Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. Narrator - ? 00:11 This podcast is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk episode, 191 I'm your co host, Dr. Kane, Dr. Khyati Patel 00:35 and I'm Dr. Patel. So in today's episode titled The Ultimate Guide to ARBs, angiotensin receptor blockers, an in depth drug class review. We are going to review the drug class the angiotensin receptor blockers to kind of discuss its pharmacology, indication, safety profile, monitoring and anything that's really unique about them, clinical evidence, you know, et cetera. Dr. Sean Kane 01:02 Dr. Patel, we've done a number of these episodes historically where we talk about, you know, what is the difference between NSAIDs or beta blockers within the drug class? And we're doing that today with ARBs. In terms of what ARBs are out there on the market, what do we need to know about them? What makes them similar and different? It's a great episode, even for that beginning learner in pharmacy school just starting to learn about the top 200 drugs, or even that experienced clinician where maybe you hear the term ARB and you know it's an ARB, but you don't know that much about it, and what's its claim to fame. And that's, you know, what we'll be talking about today. Dr. Khyati Patel 01:35 Yeah, I think first and foremost, it's important to just go over some brand generics and what different agents are available in this category. If you are listening, brand name versus generic. The generics end in Sartin. So anytime you see a drug that ends in Sartin, that's your Angiotensin Receptor Blocker. The very first one approved in the US market was back in 1995 that was Losartan. Brand name is Cozaar but then after that, we had many that came in the market. So we have candesartan, brand name Atacand; valsartan, brand name Diovan; irbesartan, brand name Avapro; telmisartan, brand name Micardis; and last but not the least, azilsartan, an ARB that came out in the market in 2011 – that's the last one. Dr. Sean Kane 02:25 And as you might expect, because these are commonly used for hypertension, there's a bunch of combinations that are available, primarily with thiazide diuretics like hydrochlorothiazide and amlodipine. Kind of historical fact, we did have a product with aliskiren in it, but that was discontinued. That was brand name, Valturna with valsartan and aliskiren. And the reason for that is, as we'll talk about, we basically don't combine aces ARBs, or, in this case, a direct renin inhibitor, except we do have a combination product that does have an ARB in it a little bit different, and that is, of course, valsartan with sacubitril, which is a neprilysin inhibitor under the brand name of ENTRESTO. But we call that drug category an ARNI – angiotensin receptor‑neprilysin inhibitor. So we do have combinations of these different ARBs and things like that, but the main thing that you're gonna see combination wise is with hydrochlorothiazide or amlodipine. Dr. Khyati Patel 03:17 Yeah. And another reason not to combine ARBs with either ACE inhibitors or other agents like renin inhibitors, because they all work in the RAS system. And so the side effect profile kind of doubles up. And so usually the rule of thumb is not to combine the RAS agents together. Dr. Sean Kane 03:33 Well, why don't we talk about how they work? So to talk about how they work, we have to talk a little bit about the renin angiotensin aldosterone system and kind of the pathway of what's going on. So the story starts with renin, angiotensinogen that gets converted to angiotensin one. And then, of course, we have an enzyme called the angiotensin converting enzyme, or the ACE enzyme, that converts angiotensin one to angiotensin two, right? Dr. Khyati Patel 03:56 And that's the angiotensin two. That's the villain in the picture. Has a lot of effects in the body, primarily on the blood pressure, fluid management and sodium regulation. So first and foremost, angiotensin is a potent vasoconstrictor. As your blood vessels are vasoconstricted, it's going to raise the blood pressure. Dr. Sean Kane 04:14 Many of these pathways kind of connect with each other, so having too much angiotensin, two gives you more aldosterone, and that causes more water retention, more sodium retention in the kidney, and then you have more intravascular volume that way. Dr. Khyati Patel 04:28 And then furthermore, it also stimulates the pituitary gland to release more vasopressin, or ADH, antidiuretic hormone. Again, that's as it name sounds, antidiuretic. It's going to lead to water resorption by the kidneys, and so you have more circulatory volume again. Dr. Sean Kane 04:45 And then, depending on the number of factors, too much angiotensin, two, can cause thirst receptors in your brain to be triggered. That tells you, hey, it's time to drink. And then you can have more