Degree Of Blood Pressure Lowering Research Articles

Analytical Methods for Determination of Certain Sartans and Diuretics

Hypertension is a progressive cardiovascular syndrome with a variety of causes, including cardiovascular risk factors that can lead to changes in heart and blood vessels function and structure. Hypertension is a chronic disease that has negative effects on human health and is the main cause of cardiovascular-disease related deaths. The main objective of the treatment of hypertension is to reduce the overall risk of long-term cardiovascular disease and cardiovascular disease-related mortality, which is closely related to the degree of blood pressure lowering. Antihypertensive drugs describe several classes of compounds with the therapeutic action of preventing, controlling, or treating hypertension. Antihypertensive drug classes differ both structurally and functionally.

Vascular legacy: HOPE ADVANCEs to EMPA-REG and LEADER: A Surprising similarity.

Recently reported cardiovascular outcome studies on empagliflozin (EMPA-REG) and liraglutide (LEADER) have spurred interest in this field of diabetology. This commentary compares and contrasts these studies with two equally important outcome trials conducted using blood pressure lowering agents. A comparison with MICROHOPE (using ramipril) and ADVANCE (using perindopril + indapamide) blood pressure arms throws up interesting facts. The degree of blood pressure lowering, dissociation between cardiovascular and cerebrovascular benefits, and discordance between renal and retinal outcomes are surprisingly similar in these trials, conducted using disparate molecules. The time taken to achieve such benefits is similar for all drugs except empagliflozin. Such discussion helps inform rational and evidence-based choice of therapy and forms the framework for future research.

Is amlodipine more cardioprotective than other antihypertensive drug classes?

Is amlodipine more cardioprotective than other antihypertensive drug classes?

Evaluation of the antihypertensive efficacy and safety of moxonidine in the treatment of uncomplicated hypertensive crisis

Aim. To evaluate the clinical efficacy and safety of the selective imidazoline I1-receptor agonist moxonidine versus the angiotensin-converting enzyme inhibitor captopril in patients with uncomplicated hypertensive crisis (UHC). Subjects and methods. Two hundred and twenty-five patients (125 women, 100 men) aged 56,2±14,4 years with UHC were examined. The patients were randomized to a group of once-daily 0.4 mg moxonidine orally (n=113) and a group of once-daily 25 mg captopril (n=112). Dynamic measurements of blood pressure (BP) and heart rate, electrocardiogram recording, and determinations of blood creatinine, potassium, and glucose levels were made along with general clinical examination. The efficacy indices in patients were time to the onset of antihypertensive action, degree of BP lowering, and duration of antihypertensive effect. duration. 24-hour BP monitoring was used to evaluate the efficacy of the drugs compared. The time course of changes in the parameters was analyzed for 12 hours. Results. Both groups achieved an antihypertensive effect as a significant reduction in systolic and diastolic BP 30 and 60 min after therapy initiation, respectively; at the same time BP decreases did not exceed 25% of the baseline levels. Moxonidine was found to be more effective mainly in the duration of its antihypertensive effect with a steady BP decline throughout the follow-up. There was evidence that moxonidine exerted a positive metabolic effect, particularly in significantly reducing blood creatinine levels. In the moxonidine group, the patients with above satisfactory efficacy were 26,9% significantly more and those with above satisfactory tolerance were 18,8% more. Conclusion. The findings suggest that moxonidine versus captopril is highly effective and well tolerated in patients with UHC. The drug may be successfully used to treat UHC, starting in the prehospital period, especially in patients with concomitant diseases (diabetes mellitus, metabolic syndrome, chronic renal failure).

