Management of Hypertension Using Olmesartan Alone Or in Combination

Cardiol Ther DOI 10.1007/s40119-017-0087-5 REVIEW Management of Hypertension Using Olmesartan Alone or in Combination Xiaoshen Zhang . Han Zhang . Yuxia Ma . Wenliang Che . Michael R. Hamblin Received: January 17, 2017 Ó The Author(s) 2017. This article is published with open access at Springerlink.com ABSTRACT incidence of hypertension. Concerning the high morbidity rate, setting up an updated Hypertension is one of the most significant and standard for hypertensive patients becomes consistent risk factors for many cardiovascular indispensable. According to the widely accepted diseases. The global prevalence of hypertension standard treatments for hypertension, these has dramatically increased over recent years. four basic principles should be taken into Life-style and genetic factors are generally con- account: low dosage; medication should pro- sidered to be primarily responsible for the vide long term-control; combination therapies are becoming common; personalized treatments are a newer approach. In most patients Enhanced content To view enhanced content for this article go to http://www.medengine.com/Redeem/ with hypertension, adequate control of BP can E097F0602FD64106. be achieved with combined therapy. Therefore, antihypertensive agents with complementary X. Zhang Á H. Zhang Á W. Che mechanisms are now recommended. In this Department of Cardiology, Shanghai Tenth Hospital review, we focus on the pharmacology, antihy- of Tongji University, Shanghai 200072, China pertensive efficacy, and adverse events (AEs) of X. Zhang olmesartan medoxomil, either alone or in Tongji University Cancer Institute, Tongji combination with other antihypertensive med- University School of Medicine, Shanghai 200092, ications. In conclusion, olmesartan medoxomil, China is an angiotensin II receptor blocker with an X. Zhang Á M. R. Hamblin (&) excellent efficacy in the reduction and stabi- Wellman Center for Photomedicine, Massachusetts lization of blood pressure. When combined General Hospital, Boston, MA 02114, USA with calcium channel blockers (CCBs) and e-mail: [email protected] diuretics, olmesartan medoxomil has a better Y. Ma effect on controlling BP and reducing AEs in Department of Internal Medicine, Cangzhou patients. Central Hospital, Cangzhou, China M. R. Hamblin Department of Dermatology, Harvard Medical Keywords: Angiotensin II receptor blockers; School, Boston, MA 02115, USA Blood pressure control; Combination drug treatment; Hypertension; Olmesartan M. R. Hamblin Harvard-MIT Division of Health Sciences and medoxomil Technology, Cambridge, MA 02139, USA Cardiol Ther INTRODUCTION with the Web of Science database. We selected influential randomized controlled trials in the Elevated blood pressure (BP) or hypertension field of hypertension research. In brief, we used has become one of the biggest single contribu- keywords such as olmesartan medoxomil tors to the global burden of disease and global monotherapy, or versus placebo or antihyper- mortality [1]. Hypertension causes the prema- tensive mono or combination therapy (trial ture death of over 9.4 million people worldwide duration at least 2 months). We included trials every year according to a 23-year-long systemic with drugs in adults, men, and non-pregnant analysis [2], and was responsible for approxi- women, with uncomplicated primary hyper- mately 10.4 million deaths in 2013 [3]. At the tension. Trials that had oral antihypertensive start of this century, it was estimated that nearly treatment with other angiotensin II receptor 972 million people worldwide had hyperten- blockers (ARBs), thiazide and thiazide-like sion, and it was predicted that the prevalence diuretics, calcium-channel blockers and would increase to over 1.56 billion by 2025 [4]. angiotensin-converting enzyme inhibitors The prevalence of hypertension among people (ACEI), as comparators, were eligible for inclu- aged 35–64 years in the US population is about sion. The contents of this article are based on 30% [5] and about 44% in European countries previously published studies and do not involve [6]. Moreover, hypertension continues to be any new studies of human or animal subjects undertreated [7, 8]. performed by any of the authors. The chief aim of the diagnosis and treatment of hypertension is to reduce death and mor- Discovery and Development bidity from cardiovascular disease [9] (see of Angiotensin Receptor Blockers Fig. 1). With optimum control of BP, it is pos- sible to prevent damage to many organ systems, and the treatment of underlying vascular dis- In 1898, the physiologist Robert Tigerstedt and eases is also an important management objec- his student, Per Bergman, working at the tive [10]. Achieving BP goals is a persistent Karolinska Institute in Stockholm, Sweden, challenge