volume retention because of that as well. Dr. Khyati Patel 04:57 And additionally, the. Vasopressin production that we talked about earlier in turn can lead to sort of like a cell growth, migration and mitosis. So we're talking about hypertrophy of the organs, or hyperplasia of given tissue, and then can also lead to atherosclerosis. Dr. Sean Kane 05:17 And then it's important to note that this whole pathway, especially angiotensin, two impacts renal perfusion. So based on how the blood vessels going to the kidney, either vasodilate or vasoconstrict, or the blood vessels post kidney, vasodilate or vasoconstrict, that changes your glomerular filtration rate in the pressure in the glomerulus, in terms of how good or bad your kidneys work, and your body relies on the system to kind of regulate that blood flow to the kidney. Dr. Khyati Patel 05:45 So this is, in a nutshell, your RAS or renin angiotensin aldosterone system, but specifically talking about the ARBs. ARBs are competitive inhibitors of the angiotensin, two on the angiotensin, mainly type one angiotensin receptors, so they're going to block the effect of angiotensin two on these type one receptors. Dr. Sean Kane 06:09 So that means that by preventing the renin angiotensin aldosterone impact on these angiotensin type one receptors, you're going to have a reversal of smooth muscle contraction in the vasculature, so vasodilation, reversal of that increased thirst, so lower intravascular volume, less aldosterone production, less catecholamine release, less vasopressin release, and then you're not going to have some of that smooth muscle based hypertrophy and hyperplasia that can cause some of That scarring and things like that. Dr. Khyati Patel 06:41 Yeah, that, that remodeling and stuff that can happen too. So yeah, that that definitely prevents it. So Dr. Kane, we can't just talk about ARBs by themselves. They're kind of go neck and neck with the ACE inhibitors, the angiotensin converting enzyme inhibitors, and so let's talk about the some of the differences and similarities between the two. They both work in the RAS system, as we know, however, they're slightly different from each other. Dr. Sean Kane 07:06 So starting with the mechanism, you know, the ACE inhibitor is blocking the ACE enzyme that makes it so you don't convert angiotensin one to angiotensin two, but that doesn't mean that you still can't make any angiotensin two. So one, you're not going to block all of the enzyme and two, there are non ace pathways to make angiotensin two. So even though you're blocking the main pathway, there's other ways that your body can make angiotensin two. In contrast, the ARB is blocking the end product, like the most distal pathway, which means that whether you produce a little bit or a lot or ancillary pathways of angiotensin two, the ARB is blocking the end effect of angiotensin two on the at one receptor. So this is more of a downstream blockade, where you're not just blocking production, but no matter what is produced from whatever pathway you're blocking its impact on the receptor. So a more distal pathway. Dr. Khyati Patel 07:58 So in the mechanism, we said that ARBs are going to block the effect of angiotensin II on those type 1 AT1 receptors. Contrary to that, ARBs actually can activate the AT2 receptors. So this is not a blocking, this is an activation of those receptors, and that's because ARBs can stimulate that renin release—ACE inhibitors can do too. However, the ARB‑induced renin release results in a much bigger increase in angiotensin II and this is going to lead to the activation of the AT2 receptors. Now, even though ARBs are going to result in much increased angiotensin II release, remember, your AT1 receptors are already blocked by the ARBs, so the activation of the AT2 receptors results in some of the protective mechanisms that are actually good, such as vasodilation, so reducing blood pressure, reduction of inflammation, as well as some end‑organ damage by preventing the cell growth, left ventricular remodeling, that hypertrophy that happens, as well as renal fibrosis. So there are some good effects of ARBs activating the AT2 Dr. Sean Kane 09:10 receptors and Dr. Patel, this is a great example of a negative feedback loop, and we see this very commonly throughout the body. So the Alpha One receptor, the adrenergic receptor, is also a good example of this, where you have activation of the Alpha One receptor causes vasoconstriction, but the activation with the same ligand of the alpha two receptor causes vasodilation. It's part of this negative feedback loop that if you have too much of one thing, you want to activate the opposite receptor to kind of calm things down. It's no different here, where too much angiotensin, two, you're going to activate this other receptor to kind of have the opposite effect of what it