Initial Therapy For Hypertension Research Articles

Effective therapy of hypertension from the standpoint of patient-centered medicine

The article presents current data on the choice of antihypertensives from the standpoint of patient-centered medicine. The advantages of combined initial therapy includes high medical adherence, achievement of target blood pressure, and organ protection. Data on the effectiveness of a fixed-dose combination of an angiotensin-converting enzyme inhibitor and a thiazide-like diuretic, in particular, the most commonly used angiotensin-converting enzyme inhibitor lisinopril and long-acting indapamide, are presented. This combination is not only highly effective, but also metabolically neutral, which allows it to be used in patients with obesity, diabetes, and liver diseases. Data are presented on the new favorable effects of lisinopril and indapamide, in particular, on the effect of indapamide on the intestinal microbiota. The potential advantages of this combination as an initial therapy for hypertension in Russian patients are described.

A Phenolic Compound of Endophytic Fungi Isolated from Stem of Syzygium aqueum and its Diuretic Activity

Guava (Syzygium aqueum), a typical Indonesian crop plant, has diuretic properties. Plants used as diuretic medicines can also be valuable sources for endophytic fungi containing diuretic drugs. The aims of this study were to isolate and identify endophytic fungi from S. aqueum stems, to isolate their secondary metabolites, and to conduct in vivo tests of the diuretic activity of an endophytic fungus extract on white male rats of the Wistar strain. Endophytic fungi were isolated by a direct plating method, and fungal isolates were identified molecularly. A phenolic compound was isolated by chromatography, and the chemical structure was identified spectroscopically. Doses of 100, 200, and 300 mg/kg BW were administered to white male rats divided into six groups (normal control, negative control, positive control, and the three treatment groups). Diuretic tests included urine volume; sodium, chloride, and calcium electrolyte levels; and pH. Phylogenetic analysis identified the endophytic fungal isolate as Trichoderma ghanense (isolation code SA1). The secondary metabolite isolated from the T. ghanense extract was a phenolic compound. Diuretic tests using the endophytic fungus extract showed the highest urine volume with a dose of 300 mg/kg BW. The diuretic test results showed an increase in urine volume and levels of sodium, potassium, and chloride ions in the urine. The extract of T. ghanense isolated from the stem of S. aqueum has the potential as initial therapy for hypertension because it contains phenolic secondary metabolites that show diuretic activity.

Carvedilol and bisoprolol as initial therapy for adult hypertension without compelling indications

Although beta blockers have been used as initial therapy for ischemic heart diseases and heart failure, the beneficial effects of beta blockers are controversial compared with other antihypertensive agents as initial therapy for hypertension without compelling indications. Moreover, atenolol has been most commonly used with beta blockers. The objective of the present systematic review associated with the Japanese Society of Hypertension (JSH) 2019 Hypertension Guideline (Clinical Question 6) was to assess the outcomes (cardiocerebrovascular mortality, total cause mortality, hypotension, bradycardia, other adverse effects, and changes in systolic blood pressure (SBP)) of currently used carvedilol and bisoprolol as initial therapy for adult hypertension without compelling indications. Two independent systematic reviewers searched randomized controlled trials (RCTs) up to October 2017 in the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, EMBASE Ovid, and ClinicalTrials.gov. Finally, eight RCTs with 2494 participants were identified to meet our inclusion criteria. There were no RCTs in which cardiocerebrovascular mortality, total cause mortality, hypotension, and bradycardia were assessed between carvedilol or bisoprolol and placebo. SBP-lowering effects were significantly increased for bisoprolol compared with placebo. Here, 50 mg carvedilol significantly reduced SBP compared with placebo, whereas 12.5 mg or 25 mg did not. Regarding adverse effects, no differences were noted between carvedilol and placebo (two RCTs, 286 participants, moderate certainly evidence). In conclusion, current evidence does not support carvedilol or bisoprolol as first-line therapy for adult hypertension without compelling indications.

What's new in the ESC 2018 guidelines for arterial hypertension : The ten most important messages.

