More must be done to address gender differences in cardiovascular drugs. Even in 2017, women are under-represented in randomised clinical trials.

Professor Juan Tamargo, Professor of Pharmacology, Universidad Complutense, Madrid, Spain talks about the need to educate cardiologists and physicians about sex-differences in heart disease, and how the guidelines must also reflect these differences.

TRANSCRIPT

Why is there a need for sex-specific labelling in CVD drugs?

I think the main point is that usually when we write a guideline or a position paper in the ESC, we just mention the compounds that are recommended with different levels of evidence. And all this evidence, in general, has been obtained from randomised clinical trials where mainly men were involved.

So we are extrapolating the data from these clinical trials to both genders and we can probably accept that it can be extrapolated. But in some cases it is not the case.

The reason why we cannot extrapolate the data is that even in 2017 women are under-represented in randomised clinical trials.

This is very important. First of all, we have the idea that women are protected during their active sexual life, but after menopause we know that things change quite dramatically. When we try to compare men and women of the same range of age, we miss the point that women live longer than men.

Sometimes, we as practitioners say ‘they are protected, this is not a problem for women,’ but it is a problem for women and we need all the information related to differences in drug response to be included in clinical guidelines.

If we have the evidence it should be mentioned in the clinical guidelines and position papers. And indeed this is what we are not doing.

What are the main sex-related differences in the pharmacokinetics of CVD drugs?

I would like to say not only pharmacokinetics. The main point is that when we put on a clinical trial we give the same dose of a certain drug to men and women, and we forget something. For instance, usually women’s weight is lower, and usually we forget that women have a different renal function which is slower than in men. So if we give the same dose to men and women, the problem is that the plasma levels usually are higher in women than in men, and this can explain simple things like the higher incidence of adverse effects in women.

When we try to compare men and women, the first thing we need to look at is the dose calculated based on body weight, and secondly it is calculated according to renal function – and in most cases this does not happen.

We must remember that women are different than men, just because of weight, dose and renal function.

And I would like to also look at pharmacodynamics, because the responses are different. If I gave torsemide, a diuretic, I know that the electrolyte disturbances are more frequent in women than in men. Adverse effects are more frequent in women than in men.

This is important because of pharmacokinetics, because of the different responses, incidences of adverse effects is greater in women. Women may stop treatment, they do not continue with the treatment, or they do not follow my indications as a general practitioner. As a result they are not protected against cardiovascular diseases. This is a real problem.

There is also the feeling – and this is funny- because men, medical doctors usually consider that women need the less strict treatment, we don’t give the same advice to men as we do to women and so on.

There are a lot of things that should be included in position papers and clinical guidelines, but this is not the case. We need to offer to the general practitioner and the cardiologist all this information, because there is misinformation.

What now needs to be done?

Education, education, education! We need to clarify to people that there is a problem and that there are some ways to improve it.

The first thing is to include information in the clinical guidelines. The second is for the next clinical trials – in how many are women represented? Women continue to be under-represented, so we need to include more women.

Then, after performing a trial, separate the results between men and women  – don’t give the full results in the full population, see if there are any differences between men and women.

It is analysing the gender differences in the final analysis and study, and also in some studies there are some end points that can be specific for women – these should also be included.

There is something else. We must understand that these gender differences must be included in the curriculum. From the beginning, medical students should be aware that there are differences.

They understand very well that men and women have different physiology and so we must also understand how sex can influence the pathophysiology of cardiovascular disease. They are not the same.

One example, heart failure with preserved ejection fraction is more frequent in women. Why?

Also, if there are any differences between men and women we need to state them on the labels. We know that most drugs that were retired from the market because of adverse effects, most of the side effects were observed in women.

So we need to include information – very easy information that can be immediately notified by the general practitioner that there are differences between men and women with this particular compound.

And any of these topics that I have already mentioned here are not accomplished. So we have a problem, we know the problem, but we need to transmit this problem and look for solutions.

There are a lot of things we can do, and the European Society of Cardiology is aware of the problem, but not too much! Everyone says ‘yes there are differences’, but we are not putting these differences in some of the guidelines or the position papers, and it should be done.

Because the main problem is that cardiovascular disease are the first cause of death and morbidity in European women. It costs a fortune, and it is a matter of public health.