为什么血管紧张素转化酶抑制剂能降低高血压患者死亡率?

最新荟萃分析发现,肾素-血管紧张素(Ang)-醛固酮系统(RAAS)抑制剂能降低高血压患者死亡率,其治疗获益全部源于血管紧张素转化酶(ACE)抑制剂(ACEIs),而非血管紧张素受体拮抗剂(ARBs)。RAAS可以归纳为2条轴:ACE-AngⅡ(1-8)-AT1受体轴和ACE2-Ang(1-7)-Mas受体轴,ACEIs对RAAS的2条轴均发挥良好作用,而ARBs主要作用于前者。各个指南推荐高血压相关心血管疾病治疗优先选择ACEIs,对不能够耐受者选择ARBs。我们应当重视ACEIs在高血压、冠心病、心肌梗死和心力衰竭防治中的应用,目的是降低心血管疾病患病率和死亡率的风险。     

Angiotensin-Converting Enzyme Inhibitors in Hypertension: To Use or Not to Use?

Most guidelines for the management of patients with cardiovascular disease recommend angiotensin-converting enzyme (ACE) inhibitors as first-choice therapy, whereas angiotensin receptor blockers (ARBs) are merely considered an alternative for ACE inhibitor–intolerant patients. The aim of this review was to compare outcomes and adverse events between ACE inhibitors and ARBs in patients. In patients with hypertension and hypertension with compelling indications, we found no difference in efficacy between ARBs and ACE inhibitors with regard to the surrogate endpoint of blood pressure and outcomes of all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. However, ACE inhibitors remain associated with cough and a very low risk of angioedema and fatalities. Overall withdrawal rates because of adverse events are lower with ARBs than with ACE inhibitors. Given the equal outcome efficacy but fewer adverse events with ARBs, risk-to-benefit analysis in aggregate indicates that at present there is little, if any, reason to use ACE inhibitors for the treatment of hypertension or its compelling indications.     

Application of Direct Renin Inhibition to Chronic Kidney Disease

Purpose  

Chronic kidney disease has serious implications with a high risk for progressive loss of renal function, increased cardiovascular events as well as a substantial financial burden. The renin-angiotensin-aldosterone system (RAAS) is activated in chronic kidney disease, especially in diabetes and hypertension, which are the leading causes of chronic kidney disease. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) decrease the rate of progression of diabetic and non-diabetic nephropathy and are recommended therapy for chronic kidney disease.     

Approach to Lipid Therapy in the Patient With Atherosclerotic Vascular Disease

Hyperlipidemia increases the incidence of atherosclerotic vascular disease and is associated with greater rates of recurrent cardiovascular events among individuals with established vascular disease. Several large population studies have confirmed the link between all cholesterol components (including elevated low-density lipoprotein [LDL] cholesterol, total cholesterol, and triglyceride levels, and reduced high-density lipoprotein [HDL] levels) with coronary heart disease and other manifestations of systemic atherosclerosis. In addition, landmark clinical trials have clearly established that lowering LDL cholesterol levels with statins (HMG-CoA reductase inhibitors) can lower recurrent cardiovascular events by nearly 25%. The benefits of altering non-LDL cholesterol levels (eg, triglycerides and HDL) are less clear, but several other medications are often used in conjunction with statins for cholesterol lowering. First-line therapy for lipid lowering in patients with atherosclerotic vascular disease includes statins and a recommendation for lifestyle changes (including diet and exercise). Second-line options for lowering cholesterol include fibrates, nicotinic acid, bile acid sequestrants, and ezetimibe. Therapeutic goals for patients with vascular disease are to achieve an LDL cholesterol level < 100 mg/dL, or <70 mg/dL in individuals at particularly high risk.     

