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Coversyl Review Article

 

Sustained elevation of systolic and diastolic blood pressure
Coversyl is an ACE inhibitor. Angiotensin II is very potent chemical that causes the muscles surrounding the blood vessels to contract and so doing it narrows the blood vessels. Consequently, when blood vessels get narrowed, it increases your blood pressure and turns down to Hypertension. Angiotensin II is formed from angiotensin I in the blood by the enzyme, angiotensin converting enzyme (ACE). ACE inhibitors are medications that slow (inhibit) the activity of the enzyme, which decreases the production of angiotensin II. As a result, when blood vessels enlarge or dilate, the blood pressure is reduced. At this stage, it makes easier for the heart to pump blood normally and in contrast it prevents from heart failure diseases. Thus, the rampant and raging of kidney disease due to high blood pressure or diabetes is slowed and getting prevented.

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Hypertension is considered dangerous because of its possible complications. There is an established relationship between blood pressure levels and morbidity and mortality. The higher the blood pressure, the higher the risk for other diseases which includes cardiovascular diseases (heart failure, heart attack, stroke) and kidney diseases (JNC 7, Merck Manual). Hypertension is is also dangerous mainly because many people are not aware that they have it. Symptoms do not appear at an early stage. In the United States only 70% of the people that actually suffer from hypertension are aware that they have this condition, 59% are on treatment, and 34% are controlled (Merck Manual).

 The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Referrence: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Hypertension is classified into two types according to its etiology. Primary hypertension or essential hypertension is the hypertension condition which has no identifiable cause. That means that no single factor is identified to be responsible for this condition. On the other hand, secondary hypertension is caused by other medical conditions such as renal diseases, alcohol or other diseases. About 85-95% of the hypertensive cases are actually primary hypertension cases.

Several risk factors have been identified for hypertension which include race (African Americans have a higher risk), obesity, stress, lifestyle (salt and alcohol intake, smoking), family history, and diabetes (PubMed Health).

Hypertension does not show in its early stages. Consequently, people can develop the different complications without even knowing it. It is thus important to have your blood pressure checked every once in a while especially if you any of the risk factors are present in your life.

Treatment

The purpose of the hypertension treatment which was set by the JNC 7th report is to reduce cardiovascular morbidity and mortality. This is achieved by reducing the blood pressure to a normal level. But if that is not possible, blodd presseure should reduced to the lowest possible value so that the patient could lead a normal, functioning life. Lifestyle modification is recommended for all stages of hypertension. It is recommended even for non hypertensive individuals in order to reduce the risk of hypertension. Lifestyle modifications include weight loss, Dietary Approaches to Stop Hypertension (DASH), salt restriction (sodium is a big factor in hypertension), physical activity, and alcohol consumption control. When lifestyle modifications do not sufficiently control blood pressure levels it is advisable that patients go for pharmacological therapy.

Several drugs have been in use to reduce high blood pressure. Drug classes include diuretics, beta blockers, calcium channel blockers, ACE inhibitors and Angiotensin II receptor blockers. Each have a specific advantage over the other. Let us focus on one drug class, the ACE inihibitors.

ACE inhibitors

ACE Inhibitors are drugs that act on the ACE or the angiotensin converting enzyme involved in the renin-angiotensin-aldosterone system (RAAS). It inhibits the activity of ACE thus stopping the conversion of angiotensin I to angiotensin II. This inhibition ultimately results in vasodilation. Figure 3 summarizes the RAAS process.
Fig 3. The Renin-Angiotensin-Aldosterone System Retrieved from Wikipedia

Several drugs belonging to this class are available on the market: Benazepril, Captopril, Enalapril, Fosinopril, Lisinopril, Moexipril, Quinapril, Perindopril, Ramipril, and Trandolapril. Among these drugs, Coversyl (Perindopril) is considered as a first choice of ACE inhibitor. It has been well studied for its efficacy in the treatment and prevention of hypertension, separately or in combination with other medication. Here are some of the studies that support this statement.

Perindopril

Coversyl is a long acting ACE inhibitor that is taken once daily.

Coversyl (Perindopril) has been proven to be effective in many studies. In a study by Cleland and colleagues (2006), they found that perindopril alone is effective in improving the symptoms and reducing the number of hospitalizations for elderly patients with chronic heart failure. In another study by Dykeret al.(2006), it was found that Perindopril is effective in reducing blood pressure without reducing the cerebral blood flow. Thus, Perindopril is effective for patients with recent cerebral ischemic stroke. This findings were further consolidated by the results of a study performed by Chapman et al. (2003). In their study called the PROGRESS Trial, they found that Perindopril was efficient in reducing the number of strokes irrespective of the type.