SummaryThe new guidelines on hypertension of the European Society of Cardiology (ESC) 2018 have refined the treatment cut-offs and therapy decisions in adults. This review highlights important recommendations of the guidelines and also on the situation of hypertension in Austria. The general treatment targets of blood pressure have been lowered to at least 130/80 mmHg for most patients. The definition of hypertension is specified as a repeated systolic blood pressure in the office of ≥140 and or diastolic BP ≥90 mmHg. For home blood pressure monitoring, an average value of ≥135/85 mmHg is now defined as hypertension. Ambulatory 24h-blood pressure measurement is recommended for diagnosis of hypertension and to demask lack of nocturnal blood pressure dipping. Whether drug treatment should be initiated immediately or after a delay with lifestyle intervention is focused on the individual high or low cardiovascular risk of the patients and the degree of hypertension. For most patients a combination therapy with single pill is now recommended as initial therapy for hypertension from the start. The salt consumption should be reduced in the majority of patients. The new guidelines have clarified the treatment of hypertension in different comorbidities.

Prestroke treatment with beta-blockers for hypertension is not associated with severity and poor outcome in patients with ischemic stroke: data from a national stroke registry.

Beta-blockers are not recommended as the initial therapy for hypertension. Reports on associations between use of beta-blockers and stroke severity are inconclusive. We assessed associations between prestroke use of beta-blockers and stroke severity, poststroke disability and death in a large group of hypertensive patients hospitalized with acute ischemic stroke. All 3915 patients with ischemic stroke, treated prestroke for hypertension and registered in the National Acute Stroke ISraeli, were included. Treatment for hypertension was classified by medication type (beta-blockers, diuretics, calcium antagonists and renin-angiotensin system blockers). Odds ratios for stroke severity by the National Institutes of Health Stroke Scale score, disability or death at discharge (modified Rankin Score ≥2) and 1-month mortality were calculated for patients treated vs. nontreated with beta-blockers, adjusted for admission SBP and additional risk factors. Use of beta-blockers was reported for 2043 (52%) participants. Mean (SD) admission SBP was lower in patients treated than nontreated with beta-blockers [156.7 (28.4) vs. 159.9 (27.8) mmHg; P = 0.0005]. Patients on combination therapy including beta-blockers used more antihypertensive medications than patients on combination therapy not including beta-blockers [mean (SD) = 2.63 (0.70) vs. mean (SD) = 2.17 (0.40); P < 0.0001]. Adjusted odds ratios (95% confidence intervals) for outcomes for beta-blocker users compared with nonusers were 1.09 (0.90-1.32) for severe stroke, 0.87 (0.73-1.03) for disability or death at discharge and 0.99 (0.74-1.31) for 1-month mortality. Findings were similar for patients on monotherapy. Prestroke use of beta-blockers in hypertensive patients with acute ischemic stroke was not associated with stroke severity, functional outcome or death.

Beta-blockers for hypertension.

