PEACE and CAMELOT

In the November 11 New York Times, Gina Kolata, referring to the CAMELOT study (just published in JAMA), states:

“A new study of heart disease patients finds that “normal” blood pressure may not be low enough. By reducing their pressure well below the levels suggested by national guidelines, patients had fewer heart attacks, strokes, cardiac arrests, hospitalizations for chest pain, procedures to open blocked coronary arteries, and deaths.”

Although strictly speaking correct, the above sentence is misleading, since it refers to a composite endpoint. Both cardiovascular deaths and overall deaths were insignificantly increased in the treatment arms compared to placebo. Anyone reading Kolata’s sentence would be forgiven for incorrectly concluding that deaths were also reduced. This is a typical example of the difficulty of accurately presenting study results in a bite-sized fashion for the general public.

As for the study itself, I’m not quite sure what it really does demonstrate.

Patients with angiographically documented coronary disease and a mean BP of 129/78 were randomized to daily amlodipine, enalapril or placebo. After two years, the composite endpoint noted above occurred in 23.1% of placebo patients, 20.2% of enalapril patients and 16.6% of amlodipine patients (significant for amlodipine vs placebo; trend not significant for enalapril vs placebo).

In their conclusion, the authors state that:

“These results suggest that the optimal blood pressure range for patients with CAD may be substantially lower than indicated by current guidelines.”

Blood pressure reduction was about 5/3 mmHg in both treatment groups vs placebo. If the main effect is via BP reduction, and BP was similarly reduced in both treatment groups, why was amlodipine more efficacious? The authors note that once daily enalapril taken in the morning may achieve an identical BP reduction later in the day, but drop off during the night. Perhaps, but just speculation. Much of the benefit of amlodipine was in reducing hospitalizations for angina. When a post-hoc analysis of mortality, MI and stroke was looked at, there was an identical but non-significant trend towards benefit in both treatment groups.

Interestingly, this study was published the same week as the PEACE trial, which appeared in the NEJM. That study looked at an ACE inhibitor, trandolapril, in patients with stable coronary disease and well controlled risk-factors. There was no benefit to the addition of the ACE inhibitor. In this study, blood pressure reduction was only about 3/1.5 mmHg compared with placebo.

Bottom line? Dropping blood pressure lower than what is currently considered normal in patients with CAD is probably good, although not dramatically so. Not a big surprise. Amlodipine reduces hospitalizations for angina. ACE inhibitors may not be the magic bullet the HOPE trial had suggested, if all other risk factors are very well controlled, or perhaps it depends on the specific ACE inhibitor used. Not clear.

I’m not sure how much useful information was added by these two studies.

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