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in atherosclerosis

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) effectively interfere with the renin-angiotensin system and exert various beneficial actions on cardiac and vascular structure and function, beyond their blood pressure-lowering effects. Randomized, controlled clinical trials have shown that ACE inhibitors improve endothelial function, cardiac and vascular remodeling, retard the anatomic progression of atherosclerosis, and reduce the risk of myocardial infarction, stroke, and cardiovascular death. Therefore, these agents are recommended in the treatment of a wide range of patients at risk for adverse cardiovascular outcomes, including those with coronary disease, prior stroke, peripheral arterial disease, high-risk diabetes, hypertension, and heart failure. ARBs are effective blood pressure-lowering and renoprotective agents and can be used in heart failure in patients who do not tolerate ACE inhibitors. The role of ARBs in the prevention of atherosclerosis and its sequelae is currently under investigation. The use of combined ACE inhibitor plus ARB therapy offers theoretical advantages over the use of each of these agents alone and is also under investigation in large, randomized clinical trials.     

Hypertension mega-trials with cardiovascular end points: effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers

Background

The renin-angiotensin-aldosterone system has a pivotal role in the short- and long-term regulation of blood pressure through its principal mediator, angiotensin II. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II-receptor blockers (ARBs) decrease the deleterious effects of angiotensin II on the vasculature and heart, but have different mechanisms of action. Although the blood pressure-lowering effect of ACE inhibitors and ARBs is equivalent to that of most other antihypertensive agents, emerging data suggest that these drug classes may have a greater effect on decreasing cardiovascular morbidity and mortality rates in specific patient populations.

Methods

We reviewed large (approximately ≥5000 patients) hypertension clinical trials using ACE inhibitors and ARBs and with cardiovascular morbidity/mortality end points.

Results

Six trials of ACE inhibitors and 5 trials of ARBs (3 completed, 2 ongoing) were selected for this analysis. Data from these hypertension mega-trials suggest that ACE inhibitors and ARBs may decrease cardiovascular morbidity and mortality rates, especially in patients with diabetes mellitus, renal dysfunction, and left ventricular hypertrophy. However, some trials showed important blood-pressure differences and are therefore partly inconclusive for particular drug effects.

Conclusions

Analysis of recently reported and ongoing mega-trials of renin-angiotensin-aldosterone system inhibitors may support the notion that their vasculoprotective properties confer greater benefit by virtue of their effects beyond blood-pressure reduction. Results from trials that will be completed in the next few years may provide further support of blocking the renin-angiotensin-system in cardiovascular protection in the management of hypertension.     

Baseline laboratory monitoring of cardiovascular medications in elderly health maintenance organization enrollees

Objectives: To identify correlates of laboratory monitoring errors in elderly health maintenance organization (HMO) members at the initiation of therapy with cardiovascular medications.
Design: Cross-sectional study in 10 HMOs.
Setting: United States.
Participants: From a 2 million-member sample, individuals aged 65 and older who received one of seven cardiovascular medications (angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), amiodarone, digoxin, diuretics, potassium supplements, and statins) and did not have recommended baseline monitoring performed during the 180 days before or 14 days after the index dispensing.
Measurements: The proportion of members receiving each drug for whom recommended laboratory monitoring was not performed. Laboratory monitoring error rates stratified by sex, age group, chronic disease score, and HMO site were examined, and logistic regression was used to identify predictors of laboratory monitoring errors.
Results: Error rates varied by medication class, ranging from 23% of patients receiving potassium supplementation without serum potassium and serum creatinine monitoring to 58% of patients receiving amiodarone who did not have recommended monitoring for thyroid and liver function. Highest error rates occurred in the youngest elderly for ACE inhibitors, ARBs, digoxin, diuretics, and potassium supplements, although in patients receiving amiodarone and statins, errors were most frequent in the oldest elderly. Errors occurred more frequently in patients with less comorbidity.
Conclusion: Laboratory monitoring errors occurred frequently in elderly HMO members at the initiation of therapy with cardiovascular medications. Further study must examine the association between these errors and adverse outcomes.     

