ARB therapy

In patients with type 2 diabetes and nephropathy, ARB therapy has been shown to significantly reduce progression of nephropathy. For patients with LV dysfunction, ARB therapy has also been shown to reduce the risk of CV events when added to a stable regimen of a diuretic, ACE inhibitor, and fi-blocker or as alternative therapy in ACE inhibitor-intolerant patients. 

Acute decreases in renal function and hyperkalemia usually resolve over several days after ACEl or ARB therapy is discontinued. Occasional patients will require management of severe hyperkalemia, usually with sodium polystyrene sulfate (see Chap. 50). ACEl or ARB therapy may frequently be reinitiated, particularly for patients with congestive heart failure, after intravascular volume depletion has been corrected or the diuretic doses reduced. The development of mild renal insufficiency (serum creatinine concentration of 2 to 3 mg/dL) may be an acceptable trade-off for hemodynamic improvement in certain patients with severe congestive heart failure or renovascular disease not amenable to invasive management. Congestive heart failure patients with greater renal insufficiency may be best treated by substitution of hydralazine and nitrates for afterload reduction. 

Persons at greatest risk for NSAID hemodynamic nephropathy generally have pre-existing renal insufficiency, medical problems associated with high plasma renin activity (hepatic disease with ascites, decompensated congestive heart failure, or intravascular volume depletion), or systemic lupus erythematosus. Additional risk factors include atherosclerotic cardiovascular disease and diuretic therapy. The elderly are also at higher risk due to interaction of prevalent medical problems, multiple drug therapies, and reduced renal hemodynamics. Advanced age, however, has not been shown to be an independent risk factor for toxicity in limited trials in otherwise healthy elderly subjects. Combined NSAID and ACEl or ARB therapy is also a concern and should be avoided. 

Taal MV, Brenner BM. Combination ACEi and ARB therapy Additional benefit in renoprotection Curr Opin Nephrol Flypertens 2002 11 377-381. 

The safety of combined ACE-1 and ARB therapy is an important issue that was evaluated in recent meta-analysis in patients with chronic proteinuric... 

Patients with asymptomatic left ventricular systolic dysfunction and hypertension should be treated with P-blockers and ACE inhibitors. Those with heart failure secondary to left ventricular dysfunction and hypertension should be treated with drugs proven to also reduce the morbidity and mortality of heart failure, including P-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and diuretics for symptom control as well as antihypertensive effect. In African-Americans with heart failure and left ventricular systolic dysfunction, combination therapy with nitrates and hydralazine not only affords a morbidity and mortality benefit, but may also be useful as antihypertensive therapy if needed.66 The dihydropyridine calcium channel blockers amlodipine or felodipine may also be used in patients with heart failure and left ventricular systolic dysfunction for uncontrolled blood pressure, although they have no effect on heart failure morbidity and mortality in these patients.49 For patients with heart failure and preserved ejection fraction, antihypertensive therapies that should be considered include P-blockers, ACE inhibitors, ARBs, calcium channel blockers (including nondihydropyridine agents), diuretics, and others as needed to control blood pressure.2,49... 

Patients with diabetes and hypertension should initially be treated with either P-blockers, ACE inhibitors, ARBs, diuretics, or calcium channel blockers. There is a general consensus that therapy focused on RAAS inhibition by ACE inhibitors or ARBs may be optimal if the patient has additional cardiovascular risk factors such as left ventricular hypertrophy or chronic kidney disease.2,3,59,67... 

Combination therapy with hydralazine and isosorbide dinitrate is an appropriate substitute for angiotensin II antagonism in those unable to tolerate an ACE inhibitor or ARB, or as add-on therapy in African-Americans. 

It was hoped that the more complete blockade of angiotensin II s AT effects would confer greater long-term efficacy with ARBs compared to ACE inhibitors. However, prospective, randomized trials suggest that the clinical efficacy of ARBs is similar to that of ACE inhibitors for reduction of hospitalizations for HF, sudden cardiac death, and all cause mortality.23-25 Despite poorer suppression of AT2, comparable efficacy of ACE inhibitors may be due to the additional effects on the kallikrein-kinin system. Although ARBs produce hemodynamic and neurohormonal effects similar to those of ACE inhibitors, they are considered second-line therapy due to the overwhelming clinical trial experience with ACE inhibitors. 

