Speaker 1 00:05 Alright, welcome to HelixTalk, a podcast presented by the Rosalind Franklin University College of Pharmacy. Narrator - Dr. Abel 00:11 This podcast is produced by pharmacy faculty to supplement study material and provide relevant drug and professional topics. Speaker 1 00:19 We're hoping that our real life clinical pearls and discussions will help you stay up to date and improve your pharmacy knowledge. Narrator - Dr. Abel 00:27 This is an educational production copyright Rosalind Franklin University of Medicine and Science. Speaker 1 00:32 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 - Dr. Abel 00:47 And now on to the show. Dr. Sean Kane 00:51 Welcome to HelixTalk. I'm your co host, Dr. Kane. Speaker 2 00:54 I'm Dr. Michael Schuman, and I'm Dr. Kathy Patel. Dr. Sean Kane 00:57 And in this episode, episode two, we're talking about the new JNC eight guidelines and the treatment of hypertension. Speaker 2 01:03 Funny thing you say, Dr. Kane, JNC eight, I like to call it, quote, unquote JNC eight, because everybody who was in support of JNC seven guidelines are not supporting JNC eight guidelines. Dr. Sean Kane 01:15 So, Dr. Patel, are you hinting at the fact that these are not fully endorsed guidelines by all major organizations that treat hypertension, that Unknown Speaker 01:24 is pretty much true. Yeah, it's Speaker 3 01:26 quite it's got quite an interesting history. It does as far as the time it's taken to kind of compile these I know it's I've been hearing personally about these guidelines for years and years, but it seemed that it hit a couple snags along the way. Dr. Sean Kane 01:37 So what caused it to take so long to be released or updated from JNC seven. Speaker 2 01:42 So you will know, as we discuss differences between JNC seven and JNC eight, that JNC eight is based mainly on the systemic review of randomized control trials only, and so this organization was actually waiting to summarize all this nice, controlled trials that were coming out. So what happened in 2008 that the National Heart, Lung and Blood Institute created a draft of JNC eight, quote, unquote, and sent it for an external review, and the guidelines then needed another revision because more randomized control trials were incorporated, and actually the NHLBI was going to send it to AHA and ACC for the review. But something happened in June 2013 where NHLBI decided to just directly publish it in JAMA. So there you go. You have your JNC eight. Dr. Sean Kane 02:31 So Dr. Patel, help me understand here, when did JNC seven come out? Unknown Speaker 02:35 JNC seven came out in 2004 Dr. Sean Kane 02:37 Okay, so that's been quite a while. And how do you have guidelines that aren't evidence based. So you mentioned that they the new JNC eight guidelines are based on systematic reviews and randomized control trials. What else is there that you can use for a guideline, Speaker 2 02:51 besides looking at the systemic review of the randomized control trials, there could be things like retrospective reviews, cohort design trials or expert opinion, and that's what was comprised of JNC seven. So there is a huge difference right there, that JNC eight looks at randomized control trials only. So I Dr. Sean Kane 03:11 guess from a clinical point of view, it's kind of a double edged sword, in a sense. So you can either have a really nice guideline like JNC seven, where it kind of fills in the gaps where you don't have good data, but experts say what they think is a good thing to do, whereas with JNC eight, it really focuses only on what we absolutely know from randomized, controlled trials, but then the reader is left not knowing exactly what to do because the gaps aren't filled in where there's a lack of data. By expert opinion, you Speaker 3 03:38 summarize this quite well, and I think there's a few other little, little too big even changes that they've made with JNC eight versus JNC seven. I believe another one that they did was whereas JNC seven had these predetermined guides for what's considered pre hypertension and what's considered hypertension, whereas instead, JNC eight really just focuses on the thresholds for pharmaceutical treatments. Dr. Sean Kane 03:59 I feel like there's probably no better way to scare a patient than to tell them that they have pre hypertension, correct. Speaker 2 04:05 And also, if you remember JNC seven, it was based on compelling indications, meaning comorbidities. If you look at JNC eight, the goals are similar for the treatment. However, it also focuses on sub populations such as race and patients with certain chronic conditions. Dr. Sean Kane 04:24 And the other thing is that in JNC seven, you know, they had a lot about lifestyle modifications, but in JNC eight, they really delegated that task of lifestyle modifications to a separate entity, citing that they'll come