Hypertension, or high blood pressure, is an all-too-common condition that affects nearly half of adults in the U.S. It is also one of the world’s leading causes of mortality. Left untreated, hypertension can reduce cardiovascular outcomes and cause several complications, including heart disease, stroke, chronic kidney disease and early death. Heart disease and stroke, in particular, are among the leading causes of death in the U.S. Unfortunately, hypertension is also considered a “silent killer” because it usually shows no symptoms until it is too late.

Globally, only one in seven hypertensive patients achieves blood pressure control. That means approximately 86% of these hypertensive patients cannot control their blood pressure. That means, among the estimated 489 million patients who are treated with antihypertension medications, about 297 million patients are unable to control their blood pressure. The health risks posed by uncontrolled high blood pressure requires new, urgent treatment strategies.

Keep reading about existing treatment options for hypertension and CinCor’s efforts to change the game of hypertension treatment.

General Treatment for Hypertension

Blood pressure research has led to the development of several medications for managing hypertension. Many of these treatments target the renin-angiotensin-aldosterone system (RAAS). This endocrine system plays a vital role in regulating blood pressure. Specifically, the RAAS controls the production of aldosterone, a hormone that tells the body when to hold onto more salt and water. Holding onto more fluid (aldosterone’s genomic effect) causes a rise in blood pressure. Excess aldosterone can also lead to increased inflammation, fibrosis, oxidative stress and cardiac muscle cell hypertrophy (aldosterone’s non-genomic effects).

Hypertension medications that target the RAAS affect the different enzymes and receptors responsible for the RAAS processes. The RAAS system has three key components: renin, angiotensin and aldosterone. Medications exist to target these components to prevent the RAAS from affecting blood pressure causing it to rise.


When beginning treatment, patients are usually prescribed medication from one of four different types of antihypertension medications:

  • Angiotensin-converting enzyme (ACE) inhibitors, which inhibit the RAAS axis by blocking the action of ACE in the lungs
  • Angiotensin receptor blockers (ARBs), which block the effects of angiotensin II at the level of the angiotensin receptor
  • Calcium channel blockers, which slow cardiac contractions by preventing calcium from entering the cells of the heart and arteries
  • Thiazide diuretics, which increase fluid excretion from the kidney by blocking the reabsorption of sodium

Other hypertension treatments include alpha-beta and beta blockers, which target the heart rate to help lower blood pressure. Other common treatments include mineralocorticoid receptor antagonists (MRAs) which block aldosterone from attaching to its receptor. Excess aldosterone plays a direct role in the development of hypertension, making it a prime target for high blood pressure medications.

Generally, hypertension medications are prescribed based on the underlying causes of a patient’s hypertension. Patients with essential hypertension (high blood pressure caused by lifestyle factors or diseases with no identifiable cause) and secondary hypertension (high blood pressure caused by an underlying health condition with a clear cause) may require different treatment.

When a patient’s multiple medications fail to lower their blood pressure, it can lead to the diagnosis of treatment-resistant and uncontrolled hypertension. Treatment-resistant hypertension, in particular, affects an estimated 17% to 20% of the total hypertension population in the U.S. Given the health risks associated with long-term, untreated hypertension, medication failure is a pressing issue.

Despite these challenges and ongoing developments in blood pressure research, there have not been any new classes of medications for hypertension in the past decade. The U.S. Food and Drug Administration (FDA), for example, has not approved new hypertension medications in the last few years.

What’s the Difference Between Treatment-Resistant and Uncontrolled Hypertension?

Uncontrolled hypertension and treatment-resistant hypertension do share some similarities; mainly, they are both characterized by a lack of response to blood pressure treatment. However, differences include the number of treatments patients are on (and their effectiveness), overall blood pressure levels and how the condition is diagnosed.

Number of treatmentsPatients with treatment-resistant hypertension cannot control their hypertension despite taking three or more hypertension medications regularly. Additionally, some research suggests that people with controlled hypertension on four or more medications are considered treatment-resistant.


Conversely, patients with uncontrolled hypertension may not even know they have the condition. In many cases, they are not taking any medication, are not taking their hypertension medications regularly or are not taking the right dosage or type of medication. If they are taking medication, patients may only be taking one or two treatments. Uncontrolled hypertension includes patients with resistant hypertension.

Patients taking five medications at the maximum recommended dosage without a significant decrease in blood pressure are considered to have refractory hypertension.