Develop a medication regimen to slow the progression of HF with the use of neurohormonal blockers such as vasodilators (ACE inhibitors, ARBs, or hydralazine/ isosorbide dinitrate), P-blockers, and aldosterone antagonists. Utilize digoxin if the patient remains symptomatic despite optimization of the above therapies. 

Many patients cannot tolerate chronic ACE inhibitor therapy secondary to adverse effects outlined below. Alternatively, the angiotensin receptor blockers (ARBs), can-desartan and valsartan, have been documented in trials to improve clinical outcomes in patients with heart failure.68,69 Therefore, either an ACE inhibitor or candesartan or valsartan are acceptable choices for chronic therapy for patients who have a low ejection fraction (EF) and heart failure following MI. Since more than five different ACE inhibitors have proven benefits in MI while only two ARBs have been studied, the benefits of ACE inhibitors are generally considered a... 

All ACE-I + diuretic or ARB blood pressure lowering Peridopril 2-8 mg daily Indapamide 1.25-5 mg daily Statin therapy ... 

Determine if drug therapy may be contributing to ARF. Consider not only drugs that can directly cause ARF (e.g., aminoglycosides, amphotericin B, NSAIDs, cyclosporine, tacrolimus, ACE inhibitors, and ARBs), but also drugs that can predispose a patient to nephrotoxicity or prerenal ARF (i.e., diuretics and anti hypertensive agents). 

ACE inhibitors and angiotensin-receptor blockers (ARB) have definite benefits in patients with nephropathy and are believed to have renoprotective effects in most patients. Due to their ability to cause an initial bump in serum creatinine, these agents should be used cautiously when employed in combination with the calcineurin inhibitors. The dihydropyridine calcium channel blockers have demonstrated an ability to reverse the nephrotoxicity associated with cyclosporine and tacrolimus (Table 52-8). In general, antihypertensive therapy should focus on agents with proven benefit in reducing the progression of cardiovascular disease and should be chosen on a patient-specific basis.55 See Chapter 2 for further recommendations for treating HTN. 

Blood pressure, renal function, and serum potassium should be evaluated within 1 to 2 weeks after therapy initiation and dose increases, with these endpoints used to guide subsequent dose changes. It is not necessary to reach target ARB doses before adding a /3-blocker. 

Combination therapy with an ARB and ACE inhibitor offers a theoretical advantage over either agent alone through more complete blockade of the deleterious effects of angiotensin II. However, clinical trial results indicate that the addition of an ARB to optimal HF therapy (e.g., ACE inhibitors, /3-blockers, diuretics) offers marginal benefits at best with increased risk of adverse effects. Addition of an ARB may be considered in patients who remain symptomatic despite receiving optimal conventional therapy. 

The combination of nitrates and hydralazine improves the composite endpoint of mortality, hospitalizations for HF, and quality of life in African Americans who receive standard therapy. A fixed-dose combination product is available that contains ISDN 20 mg and hydralazine 37.5 mg (BiDil). Practice guidelines recommend adding ISDN and hydralazine as part of standard therapy in African Americans with moderately severe to severe HF. The combination may also be reasonable for patients of other ethnicities with persistent symptoms despite optimized therapy with an ACE inhibitor (or ARB) and /Tblocker. The combination is also appropriate as first-line therapy in patients unable to tolerate ACE inhibitors or ARBs because of renal insufficiency, hyperkalemia, or possibly hypotension. 

Diuretics, ACE inhibitors, ARBs, and CCBs are primary agents acceptable as first-line options based on outcome data demonstrating CV risk reduction benefits (Table 10-2). /TBIockers may be used either to treat a specific compelling indication or as combination therapy with a primary antihypertensive agent for patients without a compelling indication. 

ARBs are acceptable as alternative therapy for patients who cannot tolerate ACE inhibitors and possibly as add-on therapy for those already receiving a standard three-drug regimen. 

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