out with a kind of a lifestyle work group, as opposed to incorporating those into the guidelines as well. Speaker 3 04:43 So the other thing I noticed about it is that right off the bat is that Gone was the beta blocker as one of the primary initial therapies. And so instead of having the five classes as initial treatment within JNC seven, they went to four classes within JNC eight. So that would be the angiotensin converting enzyme inhibitors, the ACEs, and the angiotensin receptor blockers, or the ARBs, the calcium channel blockers and the thiazide diuretics. Dr. Sean Kane 05:11 So if you want me to get on a soapbox real quick, I am passionate about my hatred for atenolol. I think that it's an easy medication to get started as kind of an anti hypertensive for a normal run of the mill patient. And not only are beta blockers not recommended as kind of initial therapy for someone without any comorbid comorbidities. The other problem with atenolol is that it's renally eliminated. So very commonly in the ICU, I'll see patients who have acute kidney injury, where they start accumulating all this atenolol and whatever gave them the acute kidney injury in the first place actually gets worse because they're accumulating all this beta blockade that causes worsening hypotension, worsening bradycardia. It causes a lot of problems, whereas the other beta blockers not renally eliminated. Good to go in terms of renal perfusion problems. Speaker 2 05:57 Way to trash atenolol Dr. Kane, love it. I'm not going to use it anymore. Dr. Sean Kane 06:02 My impression is that JNC eight really sought out to answer three very specific questions, and that's kind of how they developed the guidelines that they came out with this year. Speaker 2 06:12 And those three prime questions they're trying to address is, what are the blood pressure goals we're trying to achieve? What blood pressure level we should start the treatment and what blood pressure medications are best for our patient, especially keeping those sub population in mind. Speaker 3 06:28 And so I kind of liked it how they went by one by ones, and just looked at these recommendations. Made it pretty easy to follow. But right off the bat, they were looking at the recommendations for what are the blood pressure goals. So the first recommendation, if someone's over 60 years old, and this is the general population, not taking into account some of those comorbidities. But in that general population, a goal blood pressure is going to be less than 150 over 90, and that's in terms of millimeters mercury. And that was a strong recommendation. But there was a little bit of disagreement about the actual goal. Speaker 2 06:57 Wasn't there? Yes, there was. They were having a little hard time agreeing with the goal of less than 150 or keeping that systolic blood pressure closer to 140 if possible. And there were multiple randomized trials such as SHEP and HYVET that showed benefits of keeping our patients who are more than 60 years old systolic blood pressure around 140 millimeters mercury, instead of letting it lose to be less than 150 but I Dr. Sean Kane 07:24 really want to put this in the context of JNC seven versus eight here. So if we look at the definition from JNC seven of pre hypertension, that was a systolic less or greater than 130 now we're saying that it's okay for elderly patients to go all the way up to 150 before we really initiate treatment. I really think that highlights not only the controversy of what is a goal blood pressure, but also the fact that this idea of pre hypertension maybe wasn't the best approach in terms of classifying patients historically. Yeah. Speaker 2 07:55 And as we discuss these guidelines further and look at other governing bodies who have put out their own guidelines, you will see the discrepancy between systolic blood pressure goal in this particular age population. Speaker 3 08:08 All right, so if the in general population, the goal we set is less than 150 over 90, what are we going to do if somebody is in a high risk group? Speaker 2 08:15 So Dr. Schuman, when you say high risk group, are you thinking of patients who are African Americans who have high salt sensitivity, patients who have history of cardiovascular event, including even stroke or other multiple risk factors, such as family history. Yeah. Speaker 3 08:32 And in those individuals, they went ahead and made the goal less than 140 instead of less than 150 Dr. Sean Kane 08:38 so then I have a question. Let's say that we initiate therapy, especially one of these higher risk groups, and they walk in with a systolic of 155 and now they're down to 135 that's well below the goal that we were looking at. Does that mean that we should really back off on our therapy for them, because we've kind of achieved our goal almost too much. I thought Speaker 3 08:56 that was a