BackgroundBeta‐blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties. They have shown long‐term beneficial effects on mortality and cardiovascular disease (CVD) when used in people with heart failure or acute myocardial infarction. Beta‐blockers were thought to have similar beneficial effects when used as first‐line therapy for hypertension. However, the benefit of beta‐blockers as first‐line therapy for hypertension without compelling indications is controversial. This review is an update of a Cochrane Review initially published in 2007 and updated in 2012.ObjectivesTo assess the effects of beta‐blockers on morbidity and mortality endpoints in adults with hypertension.Search methodsThe Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to June 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 6), MEDLINE (from 1946), Embase (from 1974), and ClinicalTrials.gov. We checked reference lists of relevant reviews, and reference lists of studies potentially eligible for inclusion in this review, and also searched the the World Health Organization International Clinical Trials Registry Platform on 06 July 2015.Selection criteriaRandomised controlled trials (RCTs) of at least one year of duration, which assessed the effects of beta‐blockers compared to placebo or other drugs, as first‐line therapy for hypertension, on mortality and morbidity in adults.Data collection and analysisWe selected studies and extracted data in duplicate, resolving discrepancies by consensus. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and conducted fixed‐effect or random‐effects meta‐analyses, as appropriate. We also used GRADE to assess the certainty of the evidence. GRADE classifies the certainty of evidence as high (if we are confident that the true effect lies close to that of the estimate of effect), moderate (if the true effect is likely to be close to the estimate of effect), low (if the true effect may be substantially different from the estimate of effect), and very low (if we are very uncertain about the estimate of effect).Main resultsThirteen RCTs met inclusion criteria. They compared beta‐blockers to placebo (4 RCTs, 23,613 participants), diuretics (5 RCTs, 18,241 participants), calcium‐channel blockers (CCBs: 4 RCTs, 44,825 participants), and renin‐angiotensin system (RAS) inhibitors (3 RCTs, 10,828 participants). These RCTs were conducted between the 1970s and 2000s and most of them had a high risk of bias resulting from limitations in study design, conduct, and data analysis. There were 40,245 participants taking beta‐blockers, three‐quarters of them taking atenolol. We found no outcome trials involving the newer vasodilating beta‐blockers (e.g. nebivolol).There was no difference in all‐cause mortality between beta‐blockers and placebo (RR 0.99, 95% CI 0.88 to 1.11), diuretics or RAS inhibitors, but it was higher for beta‐blockers compared to CCBs (RR 1.07, 95% CI 1.00 to 1.14). The evidence on mortality was of moderate‐certainty for all comparisons.Total CVD was lower for beta‐blockers compared to placebo (RR 0.88, 95% CI 0.79 to 0.97; low‐certainty evidence), a reflection of the decrease in stroke (RR 0.80, 95% CI 0.66 to 0.96; low‐certainty evidence) since there was no difference in coronary heart disease (CHD: RR 0.93, 95% CI 0.81 to 1.07; moderate‐certainty evidence). The effect of beta‐blockers on CVD was worse than that of CCBs (RR 1.18, 95% CI 1.08 to 1.29; moderate‐certainty evidence), but was not different from that of diuretics (moderate‐certainty) or RAS inhibitors (low‐certainty). In addition, there was an increase in stroke in beta‐blockers compared to CCBs (RR 1.24, 95% CI 1.11 to 1.40; moderate‐certainty evidence) and RAS inhibitors (RR 1.30, 95% CI 1.11 to 1.53; moderate‐certainty evidence). However, there was little or no difference in CHD between beta‐blockers and diuretics (low‐certainty evidence), CCBs (moderate‐certainty evidence) or RAS inhibitors (low‐certainty evidence). In the single trial involving participants aged 65 years and older, atenolol was associated with an increased CHD incidence compared to diuretics (RR 1.63, 95% CI 1.15 to 2.32). Participants taking beta‐blockers were more likely to discontinue treatment due to adverse events than participants taking RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54; moderate‐certainty evidence), but there was little or no difference with placebo, diuretics or CCBs (low‐certainty evidence).Authors' conclusionsMost outcome RCTs on beta‐blockers as initial therapy for hypertension have high risk of bias. Atenolol was the beta‐blocker most used. Current evidence suggests that initiating treatment of hypertension with beta‐blockers leads to modest CVD reductions and little or no effects on mortality. These beta‐blocker effects are inferior to those of other antihypertensive drugs. Further research should be of high quality and should explore whether there are differences between different subtypes of beta‐blockers or whether beta‐blockers have differential effects on younger and older people.

The Contribution of the ACCOMPLISH Trial to the Treatment of Stage 2 Hypertension

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommended a thiazide-like diuretic, alone or in combination with other antihypertensive drug classes, as initial therapy for hypertension. JNC 7, however, did not specify preferred combinations. The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial was completed five years after the JNC 7 and demonstrated a 20% advantage in cardiovascular risk reduction when blood pressure was lowered using the single-pill combination of benazepril-amlodipine compared to benazepril-hydrochlorothiazide (Jamerson et al. 359(23):2417-28 [1]). This new and significant finding provided compelling evidence that the long-standing preference for diuretics as initial therapy could be refuted, but it may also be relevant to the lower-than-expected reduction in coronary disease related events (compared to stroke) observed for decades prior to the ACCOMPLISH approach to therapy. The JNC 8 panel members recently published their recommendations, and while the group did not recommend benazepril-hydrochlorothiazide over other combinations, they did highlight the findings of ACCOMPLISH, rating the primary ACCOMPLISH paper as "good." The American Society of Hypertension position paper and the European Hypertension Society guidelines endorse such combinations as a first-line agent for patients with stage 2 hypertension. We review the current position of ACCOMPLISH in the guidelines regarding treatment of stage 2 hypertension.