Kidney and heart: TGFβ1-mediated cross-talk

Rzeźnik et al. [1] in their recent paper published in ‘Kardiologia Polska’ found that revascularisation of unilateral or bilateral renal artery stenosis (RAS) leads to improvement in several echocardiographic parameters reflecting heart structure and function, as well as impacts on plasma transforming growth factor β1 (TGFβ1) and B-type natriuretic peptide. At least some of the effects on the heart (such as LVMI reduction) did not depend on the degree of blood pressure lowering. As can be concluded from the publication, patients did not suffer from symptomatic heart failure (HF; at least in NYHA class III–IV); however, it has been demonstrated recently that RAS revascularisation may also be associated with improvement in NYHA class and reduction in the risk of hospitalisation for HF in patients with concomitant RAS and HF [2]. The message delivered by this paper is very important for both nephrologists and cardiologists. TGFβ1 remains one of the key profibrotic growth factors in renal pathology. It is produced by damaged mesangial cells in the glomerulus (and is crucial for the development of glomerular sclerosis), injured tubular cells and resident interstitial fibroblasts (resulting in interstitial fibrosis). HF in the course of atherosclerotic RAS may develop according to least three different scenarios: (1) Both HF and RAS are consequences of the same, devastating, pathology, namely advanced atherosclerosis; (2) RAS contributes to heart remodelling and dysfunction due to significantly elevated and difficult-to-control hypertension; (3) Humoral mediators released from injured (ischaemic) renal parenchyma may remotely damage the heart (and this may be the case with TGFβ1). The role of TGFβ1 in the development of several heart diseases resulting in myocardial fibrosis has been well recognised for some years [3]. Experimental data suggest that RAS triggers the synthesis and release of several inflammatory and vasoconstrictive agents from the kidney, in addition to the activation of the renin–angiotensin–aldosterone (RAA) axis. These include, among others, endothelin, interleukin-6, TNFα and TGFβ1. It has been demonstrated that disruption of the Smad3 protein gene (signalling pathway essential for TGFβ1 effects) prevents fibrosis of the kidney supplied by stenotic artery even if stenosis persists [4]. Infusion of endothelial progenitor cells into the artery with stenosis significantly decreases plasma levels of several proinflammatory cytokines, prevents myocardial damage and remodelling, even in stenosis remains uncorrected and there is no change in systemic blood pressure [5]. TGFβ1 is one of the key effector molecules involved in epithelial-to-mesenchymal transition, the process of phenotypic change of epithelial tubular cells into fibroblast-like cells — now considered one of the most important mechanisms that lead to kidney fibrosis. A similar process has also been described for cardiac endothelium and was called ‘endothelial-to-mesenchymal transition’ (Endo-MT) [6]. These and other findings should lead to caution when interpreting apparently ‘negative’ trials published recently on RAS which did not demonstrate any substantial be nefit associated with renal artery revascularisation ± stenting vs. medical therapy — effects on blood pressure and/or kidney function were exactly the same in both types of intervention. Now it is tempting to speculate that successful RAS revascularisation might be a much more definite strategy compared to everyday use of RAA axis blockade in lowering TGFβ1 and thus in limiting the impact of this growth factor on the heart and the kidneys. It seems however plausible to expect some lag time between intervention and expected cardiac benefits, not necessarily apparent in the short time following intervention. The findings of Rzeźnik et al. [1] may hold some promise for more delayed, but possible, benefit following RAS revascularisation for the heart, and possibly for the kidneys.

Optimizing blood pressure control in hypertension: The need to use ABPM

Hypertension is the most prevalent, treatable cause of cardiovascular (CV) disease. Patients with hypertension and one or more comorbidities increasingly form a significant part of the primary care practitioner's caseload. The emphasis on intensive blood pressure (BP) lowering has softened, encouraging any degree of BP lowering, since any fall in BP is beneficial for reducing CV risk. Consistency of BP control during long-term therapy (i.e. low visit-to-visit variability) and decreasing BP variability over 24-h may be as, if not more, important than degree of BP lowering per se. Fluctuations in BP between visits as well as within a 24-h period have been associated with increased CV risk. Ambulatory BP monitoring (ABPM) is a crucial element of the clinician's armamentarium not only for assessing the “true” BP load and fluctuations under real-life conditions but for identification of various abnormal BP patterns that may require attention, including white- coat hypertension, masked hypertension, non-dipping and the morning BP surge. ABPM provides accurate assessment of treatment effectiveness over 24-h and may lead to better tailoring of therapy. This article reviews the benefits of ABPM and discusses the importance of selecting long-acting antihypertensive agents for optimizing BP control.

Sodium nitroprusside: pharmacological aspects of its interaction with hydroxocobalamin and thiosulphate.