good point, and that's why I was actually really, really glad that they were specific and how and how they targeted that question in the guidelines, and what they decided was that there's no need to change the medication as long as the individual is tolerating it. If that person maybe has some orthostatic hypotension or some issues getting up in the morning, then maybe you want to back off of it a little bit, but as long as it's being tolerated, then that's okay to use that as maybe more of a goal. Dr. Sean Kane 09:20 So moving on from our high risk group and the patients that are greater than 60, what about those who are less than 60 years of age? Speaker 2 09:27 So recommendation number two and three come for this specific age group, patients who are less than 60 in general population. Again, the goal blood pressure is defined to be less than 140 of systolic and less than 90 of diastolic, and if the blood pressure is above this goal, then we should go ahead and start the treatment. Dr. Sean Kane 09:47 So if I'm 19 years old and I just happen to have a relatively high blood pressure of, let's say 145 systolic, does that mean that I should be initiated on antihypertensive therapy, even though I'm a relatively young, healthy patient. Speaker 3 10:01 And I believe that was one of those areas where the guidelines didn't have as much of a robust evidence. This one where some of the guidelines were what they called Grade A, or a much higher level of recommendation. That guideline, in particular, for patients 18 to 29 years old was grade E, or more of an expert opinion, I believe. And so in that case, it wasn't one, wasn't a complete consensus among everyone within the panel, but that was based upon the expert opinion. Was the yes you would look at starting an individual on a blood pressure medicine. Dr. Sean Kane 10:29 So if I remember back to JNC seven, kind of everyone gets this goal of less than 140 over 90, unless you're patient with a diabetes or CKD, and then it's one less than 130 over 80. Does that rule kind of still stand with JNC eight Speaker 3 10:43 and I think that's one of the interesting areas, is they did not do that with adults that have diabetes. And that was in recommendation number five, is they went ahead for adults with either type one or type two diabetes. Goal is blood pressure is less than 140, over 90. And so a big difference there. And I know just talking to individuals within my facility, there's kind of a little bit of contention as to what are we going to do? Are we going to abide by these new guidelines, or kind of stay with the practice we've been doing for a while? Speaker 2 11:10 We skipped ahead to recommendation number five for patients with diabetes, but recommendation number four is patients with chronic kidney disease and the goal blood pressure, again, is similar to patients who are less than 60 years of age, and that is less than 140 of systolic and less than 90 of diastolic. Dr. Sean Kane 11:28 So to really summarize, our blood pressure goals, everyone has the same diastolic blood pressure goal less than 90, and then you either have a systolic blood pressure goal of either less than 150 if you're elderly, greater than 60 years of age or less than 140 if you're everyone else, Speaker 3 11:44 yes, and that's specifically for those above 60 that don't have any sort of other conditions, such as chronic kidney disease or diabetes. Speaker 2 11:52 And further recommendation then come in to consider the race as well. So recommendation number six is pertaining to non African American population. And what they recommend is that for initial treatment, we should be opting for either thiazide, calcium channel blocker ACE inhibitors or angiotensin receptor blockers. And this is a well supported evidence in clinical trials, and thus for holds Grade B recommendation. Dr. Sean Kane 12:19 So my impression of JNC seven was very much that they were in favor of thiazides. Based on the ALLHAT trial, sounds like that's no longer the contention of JNC eight that thiazides are the King of antihypertensive therapy. Speaker 3 12:30 I would there's still a good option, but they've made it kind of clear that within a non African American population, for example, that you have the option of using really out of four classes. So either the thiazides, the calcium channel blockers, and then your ACE or your ARBs. And whereas before you had yet, the thiazides were considered one of the good option but you really had amongst that, those kind of the five that you could, you could potentially pull from, especially if you're looking at the second agent to choose. Speaker 2 12:57 And definitely thiazides are falling off the favor, and that's because of the emerging evidence we have for the add-on therapy with thiazides did not really improve the outcomes other than patients who had previous