Medical Lectures

Blood Pressure Meds: You Might Be Doing It Wrong

Robert P. Wilfahrt, MD
The JNC has aided many healthcare professionals throughout the years, and for that, we are grateful. But that doesn’t mean it is always right. Learn about the textbook myths surrounding blood pressure meds and how it’s hurting patients.
9/23/2021
Family Medicine & Primary Care
GIBLIB

MYTHS ABOUT BLOOD PRESSURE

Not everything that lowers blood pressure is actually good for us. 


I started a version of this a couple of years ago was for medical students. And usually, if I would look out at a group of medical students and say, “Hey, can anybody name some treatments for high blood pressure?” And there'd be a smart alec in the back who'd say, “Yeah, massive bleeding will lower your blood pressure.” I could rely on the medical students for saying something quite helpful like that. 


But it's true. If I was in a car wreck today, my blood pressure would be lower now than it probably is. And sepsis would be an excellent treatment for high blood pressure; so is multiple bee stings. But we're not going to do that to our patients. I believe that my cat, Snuggie Bear, is good for me in multiple ways, but she is not antihypertensive. Our goal is to find blood pressure treatments that are actually good for us. 


I'm talking about blood pressure as if it's the disease. It's not. It's the biomarker that we are using to judge endothelial health, and it's a really good biomarker. It's easy to use, it's reproducible, and it turns out it's correlating really well with outcomes, but it's not exactly the same thing. And so we need to pick things that have evidence that, not only do they drop blood pressure, but they also change outcomes. 


THE CASE OF LOSARTAN AND ATENOLOL

About 15 years ago, the drug makers for Losartan did a study called the Life Study. The FDA makes us drug companies prove that their new drug is going to be at least as good for you as what you can already prescribe. And so the makers of Losartan wanted to compare themselves against something cheap. You're not going to spend a lot of money on these studies. 


So they picked atenolol. Atenolol is predictable, inexpensive. It turns out that losartan and atenolol both drop your blood pressure about 11 point systolic. But losartan prevents heart attacks and strokes and CHF, and atenolol doesn't do any of that. In fact, if you're a female who takes atenolol, you might have more strokes than if you were randomized to a placebo. 


The losartan comparison wasn't the only one that used atenolol when they were doing these FDA studies. There have been three or four now, and each one looks better than atenolol. And finally, people said, well, maybe atenolol is not worth giving.

ALLHAT STUDY

There are other studies that have suggested that there are differences between classes. Most of you have heard of the Allhat Study. The Allhat Study was an attempt to say what was the best thing to pick first? And so they picked a couple of common classes, one of which, at the time, was the alpha-blockers. 


The alpha-blockers were shown to be clearly inferior to the other commonly used classes. They're both weaker. If you use a thiazide or an ACE inhibitor, you'll get 11-ish points of systolic reduction. And the Zosyn is more like five. But not only are they weaker, but they also didn't they couldn't show any cardiovascular outcome changes. And so one of the outcomes from the Allhat Study was the conclusion that we just really shouldn't use alpha-blockers for people's hearts. 


Some of you're going to still prescribe doxazosin for prostate trouble, saying to yourself, “Well, this is a twofer. Not only am I letting George wake up fewer times per night, but also I'm meeting type targets.” And you just can't play that mental game anymore. All you're doing is treating BPH. If you wanted their blood pressure lower, you still have to do something else. 


So, if we're doing prevention – this is not for somebody who's already had a heart attack or stroke – we have limited choices. There are ACHs, ARBs, and calcium channel blockers. There are some thiazides. My cat is still good for you, but doxazosin and atenolol are not. 


NO ONE IS USING HYDROCHLOROTHIAZIDE RIGHT

Now, everybody in this room has been putting people in hydrochlorothiazide. JNC 7 has a special place in my heart because it's the one that I read when I was coming through training. It, like volumes one through six before it, kind of suggested that everybody should pick hydrochlorothiazide first. And when you did your training, your gray-haired preceptors had everybody on hydrochlorothiazide. 


Hydrochlorothiazide gives you a systolic reduction of about six points on average through a 24-hour period, which is a little less than half than every other drug class. Why is that? We don't use it right. I'm willing to bet that nobody in this room uses hydrochlorothiazide correctly. 


This is a pharmacokinetic study from the drugmakers of a fixed-dose combo that apparently you can get in Europe with fosinopril and hydrochlorothiazide. I don't know what brand that would be, but what I want you to notice is that it hits you pretty well and then it tapers off pretty quickly. Now, we might only need to be at about this concentration for the hydrochlorothiazide to be effective, but that still means that, within 14-ish hours after you've taken the pill, it's not working. 


