New blood pressure trial

A big randomised trial comparing strategies for treating high blood pressure has just ended early (paper, paywalled).  There’s good coverage in the New York Times, and there will probably be a lot more over the next week. It’s a relatively complicated story.

The main points:

• Traditionally, doctors try to get your blood pressure below 140mmHg, but some people always thought lower would be better.
• The study, funded by the US government, randomly allocated over 9000 people with high blood pressure and some other heart disease risk factor (but not diabetes) to either try to get blood pressure of 140mmHg or try to get 120mmHg.
• A previous trial with the same targets, but in people with diabetes, had been unimpressive: the results slightly favoured more-intensive treatment, but the difference was small, and well within the variation you’d expect by chance.
• In the new trial blood pressure targeting worked really well: the average blood pressure in the low group was 122mmHg, and in the normal group was 135.
• Typically, people in the low group took two or three blood pressure medications, those in the normal group typically took one or two — but in both cases with quite a lot of variation.
• There were 76 fewer ‘primary outcome events’:  heart attack, stroke, heart failure, or death from heart disease in the low BP group, and 55 fewer deaths from any cause.
• From the beginning, the plan was to stop whenever the difference in number of ‘primary outcome events’ exceeded a specified threshold, unless there was a good reason based on the data to continue. The difference had been just barely over the threshold at the previous analysis, and they continued. In mid-September it was clearly over the threshold, and they stopped.
• Stopping early will tend to overestimate the benefit, but the fact that they waited for one more analysis reduces this bias.

I’m surprised the benefit from extreme blood pressure reduction is so large (in a relative sense), but even more surprised that they managed to get so many healthy people to take their treatments that consistently for over three years.  As context for this, data from a US national survey in 2011-12 showed only about two-thirds of those currently taking medications for high blood pressure even get down to 140mmHg.

In an absolute sense the risk reduction is relatively small: for every thousand people on intensive blood pressure reduction — healthy people taking multiple pills, multiple times per day — they saw 12 fewer deaths and 16 fewer ‘events’.   On the other hand, the treatments are cheap and most people can find a combination without much in the way of side effects. If intensive treatment becomes standard, there will probably be more use of combination pills to make multiple drugs easier to take.

There’s one moderately worrying factor: a higher rate of kidney impairment in the low BP group (higher by a couple of percentage points). The researchers indicate that they don’t know if this is real, permanent  damage, and that more follow-up and testing of those people is needed. If it is a real problem it could be more serious in ordinary medical practice than in the obsessively-monitored trial.  This may well explain why the trial didn’t stop even earlier:  the monitoring committee would have wanted to be sure the benefits were real given the possibility of adverse effects — the sort of difficult decision that is why you have experienced, independent monitoring committees.