stroke or TIA. Speaker 3 13:13 Okay, so, so again, among non African Americans, we've got those four classes that are kind of recommended with JNC eight. What about within a population African American I know there wasn't always that much specifics, I believe with JNC seven, about what are you going to do amongst different races, but what did they do with JNC eight? Speaker 2 13:30 So JNC eight has a specific recommendation for African American population, and that's again, evidence coming from the clinical trials that they found that ACEs and ARBs did not work as well in this particular patient subgroup, and so what they are recommending for the initial treatment is either choose a calcium channel blocker or thiazide diuretics. But I do have to make a distinction, and that leads me to recommendation number eight, that even if your patient is African American, or, let's just say, regardless of race, if they have CKD, the go to antihypertensive would be ACE inhibitors or ARBs. Dr. Sean Kane 14:09 So Dr. Patel, why would we want to use an ACE or an ARB in a patient who has chronic kidney disease because of their nephroprotection? So it'll make them have working kidneys longer, as opposed to any other antihypertensive that doesn't have that protection for the kidney. Speaker 2 14:26 That is definitely true, and that's why we recommend ACEs or ARBs in patients who are also diabetic. Speaker 3 14:32 So what do you do if somebody is an African American, then who does have chronic kidney disease? Speaker 2 14:36 Then the first choice of antihypertensive regimen would be ACE inhibitors or an ARB. Dr. Sean Kane 14:41 So despite the fact that we've talked about CKD and diabetes, kind of one thing missing from JNC eight that we saw a lot of in JNC seven were compelling indications where, if you have heart failure, should be thinking about beta blockers, Ace ARB, maybe spironolactone, if you are post-MI patients. Definitely a beta blocker, maybe an ACE inhibitor. Those recommendations are really not present in JNC eight so what was going on with that? Speaker 3 15:07 I think one of the things they stated in some of the discussion in the article is that by name, they said congestive heart failure was an area that they yes, they didn't really cover it, but what they felt was that other organizations, such as the American Heart Association had done such a great job of covering how to treat those that they thought we will leave that area to the experts, and we'll really focus on some of these specific comorbidities, such as the diabetes and CKD. Speaker 2 15:31 But in a moment, we're going to be discussing the American Society of Hypertension and International Society of Hypertension guidelines. And those are a little bit more comprehensive, and they do delineate this different compelling indication and what the blood pressure medication regimen should be for those patients. Dr. Sean Kane 15:48 Yeah, so I think for the listener, it's important to note that if you have someone, let's say, with heart failure, the guidelines may not be specific for a heart failure patient, but there may be other guidelines out there that would give a very compelling, very reasonable and very evidence based recommendation for, let's say, a beta blocker, whereas JNC eight doesn't offer that recommendation. So now that we've identified the agent or agents that we should be starting on our patients, what's kind of the clinical approach, if you will, when you're starting to treat or changing doses on a patient with hypertension? Speaker 2 16:19 So it used to be the case where we would start a patient on a drug and a smallest dose possible, and then titrate the dose, max it out, and then, if the blood pressure is still not controlled, add another agent. What JNC eight is saying is that you can actually take a different approach, where you can start the first drug, start the second drug, before titrating the first drug to the fullest, and then kind of slowly modify the therapy as patient's blood pressure responses. Dr. Sean Kane 16:49 So Dr. Schuman give me kind of the devil's advocate approach here. Why would I not maximize my first anti hypertensive and just start a second one before I've really maxed out that first one? Speaker 3 16:58 I think part of it would be to maybe engage a couple different mechanisms in there, so that we're working maybe on the side of the kidneys, potentially with an ACE or an ARB, or potentially a diuretic. And then we maybe would use a calcium channel block, or we were working a little bit on the vasculature as well. And then maybe as well, we're looking at maybe avoiding some of the side effects you might see when you get towards the higher end of one medication, maybe we're concerned about the potassium levels either going up too high or going too low with some of those agents again, to work