About treatment-resistant hypertension

Treatment-resistant hypertension is blood pressure (BP) that remains above goal despite compliance with maximum tolerated or in-label doses of at least 3 antihypertensive medications from different classes, preferably including a diuretic.1,2 Patients who require 4 or more antihypertensive medications to achieve BP control are also considered treatment resistant, according to some sources.1

There is a critical need to find more effective treatment options to address this global health challenge. Power Over Pressure is aimed at eliminating treatment-resistant hypertension by engaging, educating, and empowering patients and healthcare professionals to better understand, treat and control treatment-resistant hypertension.

Goal BP should take patient-specific factors into consideration. In general, BP targets are:

  • <140/90 mm Hg for the overall population
  • <130/80 for patients with diabetes mellitus or chronic kidney disease2,3

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The magnitude of the problem is expected to increase

Hypertension is a major worldwide public health challenge (Figure 1).

  • In 2000, the global prevalence of hypertension was estimated at 972 million, or 26% of the adult population, and this number is expected to rise
  • By 2025, the prevalence of hypertension is expected to be 1.56 billion worldwide (29% of the adult population)4
  • Hypertension is the single most common contributor to death worldwide, being a root cause of stroke, congestive heart failure, and kidney disease5
  • While the exact prevalence of treatment-resistant hypertension is unknown, studies estimate that 34%-52% of patients being treated for hypertension may fail to reach goal BP1
POP - worldwide_prevalence

Uncontrolled hypertension is not necessarily treatment-resistant hypertension

The definition of uncontrolled hypertension is simply that a patient’s BP is above target, regardless of the reason. Hence, treatment-resistant hypertension is a subset of uncontrolled hypertension – in other words, patients with treatment-resistant hypertension are those with uncontrolled hypertension who are actively, but unsuccessfully, being treated with 3 or more antihypertensive medications from different classes. Even then, some patients with non-optimal blood pressure control might not be truly treatment-resistant. For example, the blood pressure measurement itself may be erroneously high, leading to a false-positive diagnosis.1

Many patients have essential, or primary, hypertension, meaning that their elevated BP does not stem from a known cause.6 In contrast, secondary hypertension should be carefully considered in patients with treatment-resistant hypertension as it may be reversible. Secondary causes of hypertension include1,7:

  • Primary aldosteronism
  • Chronic kidney disease
  • Renal artery stenosis
  • Hyperthyroidism or hypothyroidism
  • Pheochromocytoma
  • Cushing’s syndrome
  • Aortic coarctation

Who is at risk for treatment-resistant hypertension?

Certain patient characteristics have been found to be predictors of treatment-resistant hypertension. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a seminal US hypertension outcomes study that included a large number of diverse participants (33,000): 47% female, 35% African-American, 19% Hispanic, and 36% with diabetes. In an analysis of ALLHAT study data, older age, higher baseline systolic blood pressure, left ventricular hypertrophy, and obesity all predicted treatment resistance. Other predictors included a diagnosis of diabetes mellitus, African-American race, and female sex. Overall, the strongest predictor of treatment resistance was having chronic kidney disease as defined by a serum creatinine of ≥1.5 mg/dL.1

Treatment-resistant hypertension is associated with significant morbidities

Hypertensive cardiovascular disease occurs in stages (Figure 2). It begins asymptomatically in the prehypertension and established hypertension stages. Progressive subtle target-organ damage leads to the oligosymptomatic stage, including:

  • Nephrosclerosis
  • Left-ventricular hypertrophy
  • Retinopathy

In the symptomatic stage, patients with hypertensive cardiovascular disease might have:

  • Chronic renal failure
  • Atrial fibrillation
  • BP dysfunction
  • Coronary artery disease
  • Dementia

Ultimately, patients progress to polysymptomatic or end-stage disease, which is characterized by the following and leads to death8:

  • End-stage renal disease
  • Ventricular tachycardia/fibrillation
  • Congestive heart failure
  • Myocardial infarction
  • Stroke
Figure 2: Consequences of hypertension
POP - Phases

Adapted from: Messerli FH, et al. Lancet. 2007;370:591-603.

Treatment-resistant hypertension is associated with significantly increased risk of death

Compared with patients with controlled hypertension, patients with treatment-resistant hypertension have a substantially increased risk of cardiovascular events such as9:

  • Stroke
  • Transient ischemic attacks
  • Myocardial infarction
  • Heart failure
  • Renal failure
  • New-onset diabetes
  • Death

In a study of 340 patients with controlled hypertension and 130 with treatment-resistant hypertension, those with treatment-resistant hypertension showed significantly decreased event-free survival over 140 months of follow-up (Figure 3).10

Figure 3: Event-free survival in subjects with controlled or treatment-resistant hypertension
POP - Figure 3: Event-free survival

Adapted from Pierdomenico S, et al. Am J Hypertens. 2005;18:1422-1428.

