Ivabradine

Ivabradine is a prescription heart drug that slows the heart rate and does almost nothing else, which makes it the cleanest test there is of whether lowering resting heart rate helps. In heart failure it does. In two large trials of people with coronary disease, lowering the rate brought no benefit at all, even where the drop was about 10 beats.

If you are otherwise well, there is no case for taking a drug to lower your resting heart rate: no trial has tested it in healthy people, and outside heart failure the trials that did lower it found nothing. Its proven use is in heart failure with a fast rate.

What it is

Ivabradine slows the sinus node, the heart's own pacemaker, without affecting blood pressure or how forcefully the heart squeezes. Most heart drugs that slow the pulse, such as beta-blockers, do several other things at once. Ivabradine is close to a clean experiment on the number itself, and it has been tested in three large randomised trials, in three different groups of patients.

All three trials describe the heart's pumping by its ejection fraction: the share of blood the main pumping chamber pushes out with each beat. A healthy heart pushes out roughly 55–70%.

In heart failure, it works

The heart-failure trial enrolled 6,558 people with symptoms of heart failure, an ejection fraction of 35% or less, and a resting heart rate of at least 70 beats per minute. Over a median of about 23 months, death from cardiovascular causes or a hospital admission for worsening heart failure fell from 29% on placebo to 24% on ivabradine: about an 18% relative reduction, or roughly 5 fewer people affected per 100.^[1] The benefit came almost entirely from fewer heart-failure admissions and fewer heart-failure deaths.

Why it helps here: in heart failure, a fast heart is part of the disease. The failing ventricle compensates by beating more often, and slowing it gives it time to fill.

In coronary disease without heart failure, it did nothing

The largest test was much bigger: 19,102 people with stable coronary artery disease and no clinical heart failure. Ivabradine held the heart rate about 10 beats below placebo: at three months the average was 60.7 beats per minute on the drug against 70.6 on placebo. Cardiovascular death or a non-fatal heart attack occurred in 6.8% on the drug and 6.4% on placebo: no benefit, and if anything a nudge the wrong way.^[2] With that many people, this is not a small trial that missed a real effect.

Two further details matter:

A subgroup signal, not proof of harm. In people whose angina limited their activity, the drug was associated with more events; in those without such angina it was not. A subgroup difference inside a null trial is a reason to look again, not a finding in its own right. The trial did not show that lowering heart rate is harmful. It showed that lowering it did not help.
Who paid. The trial was funded by the drug's manufacturer.

In coronary disease with a weakened heart, also nothing

An earlier trial lowered heart rate by 6 beats per minute in 10,917 people with coronary disease and an ejection fraction below 40%, most of them already on beta-blockers. The main outcome did not move at all: the risk on the drug was exactly the same as on placebo.^[3]

In a prespecified group of patients with faster heart rates, two secondary outcomes did fall. That is where the idea for the larger coronary-disease trial came from — and that trial then tested it properly and found nothing.

Safety: a heart that goes too slow

Slowing the heart can overshoot. In the larger coronary-disease trial (the one without heart failure), 18.0% of people on ivabradine developed a heart rate slow enough to be flagged as bradycardia (an abnormally slow heart rate), against 2.3% on placebo. In the heart-failure trial, symptomatic bradycardia occurred in 5% on the drug against 1% on placebo, and 3% against 1% reported phosphenes, brief patches of brightness in their vision.

Dizziness, fainting, or breathlessness and exhaustion on exertion with a slow pulse warrant checking, whatever the cause.

What it means for resting heart rate

A fast resting heart rate predicts dying sooner in large observational studies, so it is tempting to treat it as a target. Ivabradine is the test of that idea, and outside heart failure it failed. A fast heart there looks like a readout of something else — deconditioning, an over-active stress response, inflammation, illness — and lowering the readout without changing the cause improves nothing. Trials of beta-blockers in high blood pressure and after a heart attack with normal pumping point the same way. The wider picture is on Resting heart rate.

What to do

Don't seek a drug to lower a normal resting heart rate. No trial has lowered it in healthy adults, and the trials outside heart failure give no reason to expect a benefit.
If you have heart failure with a fast rate, the heart-failure trial is the evidence your cardiologist will be weighing; this is a prescribing decision for them.
On ivabradine, report symptoms of a too-slow heart — dizziness, fainting, unusual breathlessness or exhaustion — and any new visual brightness.