TROPHY: Preventive treatment with candesartan beneficial in prehypertension patients
March 14, 2006, Atlanta—The Trial of Preventing Hypertension (TROPHY) showed a reduction in the risk of developing hypertension in study participants who were prehypertensive treated with candesartan compared to placebo. Dr. Stevo Julius presented the results of the TROPHY study at the American College of Cardiology meeting, held in Atlanta from March 11-14, 2006, and published simultaneously online by the New England Journal of Medicine.
TROPHY was a four-year, multicenter trial to evaluate the safety and potential benefit of early drug therapy in patients with high normal blood pressure (130-139/85-89 mmHg). A total of 809 participants (average entry blood pressure 134/84.8 mmHg) were randomized to candesartan 16 mg (409) or placebo (n=400), and were followed with regular blood pressure screenings. After 2 years, the drug-treated group was switched to placebo, and all participants continued on placebo for 2 years. The mean age was 48.5 years and 60% were men.
At 2 years, development was reduced by 66.3% in the candesartan group compared to placebo group (53 incidence cases vs 154 cases, respectively; P<0.0001). The relative risk reduction was 15.6% at 4 years, with 208 incident cases in the candesartan group and 240 in the placebo group (P<0.007). Treatment was well tolerated.
The authors concluded that “treatment of prehypertension appears to be feasible.”
Comment
Since JNC7 Guidelines on the Management of Hypertension identified a pre-hypertensive state, Europeans have been intrigued as to whether this was a separate entity, which required clinical scrutiny. Whilst it has been known for some time that blood pressure inexorably rises throughout life, the only motive for earlier intervention would be if one could ameliorate the rate of rise of hypertension in later life. Now for the first time, investigators from Michigan led by Professor Stevo Julius have produced a very elegant trial in subjects with a mean age of 48 years with blood pressures, which would define them by JNC criteria as having pre-hypertension (less than 139/89mmHg). Four hundred and nine subjects were randomised to receive Candesartan 16mg daily and four hundred to placebo. After 2 years those on Candesartan also received placebo and the whole cohort was followed up for a further 2 years. The rate of development of hypertension (above 140/90mmHg) was significantly attenuated by this manoeuvre with a 15.6% reduction, which was highly statistically significant. The Kaplan Myer curve however, did suggest a catch-up in the 2nd year and it may well be that antihypertensive medication has to be continued in these pre-hypertensive individuals or there is the possibility, of course, of pre-hypertensive patients receiving treatment holidays.
Nevertheless, for the first time we have evidence that earlier stages of blood pressure can be tackled with antihypertensive medication with successful outcomes in terms of keeping blood pressure down.
This concept of using drugs at an earlier stage has always been something, which has been greeted with some trepidation because of the risk benefit equation but with the introduction of angiotensin receptor blocking agents with side affects profiles equivalent to placebo, perhaps this area will be re-visited with some vigour in the next few years. It is interesting to know that serious adverse events occurred in 3.5% of the participants assigned to Candesartan and 5.9% of those receiving placebo. This area is going to be intensively researched in the next few years. |
| |
 |
|