for hypertensive patients with low to injected rabbits with different kinds of kidney moderate risk, and reaching the figure of extracts, and found some caused a rise in blood 130/80 mmHg is a goal for high-risk patients, pressure [15]. They named the active principle such as those with diabetes, cardiovascular dis- ‘‘renin’’, and suggested it was a protein due to its ease, or renal disease [11]. The guidelines for the water-soluble, non-dialyzable, and heat-labile management of hypertension in the United properties. However, this remarkable discovery States, Europe, and Japan recommend consid- remained largely unexplored for almost 40 ering a combination of two drugs at the begin- years. In the 1930s, Harry Goldblatt conducted ning of treatment in high-risk patients or those experiments in which he constricted the blood with grades 2–3 hypertension [12–14]. There- flow to the kidneys in dogs, and found that fore, in clinical practice, two or more drugs with ischemia caused the kidneys to secrete a sub- different mechanisms of action are often cho- stance that caused vasoconstriction [16]. sen, and are considered to have a better pro- Although initially it was thought that this sub- spect to achieve satisfactory BP control. stance was the same as the renin discovered by Olmesartan is classified as an angiotensin Tigerstedt, attempts to purify it produced less receptor blocker (ARB). hypertensive activity, rather than the higher activity that was expected. In 1939, renin itself was found not to cause the rise in blood pres- METHODS sure, but rather was an enzyme that catalyzed the formation of another substance that actu- The literature searches were conducted in ally was responsible, initially named ‘‘an- March to April 2016 using PubMed and giotonin’’ and ‘‘hypertensin’’, and then the Excerpta Medica Database (EMBASE) together compromise name ‘‘angiotensin’’ was agreed. It Cardiol Ther Fig. 1 Major compliances of hypertension was found that renin acts on a serum a2-glob- system have been fully explained and presented ulin produced by the liver called angiotensino- in various review articles [18–21]. The major gen, which has 453 amino acids. The cleavage actions of Ang II include potent vasoconstric- product is a small peptide called angiotensin I tion effects of arterioles throughout the body; (Ang I), which has ten amino acids, and is decreased renal blood flow and increased tubu- cleaved by angiotensin-converting enzyme lar sodium reabsorption and water retention. (ACE) to form the eight-amino-acid angiotensin Ang II stimulates aldosterone and anti-diuretic II (Ang II, Asp-Arg-Val-Tyr-Ile-His-Pro-Phe). The hormone (ADH) secretion via the hypothala- most important receptor for Ang II is called mus pituitary-adrenal axis or the local system angiotensin II receptor type 1 or (AT1). (Fig. 2). With the introduction of ACE inhibi- In the 1970s, it was found that Ang II raised tors such as captopril in the late 1970s [22], it BP, and individuals with high levels of renin was confirmed that pharmaceuticals that reduce activity in plasma were at increased risk of car- Ang II activity could treat hypertension. diovascular disease [17]. The physiological The first attempts to develop useful Ang II functions of angiotensin II in the cardiovascular receptor (AT1) antagonists focused on Cardiol Ther Fig. 2 The mechanism of ACEI and ARB function in the RAS system angiotensin peptide analogs. Saralasin contains losartan was developed. In 1995 losartan was amino acid replacements by sarcosine, valine, approved for clinical use in the US, and since and alanine (Sar-Arg-Val-Tyr-Val-His-Pro-Ala) then seven additional ‘‘sartans’’ have been and is a partial agonist of the Ang II receptor approved (irbesartan, olmesartan, candesartan, [23]. valsartan, fimasartan, eprosartan, and azilsartan) In the early 1980s it was found that some [25]. Three of these sartans (olmesartan, azilsar- imidazole-5-acetic acid derivatives diminished tan, and candesartan) are usually administered as blood pressure rise after administration of Ang II ester prodrugs. The goal of using an ester prodrug in rats [24]. Two compounds, S-8307 and S-8308, is to improve on the ADME (absorption, distri- were later found to be promising non-peptide bution, metabolism, excretion) properties of the Ang II receptor antagonists. Structural modifica- drug. In the case of olmesartan and azilsartan the tions were made, and the orally active, potent, prodrug moiety is medoxomil (5-methyl-2-ox- and selective nonpeptide AT1 receptor blocker o-1,3-dioxol-4-yl)-methyl ester. olmesartan Cardiol Ther medoxomil is hydrolyzed by several esterase hypertension and preventing cardiovascular enzymes in the intestines releasing the active events emphasizes the necessity to select the drug,

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