Viagra could double up as heart failure drug
"Sex pill Viagra could help men suffering from heart disease," reports the Mirror. This headline follows a new review into the potential heart benefits of the active ingredient in erectile dysfunction drugs such as sildenafil (Viagra), called phosphodiesterase type-5 inhibitors (PDE5is).
PDE5is work by helping blood vessels dilate, which in the case of erectile dysfunction increases blood flow to the penis.
Researchers were interested in whether this dilation effect could have benefits for certain heart conditions, such as heart failure, where the heart struggles to pump blood because of previous damage to heart muscles.
They pooled the findings of 24 randomised controlled trials (RCTs), which suggested PDE5is were better than placebos at improving some measures of heart function in men with early signs of heart disease.
Commonly reported side effects included flushing, skin rashes and headaches.
Importantly, the study did not assess the drugs' effects on the heart versus treatments currently available to treat or prevent heart conditions.
This means we that cannot say whether they are safer or more effective than existing drugs. PDE5is are currently unlicensed for the treatment of heart failure.
Where did the story come from?
The study was carried out by researchers from Sapienza University of Rome and was funded by a Ministry of Research Grant.
It was published in the peer-reviewed medical journal BioMed Central. This is an open access journal, so the study is free to read online.
Generally, the media reported the story accurately. The Mirror, for example, chose its words carefully in saying that, "The sex pill could help men suffering from heart disease". Using the word "could", rather than "does" or "would", adds a necessary element of uncertainty.
The Mirror's reporting of the study was of a reasonable quality, and included relevant quotes from the study's lead author and a useful explanation of a subtype of heart disease known as left ventricular hypertrophy. In many ways, the paper has put its "posher" broadsheet rivals to shame with its reporting.
What kind of research was this?
This was a systematic review and meta-analysis of RCTs to assess the effects of the group of drugs known as PDE5i on heart health and function.
These drugs are currently licensed to treat erectile dysfunction, and include sildenafil, which carries the widely known brand name Viagra.
PDE5is work by helping blood vessels relax and dilate, increasing blood flow through the vessels.
This effect also lowers blood pressure, so these drugs are currently contraindicated or used with caution in people with heart disease, including those who have had recent strokes or heart attacks, as the effects are unknown.
However, various research studies have continued to investigate the possibility these drugs could have a beneficial effect on heart function. This review has looked into their effect on cardiovascular outcomes further.
A systematic review of RCTs is one of the most robust study designs aimed at proving whether something works or does not work. It can also tell us whether there is simply not enough evidence to tell one way or the other.
What did the research involve?
The research team searched online medical research databases for placebo-controlled RCTs evaluating the effectiveness and safety of PDE5i for a range of heart-related measures.
They then pooled the results of a number of RCTs to create combined estimates of the effects of PDE5is in different people with different heart characteristics.
Some of the main measures they looked at to test if PDE5is improve heart health were:
- cardiac mass and structure – abnormally high mass can impair the function of the heart
- cardiac performance
- afterload – the force developed in the wall of the left ventricle (the large heart chamber that pumps blood to the rest of the body) during blood ejection
- endothelial function – the endothelium is the inner lining of blood vessels
- heart rate and blood pressure
RCT results were divided into a number of subgroups to compare:
- people with moderate-severe left ventricular hypertrophy (LVH) versus those without – LVH is where the wall of the left ventricle is enlarged and thickened, meaning it is under strain and can't pump as effectively; this is often an early sign of heart disease caused by high blood pressure
- left versus right heart disease (damage to the left or right ventricles of the heart)
- cardiac disease versus non-cardiac disease (conditions not directly related to the heart that can impact on heart functions, such as anaemia or kidney disease)
- age – 60 and under, versus over 60
All studies were RCTs, double-blind and placebo-controlled. Four studies were crossovers with variable washout periods (a period during a clinical trial where no treatment is given, allowing the effects of previously administered drugs to be "washed out" of the body).
14 trials received funding from the pharmaceutical companies Pfizer and Eli Lilly or foundations.
The main analysis compared the results of PDE5i with a placebo across the different subgroups and combined overall.
What were the basic results?
The searches returned 24 relevant RCTs containing 1,622 participants – 954 randomised to PDE5i and 772 to placebo.
The main results favoured PDE5i compared with placebo across a range of heart outcomes. Sustained PDE5 inhibition produced:
- an anti-remodelling effect by reducing cardiac mass (−12.21 g/m2, 95% confidence interval [CI] −18.85, −5.57) in people with left ventricular hypertrophy, and by increasing end-diastolic volume (volume after heart filling: 5.00 mL/m2, 95% CI 3.29, 6.71) in people without LVH
- an improvement in cardiac performance by increasing cardiac index (0.30 L/min/m2, 95% CI 0.202, 0.406) and ejection fraction (3.56%, 95% CI 1.79, 5.33) – both measures related to how much blood is ejected into the body's circulation
- no changes in afterload
- an improvement in flow-mediated vasodilation (3.31%, 95% CI 0.53, 6.08)
The commonest side effects were those known to be associated with PDE5i, such as flushing, headache, nosebleeds and gastric symptoms.
How did the researchers interpret the results?
The researchers concluded that, "PDE5i could be reasonably offered to men with cardiac hypertrophy [enlarged heart muscle] and early-stage heart failure.
"Given the limited gender data, a larger trial on the sex-specific response to long-term PDE5i treatment is required."
Conclusion
This systematic review of 24 RCTs indicated PDE5is were more effective than placebos at improving specific measures of heart health and were broadly safe.
PDE5is lower blood pressure, so these drugs are currently contraindicated or used with caution in people with cardiovascular disease, including those with low blood pressure and a history of stroke or heart attack, as the effects are unknown.
However, various research studies have continued to investigate the possibility that these drugs could have a beneficial effect on heart function.
This review has looked into their effect on cardiovascular outcomes further and found some promising results, including that they could be beneficial in people with left ventricular enlargement and high blood pressure.
But the study has only compared PDE5is with placebos, and has not assessed their effects against heart treatments currently available to treat or prevent heart conditions.
Similarly, the studies included varied in terms of:
- daily dosage of PDE5i
- length of treatment – from 4-week to 12-month study periods
- endpoint assessment method
- age
- baseline cardiovascular status
- gender – 8 trials enrolled only males and 16 trials had a mixed population of 540 females and 459 males
Pooling such diverse studies may have papered over some of the cracks and nuances in treatment efficacy and safety. For example, these drugs may work much better in some groups than others, or be less safe in some groups compared with others.
The studies provided a range of clinical data, such as changes in cardiac mass and flow-mediated vasodilation. But it is not clear what impact these measurements would actually have in terms of developing lower levels of heart disease, improving quality of life or extending disease-free life.
Most of the research was in men, so the knowledge about the effects of PDE5i in women are less clear.
Overall, the review suggests PDE5is are better than placebo for improving some measures of heart function, but the clinical implications of these findings are currently unclear.
Despite the review's conclusions that these drugs could have a good safety profile for use in people with certain heart conditions, more research looking at this specific issue is needed.
These interesting findings prompt the need for further research and, for the time being, the current prescribing information, which advises the cautious prescribing of PDE5i in people with existing cardiovascular conditions, is likely to remain in place.
