In this episode, TRC Healthcare editor, Rachel Cole, PharmD, discusses the management of resistant hypertension.
This is an excerpt from our December 2024 Pharmacy Essential Updates continuing education webinar series.
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Transcript:
00:00:00 Rachel Cole
Now let’s get into the topic of managing resistant hypertension and refresh ourselves on how to best manage this. Often hard to treat condition.
00:00:10 Rachel Cole
So, our article on this topic talks about a newly FDA approved drug called aprocitentan or Tryvio. This dual endotheline antagonist is indicated for use in patients with blood pressure above goal despite being.
00:00:24 Rachel Cole
Optimally managed on other antihypertensives.
00:00:27 Rachel Cole
The mechanism may sound familiar as we have drugs of this class approved for pulmonary arterial hypertension like bosentin or Tracleer, but aprocitentan is the first approved in resistant hypertension before diving further into details on this single drug.
00:00:45 Rachel Cole
Let’s review the approach to treatment of resistant hypertension and we’ll talk about where Tryvio may fit in.
00:00:52 Rachel Cole
So resistant hypertension is defined as when patients need more than three drugs from different classes, including a diuretic to control blood pressure and the
00:01:03 Rachel Cole
blood pressure that patients will aim for can vary, but for many patients will be aiming for a blood pressure of less than 130 / 80.
00:01:12 Rachel Cole
So, we can recommend a stepwise approach to help manage the care of patients with resistant hypertension.
00:01:18 Rachel Cole
The first step is to evaluate factors that may be contributing to elevated blood pressure.
00:01:24 Rachel Cole
The next step is to optimize first line meds and then after that we can help individualize add-on medications.
00:01:31 Rachel Cole
So, let’s take a closer look at each of these steps and start by evaluating factors that may be contributing to resistant hypertension.
00:01:41 Rachel Cole
So, we want to start by looking at adherence and whether the patient’s taking the blood pressure medications they’re prescribed.
00:01:48 Rachel Cole
This is a concern in up to 80% of patients with resistant hypertension and can play a role in pseudo resistance where the patient may not truly need more than three meds to control blood pressure, but simply because they’re not taking the meds that they are prescribed.
00:02:04 Rachel Cole
So especially for us as pharmacists and technicians, we’re in a key role to help identify patients that may struggle with adherence and to ask how often do you miss a dose.
00:02:16 Rachel Cole
And then we can help tailor solutions to the patient, such as considering combination medications like lisinopril plus hydrochlorothiazide if the patient.
00:02:25 Rachel Cole
On the two separate meds to help simplify regimens, reduce pill count, and possibly reduce cost or co-pays, or ensuring patients know why it’s important to take blood pressure meds or recommending pill boxes or smartphone.
00:02:40 Rachel Cole
To help with doses.
00:02:42 Rachel Cole
Just as a couple examples.
00:02:44 Rachel Cole
But I know many pharmacists and technicians are masters at helping patients with adherence, so I’d love to hear other ideas. You may have too.
00:02:54 Rachel Cole
And then beyond adherence as the first step, there are a number of other factors that could contribute to resistant hypertension.
00:03:01 Rachel Cole
That we can be thinking about, for example, sleep apnea or obesity or chronic kidney disease or asking about dietary sodium intake, since it can be easy to overlook hidden sources of sodium and patients should usually aim for less than 2300 milligrams per day.
00:03:20 Rachel Cole
Also asking about smoking or excessive alcohol use, which can also contribute. And then we’re also in a good spot to look for medications or supplements that could increase blood pressure.
00:03:33 Rachel Cole
For example, we can ask patients about OTC or prescription insurance or decongestants.
00:03:40 Rachel Cole
Or we can look for stimulants such as for ADHD, or some antidepressants such as SNRIs.
00:03:47 Rachel Cole
We can also ask about supplements or other products that could affect blood pressure.
00:03:52 Rachel Cole
Such as bitter orange or black licorice, which patients may not expect could raise blood pressure.
00:03:58 Rachel Cole
So again, a good opportunity that’s unique to our role to help identify potential factors that could be contributing.
00:04:07 Rachel Cole
Also review how blood pressure is being measured, which can contribute to pseudo resistance.
00:04:12 Rachel Cole
If the blood pressure simply isn’t being measured properly.
00:04:16 Rachel Cole
So, we want to ensure proper preparation and technique.
00:04:20 Rachel Cole
For example, patients should rest quietly for at least 5 minutes before checking blood pressure.
