In the second of our guest blogs for Men’s Health Week, Oxfordshire GP Richard Lehman looks at new evidence on blood pressure pills and has some questions answered about which may be best, but is left wondering about whether they are letting men down in the bedroom.

As a general practitioner, I have handed out drugs to perfectly healthy people nearly every day of the 10,000 or so days of my working career. This has been on the basis of a single risk factorAn aspect of a person's condition, lifestyle or environment that affects the chance of them getting a disease. For example, cigarette smoking is a risk factor for lung cancer.: high blood pressure. During that time, populationThe group of people being studied. Populations may be defined by any characteristics e.g. where they live, age group, certain diseases. levels of blood pressure have fallen, and so have the numbers of strokes and heart attacks. Treating high BP has done the populationThe group of people being studied. Populations may be defined by any characteristics e.g. where they live, age group, certain diseases. good, but at the cost of treating millions of people who never had any benefit as individuals. My anxiety has generally been whether the drug would bring their blood pressure down: theirs has been what it would do them in other ways.

There’s no single best choice for lowering blood pressure

Treating blood pressure is full of pitfalls. People used to be referred to as “suffering from hypertension”, although high blood pressure in itself causes no suffering at all, and “hypertension” is not a disease but a risk factorAn aspect of a person's condition, lifestyle or environment that affects the chance of them getting a disease. For example, cigarette smoking is a risk factor for lung cancer.. A very recent studyAn investigation of a healthcare problem. There are different types of studies used to answer research questions, for example randomised controlled trials or observational studies. in The Lancet shows that various aspects of BP – the systolic, the diastolic, the difference between them, and how much they vary – are all separately associated with different kinds of riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. at different times of life. And in the same way, there is no one best choice for lowering blood pressure, as successive attempts at definitive treatmentSomething done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes. guidelines have shown. The drugs recommended as first choices ten years ago are no longer recommended in the same order today; though in fact most people stay on the same drugs as they were prescribed at the start.

Thiazide diuretics, “water tablets” often used as first treatment for high blood pressure, won’t make you pee more

In many of these guidelines, whole classes of drugs are often recommended as if they all had the same action. One such class is often referred to as “diuretics”. This is doubly misleading, because although the drugs concerned do cause the kidneys to produce more urine at high doses, they have little effect at the doses used to lower BP. And among different kinds, only the diuretics called thiazides are suitable for first-line treatmentSomething done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes..  

A newly published Cochrane review gives a superb overview of the effects of each different thiazide diuretic used alone to lower raised BP. The results are surprising. They come as news to me as a “seasoned” clinician – and they need to be known by all health professionals who treat BP. Thiazides are not born equal.

All thiazide drugs are useful for lowering blood pressure

Chlortalidone was first marketed as a diuretic in 1960, and it is referred to as a “thiazide-like” diuretic because it does not have quite the same chemical structure as the rest. It has largely fallen out of use in the UK, though in fact it is has a very good BP-lowering effect which is not dose-dependentA response to a drug which may be related to the amount received (i.e. the dose). Sometimes trials are done to test the effect of different dosages of the same drug. This may be true for both benefits and harms., so low doses such as 25mg daily can be used. Hydrochlorothiazide appeared at the same time, but by contrast it has an action on BP which is dose dependent. In that respect it differs from all the other  thiazides subsequently marketed for hypertension. All of the rest work equally well at the lowest dose. Thiazides have shown different patterns of adoption in different countries. The British favourite, over three decades, was bendroflumethiazide, which is unfortunate, since it has the weakest evidence base.

The overall message from the review is that all the thiazides are useful drugs for hypertension, typically dropping systolic BP by 9 mm Hg with a single daily dose. In the case of chlortalidone, the effect may be nearer 12 mm Hg.

But might these pills be letting you down in other ways?

But what about the down side? After all, these drugs need to be taken for life to have a benefit. People taking them will never know if they prevented them having a stroke or heart attack, because it will never have happened. But the pills could meanwhile have obvious or subtle adverse effects that might make the whole of life less enjoyable.

And now for the bit that relates to Men’s Health Week. I said that as a doctor, my performance anxiety about these drugs was about how well they lower BP and prevent cardiovascular events. But as a man, I might have another kind of performance anxiety, because the thiazides have a reputation for causing erectile dysfunction. If I mention this at the outset to my male patients, it might become a self-fulfilling prophecy; if I don’t mention it, they might be too embarrassed to volunteer it, or just put it down to some other factor. So what do the randomised trialsClinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used. No matter how promising a new treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known. tell us about the varying effects of thiazides on male sexual performance? The answer seems to be nothing.

Research needs to find out about things that matter to patients

Like most trialsClinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used. No matter how promising a new treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known. of the past, the thiazide trialsClinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used. No matter how promising a new treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known. concentrated on blood pressure and metabolic outcomesOutcomes are measures of health (for example quality of life, pain, blood sugar levels) that can be used to assess the effectiveness and safety of a treatment or other intervention (for example a drug, surgery, or exercise). In research, the outcomes considered most important are ‘primary outcomes’ and those considered less important are ‘secondary outcomes’., but ignored what might be more important to patients. So if a man taking a thiazide has erectile problems, I don’t know whether he would be best to try a different thiazide or a different drug class altogether. That’s the problem with evidence based medicine: it’s based on the evidence we have, and not on the evidence we would like to have. That needs to change, but it will be a long haul.

 

About the Cochrane Collaboration 

Cochrane is a global independent network of researchers, health professionals and consumers of healthcare; carers, advocates and people interested in health. It responds to the challenge of making the vast amounts of evidence generated through researchThe term research means different things to different people, but is essentially about finding out new knowledge that could lead to changes to treatments, policies or care. useful for informing decisions about health. Cochrane is a not-for profit organisation with collaborators from over 120 countries working together to produce credible, accessible health information that is free from commercial sponsorship and other conflicts of interest. www.cochrane.org. Follow us on twitter @cochranecollab.

Links:

Musini VM, Nazer M, Bassett K, Wright JM. Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. Cochrane Database of Systematic ReviewsIn systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. 2014, Issue 5. Art. No.: CD003824. DOI: 10.1002/14651858.CD003824.pub2.

Cochrane summary of this review: http://summaries.cochrane.org/CD003824/thiazide-diuretics-for-the-treatment-of-high-blood-pressure