The European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease, or EUROPA study, is a study where Perindopril was assessed for its effectiveness in preventive therapy. Perindopril was proven to be effective in reducing the cardiovascular risk of patients with stable coronary heart disease and no heart failure. This study has been presented in the JNC 7threport which has prompted the drug to be recommended in order to prevent cardiovascular events.

Perindopril in Combination

Coversyl (Perindopril) has been frequently recommnded in mixed therapy because of its improved efficiency. In a study conducted by Asmar, London and O’Rourke (2001), the results showed that a very low dose of Perindopril and Indapamide combined together has a greater efficacy than a beta blocker alone in terms of normalizing blood pressure, pulse pressure and arterial function.

Perindopril with Indapamide therapy has been proven effective in various studies. The PROGRESS collaborative group (2003) has found the combination’s effectiveness in lowering the risks of dementia and cognitive decline. The group recommended the combination to be considered for patients with cerebrovascular diseases. In another study led by Patel et al. it is stated that this combination is effective in reducing the vascular complications in patients with type 2 diabetes and hypertension.

In another study called Anglo-Scandinavian Cardiac Outcomes Trial, Perindopril and Amlodipine were assessed for their efficacy as a combination therapy. The results of the study showed that the combination was very effective.

Coversyl and Cancer
In a study carryed out by Yoshiji et al. (2000), they found that Perindopril may be used as an anti cancer agent. The study compared different ACE inhibitors and found that Perindopril is the most potent in inhibiting tumor development. In 2003, Yoshiji led another study to further elucidate this possibility. Perindopilat, the active form of perindopril was found to significantly suppress the vascular endothelial growth factor (VEGF) which induces tumor growth.
Dosage Forms

Because of the proven effectiveness of Perindopril and Indapamide, the combination is available as Coversyl Plus.

Bibliography:

ASMAR, R.G., LONDON, G.M., & O’ROURKE, M.E. 2001. Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol. Retrieved from http://hyper.ahajournals.org/content/38/4/922.short
BROOKES, L. (2003). ASCOT: Anglo-Scandinavian cardiac outcomes trial: results from the lipid-lowering arm. Retrieved from http://www.medscape.com/viewarticle/513974
CHAPMAN, N., HUXLEY, R., ANDERSON, C., et.al. 2003. Effects of a perindopril-based blood pressure–lowering regimen on the risk of recurrent stroke according to stroke subtype and medical history – the PROGRESS TRIAL. Retrieved from http://stroke.ahajournals.org/content/35/1/116.abstract
CLELAND, J.G.F., TENDERA, M., ADAMUS, J., et.al. 2006. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Retrieved from http://eurheartj.oxfordjournals.org/content/27/19/2338.short
DYKER, A.G., GROSSET, D., & LEES, K. 1997. Perindopril reduces blood pressure but not cerebral blood flow in patients with recent cerebral ischemic stroke. Retrieved from http://stroke.ahajournals.org/content/28/3/580.short
FOX, K.M. 2003. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/13678872
HEALTH GRADES INC. Prevalence and incidence of hypertension. Retrieved from http://www.cureresearch.com/h/hypertension/prevalence.htm
MERCK MANUAL. Overview of hypertension. Retrieved from http://www.merckmanuals.com/professional/sec07/ch076/ch076a.html?qt=hypertension&alt=sh
NATIONAL HEART, LUNG AND BLOOD INSTITUTE. 2004. The seventh report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure. Retrieved from http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf
PATEL, A., et.al. 2007. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Retrieved from http://www.sciencedirect.com/science/article/pii/S0140673607613038
PUBMED HEALTH. Hypertension. Retrieved from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001502/
THE PROGRESS COLLABORATIVE GROUP. 2003. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Retrieved from http://archinte.ama-assn.org/cgi/content/abstract/163/9/1069
YOSHIJI, H., KURIYAMA, S., & FUKUI, H. 2003. Perindopril: possible use in cancer therapy. Retrieved from http://journals.lww.com/anti-cancerdrugs/Abstract/2002/03000/Perindopril__possible_use_in_cancer_therapy.3.aspx
YOSHIJI, H., KURIYAMA, S., KAWATA, M. 2000. The Angiotensin-I-converting enzyme inhibitor perindopril suppresses tumor growth and angiogenesis: Possible role of the vascular endothelial growth factor. Retrieved from http://clincancerres.aacrjournals.org/content/7/4/1073.short


 

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