Treatment of Heart Failure With Normal Ejection Fraction

Heart failure (HF) is a major cause of mortality and morbidity and one of the most frequent reasons for hospital admission in the United States and Europe. Currently, more than 50% of HF patients have a normal (N) left ventricular (LV) ejection fraction (EF) (LVEF >50%). The main pathophysiologic processes involved in HFNEF are increased LV stiffness and abnormal relaxation, resulting in impaired LV filling. Hypertension and myocardial ischemia are the most common causes of HFNEF. Precipitating factors include volume overload, tachycardia, physical exercise, systemic stressors (such as fever and infection), arrhythmia, increased salt intake, and use of nonsteroidal anti-inflammatory drugs. There is little evidence to guide treatment, as previously HFNEF patients have been excluded from clinical trials on the basis of a normal LVEF. Survival improved over time in patients with reduced (R) EF (HFREF) (LVEF <40%), reflecting the beneficial effects of treatment in this phenotype. However, survival did not improve for HFNEF patients. The approach to the treatment of HFNEF patients should focus on reducing LV filling pressure, controlling hypertension, modifying ischemia, and improving LV relaxation. Therefore, diuretics are suitable for HFNEF patients to reduce ventricular filling pressure. Hypertension can be treated by using multiple agents if necessary. Drugs of particular interest and recommended to treat hypertension are calcium channel blockers (CCBs) and antagonists of the renin-angiotensin-aldosterone system, such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and aldosterone antagonists. Ischemic heart disease can be treated with antiplatelet therapy, anticoagulants, and β-blockers. Heart rate control in atrial fibrillation can be achieved with β-blockers and digoxin. Finally, ACE inhibitors and ARBs could potentially decrease LV hypertrophy in hypertensive patients with HFNEF.     

The 2009 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 – therapy

OBJECTIVE:

To update the evidence-based recommendations for the prevention and management of hypertension in adults for 2009.

OPTIONS AND OUTCOMES:

For lifestyle and pharmacological interventions, evidence from randomized controlled trials and systematic reviews of trials was preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field. Progression of kidney dysfunction was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease.

EVIDENCE:

A Cochrane collaboration librarian conducted an independent MEDLINE search from 2007 to August 2008 to update the 2008 recommendations. To identify additional published studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence.

RECOMMENDATIONS:

For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium to less than 2300 mg (100 mmol)/day (and 1500 mg to 2300 mg [65 mmol to 100 mmol]/day in hypertensive patients); perform 30 min to 60 min of aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index 18.5 kg/m² to 24.9 kg/m²) and waist circumference (smaller than 102 cm for men and smaller than 88 cm for women); limit alcohol consumption to no more than 14 units per week in men or nine units per week in women; follow a diet that is reduced in saturated fat and cholesterol, and that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and consider stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on by the patient’s global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to lower than 140/90 mmHg in all patients, and to lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. Antihypertensive therapy should be considered in all adult patients regardless of age (caution should be exercised in elderly patients who are frail). For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin-converting enzyme (ACE) inhibitors (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin receptor antagonists (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered as the initial treatment of hypertension if the systolic blood pressure is 20 mmHg above the target or if the diastolic blood pressure is 10 mmHg above the target. The combination of ACE inhibitors and ARBs should not be used. Other agents appropriate for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine CCBs or ARBs. In patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with proteinuric nondiabetic chronic kidney disease, ACE inhibitors or ARBs (if intolerant to ACE inhibitors) are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy. Once blood pressure is controlled, acetylsalicylic acid therapy should be considered.

VALIDATION:

All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.     

