Saving Lives: A Forgotten Study?

It’s almost 12 years since a major clinical trial showed a shockingly simple way to reduce death, strokes, heart attacks and heart failure.

Saving lives: simply and safely.

Saving lives with 1 capsule once a day.

The medication used in that study is often forgotten now because it is off of patent. That means the pharmaceutical companies do not promote it.

And many doctors seem to have forgotten or do not know about this important study.

The study was called HOPE an acronym for Heart Outcomes Prevention Evaluation.

The medication is ramipril. 10 milligrams of ramipril daily was the dose that worked. 

A lower dose has not been shown to provide the same results.

Too often, I see lower doses prescribed.

Ramipril is one of 10 drugs in the U.S. classified as angiotensin converting enzyme inhibitors, or ACE inhibitors, for short. But ramipril is the only one proven to have shown this benefit in saving lives. Perindopril proved beneficial in a large study but all those patients had coronary artery disease.

The HOPE study included over 9200 people aged 55 and older.  80% had cardiovascular disease such as a previous heart attack, coronary artery bypass surgery or other evidence of coronary artery disease. About 11% of the 9200 had suffered a previous stroke. 38% of the whole group had diabetes.

And about 12 percent of the group had diabetes but no previous stroke or known heart disease. These participants with diabetes had other conditions that increased their cardiovascular risk such as high blood cholesterol or protein in their urine or tobacco use.

The people with diabetes in the HOPE trial are like many of the patients with Type 2 Diabetes doctors see in their office.

Half of the 9200 people in the HOPE trial received ramipril and the other half were given an identical appearing placebo. So this was a randomized placebo controlled clinical trial. Patients were followed for an average of 5 years.

Now you should know that ramipril is a blood pressure medication, like the other ACE inhibitors. But blood pressure was fine at the start of the study. It averaged 139/79. That level would be considered normal or acceptable control.

For those who received ramipril, the overall drop in blood pressure was very small at the office measurements: on average 3/2 mm Hg.

Despite this small change in office blood pressure, those participants receiving ramipril had dramatically better outcomes:

22% lower risk of death from cardiovascular causes

20% lower risk of heart attacks

23% less heart failure

32% lower risk of stroke

16% lower chance of dying from any cause

So why this striking reduction in bad outcomes?

How is it that ramipril led to saving of lives when the reduction in office blood pressure was rather trivial?

Well, it turns out that ramipril was given at bedtime. Ambulatory blood pressure monitoring revealed why this might have been important.

A select group of 38 participants in the HOPE trial underwent evaluation with ambulatory blood pressure monitoring. They had on average an office blood pressure of 152/83.

They wore a blood pressure cuff that gave readings over a 24 hour period while doing their usual activities during the day and night; that includes sleeping.

They used this 24 ambulatory blood pressure monitoring before starting on ramipril or placebo and then again 1 year later while in the study.

There was no difference in the office or daytime blood pressures but those on ramipril had 17/8 reduction in nighttime pressure as compared to the group receiving placebo. This meant over the 24-hour period that those on ramipril had 10/4 lower pressure than the placebo group. That’s a lot lower than what was measured in the office.

This significantly lower blood pressure at night could have explained the striking reduction in cardiovascular events in the ramipril group. Lowering blood pressure significantly in those with increased risk means saving lives. 

There may be other mechanisms by which ACE inhibitors may reduce cardiovascular risk in patients such as those in the HOPE trial. This is an area of controversy. Many experts think the results seen were simply due to blood pressure reduction.

Some patients cannot take an ACE inhibitor. The most common side effect is a tickle-in-the-throat type dry cough. This cough occurs in about 5-10 % of people. The cough is more common in women.

Those who cannot take an ACE inhibitor can take a medication called an angiotensin receptor blocker, or ARB for short. An ARB is no more likely to cause cough than is a placebo.

Telmisartan, currently marketed as Micardis, was studied in a very large trial and compared to ramipril. It was as effective as ramipril in reducing cardiovascular events. It is not known if other ARBs are as effective as telmisartan. At the time of this post, there is only one generic ARB, losartan.

The results of ramipril therapy in the HOPE trial again point to the benefit of bedtime dosing of medication for high blood pressure and the potential use of ambulatory blood pressure monitoring to guide therapy as discussed in a previous post. 

In any case, if you think you are like the people included in the HOPE trial ask your doctor if an ACE inhibitor like ramipril is right for you. Perhaps you're already taking one.

Your Diabetes Endocrine NutritionGroup