would normally have. Dr. Khyati Patel 09:46 And then there is another difference that comes in between ACE inhibitors and ARBs, and that's in the level of how much bradykinin production can happen, right? So bradykinin is a substrate of ACE. Levels of bradykinin are increased by the ACE inhibitor, and that's the one majorly responsible for the dry cough effect we get from ACE inhibitors, as well as the angioedema. However, this mechanism doesn't occur with the ARBs, and so ARBs are not responsible for that dry cough. And whenever most patients who have ACEI‑induced dry cough, we try to change them to ARBs if they're still indicated for the therapy. Dr. Sean Kane 10:23 So in terms of clinical differences, so that's the mechanistic differences. Clinically, we basically see a similar blood pressure reduction in hypertension, but we see a slightly better adverse effect profile with our ARBs, especially a lower risk of angioedema and a lower or no risk of dry cough. Dr. Khyati Patel 10:40 And talking about the angioedema, if we look at the incidences that happen with ACE inhibitors, we're looking at somewhere between 0.1 to 0.7 %—this risk is, you know, two to four times higher in Black patients. However, when we look at that incidence for ARBs, roughly around 0.1 %. Dr. Sean Kane 11:00 and then there is some data that potentially, ARBs have a slight advantage in reducing risk of renal failure in patients with diabetes who also have albuminuria. But I would say globally, we see pretty similar clinical outcomes between aces and ARBs, right? Dr. Khyati Patel 11:16 Dr. Kane, another difference that comes to mind is for the longest times, ARBs were brand name, even though ace they had become generic. So in my mind, I'm always thinking like ARBs are a little bit more expensive than AIDS inhibitors. I know there are generic ARBs out there, but market value, I've just seen ARBs being a little bit more expensive, not as easily included in those $4 lists that we normally see ace included. Dr. Sean Kane 11:38 And of course, we'll see this change over time as we get more generic ARBs in the market and things like that, Losartan, which is our oldest ARB, we're looking at 20 cents versus Lisinopril. We're looking at like five cents, right? So just kind of the classic ARB versus the classic ace. You are spending more money, but it's a pretty affordable medication in Losartan, the difference would be when we look at some of the newer agents, though, right? Dr. Khyati Patel 12:03 And that's the azilsartan, which was the newest approved ARB, we're looking at $10 per tablet. So if you think about 30 day supply, you're looking at $300 versus the newest ace inhibitor, was the trend doloprill, and that's about $1 per tablet. So again, more affordable on the ACE side, but if you're picking a Zilla, certain that's going to be a little bit highest price. Dr. Sean Kane 12:28 Yeah. And not surprisingly, one of the most common indications for our ARBs is for hypertension. It's one of our four core first line therapies for hypertension, and as we said, it has a very similar efficacy to our ACE inhibitors, our thiazides, our calcium channel blockers, which is why it is one of our four go to therapies. There was a trial called the value trial that looked at Amlodipine versus valsartan, and what they demonstrated in that trial was blood pressure reductions were similar, but the risk of new onset heart failure, new onset diabetes was a little bit lower, better with valsartan versus amlodipine, Dr. Khyati Patel 13:02 and then there is benefit for renal or kidney protection in patients with type two diabetes. So there were a couple of trials done. First one was named RENAAL trial, which looked at losartan versus placebo when it was added to other anti hypertensive medications patients were on and they were looking at doubling up the serum creatinine or progression to end stage renal disease, and they found that to be lower in the Losartan arm compared to the placebo arm. They also found 35% reduction in proteinuria in the Losartan group patients. However, when, when they looked at it overall, in terms of CV, morbidity and mortality, there was no difference. However, they spotted a small difference where reduction in first heart failure, hospitalization was noted in the treatment group. Dr. Sean Kane 13:54 And then there was another trial called the IDNT trial that looked at irbesartan versus amlodipine versus placebo. And basically they showed that if you got irbesartan, you did a little bit better from a kidney standpoint, in terms of progression of your kidney disease, right? Dr. Khyati Patel 14:08 These agents are also used in stroke prevention. So the evidence for that comes from a trial called Life trial, which looked at losartan compared with atenolol in patients who have left ventricular hypertrophy. When they looked