The Comparative Effectiveness of Angiotensin‐Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Patients With Diabetes

The evidence examining the effect of angiotensin‐converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) on mortality in high‐risk patients is conflicting. To further examine this controversy, the authors compared outcomes between ACE inhibitors and ARBs in a large clinical diabetes registry. A retrospective cohort of 87,472 incident users followed for 105,702 patient‐years was analyzed. Average age was 53.1±10.1 years, 54.2% were men, and 14.4% had cardiovascular disease. All‐cause hospitalization or all‐cause mortality, the composite primary endpoint, occurred in 10,943 (12.5%) patients. Compared with ACE inhibitors, the adjusted hazard for ARBs was 0.90 (95% confidence interval, 0.87–0.94) for all‐cause hospitalization or mortality; 0.95 (0.65–1.40) for mortality; 0.90 (0.87–0.94) for all‐cause hospitalization; and 0.81 (0.74–0.89) for cardiovascular admission. ARB use was associated with a reduced, not increased, risk of hospitalization/mortality relative to ACE inhibition. This was driven by lower hospitalization, with a null mortality result.     

Efficacy of Angiotensin Receptor Blockers in Cardiovascular Disease

The cardiovascular continuum describes the progression of pathophysiologic events from cardiovascular risk factors to symptomatic cardiovascular disease (CVD) and life-threatening events. Pharmacologic intervention early in the continuum may prevent or slow CVD development and improve quality of life. The renin–angiotensin–aldosterone system (RAAS) is central to the pathophysiology of CVD at many stages of the continuum. Numerous clinical trials of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have shown that RAAS blockade provides benefits to patients across the continuum. ARBs are as effective as ACE inhibitors in the treatment of hypertension; however tolerability and adherence to therapy appear to be improved with ARBs. Large clinical trials have shown that ARBs may provide therapeutic benefits beyond blood pressure control in patients with diabetes, heart failure or at risk of heart failure following a myocardial infarction. In addition, ARBs have been shown to provide protective effects in patients with impaired renal function or left ventricular hypertrophy. Additional clinical trials are ongoing to further characterize the role of ARBs in CVD management.     

Hypertension, obesity, erectile dysfunction. What kind of drug to choose

Hypertension is one of the most common cardiovascular diseases. The development and progression of hypertension is associated with prolonged hyper activation of the renin-angiotensin-aldosterone system. ACE inhibitors and angiotensin receptor blockers (ARBs) are highly effective medicines and are widely used in the treatment of cardiovascular diseases: hypertension, congestive heart failure, coronary heart disease. The main pharmacological effects of ACE inhibitors and ARBs are hypotensive, neurohumoral, antiproliferative, cardio- and nefroprotective functions, as well as constantly improving endothelial function. In accordance with the article, hypertensive effectiveness, tolerability and organ-protective properties of valsartan are noticeable among patients with hypertension, obesity and erectile dysfunction, taking this medicine.     

Impact of simultaneous management of hypertension and hypercholesterolemia with ACE inhibitors and statins on cardiovascular outcomes in the Brisighella Heart Study: A 8-year follow-up

Background and aimsTo evaluate the long-term effect of simultaneous treatment of hypertension and hypercholesterolemia with angiotensin-converting enzyme (ACE) inhibitors and statins on the incidence of major cardiovascular events (MACE) and other clinical outcomes.Methods and resultsWe considered data from a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. We excluded normotensive subjects and individuals with a low calculated 10-year CVD risk, hypertensive patients treated with antihypertensive drugs different from ACE inhibitors and patients who changed antihypertensive medications during follow-up. The remaining participants were divided into four groups depending on whether they were treated with (I) perindopril ± amlodipine without statin treatment (N. 132), (II) perindopril ± amlodipine and atorvastatin (N. 132), (III) an ACE inhibitor other than perindopril ± a calcium-channel blocker without statin therapy (N. 133), (IV) an ACE inhibitor other than perindopril ± a calcium-channel blocker and statin therapy (N. 145). The long-term (8 years) effects of the different combined treatment were compared among the pre-defined groups. Over the follow-up period of 8 years, the proportion of subjects who developed MACE, type 2 diabetes mellitus and hyperuricemia, and the proportion of subjects needing for the intensification of antihypertensive treatment to improve blood pressure control were statistically different among the predefined groups (P < 0.05).ConclusionCombined treatment with ACE inhibitors and statins (especially atorvastatin) in hypertensive patients seems to significantly reduce the risk of developing CVD in comparison with treatment with ACE inhibitors alone.     

