Addressing Non-Adherence in Resistant Hypertension, with Swapnil Hiremath, MD, MPH

Swapnil Hiremath, MD, MPH

Credit: University of Ottawa

High blood pressure is a risk factor for stroke, heart failure, and other cardiovascular diseases. Lowering blood pressure by only 10 mmHg can significantly reduce the risk of these events. However, resistant hypertension poses even higher risks of cardiovascular complications, including stroke and heart failure, compared to other forms of hypertension. Further increasing risk, patients with resistant hypertension often have other comorbidities like obesity, diabetes, and kidney disease.

In an interview with HCPLive, Swapnil Hiremath, MD, MPH, discusses his National Kidney Foundation (NKF) 2024 Spring Clinical Meeting presentation regarding the epidemiology, diagnosis, and pathophysiology of resistant hypertension. Hiremath is a staff nephrologist at the Ottawa Hospital, an associate professor in the Faculty of Medicine at the University of Ottawa, and an associate scientist in the Clinical Epidemiology Program at the Ottawa Hospital Research Institute.

HCPLive: How does resistant hypertension differ from other types of hypertension?

Swapnil Hiremath, MD, MPH: As blood pressure goes up, the risk of subsequent stroke and heart failure almost linearly goes up. It also increases the risk of heart disease, like coronary artery disease, and is associated with a high risk of kidney disease.

If we look at the large meta-analyses, it clearly shows that reducing blood pressure by roughly 10 mmHg will reduce the risk of heart failure and stroke by about 30%, reduce the risk of coronary artery disease by anywhere from 15 to 20%, reduce all-cause mortality by about 10%, and reduce kidney failure by about 5%. If you look at resistant hypertension, though, these patients have an even higher risk—2 to 3 times higher.

Another factor to consider is if it this has to do with resistant hypertension or if has something to do with the patient themselves. For example, in as I alluded to earlier, people who have resistant hypertension tend to be older, and are more likely to be obese, have diabetes, and have kidney disease. Therefore, some providers argue that it's not the resistant hypertension, per se, but it's all these other things combined.

Additionally, we look at the pill burden in a patient with resistant hypertension. They’re sometimes taking medications for blood pressure, diabetes, kidney medications, and heart medications. And this makes it challenging from a quality-of-life perspective as well.

HCPLive: What evidence-based approaches or guidelines are commonly used in the management of resistant hypertension?

Hiremath: There are many aspects at play here. But even in the diagnosis, we examine adherence. If they patient is not taking the medication, then their blood pressure will not be controlled.

The issue is that hypertension is asymptomatic. If my back is hurting, I feel it. If I have a headache, I feel it. If I have angina, I feel it. So, if I am prescribed I a painkiller, I'm more likely to take it because it is giving me relief. Conversely, if you give a patient a blood pressure pill, they will take it and they don't feel any difference, they are more likely to stop taking it.

Either they don't feel any different or they have side effects. For example, amlodipine can cause swelling of the legs, an angiotensin-converting enzyme (ACE) inhibitor can cause cough, and beta blockers can increase fatigue. Therefore, they take the pills because they don't feel good.

We have performed a recent systematic review where we evaluated the rates of non-adherence in the resistant hypertension. Results showed the rates of non-adherence in resistant hypertension is anywhere from 15 to 45%.

One way to determine adherence is to ask the patient if they are taking their pills. Alternatively, you can check if they are filling prescriptions, but that’s kind of an indirect assessment. But providers can also do a direct assessment by checking the patient's blood or urine to see if they have the blood pressure pill in their system. That's the more precise way. With direct methods, the non-adherence rates are closer to 45%. I would argue that this is a more accurate way of measuring non-adherence.

How do you fix adherence? You sit down and talk to the patient and ask—in a non-judgmental way—why aren’t you taking your pills? Are they having any side effects? Is it a question of finances and coverage? It requires bedside manner and time—it's nothing fancy. I talk about this because this is the area where we have done some studies, with direct observed therapy and with our systematic review.

Once you do that, you have to figure out if they have a secondary cause of hypertension. Sometimes, as people age, they have high blood pressure due to genetic or familial reasons. One of the most common reasons is something called primary aldosteronism. Another one is when there is renal artery stenosis, which is the narrowing of the kidney arteries. There are also some drugs that can cause hypertension. Once we understand the reason, we can treat accordingly.

If it's primary aldosteronism, we use a drug called eplerenone and we dose it higher to get the blood pressure under control. In terms of what evidence we have, there is a trial that took patients who were treated with 3 drugs and they added either an alpha blocker (doxazosin), a beta blocker (bisoprolol), or an aldosterone antagonist (spironolactone). Results showed that spironolactone was most effective of the 3 verse Is placebo at reducing blood pressure.

A new player in this system is something called aprocitentan, which was approved in the US in March of 2024.

The other intervention is called renal denervation, which involves placing a catheter in the kidney arteries. There are 2 devices now available to lower hypertension.

Lastly, lifestyle changes are also useful. This includes reducing salt, increasing exercise, and weight loss.

This transcript was edited for clarity.