00:04:26 Rachel Cole
They should sit in a chair with back supported, both feet on the floor and legs uncrossed, and their arms should be supported in resting at heart level.
00:04:35 Rachel Cole
We also want to ensure that they’re using proper equipment, including the correct cuffs.
00:04:40 Rachel Cole
For example, the bladder of the cuff should be at least 80% of the way around the patient’s arm.
00:04:46 Rachel Cole
And if patients are checking their blood pressure at home, we should recommend a properly sized arm monitor, which are the most accurate and discourage risk monitors except for a patient with severe obesity. If a patient does use a wrist monitor, emphasize that it must stay at heart level.
00:05:06 Rachel Cole
And of course, especially if patients have resistant hypertension, we want to reinforce exercise, a healthy diet, weight loss, smoking cessation and even things like good sleep habits and reducing stress can help too, since these factors could be contributing to high blood pressure.
00:05:26 Rachel Cole
Now the next step after ruling out other factors that could be contributing to resistant hypertension.
00:05:32 Rachel Cole
Is to help optimize the medications the patients already taking for their high blood pressure.
00:05:41 Rachel Cole
And there are 4 main classes of first line meds for hypertension, which are an ACE inhibitor such as lisinopril or an ARB such as Losartan, a calcium channel blocker like amlodipine.
00:05:56 Rachel Cole
Antithyro such as hydrochlorothiazide, these meds are all first line options for high blood pressure in general.
00:06:05 Rachel Cole
And we said that resistant hypertension is defined as needing more than three drugs, including a diuretic to control blood pressure.
00:06:13 Rachel Cole
So patients with resistant hypertension are likely going to be on an ACE inhibitor or an ARB calcium channel blocker and a thiazide.
00:06:24 Rachel Cole
And we can help ensure doses are optimized for those first line meds.
00:06:32 Rachel Cole
And there’s some other fine tuning we can consider, too. For example, we can suggest taking at least one non diuretic blood pressure Med at bedtime, especially if some blood pressure readings are high in the morning, because patients with resistant hypertension.
00:06:48 Rachel Cole
Often have blood pressure that doesn’t dip at night like it should.
00:06:52 Rachel Cole
In this relatively simple change can help the patient reach their blood pressure goal.
00:06:57 Rachel Cole
But again, consider adherence, since that’s the best predictor of blood pressure control.
00:07:03 Rachel Cole
And if introducing a bedtime dose is going to make it less convenient for patients or possibly affect them, taking the Med altogether, then this may not be the best option.
00:07:15 Rachel Cole
We can also help finetune the choice of Med if needed.
00:07:19 Rachel Cole
For example, if a patient’s on hydrochlorothiazide as their thiazide diuretic, we could suggest switching to chlorthalidone or indapamide might instead.
00:07:29 Rachel Cole
These are longer acting than hydrochlorothiazide, and they have more evidence of cardiovascular benefit.
00:07:37 Rachel Cole
But also.
00:07:37 Rachel Cole
The practicality of using one of these other thiazides.
00:07:41 Rachel Cole
For example, there aren’t many combo products available with Chlorthalidone and none within indapamide in the US.
00:07:49 Rachel Cole
So if adding another pill to the patient’s regimen may affect adherence.
00:07:54 Rachel Cole
That’s something to consider.
00:07:56 Rachel Cole
And then for patients with severe kidney disease with the creatinine clearance below, 30 mils per minute.
00:08:02 Rachel Cole
It’s preferable to switch to a loop diuretic like furosemide instead, since they’re likely to be more effective in these patients.
00:08:12 Rachel Cole
And then after we’ve helped optimize and fine tune those first line meds, the next step is to think about whether additional blood pressure lowering meds are needed and if so, which ones to use.
00:08:24 Rachel Cole
And this will be an individualized process.
00:08:29 Rachel Cole
For most patients in general, suggest adding spironolactone next.
00:08:33 Rachel Cole
It’s considered a first line add on because it’s more effective at lowering blood pressure in patients with resistant hypertension than alpha or beta blockers, and spironolactone has been studied for blood pressure control specifically in patients with resistant.
00:08:50 Rachel Cole
But we do want to advise monitoring kidney function and potassium, since spironolactone can raise potassium and may affect kidney function, especially in combination with the ACE inhibitor or ARB that the patient is already taking.
00:09:05 Rachel Cole
So adding spironolactone will usually bring patients to four medications total for lowering blood pressure.