β-Blockers as Initial Therapy for Hypertension

Are β-blockers associated with lower rates of all-cause mortality and cardiovascular events when used as initial treatment in individuals with hypertension compared with placebo, no treatment, or other drugs? Initial therapy of hypertension with β-blockers is not associated with reduced all-cause mortality but is associated with modest reductions in cardiovascular events compared with placebo or no treatment. Calcium channel blockers and renin-angiotensin system inhibitors are associated with greater reductions in cardiovascular event rates than β-blockers. This evidence derives from trials of traditional β-blockers (eg, atenolol and propranolol), because there are currently no mortality and cardiovascular event data on the new vasodilating β-blockers (eg, carvedilol and nebivolol).

Should Two-Drug Initial Therapy for Hypertension Be Recommended for All Patients?

Hypertension is a common disorder linked to increases in cardiovascular mortality and morbidity. Effective treatment decreases this excess mortality. Therapy with a single antihypertensive agent fails to achieve blood pressure goals in up to 75 % of patients. Compared to monotherapy, combination antihypertensive therapy, especially with fixed-dose (single pill) formulations, may more effectively control blood pressure and improve medication persistence while decreasing adverse effects, healthcare costs, and physician therapeutic inertia. Certain combinations, such as a calcium channel blocker and angiotensin converting enzyme inhibitor, have been associated with similar or fewer adverse effects and better outcomes than other combinations. In contrast, other combinations such as thiazide diuretics and β-blockers may cause more adverse effects than monotherapy. When choosing a thiazide diuretic, chlorthalidone is preferable to hydrochlorothiazide, given better efficacy and cardiovascular outcomes. Initial combination antihypertensive therapy may benefit patients with stage I or II hypertension and more widespread use should be encouraged.

Fixed-Dose Combinations as Initial Therapy for Hypertension

Recent guidelines recommend initiation of antihypertensive therapy with fixed-dose combinations in high-risk patients because such patients usually need two or more blood pressure (BP)-lowering agents in order to normalize their BP. Agents that block the renin-angiotensin system (ACE inhibitors or angiotensin II receptor antagonists [angiotensin receptor blockers; ARBs]) are preferred for the management of hypertension in most patients exhibiting subclinical target organ damage, or established cardiovascular or renal diseases. Unless contraindicated they should be one of the components of fixed-dose combinations, whereas the other component may be either a calcium channel antagonist or a thiazide diuretic. Fixed-dose combinations containing an ACE inhibitor or ARB plus a calcium channel antagonist appear particularly effective in preventing complications of coronary heart disease.

A randomized trial comparing losartan with amlodipine as initial therapy for hypertension in the early post-transplant period

Blockade of the renin-angiotensin-aldosterone system in the early post-transplant period remains controversial. Angiotensin II-receptor blockers (ARB) have many benefits to the patient with chronic kidney disease and these benefits may also apply to the renal transplant recipient (RTR). Additionally, there are theoretical benefits of ARB use in RTR. This study was designed to investigate the safety of early ARB use after renal transplantation. RTR with serum creatinine levels <3.0 mg/dl were randomized to receive either ARB (n = 29) or calcium-channel blocker (CCB; n = 27) as initial therapy for post-transplant hypertension. Differences in potassium, creatinine and haemoglobin concentrations were compared at baseline, 3, 6 and 12 months after transplantation. Withdrawal from the assigned treatment was high: 12 in the ARB group (due to hyperkalaemia in six) and 17 in the CCB group (due to intractable oedema in seven and post-transplant erythrocytosis requiring an angiotensin-converting enzyme inhibitor in seven). There were no differences in blood pressure, haemoglobin or creatinine concentration at any time-points. Mean potassium concentrations were only slightly higher in the ARB vs CCB group (range: 4.2-4.3 vs 3.7-3.8 mEq/l, respectively, but clinically significant) and the number of patients with potassium values >6.0 mEq/l was higher in ARB (n = 7) vs CCB (n = 1). These data suggest that hyperkalaemia is the major complication that occurs with the use of ARB in the immediate post-transplant period. ARB use does not affect renal function or complicate the post-transplant management of RTR. Other than reducing the incidence of post-transplant erythrocytosis, ARB use does not cause an excess incidence of anaemia. Strategies to reduce the risk of hyperkalaemia may allow increased use of ARB immediately after kidney transplantation.