at surrogate outcome like blood pressure controlled it was very similar between the two. However, the risk of stroke was reduced by 25% in patients who received Losartan. Dr. Sean Kane 14:33 And for heart failure, especially reduced ejection fraction heart failure, we see valsartan, losartan, candesartan as ARBs that have specifically been studied. And as we mentioned, the VALUE trial, which was looking at valsartan, again, showed that potential benefit in preventing new‑onset heart failure. Dr. Khyati Patel 14:51 And last, but not the least, you know, we're looking at benefits from ascvd risk reduction perspective in patients who have vascular disease or patients. Have diabetes and so on. ONTARGET was a trial that looked at telmisartan versus ramipril versus combination of both of them. So this is the trial where they combine the two RAS agents together primary outcome wise. You know, just like any cardiovascular outcomes trials, they were looking at overall death from cardiovascular causes and then looking at individual causes such as mi stroke, hospitalization for heart failure, and they found actually, that these primary outcomes were similar between Tommy Sartin, Ramipril, versus patients who received both the agents, risk of angioedema, however, and cough were lower in the ARB group compared to the Ramipril group, as we talked about, Aces do have higher risk. However, when they looked at side effect profile in general, there were more side effects in patients who received both agents, so combination group versus one alone. And you know, this is not new. Dr. Kane, lot of different studies have shown that adding two agents together provides not more efficacy benefit, but causes more side effects, exactly. Dr. Sean Kane 16:07 So what are some other differences? Well, you might think about pharmacokinetic differences. So bioavailability is one difference. Basically, they all have fairly low bioavailability and then high protein binding. The one exception is azilosartan has a slightly better bioavailability of about 60% versus less than 50% on average. And then we also see differences from a metabolism standpoint. So telmisartan, losartan, and azilsartan, they undergo CYP‑mediated hepatic metabolism versus the others do not, right? Dr. Khyati Patel 16:39 And then, you know, we have the Pro drugs categories too, and so in the category of ARBs, Candesartan, olmesartan and azilsartan are available as their inactive ester pro‑drugs. And when the patient takes the medication, hydrolyzation happens in the GI tract, and that converts the drug in into its more active form itself. Dr. Sean Kane 17:02 Dr. Patel, if you've ever wondered why there's like a goofy name after the ARB products like candesartan cilexetil, as an example, the cilexetil is literally the ester part of the pro‑drug that makes it a pro‑drug. Olmesartan medoxomil would be another example. Those terms are the pro‑drug suffix of the olmesartan or candesartan in this example. Dr. Khyati Patel 17:25 So why do you think they make them as Pro drugs? Dr. Kane, so Dr. Sean Kane 17:28 they have to to make the drug bioavailable enough to get into your blood. So those esters that they add are giving you more lipophilicity that allows for better oral absorption, better bioavailability. If they didn't do that, you'd have to have a bigger pill, more drug, and you wouldn't absorb as much of it Dr. Khyati Patel 17:45 makes sense. And then clinically, we are seeing some differences in effects, especially blood pressure reduction effect among these agents too. So it's known that Losartan has the weakest blood pressure lowering effect, even worse than azilsartan, candesartan, olmesartan, and valsartan. Azilsartan has the best blood pressure lowering effect; it was studied against valsartan and olmesartan, and that's where it was proven that its blood pressure lowering effect is better than those two. Dr. Sean Kane 18:18 So you do have to consider, actually Patel, that azilsartan is one of the most expensive ARBs that we have, and even though it has quote, unquote the best blood pressure effect, that cost trade off of efficacy may not be cost effective for certain patients, and you do have to consider that, right? Dr. Khyati Patel 18:33 And as I mentioned earlier, too, I mean, while they are great therapies, they're they're expensive compared to ACE inhibitors, and so got to pick a lower cost Losartan on a $4 list. That's totally okay, too. Dr. Sean Kane 18:47 And then, from a heart failure perspective, the guidelines only specifically name certain ARB, so valsartan, Losartan and candesartan and the 2022, heart failure guidelines, those are the ones that are mentioned because those are the ones that have been studied. We should note, though, that the guidelines don't say you can't use a different ARB. I think generally, most people believe that