An increase in blood pressure (BP) – defined as systemic hypertension – is considered a clinical disorder when this change threatens biological functions. Hypertension has been shown to affect the circulatory, pulmonary, and urinary systems amongst others.1

Hypertension accounts for more than 9.3 million deaths per year, surpassing tobacco with around 8 million deaths per year.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Hypertension is a major risk factor for CVD and is present in 69% of patients with a first myocardial infarction, in 77% of patients with a first stroke, in 74% of patients with chronic heart failure, and in 60% of patients with peripheral arterial disease.1,2

The International Society of Hypertension (ISH) defines hypertension as Systolic blood pressure (SBP) in the office or clinic of ≥140mmHg and/or diastolic blood pressure (DBP) of ≥90mmHg following repeated examination.3

The 2020 ISH Practice Guidelines, recommends lifestyle modifications as the first step in the treatment of hypertension. However, the majority of patients with hypertension will eventually require pharmacotherapy. Studies show that mortality risk doubles with increases in SBP from 120mmHg to 140mmHg and from 140mmHg to 160mmHg in all age groups.1,3

The guideline recommends the use of angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs), as well and dihydropyridine calcium channel blockers as initial pharmacotherapy.3

Milestone in the history of hypertension treatment

Dézsi describes the development of ARBs in the 1990s as a ‘milestone in the history of hypertension treatment’, adding to the range of possibilities for personalised therapy, especially for patients who cannot tolerate ACE-Is.4

ARBs have shown excellent efficacy, they have no negative metabolic effects and they cause no accumulation of bradykinin. They also have an ability to activate the angiotensin II type 2 receptors, which causes vasodilatation in the small vessels and may lead to additional cardiac and renal protection.4

Additive BP-lowering effects have been demonstrated when ARBs are combined with thiazide diuretics or dihydropyridine calcium channel blockers, augmenting hypertension control. Furthermore, ARBs have proven mortality and morbidity effects in heart failure and chronic renal disease, particularly when associated with type 2 diabetes (T2DM).5

Apart from heart failure and renal disease, compelling indications for the use of ARBs include post-myocardial infarction, diabetic nephropathy, proteinuria/microalbuminuria, left ventricular hypertrophy, atrial fibrillation, metabolic syndrome and obesity, renal dysfunction, chronic stable angina, and ACE-I induced cough.4,6

BP variability

Numerous studies have demonstrated that 24-hour ambulatory BP monitoring (ABPM) should be an integral part of hypertension care. ABPM plays a crucial role in quantifying the degree of BP variability over 24 hours. BP variability over this period has been shown to be a significant and independent risk factor for CV morbidity and mortality.1,7

The most commonly utilised data for clinical purposes is 24-hour average BP, daytime BP, night-time BP, and nocturnal dipping patterns. The thresholds for normality depend on the measurement used and on the current definition of normal BP.1

In most people, BP rises rapidly after waking up in the morning and at the start of daily activity. BP has two main peaks – in the morning and afternoon. Generally, a 24-hour mean BP of 125/75mmHg or less, a daytime BP of 130/80mmHg or less, or a night-time BP of 110/65mmHg or less with a nocturnal dipping of 10% to 20%, are considered normal values for ABPM.1,8

Monitoring of morning BP rise is an important aspect in the treatment of hypertension and prevention of CV complications. morning BP rise is associated with an increased risk (by 40%) of CV and cerebrovascular problems, and sudden death.8

Studies indicate adverse effects of morning hypertension such as subclinical target organ damage, namely left ventricular myocardial mass increase, left atrial dilatation, and thickening of the intima-media carotid artery complex.8

Uncontrolled morning BP is a sign of inadequate antihypertensive therapy, insufficient dosage of drugs, or use of short-acting drugs, and is detected in the majority of patients (from 17% to 60%) treated for hypertension, according to various studies.8

There are currently eight ARBs on the market. Telmisartan has the longest half-life (24-hours), followed by olmesartan (12-14 hours), irbesartan (11–15 hours), eprosartan (5-9 hours), valsartan (6 hours) and losartan (2 hours).5

Three of the eight ARBs (candesartan cilexetil, olmesartan medoxomil, azilsartan medoxomil) are prodrugs and require activation in the gastrointestinal tract and liver to their active forms (candesartan, olmesartan, and azilsartan, respectively). The ARBs eprosartan, irbesartan, telmisartan, and valsartan are not prodrugs and therefore do not require metabolic activation.5

The oral absorption of irbesartan is rapid and complete with an average absolute bioavailability of 60% to 80% (the highest among the ARBs with telmisartan in second place with 43%). Irbesartan has a faster onset of action (1.3–3 hours) compared to candesartan (2-5 hours), and valsartan (2-4 hours).5

