A cost-utility analysis of losartan versus atenolol in the treatment of hypertension with left ventricular hypertrophy

INTRODUCTION: The LIFE (Losartan Intervention For Endpoint reduction in hypertension) study demonstrated a 13% relative risk reduction in the primary composite endpoint (myocardial infarction, stroke or death) for patients with hypertension and electrocardiographically diagnosed left ventricular hypertrophy (LVH) treated with losartan compared with atenolol. Losartan recipients also had a 25% relative risk reduction for stroke compared with atenolol recipients. Incorporating the results found in the LIFE study into an economic model, an incremental cost-effectiveness analysis was performed comparing losartan with atenolol in the treatment of 67-year old patients with hypertension and LVH. METHODS: A Markov state transition model, based on published results of the LIFE trial (mean follow-up of 4.8 years), was utilised to extrapolate the outcomes observed in this trial to the patients' lifetime. Utility estimates for the associated health states were obtained from various published sources. Lifetime treatment costs were calculated adopting a societal perspective. Both costs and benefits were discounted and incremental cost-effectiveness ratios (ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed. RESULTS: The estimated ICER for losartan versus atenolol was 1337 Canadian dollars per QALY gained (1 Canadian dollar =0.75 US dollars, 2002 values). This ICER was robust to extensive sensitivity analysis, demonstrating a 95% probability that the ICER would be <20,000 Canadian dollars per QALY gained. CONCLUSION: From a Canadian societal perspective, losartan appears to be a cost-effective alternative to atenolol in patients with hypertension and LVH. The estimated ICERs, including the sensitivity analyses, were within the range of cost-effectiveness ratios for various currently funded interventions and drugs in developed countries.     

Losartan

? Losartan binds selectively to the angiotensin II subtype 1 receptor, blocking the activity of angiotensin II. ? Losartan 50–100 mg/day was compared with atenolol 50–100 mg/ day in patients with essential hypertension and left ventricular hypertrophy (LVH) [n = 9193] in the randomized, double-blind Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Two substudies compared these drugs in patients with diabetes mellitus (n = 1195) or isolated systolic hypertension (ISH) [n = 1326]. ? The target BP (‘140/90mm Hg) was achieved in ≈45% of losartan and atenolol recipients in the LIFE study. Significant regression of LVH occurred with losartan versus atenolol in the LIFE study, as well as in the diabetes mellitus and ISH substudies. ? In the LIFE study, although BP reduction was similar for the two treatments, the risk of a cardiovascular event (the composite of cardiovascular death, stroke, and myocardial infarction; primary endpoint), stroke, or new-onset diabetes mellitus was significantly lower with losartan than with atenolol. ? Losartan was generally well tolerated in patients with hypertension and LVH in the LIFE study. Significantly fewer losartan than atenolol recipients discontinued treatment because of adverse events, drug-related adverse events, or serious, drug-related adverse events.     

Losartan for LIFE in hypertension with left ventricular hypertrophy?

When ACE inhibitors are used to lower blood pressure to the same degree as beta-adrenoceptor antagonists or calcium channel blockers, ACE inhibitors do not seem to have additional benefits to these agents. In the Losartan Intervention for End Point Reduction in Hypertension study (LIFE), losartan was compared to atenolol in hypertensives with the additional risk factor of left ventricular hypertrophy (LVH). For similar effects on blood pressure, losartan had a greater benefit on the primary composite end point (cardiovascular mortality, stroke and myocardial infarction) than atenolol in the hypertensives with LVH, including a prespecified subgroup of patients with additional diabetes mellitus. Losartan also had a greater ability to reverse LVH than atenolol. Thus, losartan should become the standard treatment for hypertension when LVH is present.     

The role of angiotensin antagonism in stroke prevention in patients with hypertension: focus on losartan

Optimal management of hypertension has been shown to reduce the risk of stroke. In recent years, newer classes of antihypertensive such as the angiotensin II (Ang II) antagonists have become available. Results from the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study suggest the utility of this particular Ang II antagonist in stroke prevention. Treatment with a losartan-based regimen or an atenolol-based regimen produced similar reductions in blood pressure during almost 5 years of follow up. Losartan, however, reduced the risk of stroke by 25% compared with atenolol (p = 0.001). For a subgroup of patients with isolated systolic hypertension, losartan reduced the risk of stroke by 40% (p = 0.02). As well as blocking the Ang II type 1 receptor, losartan also acts as an antagonist at the thromboxane A2 receptor and has uricosuric effects, which may provide additional mechanisms by which losartan provides protective benefits beyond its antihypertensive action. The relevance of these molecular properties of losartan over other Ang II antagonists is further supported by comparison of the outcomes obtained in clinical trials employing two other Ang II antagonists, valsartan and candesartan.     

