CIENCIASMEDICASNEWS: Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), and Direct Renin Inhibitors for Treating Essential Hypertension: An Update - Executive Summary

sábado, 29 de octubre de 2011

Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), and Direct Renin Inhibitors for Treating Essential Hypertension: An Update - Executive Summary | AHRQ Effective Health Care Program

AHRQ’s Effective Health Care Program Releases an Update on Comparing Treatments for Hypertension

A new, updated research review concludes that there is not enough evidence to determine whether there are long-term differences in health outcomes associated with the use of three leading hypertension treatments—ACEIs, ARBs, and direct renin inhibitors—and calls for further research in the field. Nearly 75 million American adults – approximately one third – have hypertension. Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), and Direct Renin Inhibitors for Treating Essential Hypertension is an update to a 2007 AHRQ review on the same topic.
Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), and Direct Renin Inhibitors for Treating Essential Hypertension: An Update - Executive Summary AHRQ Effective Health Care Program

Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), and Direct Renin Inhibitors for Treating Essential Hypertension: An Update

Formats

This topic is an update to the original topic, "Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin II Receptor Antagonists (ARBs) for Treating Essential Hypertension." Please click on the the title to view the original research review and associated products.

Background

Almost 75 million American adults—approximately one-third—have hypertension. The prevalence of hypertension increases with advancing age such that more than half of people 55 to 74 years old and approximately three-fourths of those age 75 years and older are affected. In addition to being the primary attributable risk factor for death throughout the world, hypertension results in substantial morbidity because of its impact on numerous target organs, including the brain, eyes, heart, arteries, and kidneys.
Despite the high rates of morbidity and mortality attributable to hypertension, control of the condition remains suboptimal. In addition to several effective nonpharmacological interventions—including diet, exercise, and control of body weight—many people require antihypertensive medication to lower blood pressure.
Among the many choices in antihypertensive therapy, some of the most common are those aimed at affecting the renin-angiotensin-aldosterone (renin) system. The renin system is an important mediator of blood volume, arterial pressure, and cardiac and vascular function. Components of this system can be identified in many tissues, but the primary site of renin release is the kidney. The renin system can be triggered by sympathetic stimulation, renal artery hypotension, and decreased sodium delivery to the distal tubule. Through proteolytic cleavage, renin acts on the oligopeptide substrate angiotensinogen to produce the decapeptide angiotensin I. In turn, two terminal peptide residues of angiotensin I are removed by the angiotensin-converting enzyme (ACE) to form the octapeptide angiotensin II. Angiotensin II acts directly on the resistance vessels to: increase systemic vascular resistance and arterial pressure; stimulate the adrenal cortex to release aldosterone, which leads to increased sodium and water reabsorption and potassium excretion; promote secretion of antidiuretic hormone, which leads to fluid retention; stimulate thirst; promote adrenergic function; and increase cardiac and vascular hypertrophy.
Therapies aimed at modifying the renin system have been used extensively for treatment of hypertension, heart failure, myocardial infarction, diabetes, and renal disease. Currently, three classes of drugs that interact with this system are used to inhibit the effects of angiotensin II: the angiotensin-converting enzyme inhibitors (ACEIs), the angiotensin II receptor blockers/antagonists (ARBs), and the direct renin inhibitors. ACEIs block the conversion of angiotensin I into angiotensin II; ARBs selectively inhibit angiotensin II from activating the angiotensin-specific receptor (AT1); and direct renin inhibitors block the conversion of angiotensinogen into angiotensin I.
Although ACEIs and ARBs both target the renin system and are treated by clinicians as being equivalent, this may not be appropriate. While both drug classes reduce the downstream effects of angiotensin II, it is not clear that these medications are in fact clinically equivalent. ACEIs, for example, do not entirely block production of angiotensin II because of the presence of unaffected converting enzymes. Also, ACEIs have well-known side effects not shared by ARBs, including cough (estimated incidence 5 to 20 percent) and angioedema (estimated incidence 0.1 to 0.2 percent, with a lesser reported risk with ARBs). Additional considerations arise with the newer direct renin inhibitors, because their side-effect profiles and efficacy may differ significantly from ACEIs or ARBs. Given the public health importance and widespread use of these agents, it is important to understand their comparative effects on clinical outcomes.
This review summarizes the evidence on the comparative long-term benefits and harms of ACEIs, ARBs, and direct renin inhibitors, focusing on their use for treating essential hypertension in adults. It is an update of a 2007 report that evaluated the scientific literature on ACEIs and ARBs for adults with essential hypertension and adds an evaluation of direct renin inhibitors, which were not covered in the original report. The need for this updated report was determined by an analysis conducted by the Southern California Evidence-based Practice Center. In that analysis, investigators assessed the conclusions from the original comparative effectiveness review, performed a limited literature search of potentially new evidence, and solicited expert opinions concerning the state of the evidence and validity of the original report.
Key Questions addressed are:
Key Question 1. For adult patients^a with essential hypertension, how do ACEIs (angiotensin-converting enzyme inhibitors), ARBs (angiotensin II receptor antagonists), and direct renin inhibitors^b differ in blood pressure control, cardiovascular risk reduction, cardiovascular events, quality of life, and other outcomes^c?
^a “Adult patients” are defined as adults, age 18 years or older.
^b ACEIs evaluated are: Benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik). ARBs considered are: Candesartan cilexetil (Atacand), eprosartan (Teveten), irbesartan (Avapro), losartan (Cozaar), olmesartan medoxomil (Benicar), telmisartan (Micardis), and valsartan (Diovan). Direct renin inhibitors considered are: Aliskiren (Tekturna).
^c Outcomes considered include:
Primary outcomes:

Blood pressure control (we will prefer seated trough blood pressure, where reported).
Mortality (all-cause, cardiovascular disease-specific, and cerebrovascular disease-specific).
Morbidity (especially major cardiovascular events [myocardial infarction (MI), stroke] and measures of quality of life).
Safety (focusing on serious adverse event rates, overall adverse event rates, and withdrawals due to adverse events, withdrawal rates, and switch rates).
Specific adverse events (including, but not limited to, weight gain, impaired renal function, angioedema, cough, and hyperkalemia).
Persistence/adherence.
Rate of use of a single antihypertensive medication for blood pressure control.

Secondary outcomes:

Lipid levels (high-density lipoprotein, low-density lipoprotein, total cholesterol, and triglycerides).
Rates of progression to type 2 diabetes.
Markers of carbohydrate metabolism/diabetes control (glycated hemoglobin [HbA1c], dosage of insulin or other diabetes medication, fasting plasma glucose, or aggregated measures of serial glucose measurements).
Measures of left ventricular mass/function (left ventricular mass index and ejection fraction).
Measures of kidney disease (creatinine/glomerular filtration rate [GFR], proteinuria)

Key Question 2. For adult patients with essential hypertension, how do ACEIs, ARBs, and direct renin inhibitors differ in safety,^d adverse events,e tolerability, persistence with drug therapy, and treatment adherence?
^d Safety outcomes considered include: Overall adverse events, withdrawals due to adverse events, serious adverse events reported, withdrawal rates, and switch rates. (For practical reasons, we separate safety/adverse events and tolerability/persistence [including switch rates], as the latter may or may not be due to identifiable adverse events.)
^e Specific adverse events: These included, but were no limited to, weight gain, impaired renal function, angioedema, cough, and hyperkalemia.
Key Question 3. Are there subgroups of patients—based on demographic and other characteristics (i.e., age, race, ethnicity, sex, comorbidities, concurrent use of other medications)—for whom ACEIs, ARBs, or direct renin inhibitors are more effective, are associated with fewer adverse events, or are better tolerated?