Factores de influencia en el clima

Example include Omapatrilat ¹⁰¹

This group of medicines was found to have a dual action, inhibiting neutral endopeptidase (NEP) and ACE, resulting in enhancement of the activity of vasodilatory and antiproliferative peptides. It also directly inhibits production of the powerful endogenous vasoconstrictor Angiotensin II. The drug however was not approved by the US FDA due to the concerns of angioedema.

Newer therapeutic approaches in managing hypertension

There have been recent advances in the management of hypertension. These newer developments in therapeutic approaches to managing hypertension include the renal sympathetic denervation, carotid baroreceptor sensitization and immunization against the components of the renin Angiotensin system.^102,103

These various modalities of treatment are still undergoing trials to determine their eventual contributions to managing hypertension.

2.5: Hypertension Guidelines on Pharmacological Therapy

Various countries and hypertension societies have developed national guidelines to rationalize the use of antihypertensive medicines in their environment and they suggest varied recommendations to suit different clinical scenarios.

Historically, the development of hypertension guidelines stemmed from accumulation of data from different studies that had been carried out prior to 1973 on drug treatment of hypertension, when the task force of the National Heart Lung and Blood Institute of the United States issued a set of recommendations towards treating hypertension.^104,105

A stepped care approach was utilized in managing hypertension with then available medicines such as thiazide diuretics as first step, methyldopa, hydralazine and guanethidine

49 as second, third, and fourth step respectively, all used in a stepwise manner.¹⁰⁵ Elevated diastolic blood pressure greater than or equal to 105mmHg was used as the threshold in deciding treatment. Subsequent reviews and development of guidelines by other countries still follow essentially this stepped care approach but with evidences from their local setting dictating their choice of antihypertensives

WHO/ISH Recommnedations and consensus statement.

The WHO/ISH had published a guideline on the management of hypertension in 1999 ¹¹ that provided evidence from observational data that blood pressure should be lowered to values less than 160/90 mmHg. However, following some new evidences,^106,107 another set of recommendations in released 2003¹⁰⁸ supported the lowering of systolic blood pressure threshold levels to values less than or equal to 140mmHg, in low risk individuals and especially in high risk individuals. It was concluded that a diuretic should be considered as first choice of therapy based on trial data and cost.

The International Collaborative Study on Hypertension in Blacks (ISCHIB)

This group also released a consensus statement concerning management of high blood pressure in African Americans in 2003.¹⁰⁹ This was based on studies that gave evidence on the poor outcomes from hypertension in this subset population. Their recommendations were geared towards reducing the level of blood pressure by, starting a patient on 2 medicines as initial therapy, at systolic blood pressure of 15mmHg or more and a diastolic blood pressure of 10mmHg or more above the target blood pressure, they also recommended the use of any antihypertensive agents as first choice.

A note of caution was raised regarding angioedema and dry cough following ACEI use in African Americans, due to the higher incidence of these reactions reported in this population.

50 Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure JNC VII

The US Guidelines which was released in 2003¹², classified hypertension into two stages, and recommended that thiazide-type diuretic, may be used as the initial therapy for most uncomplicated hypertensive patients in stage one, although the other classes could be prescribed singly or in combination. For patients in stage two, it was recommended that a two-drug combination be prescribed as initial therapy and should include a thiazide type diuretic.

For patients with compelling indications such as Diabetes, Chronic Kidney Disease, it was recommended that the initial drug should be the Angiotensin Converting Enzyme Inhibitor (ACEI) or the Angiotensin Receptor Blocker (ARB) which has been proven to reduce cardiovascular events in those disease states.

In patients not at goal of therapy, (20mmHg above systolic goal and 10mmHg above diastolic goal) their recommendations were to add a drug from another class. It was also recommended the use of a fixed dose combination drug which may be cheaper and cautioned initiating multiple agents in elderly people and those with autonomic dysfunction to reduce the risk of orthostatic hypotension.

International Forum for Hypertension control and prevention in Africa (IFHA)

This group published recommendation for managing hypertension in sub Saharan Africa and suggested the use of low dose thiazide diuretics as first line medicines in the absence of compelling indications. ¹³ If blood pressure was not well controlled on this, the recommendation was to increase the dose or add another medicine from a different class (preferably generic formulations).

The use of centrally acting agents, alpha blockers and vasodilators such as hydralazine were however restricted to patients with resistant hypertension.

51 The Nigeria Hypertension Society Guideline

In 2005, the society released another edition of the National Guideline⁵ tailored towards use in Nigeria, which recommended the use of thiazide diuretics as first line therapy and also the addition of another diuretic with a different site of action, if the blood pressure is 20/10mmHg higher than target BP or if no appreciable response seen after 4 weeks.

It also states that depending on considerations such as affordability, availability and the clinical setting, medicines from other classes may be used as first line or added to a diuretic.

The recommendation went on to further state the effectiveness of calcium channel blockers and diuretics in Nigerians, while a combination of methyldopa with a thiazide was stated to be quite efficacious and cost effective.

The use of ACEI in diabetics and those with Chronic Kidney Disease was also recommended.

It was also advised that adverse effects should be sought from patients who would not normally volunteer.

The British Hypertension Society

The latest guideline from this society released in 2004, ¹⁴ the fourth in the series also gives a guide as to the use of antihypertensive medicines in uncomplicated and high risk hypertensive individuals. However, a pharmacological update that was released in 2006¹¹⁰ changed the recommendations in the 2004 guideline.

The recommendations however differed from the JNC VII in the use of initial drug of choice by following an algorithm ACD (A -Angiotensin Converting Enzyme, C- Calcium Channel Blockers and D- Diuretics) which tends to separate patients into high or low renin states.

People of African descent have been shown to exhibit low renin states and thus the drug of first choice were diuretics or calcium channel blockers, and in those with sub optimal control, a combination of these two classes were suggested. In patient with high renin states (younger Caucasians) ACEI were recommended as drug of first choice. Beta blockers which were

52 initially in the 2004 guideline were removed due to new evidence that it was associated with higher metabolic complications.

The use of fixed dose combinations was also recommended as a way of reducing cost and potentially improving adherence. However the guidelines state that in the absence of compelling indication the cheapest available drug should be used. In diabetics and those with CKD, the use of ACEI or ARB’s was also advocated.

European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

A more recent guideline released by the European Society for Hypertension in collaboration with the European Cardiac Society in 2007,¹⁵ recommends the use of any of the different medicine classes as initiation therapy. The following points were to be considered: previous usage of a class of drug, effect of the drug on the cardiovascular status in relation to the patient, presence of subclinical organ damage and co-morbid states that may require specific medicines, possibilities of interaction with other concomitant medicines and the cost of these medicines. However, the need to be vigilant about adverse effects also was reiterated as it is one of the most important cause of non adherence.

The different guidelines emphasized the use of medicines with a 24hour efficacy to improve adherence and also non pharmacologic measures as an important part of therapy.