The role of angiotensin antagonism in stroke prevention in patients with hypertension: focus on losartan

Summary

Optimal management of hypertension has been shown to reduce the risk of stroke. In recent years, newer classes of antihypertensive such as the angiotensin II (Ang II) antagonists have become available. Results from the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study suggest the utility of this particular Ang II antagonist in stroke prevention. Treatment with a losartan-based regimen or an atenolol-based regimen produced similar reductions in blood pressure during almost 5 years of follow up. Losartan, however, reduced the risk of stroke by 25% compared with atenolol (p = 0.001). For a subgroup of patients with isolated systolic hypertension, losartan reduced the risk of stroke by 40% (p = 0.02). As well as blocking the Ang II type 1 receptor, losartan also acts as an antagonist at the thromboxane A₂ receptor and has uricosuric effects, which may provide additional mechanisms by which losartan provides protective benefits beyond its antihypertensive action. The relevance of these molecular properties of losartan over other Ang II antagonists is further supported by comparison of the outcomes obtained in clinical trials employing two other Ang II antagonists, valsartan and candesartan.     

Potential mechanisms of stroke benefit favoring losartan in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study

ABSTRACT

Introduction: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study is the first, and, so far, the only endpoint trial in patients with hypertension and left ventricular hypertrophy (LVH) to show a divergent therapeutic outcome of one treatment modality over another with equivalent blood pressure control. The purpose of this article is to review post hoc sub-analyses of LIFE study data and other clinical studies that offer some insight into possible treatment-related differences contributing to the superior stroke outcome of losartan versus atenolol beyond blood pressure reduction.

Methods: Relevant randomized clinical trials and review articles were identified through a MEDLINE search of English-language articles published between 1990 and 2006 using the search terms losartan, atenolol, LIFE, hypertension, and LVH. Articles describing major clinical studies, new data, or mechanisms pertinent to the LIFE study were selected for review.

Results: Differences in blood pressure or in the distribution of add-on medications were not evident between study groups in the LIFE study. Thus, the observed outcomes benefits favoring losartan may involve other possible mechanisms, including differential effects of losartan and atenolol on LVH regression, left atrial diameter, atrial fibrillation, brain natriuretic peptide, vascular structure, thrombus formation/platelet aggregation, serum uric acid, albuminuria, new-onset diabetes, and lipid metabolism. Alternative explanations for the LIFE study findings have also been put forward, including the choice of atenolol as an appropriate active comparator and differential effects between treatment groups on central pulse pressure. Additional clinical trials are needed to determine if the beneficial effects of losartan seen in LIFE are shared by other inhibitors of the renin–angiotensin system.

Conclusion: Sub-analyses of the LIFE study data suggest that losartan's stroke benefit may arise from a mosaic of mechanisms rather than a single action. Further studies are expected to continue to delineate the mechanisms of differential responses to treatments in LIFE.     

Losartan for the treatment of hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study

Losartan is an orally active, selective, nonpeptide, angiotensin-II Type I-receptor antagonist, and was the first drug marketed in this class. It has been approved for the treatment of hypertension, and may be used alone or in combination with other antihypertensive agents. Based on the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, losartan has been approved for the reduction of cardiovascular events in patients with hypertension and left ventricular hypertrophy, but there is evidence that this benefit does not apply to black patients. Based on the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, losartan is also indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria, in patients with Type 2 diabetes. The focus of this review is the LIFE study.     

Losartan for the treatment of hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study

Losartan is an orally active, selective, nonpeptide, angiotensin-II Type I-receptor antagonist, and was the first drug marketed in this class. It has been approved for the treatment of hypertension, and may be used alone or in combination with other antihypertensive agents. Based on the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, losartan has been approved for the reduction of cardiovascular events in patients with hypertension and left ventricular hypertrophy, but there is evidence that this benefit does not apply to black patients. Based on the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, losartan is also indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria, in patients with Type 2 diabetes. The focus of this review is the LIFE study.     