Hydroxocobalamin (HOCb), when mixed with sodium nitroprusside (SNP) in a 10:1 or 1:1 molar ratio and injected (i.v.) into the anaesthetized rat, prolonged the depressor response to SNP by 25-50%, but did not affect the degree of blood pressure lowering. Both the 'onset' and 'offset' components of the response were prolonged. Injecting [14C]SNP along with a 10-fold molar excess of HOCb resulted in a 2- to 3-fold elevation of plasma radioactivity which was maintained during the first 10 min of a 40 min experimental period. These effects of HOCb on the pharmacodynamics and pharmacokinetics of SNP are probably due to complex formation between the two compounds. Sodium thiosulphate (ST) added to SNP (12:1 molar ratio) had no effect on the depressor response to SNP. This mixing of ST and SNP had a less-marked influence on the plasma [14C] SNP-derived radioactivity than occurred with HOCb. There was no initial elevation of radioactivity, but the levels were raised by 50-60% at 4, 6 and 10 min. Since the depressor response to SNP was unaffected by ST, it is presumed that the higher concentrations of radioactivity were due to inactive degradation products rather than the active species itself.

Optimal management of hypertension in elderly patients.

Hypertension is a common and important modifiable risk factor for cardiovascular and kidney diseases. The prevalence of hypertension, particularly isolated systolic hypertension, increases with advancing age, and this is partly due to the age-related changes in the arterial tree, leading to an increase in arterial stiffness. Therapeutic lifestyle changes, such as reduced dietary sodium intake, weight loss, regular aerobic activity, and moderation of alcohol consumption, have been shown to benefit elderly patients with hypertension. Lowering blood pressure (BP) using pharmacological agents reduces the risk for cardiovascular morbidity and mortality, with no difference in risk reduction in elderly patients compared to younger hypertensives. Guidelines recommend a BP goal of <140/90 in hypertensive patients regardless of age and <130/80 in patients with concomitant diabetes or kidney disease, and lowering the BP further has not been shown to confer any additional benefit. Moreover, the choice of antihypertensive does not seem to be as important as the degree of BP lowering. Special considerations in the treatment of elderly hypertensive patients include cognitive impairment, dementia, orthostatic hypotension, and polypharmacy.

Blood pressure reduction for the secondary prevention of stroke: a Chinese trial and a systematic review of the literature

We assessed, in a double-blind, placebo-controlled trial, whether lowering blood pressure (BP) prevents the recurrence of stroke in Chinese patients with cerebrovascular disease. Patients were randomized into two groups: 2825 patients received a placebo and 2840 patients received 2.5 mg of indapamide daily. The primary and secondary outcomes were the recurrence of fatal or nonfatal stroke and major fatal and nonfatal cardiovascular events, respectively. The average systolic/diastolic BP at randomization was 153.8/92.8 mm Hg. At median follow-up (2 years), BP was, on an average, 6.8/3.3 mm Hg lower in patients on active treatment. In total, 143 patients on indapamide and 219 patients on placebo had recurrent strokes (hazard ratio for indapamide, 0.69; 95% confidence interval (CI): 0.54-0.89; P<0.001). In addition, 199 patients on indapamide and 258 patients on placebo had a cardiovascular event (hazard ratio, 0.75; 95% CI: 0.89-0.62; P=0.002). We performed a systematic review of literature that included our new results. Across 10 trials, the odds ratio for the prevention of stroke recurrence by BP lowering was 0.78 (95% CI: 0.68-0.90; P=0.0007). The pooled odds ratio was 0.63 (95% CI: 0.54-0.73; P<0.0001) for trials involving diuretics as a component of therapy and 0.93 (95% CI: 0.87-1.01; P=0.086) for trials in which treatment included renin system inhibitors (P<0.0001 for heterogeneity). The weighted correlation between the odds for stroke recurrence and the reduction in systolic BP was -0.57 (P=0.067). In conclusion, BP lowering by indapamide treatment reduced the recurrence of stroke and the incidence of cardiovascular events in Chinese patients with cerebrovascular disease. Whether prevention of stroke recurrence depends on drug class, degree of BP lowering or both requires further investigation.

The Effect of Antihypertensive Drugs on Carotid Intima Media Thickness: An Up-to-Date Review

Atherosclerosis and hypertension are two important pathological vascular processes which share a crucial common pathway: an altered vascular homeostasis characterized by endothelial dysfunction. Carotid intima-media thickness (CIMT) measured by ultrasound has been shown to correlate with the presence of cardiovascular disease and is now widely accepted as a subclinical marker for atherosclerotic disease. Large body of evidences has shown that antihypertensive drugs exert important anti-atherosclerotic effects, which depend to some extent on the degree of blood pressure lowering provided by these drugs. Many randomized clinical trials of antihypertensive drugs (calcium channel blockers, angiotensin converting enzyme inhibitors, alpha- and beta-blockers, diuretics, and angiotensin-1 receptor blockers) compared with placebo or no-treatment have demonstrated both a reduction of CIMT, a validated measure of subclinical atherosclerosis and predictor risk for clinical cardiovascular events, than a protection against clinical stroke events. However, important technical aspects of CIMT measurement must be considered. Over the last twenty years there have been great changes in the sensitivity of transducers and hence accuracy of measurement. This review explores the effectiveness of antihypertensive drugs in preventing CIMT progression and/or regression.