on the kidney, and so maybe to avoid that, we kind of keep a moderate level of two different drugs instead. Dr. Sean Kane 17:33 So your argument would almost be a dose response effect, where you get a lot of benefit with lower doses and then the benefit really wanes off as you get to those higher doses. Yeah, I think that would be a good way of looking at it. So, Dr. Patel, what about the opposite way? Why would you make the argument that you should max out that first drug before going to that second drug? Speaker 2 17:51 So in order to minimize polypharmacy, that would be one of the reasons that you want to be just using one drug. If you put it out to patients that, hey, you have high blood pressure, and today, I'm going to start you on two medication. Patient might not take it as well as if you were to take a little slower approach and then see how the medication reacts in the body. Third reason would be, if a patient were to experience side effects, we wouldn't know what medication is causing the side effect. And then the cost, cost of starting two medication at the same time, depending on patient insurance, it could be a little bit higher than just working with one medication. So I Dr. Sean Kane 18:26 think kind of the take home point here from JNC eight is that there's a lot of different ways to do it with very different approaches and reasons for doing it that way. And we don't really have a very strong recommendation to do one way or the other. It's probably more of a patient specific approach. Speaker 2 18:40 I do have a strong recommendation. However, you can combine all the agents if you wanted to control the blood pressure, but please, please do not combine ACEs and ARBs together. And why is that? Because of the risk of side effects such as hyperkalemia and kidney injury. All right. So we had a really nice review of JNC eight and what it comprises of. However, we think, still think that those guidelines do not address everything in detail. So American Society of Hypertension, ASH and International Society of Hypertension ISH came out with the guidelines just a little before JAMA had published JNC eight, and those are considered to be a little bit more comprehensive. They're not a systemic review, but the evidence is beyond the randomized control trials that mean it includes expert opinion and experience as well. All right, so we Speaker 3 19:33 got a little bit of a fight brewing, so what kind of things did they change with it? I believe the first one was they changed a little bit of the goal blood pressures. Dr. Sean Kane 19:40 So for most patients, the goal blood pressure is less than 140 over 90, which, if you'll recall, was in concordance with what JNC eight had if you're less than 60 years old, with no compelling risk factors. For those who are quite elderly greater than 80 years of age, the goal is 150 over 90. So JNC eight said greater than 60 years of age. For ASH, ISH, they're saying greater than 80 years of age, and patients who have CKD or albuminuria, they say even lower, less than 130, over 80, to try to get as much nephroprotection as possible, Speaker 3 20:12 all right? And I think they made a little bit of a change in terms of some of the drug selection as well. Speaker 2 20:16 Yes, they definitely did so for again, non African American patients who are younger than 60, they are asking us to go with ACE inhibitors and ARBs first, instead of the four drug choices we had with JNC eight, for patients who are non African American but older than 60, they recommend going along with calcium channel blockers and thiazide first. However, they say you can still use ACE inhibitors and ARBs if the former two are not the proper choice. Speaker 3 20:45 And then, I think they also said for all ages, you can either use a calcium channel blocker or a thiazide diuretic in African American. And then if you have hypertension plus diabetes or hypertension plus chronic kidney disease or hypertension plus stroke, then they came out with a little bit more specific in terms of a first line, second line, third line, they said an ACE inhibitor or an ARB for first line, calcium channel blocker or a thiazide diuretic for second or third you could use an alternative of one of those other agents, one of those second line agents. Dr. Sean Kane 21:15 They mentioned that if you're a hypertensive patient who has coronary artery disease, the first line go to agent is going to be a beta blocker with an ACE or an ARB. Second line would be a calcium channel blocker or thiazide. Third line would be, again, an alternative agent. Speaker 2 21:28 And here is your hypertension and CHF patient regimen. What they recommend is using either ACE or ARB, adding a beta blocker, adding a diuretic and adding spironolactone, regardless of what patient's blood pressure is, and if we need further blood pressure