Use of losartan in diabetic patients in the primary care setting: review of the results in LIFE and RENAAL

OBJECTIVE: To review outcomes of diabetic patients treated with losartan in two recent randomized, double-blind, clinical trials and compare outcomes to similar studies in diabetics. METHODS: The Reduction in ENdpoints with the Angiotensin II Antagonist Losartan (RENAAL) study recruited 1513 patients with type 2 diabetes and nephropathy. The Losartan Intervention For Endpoint reduction (LIFE) study recruited 9193 hypertensive patients with left ventricular hypertrophy (LVH) including 1195 with diabetes mellitus. The maximum losartan dose in both studies was 100 mg daily. All study patients could receive additional antihypertensive medications, excluding angiotensin converting enzyme inhibitors (ACEIs) and other angiotensin receptor blockers (ARBs), if blood pressures (BP) < 140/90 mmHg were not achieved. In RENAAL, the control group received placebo whereas in LIFE, controls received atenolol. BP reductions were comparable in the treatment and control groups of both studies. In RENAAL, the primary outcome was the composite of doubling of serum creatinine, end-stage renal disease, or death. In LIFE, the primary composite outcome was cardiovascular death and non-fatal myocardial infarction or stroke. RESULTS: In RENAAL, losartan reduced the primary composite end-point 16% (p = 0.02) and the incidence of end-stage renal disease (ESRD) 28% (p = 0.002). In LIFE, the primary composite endpoint among diabetics was reduced 24% (p = 0.03), cardiovascular mortality was reduced 37% (p = 0.03) and total mortality was reduced 39% (p = 0.002). DISCUSSION: In diabetic patients with nephropathy, losartan reduces progression to endstage renal disease. In hypertensive diabetic patients with LVH, losartan reduces cardiovascular morbidity and mortality and total mortality. Angiotensin receptor blockade with losartan appears to confer benefits beyond BP reduction in diabetic patients at high-risk for cardiovascular and renal events.     

Implications of the LIFE trial

The recent Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study was conducted in patients with essential hypertension with electrocardiogram evidence of left ventricular hypertrophy. This showed that losartan compared to atenolol resulted in a significant reduction in the primary endpoint of cardiovascular morbidity and mortality, as well as a greater reduction in electrocardiographically-defined left ventricular hypertrophy. Importantly, this was despite a mean blood pressure reduction which was similar in both groups. Furthermore, the atenolol arm was associated with higher incidence of newly diagnosed diabetics. The LIFE study has firmly confirmed a place for losartan (and other angiotensin receptor blockers) in the management of hypertension. Losartan has also been shown to be effective in diabetics and in patients with atrial fibrillation, as well as in left ventricular hypertrophy regression. This trial also raises the possibility that beta-blockers should perhaps not be used as first-line monotherapy.     

Implications of the LIFE trial

The recent Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study was conducted in patients with essential hypertension with electrocardiogram evidence of left ventricular hypertrophy. This showed that losartan compared to atenolol resulted in a significant reduction in the primary endpoint of cardiovascular morbidity and mortality, as well as a greater reduction in electrocardiographically-defined left ventricular hypertrophy. Importantly, this was despite a mean blood pressure reduction which was similar in both groups. Furthermore, the atenolol arm was associated with higher incidence of newly diagnosed diabetics. The LIFE study has firmly confirmed a place for losartan (and other angiotensin receptor blockers) in the management of hypertension. Losartan has also been shown to be effective in diabetics and in patients with atrial fibrillation, as well as in left ventricular hypertrophy regression. This trial also raises the possibility that β-blockers should perhaps not be used as first-line monotherapy.     

Reversal of Left Ventricular Hypertrophy

Regression of left ventricular hypertrophy (LVH) is an important intermediate target for antihypertensive therapy. Thus, several trials and meta-analyses have attempted to compare the effects of different antihypertensive agents on LVH, but flawed study designs and methodologic problems have limited the utility of these studies. PRESERVE (Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement), LIVE (LVH: Indapamide Sustained Release Versus Enalapril) and LIFE (Losartan Intervention For Endpoint reduction in hypertension) represent a new generation of large well designed trials with the power to compare different antihypertensive drugs. These studies have shown that treatment regimens based on enalapril and a nifedipine gastrointestinal therapeutic system are of similar efficacy (PRESERVE), that indapamide sustained release (SR) is superior to enalapril (LIVE), and that a regimen based on losartan is superior to a regimen based on atenolol (LIFE) in reversing hypertensive LVH. LIVE incorporated on-treatment echocardiographic quality control, with centralized readers blinded for both treatment and sequence of recording. The findings of these rigorous studies, to some extent in disagreement with results of previous meta-analyses, support the notion that antihypertensive drugs need to be judged on their individual effects on important intermediate endpoints such as LVH in well designed and adequately sized studies. However, extrapolation of the results of these studies in terms of class effects could be misleading and should be made with caution.     