Your patient took it in the morning because they didn't want to be up all night peeing. And then they came to your clinic when it was still effective. So you feel good about yourself. But the next morning when they were going to have their acute coronary syndrome, it's not there. If you're going to use hydrochlorothiazide in an appropriate way, it's a b.i.d. drug.


MORE CORRECTIONS TO THE JNC 7

And here's another study that shows the amount of blood pressure reduction that you get from thiazide options. Now, remember, JNC 1 is an old document, so the people who wrote that didn't have the kind of options that you guys do. They had atenolol, which we know isn't good, and hydrochlorothiazide. 


So if you came to the clinic and said, “Hey, I'm taking hydrochlorothiazide. Twenty-five milligrams once a day, but my blood pressure is still high.” The doctors at that point said, “Well, let's take a little more,” because that's all they had.


The doses that proved that hydrochlorothiazide had a cardiovascular benefit are between 50 and 100 milligrams twice per day. How many of you use 200 milligrams a day of hydrochlorothiazide? Nobody. Your teachers would say, “I'm not going even to 50 once a day. All my patients will be hyperkalemia.” That's because it’s finally strong enough to do anything. 


So, compared to chlorthalidone, you've got to get up to at least 50, probably 100 milligrams twice a day now of hydrochlorothiazide to have the same potency as the introductory dose of chlorthalidone. I think that if you wanted to use it correctly as your first dose, that you couldn't be blamed. Your patients aren't going to like you. But the evidence-based dosing of hydrochlorothiazide should probably be 100 milligrams twice a day. That's why I think you should stop using it. 


LET'S BE BRAVER ABOUT ACE INHIBITORS

When you were doing your training, your preceptor said, “Hey, put somebody on your favorite pro, check the BNP in a week or two.” If the creatine goes up more than how much? 0.3. Then you're supposed to feel bad about it. Take them off it. 


The new teaching is to ignore that creatinine bump. There is no creatinine level that is too high for an ACE inhibitor. Why is that? 


The arterial leaving the glomerulus, the efferent, is where the ACE inhibitors air do most of their work. They preferentially decrease resistance there. So if you decrease resistance there, then the pressure in the nephron goes down, and you're driving less waste into the urine. So your GFR goes down, your creatinine goes up. Creatinine rise means the ACE inhibitor is working. 



COMMON CLINICAL CHECK-UPS THAT GO AWRY

There are some people for whom that afferent, the incoming arterial, was disease. So if you drop the pressure on the outflow tract and therefore drop the pressure in the glomerulus, But they couldn't make up for it because there were too many cheese curds in afferent arteriole or the person had to pump failure and couldn't compensate, then those people's GFR goes down further than you might have expected. Their creatinine goes up higher than is expected. 


Now, it turns out the single most common reason for that is because we've overdone other medicines. And perhaps if you saw that on your first check, and if you saw it went up to .6 instead of .2, you could just correct overdiuresis, and you'd see that it got better.


It would still be nice if we started our ACE or ARB, check the creatinine, and it didn't change much. We say, “Great, you're on autopilot.” but maybe there are those people who have declared themselves as having more trouble in the afferent arteriole. Those people MUST stay on their ACE or ARB. 


The number needed to treat is five for death within six years in that group. They have declared themselves as being the ones most likely to benefit from treatment. Don't take them off it because nothing you do for the rest of the year is going to be as good as an entity of five for death. 


So I think, if those folks with the big creatinine bump after you've initiated the ACE and ARB, you correct their overdiuresis, as long as the creatinine hits a plateau, whatever that is, you're golden. Keep them on it. They will have defined themselves as having CKD. So you're still going to have to do prudent monitoring, but it doesn't mean you stop the pill. Only if the creatinine is progressive or comes wed to hyperkalemia, is it a deal-breaker. Those are the folks that get the ultrasound in the NFC console. The nephrologist won't take them off the ACE inhibitor either. 


POLYPHARMACY

Polypharmacy is better than dose-titration. I'm glad there's still a lot of people who are nervous to ask their patients to take more than one pill at a time, which is expensive and a hassle.


People who were in a study in which olmesartan was compared to placebo, turns out placebos are apparently good for your blood pressure. About as good as Snuggie Bear. But the introductory dose will drop your systolic about nine-ish points. Case of any patient called back to the clinic and say, “Well, thanks very much. My blood pressure still met at target.” And you said, “Well, how about increasing?” 