there's an ARB class effect, and it's important to draw the distinction that unlike with ARBs, where it's probably a class effect, with beta blockers, it is not considered a class effect. And we do have some data that certain beta blockers may be better than others. So even though the guidelines specifically call out valsartan, Losartan, candesartan, you might still see some patients taking a different ARB for whatever reason. Although I don't know why you would bother doing that, the guidelines don't say you can't use these other ARBs on the market. Dr. Khyati Patel 19:37 Yeah, but just something to keep in mind that that's what your guidelines include. The other thing to look at is the duration of effect, and that could be blood pressure reducing effect that we're talking about here, that some of the ARBs have shorter duration of effect, so patients may have to take it once daily or twice daily. Their half lives are about nine hours, and we're talking about valsartan and losartan here. Dr. Sean Kane 20:04 And then all of the other ARBs, aside from those two, valsartan, losartan, they have long enough effects and long enough half lives from nine to 24 plus hours. You only dose those once daily. So it's really just valsartan and losartan that you might see BID, but you can still see them once daily. Dr. Khyati Patel 20:21 And the other thing Dr. Kane is the the non RAS effect of some of these ARB agents. And I was actually very intrigued to know about these, because I did not know them earlier. But apparently, like telmisartan, also had some agonism activity of PPAR Gamma, which, if you think about those, thiazolidinediones are also PPAR‑gamma agonists, so it does actually help improve insulin sensitivity a little bit. Dr. Sean Kane 20:48 Then Losartan can actually help you get rid of uric acid in your blood. So by increasing the amount of renal elimination of uric acid, it can be maybe a little bit helpful in patients with gout. So if you have that patient with gout, and you're choosing between Losartan versus a different ARB, you might as well pick the one that also helps gout a little bit, right? Dr. Khyati Patel 21:07 And then olmesartan carries a rare but serious risk of sprue, like enteropathy, so in patients who have like unexpected chronic diarrhea occur, like occurring, and if they're on olmesartan, that might be a reason to look out for Dr. Sean Kane 21:23 and just for context, the other ARBs are not associated with that, so it's just interesting that it's not a class effect for that enteropathy. It's just for all the certain so what are some common side effects that we should be aware of? We mentioned a couple of these, but Dr. Patel, what are your go to? Must know ARB side effects. Dr. Khyati Patel 21:41 Well, thanks to mine, we're gonna talk about potassium and renal monitoring, right? So higher risk of hyperkalemia, so increased serum potassium levels as well as increased in serum creatinine, has been noted. And obviously the risk is carried with monotherapy, but definitely higher risk if you combine. So therefore, again, as we mentioned earlier, the RAS agents should not be combined together. And then whenever we put the patient on ARB agents, whenever we initiate the dose or increase the dose, these parameters should be monitored at least one to two weeks after the initiation or modification of the dose. And the reason to monitor, you know, obviously this one to two week monitoring is for any patient, but in patients who have underlying renal impairment or renal artery stenosis, existing renal disease, or in patients who are even taking NSAIDs for pain management purposes, we may have to monitor this a little bit closely. They're at a higher risk for renal impairment. It's like a double edged sword in terms of ARB. We know that there is a benefit in terms of renal protection, but also because of that dilation and constriction of those renal arteries, we can also see reduction in the eGFR (aka renal impairment). So these patients should be monitored a little bit closer. Dr. Sean Kane 23:00 And then we already mentioned this, but because ARBs are not changing bradykinin breakdown, unlike ACE inhibitors, we have effectively very low risk of cough, less risk of angioedema. And it's very common that if a patient truly is indicated for an ACE inhibitor, but can't take it because of angioedema, as long as it was not a very severe life threatening reaction, and especially if it's someone with, let's say, heart failure, where they could have a mortality benefit from an ARB. It is pretty common to transition those patients to ARBs, but you just monitor closely. Also very common to have a washout period, where you wait four to six weeks after the angioedema event just to make sure everything's calmed down before you start your new therapy with an ARB. And then finally, a common