Management of Hypertension and Cerebrovascular Disease in the Elderly

Cardiovascular disease and stroke disproportionately affect the elderly. The risk for stroke and transient ischemic attack increases exponentially with age. Blood pressure is a potent modifiable target for reducing the risk for stroke in the elderly. In elderly patients with isolated systolic hypertension and those with intracranial atherosclerotic disease, blood pressure lowering has consistently been shown to be well tolerated and effective in reducing the risk for stroke and its complications. Evidence suggests that ambulatory blood pressure monitoring may provide a more sensitive means of detecting patients at risk and monitoring therapeutic effect. Agents that modify the renin-angiotensin system, particularly angiotensin receptor blockers, may confer additional benefit in stroke protection beyond blood pressure lowering. Several clinical trials currently in progress promise to provide guidance regarding the optimal choice of agent and degree of blood pressure lowering for prevention of stroke and cognitive decline in elderly patients.

Management of Hypertension in Patients with Cardiac Disease: Use of Renin-Angiotensin Blocking Agents

Inhibition of renin-angiotensin system (RAS) activity using angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ARBs) is beneficial in patient populations with left ventricular dysfunction or systolic heart failure (HF) and other forms of heart disease. In high-risk patients with coronary heart disease (CHD), treatment with these agents reduces the mortality rate and improves secondary outcomes. Individuals with stable CHD who are at lower risk benefit less from treatment. RAS inhibition also provides some clinical benefit to patients with diastolic HF and preserved left ventricular function. Left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular events and all-cause mortality in patients with hypertension. Treatment with an ARB reduces the risk for adverse cardiovascular outcomes in patients with hypertension and LVH. The benefits correlate with regression of LVH, and the effect is independent of the degree of blood pressure lowering. Finally, studies indicate that a history of hypertension in patients who have not had a myocardial infarction (MI) increases the risk for HF after MI; the risk is decreased in patients with hypertension who receive treatment with a RAS inhibitor.

Pharmacological interventions for hypertensive emergencies: a Cochrane systematic review

Hypertensive emergencies occur when high blood pressure is associated with the presence of acute end-organ damage, such as hypertensive encephalopathy. There is controversy as to when and which antihypertensive drugs to use in these situations. Using a comprehensive search strategy in electronic sources, MEDLINE, EMBASE and Cochrane clinical trial register, we conducted a systematic review to look all randomized control trials (RCTs) that compare an antihypertensive drug versus placebo, no treatment or another antihypertensive drug. Fifteen RCTs (representing 869 patients) met the inclusion criteria. Two trials included a placebo arm. All studies (except one) were open-label trials. Seven drug classes were evaluated in those trials: nitrates (nine trials), angiotensin-converting enzyme inhibitors (seven), diuretics (three), calcium channel blockers (six), alpha-1 adrenergic antagonists (four), direct vasodilators (two) and dopamine agonists (one). Mortality event data were reported in seven trials. Due to insufficient data, no meta-analysis was performed for clinical outcomes. Differences in blood pressure changes between antihypertensives were minor. There is no RCT evidence demonstrating that antihypertensive drugs reduce mortality or morbidity in patients with hypertensive emergencies. Furthermore, there is insufficient RCT evidence to determine which drug or drug class is most effective in reducing mortality and morbidity. There were some minor differences in the degree of blood pressure lowering when one class of antihypertensive drug is compared to another. However, the clinical significance is unknown. RCTs are needed to assess different drug classes to determine initial and longer-term mortality and morbidity outcomes.

