BP-lowering Agents Research Articles

Primary prevention of cardiovascular disease: new guidelines, technologies and therapies

A trend in primary prevention of cardiovascular disease (CVD) has been a move away from managing isolated risk factors, such as hypertension and dyslipidaemia, towards assessment and management of absolute CVD risk. In Australian guidelines, absolute CVD risk is calculated as the probability of a stroke, transient ischaemic attack, myocardial infarction, angina, peripheral arterial disease or heart failure occurring within the next 5 2013s. Absolute CVD risk should be regularly assessed in patients aged 45 2013s or older (35 2013s or older in Aboriginal and Torres Strait Islander people) using the Australian absolute CVD risk calculator (http://www.cvdcheck.org.au). For patients currently taking a blood pressure (BP)-lowering or lipid-lowering agent, pretreatment values should be used to calculate risk. Patients at high absolute risk of CVD (> 15% over 5 2013s) should be treated with both BP-lowering and lipid-lowering agents, unless contraindicated or clinically inappropriate. For patients at moderate absolute risk of CVD (10%-15%) treatment with a BP-lowering and/or a lipid-lowering agent should be considered if the risk remains elevated after lifestyle interventions, BP is ≥ 160/100 mmHg, there is a family history of premature CVD, or the patient is of South Asian, Middle Eastern, Maori, Pacific Islander, Aboriginal or Torres Strait Islander ethnicity. BP measurements taken using an oscillometric device can be used to approximate mean daytime ambulatory BP.

The Evening versus Morning Polypill Utilization Study: the TEMPUS rationale and design

In clinical practice, blood pressure (BP)-lowering agents are generally prescribed for use in the morning, whereas (short-acting) statins are recommended for use in the evening. There is evidence that the reduction in LDL cholesterol (LDL-c) achieved with short-acting statins is superior when taken in the evening and reported improvement in BP control when aspirin and BP-lowering agents are taken in the evening. However, it is unclear whether the additional reduction in LDL-c and BP is offset by a reduction in adherence, given that taking medication in the evening may be less typical or convenient. There is therefore uncertainty concerning the best timing of administration of a cardiovascular combination pill such as the polypill. The aim of TEMPUS (NCT01506505), a prospective randomized open blinded endpoint (PROBE) crossover trial, is to evaluate whether there is a difference in LDL-c levels or 24-hour ambulatory BP in individuals at increased risk of cardiovascular disease when the cardiovascular polypill is taken in the evening compared to the morning. An additional aim is to assess the effect of the polypill on LDL-c and BP compared to the administration of separate pills of identically dosed components of the polypill. In total 75 participants with established cardiovascular disease or an intermediate to high risk for cardiovascular disease are randomly allocated to the sequence of three different treatments of 6-8 weeks: (1) the cardiovascular polypill (aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg, and hydrochlorothiazide 12.5 mg) in the evening; (2) the polypill in the morning; and (3) the use of the identically dosed agents in separate pills taken at different time points during the day. The primary endpoint is the difference in LDL-c and mean 24-hour ambulatory systolic BP. Secondary outcomes are the difference in relative risk reduction, biochemistry, platelet function and pulse wave analysis, participants' adherence, and acceptability. TEMPUS will evaluate the effect of timing of the administration of a cardiovascular polypill on LDL-c and BP measurements in patients with an intermediate or high risk for cardiovascular disease.

The combined use of aspirin, a statin, and blood pressure-lowering agents (polypill components) in clinical practice in patients with vascular diseases or type 2 diabetes mellitus

Based on guidelines, patients with established cardiovascular disease are likely to already receive a combination of aspirin, a statin, and blood pressure (BP)-lowering agents. Combining these pharmacological agents into a cardiovascular polypill could be considered in these patients to reduce prescription gaps and non-adherence. We aimed to assess the prevalence of the combined use of aspirin, statin, and BP-lowering agents in patients with established cardiovascular diseases or type 2 diabetes mellitus (DM2) in the period 1996-2009. In total, 5702 patients with coronary artery disease (CAD), cerebrovascular disease (CVD), peripheral arterial occlusive disease (PAOD), abdominal aortic aneurysm (AAA) or, DM2 were included in the period 1996-2009. The overall use of combination therapy with aspirin, statin, and ≥ 1 BP-lowering agent increased substantially from 9% in 1996 to 66% in 2009 and ≥ 2 BP-lowering agents increased from 1% to 47%. In 2009, combination therapy with ≥ 1 BP-lowering agent was used by 83% of those with CAD, 48% of those with CVD, 43% of those with PAOD, 36% of the patients with AAA, and 19% of the patients with DM2. In most patient groups, obesity, metabolic syndrome, hypertension concomitant CAD, CVD, or DM2 were related to the use of combination therapy in models adjusted for age and gender. A high proportion of patients with established cardiovascular diseases already uses a combination of pharmacological agents. Introduction of a polypill in high-risk patients might be feasible to reduce prescription gaps and increase adherence to indicated therapy.