side effect of all anti hypertensives is going to be the risk of low blood pressure or hypotension. And the main manifestation of that is going to be dizziness, fatigue, feeling light headed, orthostasis, where they get up too quickly and then get really light headed, things like that. Yeah. Dr. Khyati Patel 23:59 So continuing the safety discussion, Dr. Kane talking about drug interaction, it's no brainer that we have been talking about don't combine it with other RAS agents, so either ACE inhibitors or aliskiren, which is a renin inhibitor; the risk of hyperkalemia and renal impairment is high, and that's the reason we avoid combination. Dr. Sean Kane 24:20 Another drug interaction to be on the lookout for would be combination of R plus a potassium sparing diuretic or potassium supplements. You can get these over the counter. It could even be a salt substitute. And it's not that a patient can't be on these, but you do definitely need to look out for the risk of hyperkalemia with better monitoring things like that. So if they're at the high end, you wouldn't be adding, let's say, a potassium sparing diuretic if their potassium levels are already high, right? Dr. Khyati Patel 24:47 And as we talked about earlier, you know patients who are using NSAIDs, because NSAIDs take away those protective prostaglandins, it impairs the blood pressure lowering effect of the ARBs. You. Increases the risk of that renal injury. Dr. Sean Kane 25:02 And then lastly, lithium. If you initiate an ARB on a patient already on a stable lithium dose, their lithium levels can get higher, so that needs to be monitored, and potentially a dose adjustment with the lithium needs to occur. Dr. Khyati Patel 25:16 So then, who should not receive ARBs? You may ask, right? What are those absolute versus relative contraindication? Well, the Absolute One, Dr. Kane, comes to mind. The first one is pregnancy, because these are shown to cause fetal renal damage, oligohydrominosis, skull hyperplasia, even fetal death, especially when it's taken during second and third trimester. These are category X. If you have a patient who is a child bearing age, they know they're planning to have a child the best idea is to switch them to a safer antihypertensive agent, rather than keeping them on ARBs. Dr. Sean Kane 25:53 Another absolute contraindication is a known or suspected bilateral renal artery stenosis. So this is where the blood vessels feeding both the kidneys are very stiff or stenotic, and we can't give ARBs to those patients, because the risk of having acute kidney injury is really, really high because, again, the kidney relies on angiotensin two to regulate blood flow the kidney, if you block that compensatory mechanism, they're at a higher Risk of Aki. Dr. Khyati Patel 26:20 And then there are some situations where we would be cautious in using ARBs, right? They're not complete contraindication, but there will be relative contraindication. We talked about. One of the side effects was hyperkalemia. So if you're looking at a potassium of more than 5.5 that's not probably the best time to initiate or modify or increase the dose of an ARB, probably we are looking at holding Situation monitoring the lab again, resuming the therapy as appropriate thereafter. Dr. Sean Kane 26:48 And then, for those with hepatic impairment, if you pick an ARB that goes through the liver for metabolism, you need to be more careful or just pick a different ARB. And again, those were telmisartan, losartan, and azilsartan. Dr. Khyati Patel 26:59 And while there are benefits of using ARBs in renal protection, in severe renal impairments, if we're talking about creatinine clearance below 30, it's risk versus benefit analysis to see if at that point, adding an ARB would be more beneficial or harmful to the kidneys. Dr. Sean Kane 27:15 And then someone who currently is really dehydrated, so severe volume depletion, they're going to have a higher risk of hypotension, acute kidney injury, like pre renal acute kidney injury, so we'd want to hold it when they get really dehydrated, because of those two risks. Dr. Khyati Patel 27:31 So that said, Dr. Kane, with all the safety issues and stuff, just to summarize again, how do we monitor somebody's arm therapy when they're started? Well, first of all, before starting at baseline, we're going to make sure they have good renal function and also that potassium. So doing a BMP, will check all those lists, and then obviously blood pressure. We're going to have to have a baseline blood pressure. And then Dr. Sean Kane 27:54 you don't want to check labs and their vitals the next day. You want to give it some time to get to steady state. So about one to two weeks after you initiate therapy or increase the dose, you're going to want to get a new serum creatinine to look for acute kidney injury, a new potassium to look for