How is it that, for some patients, ACE-Inhibitors can have no measurable effect on the blood pressure (BP), but CCBs work?

What has me stumped is how this is theoretically possible.

  • Drugs may affect people differently. My cardiologist gave me those 2 types and Beta channel blocker; no individual drug worked. My BP is controlled with Lotrel which is an ACE plus a Ca channel blocker. Oct 17 '18 at 15:41
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    This is a personal experience. Others will report the opposite results. Can you frame the question in a more general sense? Because otherwise it looks like a request for personal medical advice.
    – Carey Gregory
    Oct 18 '18 at 1:59
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    @Narusan - Much better wording, thanks. I hope you don't mind me rephrasing accordingly Oct 18 '18 at 13:24
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    The theory is kind of hand wavy, but there is good clinical data re: variability in response, including some subgroups that tend not to respond to ACE inhibitors. I'm not sure which direction to go with an answer...
    – De Novo
    Oct 18 '18 at 18:19
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    @DeNovo I would quickly talk about the MOA of both inhibitors/blockers, and then explain why one might not respond to ACE. Basically, that they function entirely differently should be enough information.
    – Narusan
    Oct 18 '18 at 21:09

ACEI work on the renin–angiotensin–aldosterone system (RAAS) whereas Ca++ blockers primarily work on cardiac contractility, HR, and vessel constriction.

For the ACE-Inhibitor:

Cells in the kidney release the enzyme, renin. Renin converts angiotensinogen, which is produced in the liver, to the hormone angiotensin I. An enzyme known as ACE or angiotensin-converting enzyme found in the lungs metabolizes angiotensin I into angiotensin II. Angiotensin II causes blood vessels to constrict and blood pressure to increase.

Source: ibid

An ACE-Inhibitor inhibits the functioning of the ACE Enzyme, so less angiotensin II is produced and hence blood-vessels widen, which results in a lower blood pressure.

For CCB:

CCBs reduce blood pressure by limiting the amount of calcium or the rate at which calcium flows into the heart muscle and arterial cell walls. Calcium stimulates the heart to contract more forcefully. When calcium flow is limited, your heart’s contractions aren’t as strong with each beat, and your blood vessels are able to relax. This leads to lower blood pressure.

Source: Healthline.com

This is a good article for patient education on HTN treatments.

It is seen clinically all the time that someone responds better to one class of medication than another. We see patients whose BP drops dangerously low with a tiny dose of an ACEI, and others whose BP is barely touched by high doses. High blood pressure is multifactoral and individuals may have different responses to medications for several reasons.

  • Pharmacokinetics: Liver enzymes process (activate OR break down) medications at different rates AND/OR kidneys excrete at different rates

  • The mechanism of blood pressure dysregulation: may differ, e.g. more related to vessel stiffness vs RAA dysregulation

  • Feel free to add to my answer @DeNovo or Narusan - I have minimal time to answer so would love some help with resources and fleshing out!
    – DoctorWhom
    Oct 19 '18 at 14:38
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    +1 good answer. I added a bit in mine.
    – De Novo
    Oct 19 '18 at 21:47
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    I‘ve allowed myself to flesh in a bit regarding RAAS and ACE, I hope your okay with that. The added information wasn’t as significant as to warrant a third answer.
    – Narusan
    Oct 20 '18 at 8:26

As @DoctorWhom says, there is a great deal of variability in the effectiveness of single agents for blood pressure control. There are some subgroups of patients who are more likely to respond or not respond to certain drugs, though. In the U.S., Black Americans tend to be less likely to respond to ACE inhibitors (and more likely to respond to thiazide diuretics, though that wasn't a drug in the question), and this difference is incorporated into the guidelines for choosing initial monotherapy (a single drug). There is some evidence that older patients are also less likely to respond to ACE inhibitors, but this isn't quite as clear cut. Regional differences may be more important than racial differences, suggesting the effect is mediated by environment and lifestyle, rather than genetics.

For a while, European guidelines recommended exactly the pattern described in the OP for older or non-white patients (avoid ACE-inhibitors, use calcium channel blockers), because these patients were often observed to have low renin hypertension (see @DoctorWhom's answer, ACE-inhibitors work by inhibiting the renin-angiotensin-aldosterone, or RAA, axis, so a low renin hypertension wouldn't be improved with this therapy). Updated European guidelines no longer make that recommendation. Regardless (outside of disease related reasons for choosing or avoiding a specific drug class) the best approach is to find and stick with a drug or combination that brings blood pressure to the desired target.

Importantly, for anyone who might be reading this and wondering why a particular combination of antihypertensive drugs were chosen in their case, these drugs are generally given to reduce the risk of vascular and heart disease (e.g., heart attack, stroke, heart failure, and others). They target a disease determinant, blood pressure. There are goals related to that determinant, but the primary goal is downstream of the elevated blood pressure. Because of this, there are sometimes reasons to choose a drug that is more effective at preventing the end point of concern for a particular individual. These reasons might not be explained to a patient. I wish we were better at this. Some medications provide nice immediate positive feedback when taken and some don't. I've often seen patients who were put on a beta-blocker after a heart attack stop taking it, and I have to explain that their cardiologist didn't put them on the beta blocker to help them feel better, but to keep them from dying. You can read about this in a very dry, slightly impenetrable format in the most recent US guidelines, and in, I think, a more readable format in Cecil Medicine Ch 67.

  • Thanks! Between yourself and @DoctorWhom that is a nice overview. I have plenty or research to do to understand the details :P... Great links! Oct 20 '18 at 6:24

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