Even a small reduction in BP can result in a significant reduction in cardiovascular risk

Importantly, even a small reduction in BP can result in a significant reduction in cardiovascular risk (Figure 4).

  • Data from a meta-analysis of individual data for 1 million adults (40-89 years; 70% Europe, 20% North America or Australia, 10% Japan or China) from 61 prospective observational studies of BP and mortality demonstrated that even a small 2 mm Hg reduction in mean office SBP was associated with a large absolute reduction in the risk of premature death and disabling stroke
  • In middle age, a 2 mm Hg decrease in mean SBP could lead to approximately a 10% lower risk of death from stroke and a 7% lower risk of death from ischemic heart disease or other vascular cause11
POP - reduction_chart

The economic burden of hypertension is staggering

  • The cost of hypertension was estimated at $370 billion worldwide in 2001
    • This represents 10% of total global healthcare costs12
  • Cardiovascular disease (including coronary heart disease, heart failure, myocardial infarction, and stroke) is the most frequent reason for hospitalization in the United States
    • Hypertension is the leading comorbidity associated with these hospitalizations
  • Poor control of hypertension for any reason has been associated with higher drug costs and more physician visits13

Treating hypertension is cost-effective

Hypertension is the most common risk factor for the development of cardiovascular disease, and is associated with subsequent adverse cardiovascular events. The cost of diagnosing and treating cardiovascular complications remains significant, but these complications can be preventable if hypertension is controlled.2

Several studies show that treatment of hypertension is cost-effective in high-risk patients because the reduction in incidence of cardiovascular disease and associated complications largely offsets the cost of treatment. Some experts have suggested that the overall benefit is even greater than that indicated by the events saved per year of hypertension treatment, or number needed to treat (NNT) (Figure 5). This is because the difference in incidence of events between treated and control groups may increase over time, and because the seemingly smaller benefit in younger, low-risk patients may translate into a more substantial number of added life-years.2

Figure 5: Number Needed to Treat for Hypertension and Related Disorders
POP - Number_to_treat

Outcomes used to calculate NNT: hypertension—overall prevention of a cardiovascular event for 5 years; myocardial infarction—prevention of one vascular death at 5 weeks; peripheral artery disease—prevention of critical cardiac events at one year compared with placebo.

Adapted from McQuay H, Moore RA. Ann Intern Med. 1997;126:712-720.

Treatment-resistant hypertension exerts an emotional toll

A recent survey of more than 4,500 patients with uncontrolled hypertension, conducted by Medtronic and Harris Interactive, underscored the emotional burden of treatment-resistant hypertension. Eighty percent of patients with treatment-resistant hypertension reported that their high BP has had a negative impact on their overall peace of mind. Eighty-seven percent reported a negative impact on their overall health. Additionally, 75% of patients reported worrying about the number of medications they take, while 84% of respondents wished it were easier to manage their hypertension (Figure 6).14

Figure 6: Patients with Treatment-Resistant Hypertension Want More Options
POP - median_pills

HB = High blood pressure

“Power Over Pressure Emotional Impact of Treatment-Resistant Hypertension,” Medtronic/Harris Interactive, 11/2011.


  1. Calhoun DA, Jones D, Textor S, et al. Circulation. 2008;117:e510-e526.
  2. Mancia G, De Backer G, Dominiczak A, et al. Eur Heart J. 2007;28:1462-1536.
  3. Chobanian AV, Bakris GL, Black HR, et al. Hypertension. 2003;42:1206-1252.
  4. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Lancet. 2005;365:217-223.
  5. World Health Organization. World Health Report 2002: Reducing Risks, Promoting Healthy Life. Geneva, Switzerland.
  6. Cowley AW, Jr. Nat Rev Genet. 2006;7:829-840.
  7. Kaplan NM, Victor R. Kaplan's Clinical Hypertension. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2010.
  8. Messerli FH, Williams B, Ritz E. Lancet. 2007;370:591-603.
  9. Doumas M, et al. Int J Hypertens. 2011;doi:10.4061/2011/318549.
  10. Pierdomenico SD, Lapenna D, Bucci A, et al. Am J Hypertens. 2005;18:1422-1428.
  11. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Lancet. 2002;360:1903-1913.
  12. Gaziano TA, Bitton A, Anand S, Weinstein MC. J Hypertens. 2009;27:1472-1477.
  13. Elliott WJ. J Clin Hypertens (Greenwich). 2003;5:3-13.
  14. Power Over Pressure Emotional Impact of Treatment-Resistant Hypertension. 2011. Medtronic/Harris Interactive.

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