Use of losartan in diabetic patients in the primary care setting: review of the results in LIFE and RENAAL

SUMMARY

Objective: To review outcomes of diabetic patients treated with losartan in two recent randomized, double-blind, clinical trials and compare outcomes to similar studies in diabetics.

Methods: The Reduction in ENdpoints with the Angiotensin II Antagonist Losartan (RENAAL) study recruited 1513 patients with type 2 diabetes and nephropathy. The Losartan Intervention For Endpoint reduction (LIFE) study recruited 9193 hypertensive patients with left ventricular hypertrophy (LVH) including 1195 with diabetes mellitus. The maximum losartan dose in both studies was 100?mg daily. All study patients could receive additional antihypertensive medications, excluding angiotensin converting enzyme inhibitors (ACEIs) and other angiotensin receptor blockers (ARBs), if blood pressures (BP) < 140/90?mmHg were not achieved. In RENAAL, the control group received placebo whereas in LIFE, controls received atenolol. BP reductions were comparable in the treatment and control groups of both studies. In RENAAL, the primary outcome was the composite of doubling of serum creatinine, end-stage renal disease, or death. In LIFE, the primary composite outcome was cardiovascular death and non-fatal myocardial infarction or stroke.

Results: In RENAAL, losartan reduced the primary composite end-point 16% (?p = 0.02) and the incidence of end-stage renal disease (ESRD) 28% (?p = 0.002). In LIFE, the primary composite endpoint among diabetics was reduced 24% (?p = 0.03), cardiovascular mortality was reduced 37% (?p = 0.03) and total mortality was reduced 39% (?p = 0.002).

Discussion: In diabetic patients with nephropathy, losartan reduces progression to end-stage renal disease. In hypertensive diabetic patients with LVH, losartan reduces cardiovascular morbidity and mortality and total mortality. Angiotensin receptor blockade with losartan appears to confer benefits beyond BP reduction in diabetic patients at high-risk for cardiovascular and renal events.     

Do losartan and atenolol have differential effects on BNP and central haemodynamic parameters?

INTRODUCTION: It has been suggested that angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) have a differential effect on brachial and aortic haemodynamics. This is why they seem to have beneficial effects that are beyond brachial blood pressure (BP) lowering. We aimed to investigate if this was the case with losartan when compared to atenolol. We also investigated the differential effect of losartan and atenolol on the prognostic marker, brain type natriuretic peptide (BNP). METHODS: We studied 17 patients who were similar to those in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Patients were randomised to receive four months of losartan and atenolol in a crossover fashion. Main outcome measures were BNP and Augmentation index (AIx), which gives an indication of central haemodynamics. Brachial pulse wave velocity (PWV) and time to reflected wave (Tr) were measured as an indication of vascular stiffness. RESULTS: BNP was significantly lower on losartan than atenolol (p=0.007). AIx was lower on losartan than atenolol (p=0.03), however, this result was not significant when heart rate was considered as a covariate (p=0.09). Heart rate was significantly lower on atenolol than losartan (p=0.03). There was no difference between treatments for both brachial PWV and Tr (p=0.2 and p=0.99, respectively). CONCLUSION: The benefits seen when losartan was compared to atenolol in the LIFE trial may be due to a reduction in BNP. We failed to detect a differential effect in central compared to peripheral haemodynamics when losartan was compared to atenolol.     