The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 �C therapy

OBJECTIVE:

To update the evidence-based recommendations for the prevention and treatment of hypertension in adults for 2010.

OPTIONS AND OUTCOMES:

For lifestyle and pharmacological interventions, randomized trials and systematic reviews of trials were preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the general lack of long-term morbidity and mortality data in this field. Progressive renal impairment was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease.

EVIDENCE:

A Cochrane Collaboration librarian conducted an independent MEDLINE search from 2008 to August 2009 to update the 2009 recommendations. To identify additional studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence.

RECOMMENDATIONS:

For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium to 1500 mg (65 mmol) per day in adults 50 years of age or younger, to 1300 mg (57 mmol) per day in adults 51 to 70 years of age, and to 1200 mg (52 mmol) per day in adults older than 70 years of age; perform 30 min to 60 min of moderate aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index 18.5 kg/m² to 24.9 kg/m²) and waist circumference (less than 102 cm for men and less than 88 cm for women); limit alcohol consumption to no more than 14 standard drinks per week for men or nine standard drinks per week for women; follow a diet that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources, and that is low in saturated fat and cholesterol; and consider stress management in selected individuals with hypertension.For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on the patient’s global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to less than 140/90 mmHg in all patients, and to less than 130/80 mmHg in patients with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. Antihypertensive therapy should be considered in all adult patients regardless of age (caution should be exercised in elderly patients who are frail). For adults without compelling indications for other agents, considerations for initial therapy should include thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered as initial treatment of hypertension if systolic blood pressure is 20 mmHg above target or if diastolic blood pressure is 10 mmHg above target. The combination of ACE inhibitors and ARBs should not be used, unless compelling indications are present to suggest consideration of dual therapy.Agents appropriate for first-line therapy for isolated systolic hypertension include thiazide diuretics, long-acting dihydropyridine CCBs or ARBs. In patients with coronary artery disease, ACE inhibitors, ARBs or beta-blockers are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with proteinuric nondiabetic chronic kidney disease, ACE inhibitors or ARBs (if intolerant to ACE inhibitors) are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. In selected high-risk patients in whom combination therapy is being considered, an ACE inhibitor plus a long-acting dihydropyridine CCB is preferable to an ACE inhibitor plus a thiazide diuretic. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian lipid treatment guidelines. Selected patients with hypertension who do not achieve thresholds for statin therapy, but who are otherwise at high risk for cardiovascular events, should nonetheless receive statin therapy. Once blood pressure is controlled, low-dose acetylsalicylic acid therapy should be considered.

VALIDATION:

All recommendations were graded according to the strength of the evidence and voted on by the 63 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 80% consensus. These guidelines will continue to be updated annually.

SPONSORS:

The Canadian Hypertension Education Program process is sponsored by the Canadian Hypertension Society, Blood Pressure Canada, the Public Health Agency of Canada, the College of Family Physicians of Canada, the Canadian Pharmacists Association, the Canadian Council of Cardiovascular Nurses, and the Heart and Stroke Foundation of Canada.     