We've all done that. I know we have. Coming back in a month, their blood pressure will have gone from 9.6 to 9.8 points of systolic production. So then let's say you double it again from 5 to 10. Well, you gained another point. You go all the way up to 80. You've gained a couple points. That late 40 mg bump had less of an effect on the person's blood pressure than the first two and a half mg bump. 


So it's not from pharmacology class. It's not a zero-order, linear relationship. It's the first order one where all of the benefit comes right away, and then it hits a plateau. If your patients did not go on the introductory dose, they're not going to get to go. 


MORE INTRODUCTORY DOSES – OLMESARTAN, CHLORTHALIDONE, AND MORE

Olmesartan is not the only one. Chlorthalidone, which I like quite a lot, is the one we should use right now, not hydrochlorothiazide. But still, the first dose gives you most of the benefit. Twenty-five milligrams is kind of the usual dose, but if you doubles that, triple that, it’s not much different. So there's just not a role for dose-titration here. 


The introductory dose of your ACE inhibitor gets him 11-ish points of systolic production. Double it, 11-ish points. Max it out, it's 12-ish points. The same thing is true for ARBs. There's a little more variation in the class, but still, it's not a huge change. 


Hydrothiazides only gets an Asterix because the quarter dose is useless. That's the one that we're using. And so it's really important that when our patients call and say, “I'm not yet to goal,” our answer isn't to jack up the dose of the one pill, but is instead to add a second pill or a third or fourth.


Statins are quite different. If we're doing prevention with lipidemia, I understand there's PSCK9’s now, but not very many people are buying those. So, really, prevention of lipidemia is just statins. It’s monotherapy. It's the opposite for hypertension. 


THE NATIONAL INSTITUTE OF CLINICAL EXCELLENCE GUIDELINES (NICE) 

Apparently, the generalists in Great Britain have about double the success of meeting their hypertensive goals. North American family physicians do not, which should embarrass all of us. 


The nice guidelines are more prescriptive than the JNC American Heart Association guidelines are. So, if you read JNC 8 or the AHA guidelines, they have some sort of vague suggestions about what it is you should use, but they want to leave it up to you. There they're more about describing the evidence and suggesting targets, whereas the Brits said, “No, do it this way.” 


If your patient has hypertension, of course, you're going to talk about not eating refined foods. The first step after therapeutic lifestyle choices should be either an ACE/AAB, and I don't care which one, or a calcium channel blocker. 


We should probably pick the ACE or ARB for diabetics. Or, if you have proteinuria, we maybe should pick this CCB first, if the patient you're working with is black, but the outcomes data is pretty similar. So the Brits think you could pick either one of them and be OK. 


ADDING CHLORTHALIDONE

So now we've got a patient who started out with blood pressure that was 180. You put him on one pill, they got to 168. We added the second pill, they got to 156. We wanted the land in the 130, so we put them on chlorthalidone, now they’re down to 144. But they haven't yet made their goal. 


It's starting to get weird now. Three good drugs, and they're still not on target. The first few JNC reports suggested that, at diagnosis of hypertension, everybody should get this set of labs and maybe an EKG. They wanted us to go looking for secondary causes of hypertension before we even bothered to start treatment. They backed away from that now. 


But I'd like you to think about that. If it's time for drug number four, the pool of people who are left that need a fourth medicine overrepresent people who have a secondary cause. And it turns out that, by a lot, the most common cause of secondary hypertension is hyperaldosteronism. 


CONCLUSION

I don't like cookbooks when it comes to medicine. I would prefer to feel creative, but it turns out that sometimes cookbooks make us better chefs. And so I don't think there's a lot of room for creativity here. If we were better at getting our patients to target, then we could talk. But if only a third of our patients are actually landing on targets, then maybe we should follow guidelines. 


In summary, not all that lowers blood pressure prevents cardiovascular events. So we have a duty to migrate our patients off the atenolol that they've been using for the last 40 years. We've been refilling it off of inertia because we didn't want to upset great-grandma. But we have a responsibility to her to get her on something useful. 


And we've got to stop thinking we've got a twofer when we're using Doxazosin. Chlorthalidone is the only useful once-daily thiazide. If you want to use hydrochlorothiazide at smallish doses to get a smallish benefit as an add-on, I can't beat you up, but it's not monotherapy. 


Use an ACE inhibitor regardless of a person's creatinine level. Polypharmacy is the rule and love the NICE guidelines.


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