00:09:15 Rachel Cole
And then after that, if we’re thinking about adding a fifth medication for resistant hypertension.
00:09:21 Rachel Cole
Then the choice is really going to come down to comorbidities, such as whether a patient could benefit from a Med for another reason and get a 2 for one benefit and side effects. And some of this can be more art than science.
00:09:37 Rachel Cole
Along with really individualizing, the choice for your patient.
00:09:41 Rachel Cole
For example, consider an alpha blocker like doxazosin. For patients with benign prostatic hyperplasia, or BPH since alpha blockers are often used to help improve urine flow in these patients, and may also help lower blood pressure.
00:09:58 Rachel Cole
But caution about dizziness and orthostatic hypotension or blood pressure that quickly drops when getting up from a sitting or lying down position.
00:10:07 Rachel Cole
Or you may lean toward a beta blocker like metoprolol. If a patient also needs a medication to help prevent migraines.
00:10:15 Rachel Cole
Since beta blockers are first line option for migraine prevention.
00:10:19 Rachel Cole
Or a beta blocker may be needed for patients who also have heart failure or after a heart attack.
00:10:26 Rachel Cole
But patients may need to monitor their heart rate or for some patients, consider carvedilol or labetalol, which are beta blockers that also block A1, since some evidence suggests that these might lower blood pressure a bit more and could be worth a try instead.
00:10:46 Rachel Cole
And then you might think about Clonidine or guanfacine to help lower blood pressure if other add-ons are not tolerated.
00:10:53 Rachel Cole
But again, we need to individualize and think about side effects.
00:10:57 Rachel Cole
For example, either of these could cause dry mouth and sedation.
00:11:01 Rachel Cole
And these meds need to be tapered. If they’re stopped to limit rebound hypertension.
00:11:06 Rachel Cole
And the.
00:11:07 Rachel Cole
Will be based on cost, dosing, side effects and other factors.
00:11:12 Rachel Cole
For example, Clonidine tablets require twice daily or three times daily dosing.
00:11:18 Rachel Cole
So a Clonidine patch may be more convenient than other tablets, but the patch can also cost more.
00:11:27 Rachel Cole
Now let’s circle back to aprocitentan or Tryvio the newly approved medication for use in combination with other antihypertensive medication when the patient is not reaching blood pressure goals.
00:11:40 Rachel Cole
This dual endotheline antagonist is only available through the trivial REMS program.
00:11:46 Rachel Cole
The embryo fetal toxicity, so prescribers and pharmacies must register with the program, which usually involves completing some training and also consider the possible cost to the patient before prescribing.
00:12:02 Rachel Cole
So evidence suggests the aprocitentan 12.5 Mg tablet once daily decreases systolic blood pressure by about 4mm of mercury versus placebo after four weeks in patients with resistant hypertension.
00:12:18 Rachel Cole
Not controlled when taking at least three antihypertensives and safety and efficacy past 48 weeks isn’t known.
00:12:28 Rachel Cole
Aprocitentan can be used with spironolactone.
00:12:31 Rachel Cole
It has no significant drug interaction and does not cause hyperkalemia. The most common adverse effects are fluid retention, anemia and hepatotoxicity.
00:12:42 Rachel Cole
So, monitoring hemoglobin and weight is recommended.
00:12:46 Rachel Cole
See our article for more details.
00:12:51 Rachel Cole
And finally, here are a few helpful pearls when dispensing aprocitentan after registering with the trivia REMS program.
00:13:00 Rachel Cole
Must be obtained for dispensing each prescription.
00:13:03 Rachel Cole
Keep patient profiles up to date with pregnancy status.
00:13:07 Rachel Cole
And the patient should be counseled to conduct a monthly pregnancy test and confirm that patients of childbearing age are using contraception prior to, during and a month after the last dose.
00:13:21 Rachel Cole
And make sure the pharmacy can get the medication before billing insurance and anticipate rejects, since it may only be supplied through specialty pharmacy.
00:13:32 Rachel Cole
And the tablets should be kept in the original container with the desiccant packet and the cap tightly closed.
00:13:40 Rachel Cole
So, on our website we have this frequently asked question called treatment of hypertension which has more details about some of those meds that aren’t used as often for high blood pressure such as hydralazine or minoxidil and sections on treatment of hypertension in patients with diabetes and resistant hypertension.
00:13:59 Rachel Cole
And other considerations with Med combos to avoid.