Effectiveness of angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers on total and cardiovascular mortality and morbidity in primary prevention: A nationwide study based on French Health Insurance Data (SNDS)

Angiotensin‐converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) both inhibit the renin‐angiotensin system (RAS) but have different sites of action. Whether clinically meaningful differences exist is still debated. The authors set up a population‐based nationwide retrospective cohort study with at least 5 years of follow‐up based on the comprehensive French Health Insurance Database linked to the French hospital discharge database. Patients aged 50 or above, identified as ARB or ACE inhibitor new users in 2009 (at least one delivery during the year and no such delivery in 2008) were eligible. Exclusion criteria included history of cancer, cardiovascular disease, or chronic renal insufficiency. Main outcome measure was overall mortality. Secondary outcomes were cardiovascular deaths, major cardiovascular events, and major or other cardiovascular events. Out of 407 815 eligible patients, 233 682 (57%) were ARB users; two‐third had no previous exposure to antihypertensive drug. Based on propensity‐score based Cox model, ARB new user group had a better overall (HR: .878, 95%CI, .854 to .902), and cardiovascular (HR: .841, 95%CI, .800 to .84) survival and had a lower risk for major cardiovascular events (HR: .886, 95%CI, .868 to .905). Statistically significant quantitative interactions were detected with diabetes. Considering subgroup analyses, ARBs had a better survival than ACE inhibitors in nondiabetic patients.     

Angiotensin receptor blockers: evidence for preserving target organs

Hypertension is a major problem throughout the developed world. Although current antihypertensive treatment regimens reduce morbidity and mortality, patients are often noncompliant, and medications may not completely normalize blood pressure. As a result, current therapy frequently does not prevent or reverse the cardiovascular remodeling that often occurs when blood pressure is chronically elevated. Blockade of the renin-angiotensin system (RAS) is effective in controlling hypertension and treating congestive heart failure. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) inhibit the activity of the RAS, but these two classes of antihypertensive medications have different mechanisms of action and different pharmacologic profiles. Angiotensin-converting enzyme inhibitors block a single pathway in the production of angiotensin II (Ang II). In addition, angiotensin I is not the only substrate for ACE. The ACE inhibitors also block the degradation of bradykinin that may have potential benefits in cardiovascular disease. Bradykinin is, however, the presumed cause of cough associated with ACE inhibitor therapy. Data from clinical trials on ACE inhibitors serve to support the involvement of the RAS in the development of cardiovascular disease. Angiotensin receptor blockers act distally in the RAS to block the Ang II type 1 (AT1) receptor selectively. Thus, ARBs are more specific agents and avoid many side effects. Experimental and clinical trials have documented the efficacy of ARBs in preserving target-organ function and reversing cardiovascular remodeling. In some instances, maximal benefit may be obtained with Ang II blockade using both ARBs and ACE inhibitors. This review describes clinical trials that document the efficacy of ARBs in protecting the myocardium, blood vessels, and renal vasculature.     

Angiotensin converting enzyme inhibitors or angiotensin receptor blockers in nephropathy from type 2 diabetes

Type 2 diabetes is the most common cause of end-stage renal disease in the United States, and type 2 diabetes has been shown to be a myocardial infarction equivalent in regard to risk of death from a cardiovascular event. Proteinuria is a surrogate marker for renal disease progression, and although data favor both the angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in reducing proteinuria, data for renal outcomes, such as time to dialysis, only exist for the ARBs, which clearly increase the duration to dialysis. Conversely, ACE inhibitors have overwhelming data that show substantial risk reduction from cardiovascular events and death in people with type 2 diabetes. Similar data on cardiovascular risk reduction are not yet available with ARBs, although two trials of renal disease progression did have cardiovascular endpoints as secondary outcomes. There were no significant differences between the ARB and control group except for first hospitalization with heart failure, where losartan reduced the risk by 32%, but there was a trend, albeit not significant, toward reduction of myocardial infarction. The first information regarding ARB effects on cardiovascular events as primary outcomes will come from the Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension study. Therefore, as of this writing, all patients with type 2 diabetes and no evidence of nephropathy, ie, proteinuria and an elevated creatinine > 1.5 mg/dL, should be placed on an ACE inhibitor for cardiovascular risk reduction. If nephropathy is present, the evidence would support an ARB for therapy in concert with a a-blocker for cardiovascular risk reduction and renoprotection.