Losartan: a review of its use, with special focus on elderly patients

Losartan is an orally active, nonpeptide, selective angiotensin subtype 1 (AT1) receptor antagonist. It provides a more specific and complete blockade of the actions of angiotensin II than renin or ACE inhibitors. Short term (up to 12 weeks' duration) clinical trials have shown losartan to be as effective at lowering blood pressure (BP) [causes a decrease in BP < or = 26/20 mm Hg] in elderly patients with hypertension as recommended dosages of captopril, atenolol, enalapril, felodipine and nifedipine. In patients with isolated systolic hypertension (ISH) the efficacy of losartan was similar to that of atenolol. The addition of hydrochlorothiazide to losartan therapy provides greater antihypertensive efficacy, equivalent to that seen with captopril plus hydrochlorothiazide. Preliminary evidence also indicates that losartan therapy contributes to the regression of left ventricular hypertrophy associated with chronic hypertension. Exercise capacity is increased by losartan in patients with either asymptomatic or symptomatic heart failure. Results from the Losartan Heart Failure Survival or ELITE II (Evaluation of Losartan in the Elderly II) study indicate that there was no statistically significant difference between losartan and captopril in reducing overall deaths or in reducing sudden cardiac death and/or resuscitated cardiac arrest in patients with heart failure. Other than ELITE II, little conclusive long term mortality and morbidity data exist for losartan. Additional long term trials to evaluate the survival benefits of losartan in elderly patients with hypertension, renal disease or after an acute myocardial infarction are currently in progress. In elderly patients with hypertension, the incidence of treatment-related adverse events associated with once daily losartan (alone or in combination with hydrochlorothiazide) [19 to 27%] was similar to felodipine (23%) and nifedipine (21%), however, losartan tended to be better tolerated than captopril (11 vs 16%). Losartan was also better tolerated than atenolol in patients with ISH (10.4 vs 23%). In patients with heart failure the renal tolerability of losartan was similar to that of captopril, but losartan was associated with a lower withdrawal rate because of adverse events. No dosage adjustment is required in elderly or in patients with mild to moderate renal dysfunction, and the risk of first-dose hypotension is low. Conclusions: comparative data have shown losartan to be as effective as other antihypertensive agents in the treatment of elderly patients with hypertension. Treatment with losartan is therefore an option for first-line therapy in all patients with hypertension, particularly those who are not well managed with or who are intolerant of their current therapy. Morbidity and mortality data from the Losartan Heart Failure Survival (ELITE II) study show that losartan has potential in the treatment of heart failure.     

Blood pressure reduction and antihypertensive medication use in the losartan intervention for endpoint reduction in hypertension (LIFE) study in patients with hypertension and left ventricular hypertrophy

ABSTRACT

Objective: To compare blood pressure response and antihypertensive medication use visit-by-visit from baseline in patients receiving losartan-based or atenolol-based therapy in the LIFE study.

Research design: LIFE was a randomized, double-blind trial comparing losartan-based and atenolol-based treatment regimens on the primary composite endpoint of death, myocardial infarction (MI), or stroke in 9193 patients aged 55–80 years with hypertension and left ventricular hypertrophy. Systolic and diastolic, pulse, and mean arterial pressures, blood pressure responder rates, distribution of open-label antihypertensive agents utilized, and the proportion of patients on randomized treatment were determined for each group at each clinic visit over a follow-up period of at least 4 years.

Results: Overall blood pressure reductions were comparable in the losartan-based and atenolol-based treatment groups. The mean reductions in sitting trough systolic and diastolic blood pressures from baseline to the end of follow-up (or last visit before a primary endpoint event) were 30.2/16.6?mmHg in the losartan group and 29.1/16.8?mmHg in the atenolol group. The time-averaged difference in overall mean arterial pressure was similar between groups. The proportion of patients on individual dose combinations varied visit by visit but was generally comparable between groups. During the entire study, 56% (2579/4605) of losartan-treated patients received at least one dose of the combination of losartan 100?mg plus hydrochlorothiazide 12.5?mg and 51% of atenolol-treated patients received 100?mg of atenolol plus hydrochlorothiazide 12.5?mg at some time during the study.

Conclusions: Differences in blood pressure or distribution of add-on medications between treatment groups were not evident in the LIFE trial and, thus, cannot account for the observed outcome difference in the primary endpoint of risk reduction of the composite of cardiovascular death, stroke and MI favoring losartan.     

Uric acid levels and vascular disease

SUMMARY

There is evidence showing that serum uric acid (SUA) levels predict the risk for vascular events. For example, up to 29% of the reduction in the primary composite endpoint seen in the LIFE trial (favouring losartan versus atenolol) can be attributed to a fall in SUA levels. We also discuss the findings of the GREACE study (treating to target with atorvastatin versus ‘usual’ care) in relation to SUA levels. In this brief comment we extend this argument to consider the SUA-lowering effect of other drugs commonly prescribed in patients with vascular disease (e.g. statins, fibrates and antihypertensive agents).     