hyperkalemia. And of course, you want to check the blood pressure to see if the blood pressure is where it needs to be, or if it's too high or too low, and do something about it, right. Dr. Khyati Patel 28:16 And then for patients who monitor these symptoms at home, we're going to ask them to check for signs and symptoms of hypotension. So we talked about that dizziness, that fatigue, that lightheadedness, instability associated with like positional changes, you know, those to be monitored. And then also look out for those signs and symptoms of Angular edema, so the swelling of the mucosal area of the face, the lips, et cetera. Dr. Sean Kane 28:39 And then Dr. Patel, in terms of kind of wrapping things up, some clinical pearls or counseling points for ARBs, a patient should know that they need to take it as directed, so every single day they should be compliant with their regimen, and then that they are going to have to have their blood drawn for appropriate monitoring. They're going to have to have their blood pressure checked so it's not a set it and forget it kind of situation. They do have to have follow up appointments with their new ARB that they're taking, right? Dr. Khyati Patel 29:01 And I think that's kind of like the condition or the deal you make with the patient, like, yes, you will choose this therapy only if you're able to come to the lab, also making sure we are discussing alternative therapies, as I said earlier, if they are going to be in that conceiving period of time as these agents are teratogenic, we may need to change up the antihypertensive agent before the actual pregnancy begins. Dr. Sean Kane 29:26 And then finally, and this is something that wouldn't likely be on a patient's radar if they take a salt substitute, which is typically a potassium chloride, like a new salt. And Nu-Salt, for example, their provider needs to know because they're literally taking potassium. And of course, the risk of hyperkalemia is going to be higher. They should also potentially have a psychiatric consultation, Dr. Patel, because these salt substitutes are absolutely nasty tasting, and I don't know why anyone would take them, but they should at least tell their provider to know about the risk of hyperkalemia. All right, so Dr. Patel, to wrap today's episode up, and we have. Some show notes at HelixTalk.com again. This is episode 191 I think it's important that we recognize that ARBs are equally effective to ACE inhibitors for hypertension, heart failure with reduced ejection fraction, chronic kidney disease with proteinuria. and post‑MI care, we have a little bit of limited evidence that maybe they're better in treating CKD with albumin area in patients with diabetes, generally speaking, ARBs are better tolerated because of a lower risk of angioedema and low risk of dry cough. Dr. Khyati Patel 30:29 And while most ARBs are comparable to each other in terms of that, you know, clinical benefit, blood pressure reduction benefit, minute differences do exist between them, such as, you know, some have that hepatic metabolism. So looking out for the SIP interactions, the degree of blood pressure lowering, as well as other things such as additional pharmacologic effects that are non‑RAAS dependent. But other than that, they class wide, have similar, similar effects. Dr. Sean Kane 30:57 And then, in terms of contraindications, the herbs are contraindicated in pregnancy, bilateral renal artery stenosis, and those that have had a previous history of angioedema to that same drug class. So if you had angioedema to losartan, you should not take valsartan, for example. Other common side effects are hypotension, hyperkalemia, and then in rare cases, acute kidney injury. Dr. Khyati Patel 31:20 To monitor the therapy appropriately. We're going to check baselines on creatinine and potassium as well as blood pressure. And after the medication starts or the dose is increased, in one to two weeks, we're going to repeat these parameters. And then at home, patients are going to monitor those signs and symptoms of hypotension, the dizziness, that lightheadedness, and also any kind of facial swelling for angioedema. Dr. Sean Kane 31:43 So Dr. Patel, that wraps up today's episode for the listeners. If you want to see show notes, we're at HelixTalk.com episode 191, we still love the reviews in iTunes, so keep those coming, especially the five star ones. We have a mailing list. If you want to get an email when new episodes come out, you can subscribe at HelixTalk.com and add your email address to the mailing list. So with that, I'm Dr. Kane Dr. Khyati Patel 32:04 and I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 32:09 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store. Search for HelixTalk and place your review there Narrator - ? 32:20 to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.