The lives of 10,000 patients could be saved each year by a “breakthrough pill”, according to the Daily Express.
The news story comes from a study that looked at whether a drug called ivabradine could help prevent deaths or hospital admissions due to chronic heart failure. This relatively common condition occurs when the heart is no longer able to pump enough blood to meet the demands of the body. The study found that over an average of 23 months, patients taking the drug experienced fewer cardiovascular deaths or hospital admissions with worsening heart failure than people taking an inactive placebo pill.
Ivabradine is a drug that lowers the heart rate and is already prescribed for some people with angina. The results of this large, multinational study demonstrate that heart rate reduction could improve the outcome for people with chronic heart failure. However, as the authors note, its results only apply to patients with a certain type of chronic heart failure that meets specific criteria. It cannot be assumed that these results apply to all patients with chronic heart failure.
Where did the story come from?
The study was carried out by researchers from a number of centres in Europe and the US, including the University of Gothenburg, Sweden. It was funded by Servier, a French pharmaceutical company, which was also responsible for the study’s data management and final data analysis (although these were verified by an independent statistical centre). It was published in the peer-reviewed medical journal The Lancet.
The study was widely covered by the media, and reports featured quotes from experts that suggested the drug could save 10,000 lives a year. It is unclear how this figure was reached. The study itself calculated that 26 patients would need treatment for one year to prevent one cardiovascular death or one hospital admission for worsening heart failure (the main outcomes of the study). The BBC’s headline that the drug may ‘prevent’ heart failure is misleading.
What kind of research was this?
This randomised controlled trial, in which both the researchers and participants were blinded, investigated whether the drug ivabradine had any effect on cardiovascular outcomes, symptoms and quality of life in patients with heart failure when used in addition to standard treatment. This kind of trial, in which patients are randomly assigned to either an active treatment or a placebo, is the best way to find out about the effects of medical treatments.
The researchers say that chronic heart failure, which affects 2-3% of the population in many industrialised countries, has a fairly poor prognosis and that the development of new medicines to treat it is crucial. In chronic heart failure, the heart is unable to pump enough blood around the body. The researchers say that reducing the heart rate could be particularly important in improving some types of chronic heart failure. This is because a lower heart rate would allow more blood to enter the chambers of the heart between each beat and reduce the effect of low blood supply to the heart muscle.
The benefits of one standard treatment for heart failure, called beta-blockers, seem to be linked in part to its heart rate-lowering properties. However, beta-blockers can have undesirable effects for heart failure patients. Ivabradine, say the researchers, seems to reduce heart rate without these side effects on the heart. It is currently licensed for use in people with angina who have a normal, regular heartbeat (sinus rhythm), either in combination with a beta-blocker or without if a beta-blocker is unsuitable or not tolerated.
What did the research involve?
The study was undertaken in 677 medical centres in 37 countries. Researchers enrolled 6,558 patients with moderate to severe heart failure associated with left ventricular systolic dysfunction (where contraction of the lower left heart chamber pumps an inadequate amount of blood to the rest of the body). The patients had to meet various other selection criteria, including being on stable background treatment and having a resting heart rate of at least 70 beats a minute.
Between October 2006 and June 2009, the patients were randomly assigned to receive either ivabradine or an inactive placebo drug. Both groups continued to take their standard heart failure medications, including beta-blockers. Neither patients nor researchers knew which patients were in which group. The dose of ivabradine was started at 5mg twice a day and was increased (up to a maximum dose of 7.5 mg twice a day) or decreased according to the change in each patient’s heart rate.
The patients were followed up for an average of 22.9 months. Researchers looked primarily at the “combined outcome” of cardiovascular death or admission to hospital with worsening heart failure (i.e. the occurrence of either or both outcomes). They also separately looked at a number of secondary outcomes, including deaths from any cause and all hospital admissions. All the results were analysed using standard statistical methods.
What were the basic results?
A small number of patients were removed from the study due to various problems. After these exclusions, final results were available for 3,241 patients in the ivabradine group and 3,264 patients in the placebo group. The main results were as follows:
- 24% of patients taking ivabradine experienced cardiovascular death and/or admission to hospital because of worsening heart failure, compared to 29% of those taking placebo (an 18% reduction in risk, hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.75 to 0.90).
- When the results were analysed separately, 16% of patients taking ivabradine were admitted to hospital with worsening heart failure, compared to 21% taking a placebo (a 26% risk reduction, HR 0.74, 95% CI 0.66 to 0.83).
- 3% of patients on ivabradine died of heart failure, compared with 5% taking a placebo (a 26% risk reduction, HR 0.74, 95% CI 0.58 to 0.94).
Adverse effects were also examined:
- 5% of ivabradine patients had bradycardia (an abnormally low heart rate) compared to 1% of the placebo group.
- 3% of patients on ivabradine had blurred vision compared to 1% of the placebo group.
- 21% of patients on ivabradine withdrew from the study compared to 19% of patients on the placebo.
The researchers note that the overall effects of ivabradine were less marked in patients taking at least 50% of a standard dose of beta-blockers.
How did the researchers interpret the results?
The researchers concluded that ivabradine significantly reduced the major risks associated with heart failure when added to standard treatments. They also said the findings suggest that those with higher heart rates will benefit most.
Treatment with ivabradine was also associated with a reduction in heart rate of 15 beats a minute. Heart rate is an important physical factor that contributes to heart failure and reducing it can interrupt progression of the disease, the study authors suggest.
This large, well-conducted study has demonstrated the role that heart rate reduction may have in improving outcomes of people with heart failure. It found that the drug ivabradine, which slows heart rate, significantly reduced cardiovascular deaths and hospital admissions due to heart failure when combined with standard treatments.
The findings of this research could have implications for the treatment of some, but not all, patients with heart failure. As the researchers note, its results apply to a specific group of patients with both a stable, regular baseline heart rate of at least 70 beats a minute and left ventricular systolic function (an enlargement of the lower left chamber of the heart that means it is unable to pump enough oxygenated blood to the rest of the body). People with irregular heartbeat patterns, such as atrial fibrillation or flutter, were also excluded from the study. Overall, the effect of ivabradine in this trial cannot be said to be applicable to everyone with chronic heart failure.
It is also important to note that the results were achieved alongside the patients’ existing treatment programmes, which included beta-blockers, so no conclusions can be drawn about the effects of ivabradine in the absence of these drugs or as a replacement for them. As the researchers also point out, in many cases the recommended target doses of these other standard heart failure medications had not been reached, so it is not known whether this particular population would have been able to tolerate high doses of a beta-blocker.
Overall, the research supports the potential beneficial role of ivabradine in particular subgroups of people with heart failure.
Analysis by Bazian
Edited by NHS Website
Links to the science
The Lancet, August 29 2010 (early online publication)