controls, we always have our calcium channel blockers to add on board. Dr. Sean Kane 21:48 I think it's important that to note that we have two different kinds of calcium channel blockers, right? So we have our dihydropyridine and our non dihydropyridine. Dihydropyridine is kind of all calcium channel blockers except for diltiazem and verapamil, and in patients who have systolic heart failure, diltiazem and verapamil not good options. Increases mortality over time. Speaker 2 22:09 We were waiting and waiting for JNC to come out, and now we had publications from JNC eight, the International Hypertension Society and American Hypertension Society. And then Europe decided to join hands too, and they published their recommendations in August 2013 that comes from the European Society of Hypertension and European Society of Cardiology. And main differences, when we compare with the other guidelines we discuss are the blood pressure goals. And they're saying in all patients who do not have diabetes, the blood pressure goal should be less than 140 over 90. But if the patient who has diabetes, the goal should be less than 140 over 85 Dr. Sean Kane 22:48 so that's pretty interesting. I think if I go back to my pharmacy school days, the difference of five millimeters of mercury was probably the difference of passing or failing my skills assessment. But at the same time, that's a pretty specific blood pressure parameter difference between 85 and 90 that clinically, I don't know that we're going to be that specific when we're pulling a patient into a clinic and really knowing where they're they're living with their normal blood pressure. Speaker 2 23:11 And despite of all these new guidelines coming up, we do know that American Diabetes Association publishes their guidelines annually in January. So on top of having this evidence available to ADA, they still have their blood pressure goal to be less than 140 over 80. Dr. Sean Kane 23:28 So just to be specific, then the American Diabetes Association says less than 140 over 80, not less than 140 over 90. Even though many of the other guidelines have a diastolic blood pressure goal of 90, Speaker 2 23:41 I would still go ahead and keep my diabetic patient's blood pressure try to keep it at less than 140 over 80. Dr. Sean Kane 23:47 So it really seems to me that we probably have too many cooks in the kitchen, if you will, in terms of where our blood pressure goal should be, what kinds of agents we should be using. There's a lot of disagreement, which is both good and bad. So I think to kind of wrap up, I'd like to just mention one thing that is really a strong take home point for each of us. The one thing I really like about JNC eight is that it really relaxed our blood pressure goal for elderly patients greater than 60 years of age who are not high risk, and high risk would be people who have had MI stroke, African Americans, or anyone with multiple risk factors for cardiovascular disease. The reason I like that goal is those patients who are elderly are more inclined to have orthostasis, more inclined to have falls, and at some point there's a risk benefit that we have to think about. And that's why I really like that. Speaker 3 24:32 And I know I kind of picked up on the noticeable absence of the beta blockers, that if you're looking at JNC eight in terms of those first line options, it's not recommended that that's one of the first ones you go in. Speaker 2 24:43 What struck me with my interest in diabetes is the discrepancy between the diastolic blood pressure goal for patients who are diabetic. So we have JNC eight, who says, let's keep that less than 90. We have European Society of Hypertension who says, let's keep it less than 85 and we have the American Diabetes Association that says, let's keep it less than 80. I definitely would try to keep it as low as possible. I know we discussed about the five millimeters of mercury difference and how clinically relevant that is, but if your patient is tolerating and if you can keep that diastolic blood pressure less than 80, we might be able to see long term benefits. However, some of these groups have concluded that larger clinical trials involving the sub patient population are actually required to find out exactly if that five millimeters of mercury is going to make a clinical difference. Dr. Sean Kane 25:35 So that wraps up episode two of HelixTalk. If you haven't done so already, we'd love a positive review in the iTunes store so that other clinicians and pharmacy students and healthcare students in general are able to find the podcast. With that, I'll conclude I'm Dr. Kane, I'm Dr. Schuman, Speaker 2 25:51 and I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 25:57 Thank you for listening to this episode of HelixTalk. For more information about the show, please visit us at HelixTalk.com you.