Dual Therapy in Hypertensive Patients with Coronary Artery Disease: The Role of Calcium Channel Blockers and β-Blockers

BP is the most important determinant of the risk of stroke. A small reduction in BP results in a substantial reduction of both ischemic and hemorrhagic stroke. Any of the commonly used antihypertensive drugs lower the incidence of stroke, with larger reductions in BP resulting in larger reductions in risk. Experimental evidence has linked the renin-angiotensin system (RAS) to the development and progression of cerebrovascular disease. Inhibition of the RAS has beneficial cerebrovascular effects and may reduce the risk of stroke in a manner possibly independent from the alterations of BP. Some clinical trials even suggest that ACE inhibitors and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) exert cerebroprotective effects beyond BP lowering, but the evidence is controversial. Studies on specific protective actions of antihypertensive drugs are generally hampered by the fact that any treatment-related difference in BP may play a dominant role in the prevention of stroke. There are also indications that the protective potency of ARBs might be superior to that of ACE inhibitors, due to their differential activation of angiotensin II type 2 receptors, but the clinical relevance of this mechanism is unclear. Some studies in primary prevention of stroke, acute stroke, and secondary prevention show advantages for ARBs beyond controlling BP alone. In primary prevention, the LIFE randomized trial showed a significant difference in stroke rate in favor of losartan compared with atenolol despite similar reductions in BP. In acute stroke, the role of hypertension and its treatment remains controversial. ACCESS, however, suggested that an ARB is safe in hypertensive acute stroke patients and may offer advantages independent from BP control. In secondary stroke prevention, there are very few antihypertensive trials. These trials show that BP lowering is at least as successful as in primary prevention, but the absolute stroke risk is much higher. An ACE inhibitor was effective compared with placebo in the PROGRESS trial. The MOSES study showed that eprosartan prevented vascular events more effectively than nitrendipine, despite similar BP-lowering effects. Hypertension is not only the most important risk factor for stroke, but is also closely correlated with cognitive decline and dementia. Therefore, prevention of cognitive decline or even improvement of slightly diminished brain function should be an important goal for antihypertensive treatment in the future. Some clinical data suggest advantages for ACE inhibitors, ARBs, and calcium channel antagonists. Currently, however, the existing data are not sufficient for clinical recommendations. Therefore, ongoing trials will further define the exact role of inhibitors of the RAS and are urgently needed in secondary prevention, in acute stroke, and in the prevention of cognitive decline.     

洛沙坦与苯那普利治疗原发性高血压左室肥厚的对比研究

评价洛沙坦治疗高血压左室肥厚的疗效并与苯那普利作比较。原发性高血压左室肥厚患者５０例,随机分为洛沙坦治疗组（２５～５０ｍｇ／ｄ）、苯那普利治疗组（５～２０ｍｇ／ｄ）,疗程４个月,结果洛沙坦或苯那普利治疗后血压比治疗前显著降低,两组对左室肥厚的逆转率分别为８０％与７２％,逆转作用无差别,不良反应发生率洛沙坦比苯那普利明显减少。本文资料显示,洛沙坦是降低血压、逆转左室肥厚疗效较好的药物。     

Angiotensin II antagonism and the heart: valsartan in left ventricular hypertrophy

Left ventricular hypertrophy (LVH) represents an independent risk factor for cardiovascular morbidity and mortality, and normalization of left ventricular mass has become a desirable goal of antihypertensive treatment. In a randomized, double-blind study, the angiotensin II (AT1-receptor) antagonist valsartan (Diovan ; 80-160 mg q.d.) was compared with the beta-blocker atenolol (50-100 mg q.d.) over 8 months in previously untreated patients with essential hypertension and LVH. Sixty-nine patients were randomized, of whom 58 were evaluated by echocardiography. After 8 months of treatment in the atenolol group [n = 8 with additional hydrochlorothiazide (HCTZ)], initial blood pressure was reduced from 160/103 to 147/92 mm Hg (p < 0.0001). In the valsartan group (n = 9 with HCTZ), blood pressure decreased from 163/101 to 146/90 mm Hg (p < 0.0001). Left ventricular mass index decreased from 127 to 117 g/m2 in the atenolol group and from 127 to 106 g/m2 in the valsartan group. Long-term treatment with valsartan resulted in a significant reduction of LVH in patients with essential hypertension.