Blood pressure levelsGenerally, hypertension is diagnosed in people with a blood pressure higher than 130/80 mmHg. Treatment-resistant hypertension is diagnosed in people taking at least three medications and still have a blood pressure measurement above their goal level of 130/80 mmHg. Patients may also be diagnosed with treatment-resistant hypertension if their blood pressure is controlled only by taking four or more medications. People with uncontrolled hypertension often present with blood pressure levels of at least 140/90 mmHg.

Measuring ambulatory blood pressure is an ideal way to collect accurate blood pressure measurements for both treatment resistant and uncontrolled hypertension. Often, hypertensive patients taking medication show high blood pressure levels in a clinic, but healthier levels as they go about their daily life. This phenomenon is known as white coat hypertension, resulting in apparent treatment resistant hypertension in a clinic. Referring to the coat a doctor wears, white coat hypertension is often caused by the anxiety of being in a doctor’s office.

DiagnosisUncontrolled hypertension is usually diagnosed in someone taking at least one medication for hypertension but has blood pressure of around 140/90 mmHg. On the other hand, treatment-resistant hypertension is usually diagnosed in people taking three or more medications, but blood pressure is still below target levels (usually higher than 130/80 mmHg).

People with treatment-resistant hypertension may also have to undergo additional tests that could help confirm if there is a secondary cause of their treatment resistance. Secondary hypertension is a common cause of treatment-resistant hypertension. These secondary causes are usually an underlying medical condition, such as renal artery stenosis, obstructive sleep apnea or primary aldosteronism. Some studies have shown that oral contraceptives may also impact blood pressure levels in women.

What are Common Treatments for Treatment-Resistant Hypertension?

The current standard of care for treatment-resistant hypertension is introducing an MRA as an additional hypertension medication to a patient’s regimen. Spironolactone and eplerenone are the most common MRA medications added at this stage in a patient’s treatment journey. However, most patients who present with treatment-resistant hypertension are already taking three other medications (including a thiazide diuretic) to block aldosterone production.

MRAs, however, have significant limitations, including increased circulating aldosterone. In addition, MRAs may need to be taken at higher dose levels to achieve adequate treatment goals, which can cause dangerously high levels of potassium, especially in combination with other drugs that work in RAAS pathway or in patients with compromised renal functions (like chronic kidney disease patients). MRAs can also cause breast tenderness and enlargement in men, decreased libido in men and menstrual irregularities in women.

What are Common Treatments for Uncontrolled Hypertension?

Treatment involves introducing an additional medication to a patient’s treatment regimen. The specific type of medication added will depend on which other medications a patient is already taking.

A doctor may also order tests to look for other conditions causing hypertension. These tests can help identify more targeted ways to treat a patient’s hypertension.

Hypertension Treatment Challenges and Potential New Options

Many standard medications are effective hypertension treatments but, for various reasons, do not have the same effects on all patients. For example, some patients taking ACE inhibitors and ARBs commonly experience brief periods of aldosterone reduction, followed by increased aldosterone production (called aldosterone breakthrough). Unfortunately, these medications may be less effective at inhibiting aldosterone production than those that directly target aldosterone synthesis. As a result, millions of hypertensive patients live with uncontrolled or treatment-resistant hypertension because of ineffective treatment.

Amid the challenges of treating hypertension, CinCor is working to change the game through the development of baxdrostat. This highly selective aldosterone synthase inhibitor is being investigated for the treatment of patients with treatment-resistant hypertension, hypertension caused by primary aldosteronism or patients with hypertension and chronic kidney disease.

CinCor believes that an aldosterone synthase inhibitor may help manage aldosterone levels more effectively than medications inhibiting aldosterone production alone, and that high selectivity for the inhibition of aldosterone without meaningfully effecting cortisol is a must.

Based on its unique mechanism of action, CinCor believes that baxdrostat has the potential to achieve the goal of reducing the deleterious genomic and non-genomic effects of aldosterone, regardless of whether aldosterone production is RAAS-mediated or renin-independent, while having minimal effects on plasma potassium, sodium and cortisol levels.

CinCor is currently conducting trials of baxdrostat for patients with treatment-resistant hypertension (the BrigHtn study), for patients with uncontrolled hypertension (the HALO study), and patients with uncontrolled hypertension and chronic kidney disease (FigHtn-CKD study). To learn more about the clinical trials CinCor is conducting for baxdrostat, check out our clinical trials page.