Pharmacological interventions for hypertensive emergencies

Hypertensive emergencies, marked hypertension associated with acute end-organ damage, are life-threatening conditions. Many anti-hypertensive drugs have been used in these clinical settings. The benefits and harms of such treatment and the best first-line treatment are not known. To answer the following two questions using randomized controlled trials (RCTs): 1) does anti-hypertensive drug therapy as compared to placebo or no treatment affect mortality and morbidity in patients presenting with a hypertensive emergency? 2) Does one first-line antihypertensive drug class as compared to another antihypertensive drug class affect mortality and morbidity in these patients? Electronic sources: MEDLINE, EMBASE, Cochrane clinical trial register. In addition, we searched for references in review articles and trials. We attempted to contact trialists. Most recent search August 2007. All unconfounded, truly randomized trials that compare an antihypertensive drug versus placebo, no treatment, or another antihypertensive drug from a different class in patients presenting with a hypertensive emergency. Quality of concealment allocation was scored. Data on randomized patients, total serious adverse events, all-cause mortality, non-fatal cardiovascular events, withdrawals due to adverse events, length of follow-up, blood pressure and heart rate were extracted independently and cross checked. Fifteen randomized controlled trials (representing 869 patients) met the inclusion criteria. Two trials included a placebo arm. All studies (except one) were open-label trials. Seven drug classes were evaluated in those trials: nitrates (9 trials), ACE-inhibitors (7), diuretics (3), calcium channel blockers (6), alpha-1 adrenergic antagonists (4), direct vasodilators (2) and dopamine agonists (1). Mortality event data were reported in 7 trials. No meta-analysis was performed for clinical outcomes, due to insufficient data. The pooled effect of 3 different anti-hypertensive drugs in one placebo-controlled trial showed a statistically significant greater reduction in both systolic [WMD -13, 95%CI -19,-7] and diastolic [WMD -8, 95%CI, -12,-3] blood pressure with antihypertensive therapy. There is no RCT evidence demonstrating that anti-hypertensive drugs reduce mortality or morbidity in patients with hypertensive emergencies. Furthermore, there is insufficient RCT evidence to determine which drug or drug class is most effective in reducing mortality and morbidity. There were some minor differences in the degree of blood pressure lowering when one class of antihypertensive drug is compared to another. However, the clinical significance is unknown. RCTs are needed to assess different drug classes to determine initial and longer term mortality and morbidity outcomes.

ORIGINAL RESEARCH—BASIC SCIENCE: Effects of ACE Inhibition and Beta-Blockade on Female Genital Structures in Spontaneously Hypertensive Rats

ABSTRACT Introduction and Aim This study evaluated the possible differences between an angiotensin converting enzyme (ACE) inhibitor and a beta-blocker concerning their potential protective role on female external genitalia in spontaneously hypertensive rats (SHR). Main Outcome Measures Morphological changes in the clitoris after antihypertensive treatments. Methods For 6 months, SHR received no treatment; SHR+ramipril (RAM), SHR+atenolol (AT), and control Wistar Kyoto (WKY) rats received no treatment. Clitorises were processed for immunohistochemistry using anti-α-smooth muscle actin (α-SMA), anti-collagen I and III, anti-transforming growth factor β1 (TGFβ1), and anti-endothelial nitric oxide synthase (eNOS) antibodies. Results SHR+RAM and SHR+AT presented significantly lower blood pressure in both groups vs. untreated SHR. Compared with WKY, α-SMA was increased in the arteries and in the cavernous spaces of the clitoris together with a marked increase in wall/lumen ratio in clitoral vessels in untreated SHR. All these alterations were diminished in SHR+AT (P &amp;lt;0.01). SHR+RAM presented differences with respect to SHR+AT in the reduction of these variables. TGFβ1 expression in the vessel wall from the clitoris and collagen I and III deposition in the interstitium from the clitoris in untreated SHR were significantly more (P &amp;lt;0.01) than in WKY. While SHR+AT showed a mild decrease in these variables, SHR+RAM presented a significant reduction (P &amp;lt;0.01) in TGFβ1 expression interstitial fibrosis and in both types of collagens. Positive immunostaining of eNOS in the sinusoidal endothelium from the clitoris was less (P &amp;lt;0.01) in untreated SHR (3.4 ± 1.3%) and SHR+AT (5.1 ± 1.2%) than in SHR+RAM (17.2 ± 1.6%) and WKY (15.9 ± 1.7%). Untreated SHR and SHR+AT presented more surrounding connective tissue at the perineurium in the clitoris (P &amp;lt;0.01) than SHR+RAM. Conclusion ACE inhibition provided a considerable protective role on the female external genitalia structures in SHR by a mechanism that may be, at least in part, independent of the degree of blood pressure lowering.