ARB efficacy and safety

Irbesartan has demonstrated high efficacy in lowering BP – comparable with ACE-I and superior to other ARBs. Irbesartan 300mg/day has been found to have superior antihypertensive effects compared to losartan 100mg/day, while irbesartan 150mg/day demonstrated greater BP reductions than valsartan 80mg/day.5,9,10

The tolerability profiles of ARBs are similar to placebo and superior to ACE-Is. ACE-Is have been shown to increase the risk of cough two- to three-fold over placebo and may cause up to 0.1%-0.2% rates of angioedema, which can be life-threatening in some cases.5

Cough and angioedema most likely result from the accumulation of bradykinin and substance P, which are both degraded by ACE, and they recur with the reintroduction of ACE-Is inhibitor or use of another ACE-I.5

A number of studies evaluating the comparative efficacy and safety ARBs reported low discontinuation rates in irbesartan. One study reported a 1.2% discontinuation rate in the irbesartan group due to adverse events including fatigue, malaise, and cough, while others reported a 1.4%, 2.1% and 0.5% rate, which is comparable to placebo (3.4%), and the lower dose of irbesartan (150mg) (2.1%).9,10,11

Irbesartan in diabetes and kidney disease

The prevalence of chronic kidney disease (CKD) is estimated to be around 22%. Patients with uncontrolled BP, overweight/obesity, dyslipidaemia, and diabetes have the highest risk (43.3%, 33.7%, 27.3% and 28.2% respectively). Age was an independent risk factor.13

Irbesartan is indicated for the treatment of renal disease in adult patients with hypertension and type 2 diabetes mellitus (T2DM). In the Irbesartan Diabetic Nephropathy Trial involving hypertensive patients with diabetic nephropathy, the irbesartan arm had a 37% lower risk of doubling the serum creatinine versus the amlodipine arm and 33% lower than the placebo group. Development of end-stage renal disease was nominally lower with irbesartan use compared with amlodipine use and placebo.8

The Irbesartan in Patients with T2D and Microalbuminuria trial showed that over a period of 12 months, patients with hypertension, T2DM and microalbuminuria, fewer participants progressed to macroalbuminuria when treated with irbesartan compared to placebo with hazard ratios of 0.30 in the irbesartan 300mg/day and 0.61 in the irbesartan 150mg/day.12

In the case of chronic kidney disease, renal excretion of serum uric acid (SUA) is decreased, resulting in hyperuricemia. Several observations indicate that hyperuricemia is an independent risk factor for CVD. About 25% of patients with hypertension have raised SUA levels, which increase if loop or thiazide diuretics are added to therapy.7

Irbesartan reduced BP significantly after one, six and 12 months’ treatment. No participants showed significant change in the estimated glomerular filtration rate from baseline level throughout the period. The multiple logistic regression analysis revealed that SUA baseline significantly influenced SUA decline after six to 12 months. In patients whose SUA baseline was ≥5.9mg/dL, the SUA was significantly decreased from 6.6±0.16 mg/dL to 6.2±0.16mg/dL, after 12 months’ irbesartan treatment. In the SUA baseline <5.9mg/dL group, the SUA did not show significant change over the monitoring period.7

It has also been shown to be more cost-effective than standard therapy including beta-blockers, diuretics and non-dihydropyridine calcium channel blockers at all stages of kidney disease. Based on efficacy data from the Irbesartan Diabetic Nephropathy Trial and Reduction of Endpoints in non-insulin dependant DM) with the Angiotensin II Antagonist Losartan Study, it has also demonstrated cost savings over losartan in late-stage renal disease.6


ACE-1 and ARBs are recommended by guidelines as first-line pharmacotherapy for the treatment of hypertension. Apart from superior BP lowering and few side effects, irbesartan also offers renal protection to hypertensive patients at risk of renal disease. 


  1. Pena-Hernandex C, Nugent K and Tuncel M. Twenty-Four-Hour Ambulatory Blood Pressure Monitoring. J Prim Care Community Health, 2020.
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  3. Unger T, Borghi C, Charchar F et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension, 2020.
  4. Dezsi CA. The Different Therapeutic Choices with ARBs. Which One to Give? When? Why? Am J Cardiovasc Drugs, 2016.
  5. Abraham HMA, White CM and White WB. the Angiotensin Receptor Blockers in the Management of Hypertension and Other Cardiovascular Diseases. Drug Saf, 2015.
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  12. Parving HH et al. Irbesartan in Patients with T2D and Microalbuminuria. N Eng J Med, 2001.
  13. Bahrey D, Gebremedhn G, Mariye T et al. Prevalence and associated factors of chronic kidney disease among adult hypertensive patients in Tigray teaching hospitals: a cross-sectional study. BMC Research Notes, 2019.