the stage of designing the study and then in analyzing the results of the study. It was a very friendly and successful collaboration. The FEVER study is the most important study to show the benefit of lowering blood pressure（BP） below 140mmHg which is part of the recommendation of the guidelines and largely based on the findings of the FEVER study. The FEVER study compared more intensive with less intensive treatment. All the patients received a small dose of a diuretic， hydrochlorothiazide， and on top of that they received either placebo or a small dose of a calcium channel blocker（CCB）and a BP difference of 4-5mmHg was seen， just crossing this 140mmHg margin. One group had 142mmHg and the other group 138mmHg， but importantly， the group with BP just below 140mmHg had a 28% reduction in cardiovascular（CV） events. Stroke first of all， because stroke is the most frequent CV event in China， but also the non-stroke CV events like MI and coronary events were significantly reduced in the FEVER study. It is the backbone of evidence showing that we should reduce BP at least below 140mmHg. There are sub-studies that have been running and we are presenting some preliminary data at this meeting， mainly to see if this is true in various sub-groups. The cohort of hypertensive patients randomized in FEVER was a roughly 50/50 mix of those with previous CV events or who had diabetes， and those without previous CV events and uncomplicated hypertensive patients. So these are good results， in spite of there being complications or no complications， and because we have no clear evidence from previous trials， as underlined by the recent reappraisal of the European Guidelines by a taskforce from the ESH， on lowering BP below 140mmHg in uncomplicated hypertensive patients. It seems this sub-analysis of the FEVER study， with the limitation of being a post-hoc analysis， gives the first clear evidence that there are benefits also in uncomplicated (no previous events and without diabetes) hypertensive patients (5000 randomized) in terms of a lowering of BP and significantly less CV events.

    <International Circulation>: We know there are differences in epidemiological characteristics between Chinese and Western population， particularly stroke and hypertension which are more prevalent in the Chinese population. So what do you think is the significance of the FEVER study， which was performed in the Chinese setting， for western clinicians in managing such hypertensive patients?
    Professor Zanchetti:This is a very important and relevant question. Of the CV events that are associated with BP， stroke is the one that is most closely related to BP. Although in Western populations， the overall incidence of MI and coronary events is somewhat greater than stroke， while in China it is vice versa， I think the information from the FEVER study is still important for stroke prevention in the Western countries. Stroke is less frequent than MI in the younger population， but as we get into the older population， and the Western population is becoming more elderly， then stroke becomes more important than coronary disease. So this study reflects favorably on how stroke can be prevented in Western populations. However， I have to stress that in the FEVER study， when we analyzed coronary events separately， they were affected also in a favorable way but about half of that of stroke which one would expect in a Chinese population， so the fact they were influenced less frequently is still significant.

    <International Circulation>:Regardless of whether they are in China or in Western countries and considering now that we have seen results even from ACCORD， would you want to go lower than 140mmHg for those patients who are at a very high risk for stroke?
    Professor Zanchetti: I think there is good evidence now for all hypertensive patients to go below 140mmHg certainly for high risk patients and the sub-analysis findings of the FEVER study tell us that this is also true for uncomplicated， lower risk hypertensive patients. We were also able to show that women， who are at a lower risk， there was a benefit in reducing BP below 140mmHg.

    <International Circulation>:Based on these findings， can we conclude that there is a certain CCB， or maybe all CCB， should be considered as the first option for hypertensive patients with previous stroke or at risk for stroke?
    Professor Zanchetti: The FEVER study did not compare the class of drug with another one， so it would be improper to draw conclusions. Certainly， with a small dose of CCB， it seemed to work very well in BP reduction and be well tolerated. We know that CCBs are useful in reducing BP in the elderly and are effective in this way in preventing strokes but the mechanism is probably more directly related to reducing BP. This is an area for further study and perhaps requires another collaboration with Chinese researchers as this collaboration has been very fruitful and I would like to see this collaboration continue. There is room for investigating even lower BP targets which may be useful to see whether the lower the better on the J-curve is possible – from less than 140mmHg maybe down to 120mmHg. This is unknown and we are hoping to commence further study in that direction.