ALLHAT Debate: Diuretics Are Not Preferred, First-Line Initial Therapy for Hypertension—Reply

ALLHAT Debate: Diuretics Are Not Preferred, First-Line Initial Therapy for Hypertension—Reply

Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial

Background Recent reports suggest that existing antihypertensive agents may not have sufficient efficacy to control blood pressure (BP) in many patients. Omapatrilat, an agent under development, has been shown to have significantly greater antihypertensive efficacy than existing agents, but may also carry increased risk of angioedema. We compared the efficacy and safety of omapatrilat to a representative angiotensin-converting enzyme (ACE) inhibitor, enalapril. Methods The Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial is a multicenter, randomized, double-blind, active-controlled, 24-week trial in 25,302 patients with untreated or uncontrolled hypertension conducted in 3298 office-based sites in 12 countries. Subjects were randomized to omapatrilat 10 mg or enalapril 5 mg as initial therapy for hypertension (group 1, n = 9292), replacement for existing antihypertensive therapy (group 2, n =11,224), or in addition to existing antihypertensive therapy (group 3, n = 4751). Study drug was force-titrated at week 2 and electively titrated at weeks 4 and 6 to a maximum of omapatrilat 80 mg or enalapril 40 mg once daily. At weeks 8 and 16, adjunctive antihypertensive medications were added electively to achieve target BP. Results Omapatrilat reduced systolic BP 3.6 mm Hg more than enalapril at week 8, and was associated with less use of adjunctive antihypertensive therapy by week 24 (19% v 27%; P < 0.001 for both comparisons). Subjects randomized to omapatrilat were more likely to reach BP target, regardless of demographics or comorbid conditions and whether omapatrilat was used as initial therapy, replacement for existing therapy, or in addition to existing therapy. Angioedema was more frequent with omapatrilat than enalapril (2.17% v 0.68%). Two omapatrilat-treated subjects experienced angioedema with airway compromise, which was successfully treated. Conclusions Omapatrilat provided broadly superior antihypertensive efficacy when used in a setting resembling clinical practice. Angioedema was more common than with enalapril but life-threatening angioedema was rare. The risk–benefit profile for omapatrilat in clinical use therefore appears likely to be favorable in appropriate patients.

Study Design of HOMED-BP: Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure

The issue of how far blood pressure (BP) should be lowered to achieve the greatest reduction in the risk of cardiovascular disease has been a matter of scientific debate. Although a few trials tried to answer this question, they failed to convincingly show the optimal target BP level, in part because of poor reproducibility and wide variability of conventional casual BP measurement used in these trials. On the other hand, in Japan, calcium antagonist (Ca-A) and angiotensin converting enzyme inhibitor (ACE-I) have been two major medications of initial therapy for hypertension, while angiotensin II receptor antagonist (ARB), which has recently been introduced, is also used now widely as an initial therapy. However, no large-scale interventional trial has been conducted to show which of these three initial medication can give the greatest benefit in terms of reduced cardiovascular disease risk in the Japanese hypertensive patients.

The Verdict From ALLHAT—Thiazide Diuretics Are the Preferred Initial Therapy for Hypertension

Quite simply, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is one of the most important trials of antihypertensive therapy. For decades, experts have passionately debated which class of drugs should be initial therapy for hypertension. Resolution of this issue, which has enormous clinical, public health, and economic implications, comes at a time of intense pressure to reduce health care costs while improving clinical outcomes. In this setting, the ALLHAT results, reported in this issue of THE JOURNAL, are particularly noteworthy, because there is no cost-quality tradeoff; the most effective therapy was also the least expensive.

Rationale and design of HOMED-BP Study: Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure Study

