Efficacy and Safety of Quarter-Dose Blood Pressure–Lowering Agents -- commentary

In the news: Efficacy and Safety of Quarter-Dose Blood Pressure–Lowering Agents

A Systematic Review and Meta-Analysis of Randomized Controlled Trials (doi: 10.1161/HYPERTENSIONAHA.117.09202)

This article has been widely reported, and is best read along with the editorial comment. (doi: 10.1161/HYPERTENSIONAHA.117.09352)

Here is my commentary for members of the AF forum, for whom blood pressure control is often yet one more feature of our lives, and some medicines have multiple effects, such as betablockers which affect blood pressure and heart rate.

Drug combinations are a regular part of our lives. I use three drug interaction sites before taking anything new and always double check the advice of a doctor.

We also know that some drugs such as Flecainide make things worse at high doses therefore, unless there is a good reason (like with antibiotics) to use a high initial dose, probably the best way is to start small and slowly increase.

Also, reducing the number of drugs taken is probably wise and there is a bias against taking more medicines. Yet, it is commonly known on this forum that a very small dose of Bisoprolol has the effect on Flecainide of reducing its bad-rhythm-inducing effects and possibly keeping the dose down therefore they are often prescribed together.

Rightly, the abstract of the article points out that there is little data on “very-low-dose therapy”. My experience is doctors regard low doses as placebo, a form of homeopathy! Not surprising when even the BNF recommends minimal doses which even some patients know is too high. On the other hand, the BNF does talk about combination therapy. The loop diuretic Lasix, taken with the Angiotensin II antagonist Losartan, nicely balances opposing effects on Potassium levels.

Table 1 provides what the authors think is the “standard dose selected for this review”. This dose is already quite high! To take two drugs I know about. Bisoprolol is set at 10mg, yet even I know that taking ONLY 2.5mg or even 1.25mg can lower the blood pressure as well as the heart rate. Amlodipine is also known to work well at 2.5mg instead of the standard minimum 5mg daily.

The editorial mentions some limitations of the meta-analysis, which are worth quoting and commenting.

“One, the results on the quadruple quarter dose combination treatment are based on a single study with a small sample size (18 patients).” So why are they being trumpeted?

“Two, the on-treatment duration was variable between studies (4–12 weeks) but on average short (7 weeks only), which does not ensure that the favorable blood pressure effects of low-low dose combination treatment seen in the early treatment phase are maintained over the long term.”. Well said. So how did these studies even get published?

“Three, no data are yet available on the effects of a quarter dose triple combination on blood pressure and the side effect profile despite the fact that 3 anti-hypertensive drugs exhibit are more and more frequently used for their superior blood pressure– lowering effect over the 2 drug combinations.”.

“ Finally, it would be important to expand the information provided by the meta-analysis of Bennett et al to ambulatory or home blood pressure to see whether the remarkable ability of the quarter dose combination treatment to lower blood pressure is consistent over the 24 hours.”. And make sure the studies are longer than 12 weeks.


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