Hypertension Treatment—A Success Study

Hypertension Treatment—A Success Study

More Confusing Messages From the Hypertension Treatment Trials

More Confusing Messages From the Hypertension Treatment Trials

The value of lowering blood pressure

According to the Canadian Heart Health Survey, only 14% of Canadian hypertensive patients are aware of their disease and are treated appropriately. One of the reasons for this could be that physicians are confused by an excess of confusing and contradictory information regarding the choice of drugs. Two recent publications may contribute to a much-needed simplification of the problem. The Blood Pressure Lowering Treatment Trialists' Collaboration published a meta-analysis based on 29 randomized trials that comprised a total of more that 162,000 participants. The treatment regimens were based on angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, beta-blockers and calcium channel blockers. The main finding of the meta-analysis was that treatment with any of the blood pressure-lowering regimens reduced the risk of major cardiovascular events, and the extent of these risk reductions was directly related to the degree of blood pressure lowering. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) compared valsartan with amlodipine. At the end of the study, the reductions in blood pressure from baseline were 17.3/9.9 mmHg in the amlodipine group and 15.2/8.2 mmHg in the valsartan group (P<0.0001). There was a significantly lower incidence of myocardial infarction in the amlodipine group (4.1%) than in the valsartan group (4.8%). From these two studies, it would be reasonable to conclude that the treatment of elevated blood pressure has two main goals: to achieve a normal blood pressure and to produce a happy patient. The agent or agents used to obtain these goals are relatively unimportant.

Importance of controlling blood pressure

Cardiovascular disease is the leading cause of death and disability world-wide. Blood pressure, throughout the range seen in developed countries, is the most important risk factor for cardiovascular disease. Lowering blood pressure within the whole population by lifestyle interventions, such as reducing dietary salt intake and increasing the consumption of fruit and vegetables, will be of great benefit. Blood pressure-lowering trials also demonstrate immense benefits in preventing strokes, heart failure and coronary heart disease. There are no differences in outcome between the different methods used to lower blood pressure and the benefit is proportional to the degree of blood pressure-lowering.Thiazide diuretics are effective in lowering blood pressure and have been the most widely prescribed blood pressure-lowering drugs. They work by causing both sodium and water loss, but also cause potassium loss and a fall in plasma potassium levels. The latter may mitigate the beneficial effects from blood pressure-lowering. Some diuretics, such as spironolactone, affect the distal tubule and do not cause a fall in plasma potassium levels. However, spironolactone has endocrine side-effects associated with the fact that it is not specific for the mineralocorticoid receptor. The development of a more selective aldosterone antagonist without endocrine side-effects could be a major advance as it would be able to oppose the effects of aldosterone, both on sodium retention and potassium loss and the other vascular effects.

Update on the management of hypertension: do recent clinical trial results indicate a change in national recommendations for therapy?

Numerous hypertension treatment trials have been reported during the past several years. In comparative studies it has been shown that the use of diuretics or diuretics/beta blockers has resulted in a reduction in morbidity/mortality equivalent to the use of other antihypertensive medications. This is true in both young and elderly patients. In one large 8-year study in diabetics, the use of a beta blocker/diuretic combination was shown to be as effective in reducing overall cardiovascular events as an angiotensin-converting enzyme (ACE) inhibitor/diuretic treatment program. Although most data indicate that the degree of blood pressure lowering accounts for most of the benefit, there are some differences in outcome that may be explained by different mechanisms of drug action. For example: 1) diuretics are more effective in preventing heart failure and overall cardiovascular events than alpha blockers; 2) an ACE inhibitor-based program is more effective in the elderly in reducing myocardial infarctions and heart failure than a calcium channel blocker-based program; and 3) a nondihydropyridine is more effective in reducing strokes, but less effective in preventing myocardial infarctions or heart failure, than a program based on diuretic therapy. There is also abundant evidence that the use of ACE inhibitors may prevent the occurrence of diabetes in hypertensive individuals and will reduce cardiovascular events in diabetics. Finally, the angiotensin receptor blockers have been shown to slow the progression of renal disease and prevent the occurrence of end-stage renal disease when compared to treatment regimens that do not include an angiotensin receptor blocker or ACE inhibitor. Updated treatment recommendations should include an ACE inhibitor and possibly an angiotensin receptor blocker along with diuretics and beta blockers as initial therapy. In addition, recommendations for the use of multiple-drug therapy have been reinforced by recent trials. Goal pressures are not readily achieved with monotherapy, especially in high-risk patients.