How far should blood pressure (BP) be lowered to achieve the greatest reduction in the risk of cardiovascular disease? Although a few trials have tried to answer this question, they failed to convincingly establish an optimal target BP level, in part because of poor reproducibility and the wide variability of conventional casual BP measurement they used. At the same time, in Japan, calcium antagonist (Ca-A) and angiotensin-converting enzyme inhibitor (ACE-I) have been two major medications in initial therapy for hypertension, while angiotensin II receptor antagonist (ARB), which has recently been introduced, is also now used widely as an initial therapy. However, no large-scale interventional trial has been conducted to show which of these three initial medications can give the greatest benefit in reducing the risk of cardiovascular disease in the Japanese hypertensive patient. The objectives of the study are, first, to determine an optimal target BP level, based on BP values self-measured at home (home BP). This way of measurement provides more reproducible and less variable BP values than conventional casual measurements. Secondly, we seek to determine the optimal initial antihypertensive medication for the Japanese hypertensive population. The study is a 2 x 3 factorial randomized controlled trial conducted with a prospective randomized open-blinded endpoint design. The study will include a total of 9000 untreated essential hypertensive patients aged 40 to 78 years with home BP values > or = 135/85 mmHg. Eligible patients are randomized to one of the two home BP target groups (systolic/diastolic home BP within the range of 134-125/84-80 mmHg, or > or = 125/80 mmHg), and to regimens based on one of three initial antihypertensive drugs (Ca-A or ACE-I or ARB). These randomizations, performed by our host computer, are transmitted to terminals at the outpatient clinic through the Internet. The patient measures BP at home with newly developed equipment (HEM-7471C-N; Omron, Japan) that records BP values, the date, and the time of each measurement. The data are downloaded to the outpatient terminal at every clinic visit then transmitted to the host computer via the Internet. Based on these home BP values, the host computer determines the necessity of additional therapy or dose increments in four further steps to reach the randomized target BP, and then transmits the information to the terminal at the outpatient clinic. The primary study outcome is a composite of non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death. The scheduled average post-randomization duration of follow-up is 7 years. This is the first large-scale home BP-based and Internet-connected intervention trial on antihypertensive treatment. The HOMED-BP study (Hypertension Objective treatment based on Measurement by Electrical Devices of BP) will improve the recruitment of general practitioners and participants and will supply unbiased BP data, providing reliable information on optimal target BP levels and the optimal initial antihypertensive medication.

Do drug company promotions influence physician behavior?

Do drug company promotions influence physician behavior?

Irbesartan: an updated review of its use in cardiovascular disorders.

Irbesartan interrupts the renin-angiotensin system via selective blockade of the angiotensin II subtype 1 receptor; the latter being responsible for the pressor related effects of angiotensin II. As treatment for mild to moderate hypertension, irbesartan 150 mg/day controlled diastolic BP in 56% of patients according to pooled data from several phase III studies and 77% of patients in a large phase IV study. in comparative trials, irbesartan was significantly more effective than losartan and valsartan as treatment for mild to moderate essential hypertension and as effective as enalapril or atenolol. Results from many studies show an additive antihypertensive effect when hydrochlorothiazide is added to irbesartan monotherapy. The drug also induces statistically significant regression of left ventricular mass in patients with hypertension and left ventricular hypertrophy, and preliminary evidence suggests it has beneficial haemodynamic effects in patients with heart failure. Irbesartan is very well tolerated, exhibiting an adverse event profile similar to that seen with placebo in comparative trials. In conclusion, although the role of irbesartan as a treatment for heart failure is little clearer than it was 2 years ago, the place of the drug in the management of hypertension is now better established. There is evidence to suggest the drug may have a role as initial therapy for hypertension, although formal recommendation in management guidelines will almost certainly not occur until long term morbidity and mortality benefits are established.

α-Blocker Therapy of Hypertension

For various reasons, the alpha 1-receptor blocker prazosin has been used infrequently as initial therapy for hypertension. The introduction of additional agents of this class with properties different from prazosin provides slower onset of action, which should reduce the degree of first-dose and postural hypotension and a longer duration of action, which allows for once-a-day dosage. A summary of the published data on efficacy, side effects, and special properties of this class of agents indicates that they will probably be used more extensively, particularly because of their ability to improve lipid and glucose-insulin metabolism.

Initial Therapy for Hypertension—Individualizing Care

Of the approximately 58 million Americans with hypertension, the majority have only mild increases in blood pressure and individually are at low risk. Large group studies, however, have demonstrated the efficacy of treating mild hypertension. Public health efforts during the past 16 years have increased the number of hypertensive patients made aware of their condition and brought into treatment. A major problem, however, is consistently maintaining patients on long-term therapy. A large number of nonpharmacologic and pharmacologic treatments have become available for the management of hypertension. These treatments must be applied individually to enhance benefit, minimize potential harm, and increase the likelihood of long-term compliance for what is often a lifelong disorder. For accomplishing this goal, a thorough understanding of important characteristics of both the individual patient and the available therapeutic modalities is needed.