Abstract P329: The Use of Polypill Components is Related to Lower Vascular Morbidity Aand Mortality in Patients With Vascular Diseases or Type 2 Diabetes Mellitus

Background and aims Patients with established cardiovascular disease or diabetes mellitus type 2 (DM2) are likely to receive separate treatment of an aspirin, a statin and blood pressure (BP)-lowering agents. Combining these pharmacological agents into a cardiovascular polypill, could be considered in these patients to reduce prescription gaps and increase adherence. We evaluated the effect of the concomitant use of aspirin, a statin and BP-lowering agent(s) in patients with vascular diseases or DM2 on vascular morbidity and mortality in current clinical practice. Methods In total 5783 patients with coronary artery disease, cerebrovascular disease, abdominal aortic aneurysm, peripheral arterial occlusive disease or DM2 enrolled in the Second Manifestations of ARTerial disease study were followed/up for the occurerence of a subsequent vascular event (i.e. myocardial infarction (MI), ischaemic cerebrovascular accident (iCVA), vascular death), composite vascular endpoint (combination of previous mentioned) and all-cause mortality. Results In total 2456 (42%) used aspirin, a statin and 1 BP lowering agent. During a median of 5.3 years (interquartile range 2.7-9.3 years), 758 patients experienced a new vascular event and 737 died. Combination therapy with aspirin, statin and ≥1 BP lowering agent was associated with a lower risk of MI (HR 0.77; 95%CI 0.62-0.97), iCVA (HR 0.75; 95%CI 0.52-1.08), vascular mortality (HR 0.56; 95%CI 0.44-0.72), composite vascular endpoint (HR 0.52; 95%CI 0.43-0.63) and all-cause mortality (HR 0.52; 95%CI 0.43-0.63) after adjusting for confounding covariates ( Table 1 ). Table Aspirin, statin and ≥1 BP lowering agents Study endpoint No. of events HR (95%-CI) Coronary Artery Disease I 418 0,79 (0,63-0,97) II 0,77 (0,62-0,95) III 0,77 (0,62-0,95) IV 0,79 (0,63-0,99) PS 0,77 (0,62-0,97) Cerebrovascular accident I 181 0,65 (0,46-0,91) II 0,64 (0,46-0,90) III 0,65 (0,46-0,91) IV 0,78 (0,54-1,13) PS 0,75 (0,52-1,08) Composite Vascular Endpoint I 720 0,73 (0,62-0,86) II 0,72 (0,61-0,85) III 0,73 (0,61-0,86) IV 0,78 (0,65-0,94) PS 0,75 (0,62-0,89) Vascular Mortality I 428 0,59 (0,47-0,75) II 0,62 (0,49-0,78) III 0,60 (0,48-0,76) IV 0,63 (0,49-0,80) PS 0,56 (0,44-0,72) All-cause Mortality I 737 0,54 (0,45-0,65) II 0,56 (0,47-0,67) III 0,56 (0,47-0,68) IV 0,57 (0,47-0,69) PS 0,52 (0,43-0,63) Model I: Crude II: Adjusted for gender, age III: II + additional adjustment for BMI, current smoking, packyears, concommitent cardiovascular disease IV: III + additional adjustment for LDL, systolic BP Propensity Score: composed of gender, age, BMI, current smoking, packyears, concomitant cardiovascular disease, LDL cholesterol and systolic BP Conclusion The combined use of aspirin, statin and at least 1 BP lowering agent was associated with a lower risk of vascular morbidity and mortality in patients with established cardiovascular disease or DM2. Introduction of a polypill in these high risk patients may promote the use of preventive pharmacologic treatment and contribute to better adherence thereby decreasing the risk for vascular morbidity and mortality.

Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73 913 patients

Guidelines generally recommend intensive lowering of blood pressure (BP) in patients with type 2 diabetes. There is uncertainty about the impact of this strategy on case-specific events. Thus, we generated estimates of the effects of BP reduction on the risk of myocardial infarction (MI) and stroke in diabetic patients. We selected studies which compared different BP-lowering agents and different BP intervention strategies in patients with diabetes. Outcome measures were MI and stroke. We abstracted information about study design, intervention, population, outcomes, and methodological quality for a total of 73,913 patients with diabetes (295,652 patient-years of exposure) randomized in 31 intervention trials. Overall, experimental treatment reduced the risk of stroke by 9% (P = 0.0059), and that of MI by 11% (P = 0.0015). Allocation to more-tight, compared with less-tight, BP control reduced the risk of stroke by 31% [relative risk (RR) 0.61, 95% confidence interval (CI) 0.48-0.79], whereas the reduction in the risk of MI approached, but did not achieve, significance [odds ratio (OR) 0.87, 95% CI 0.74-1.02]. In a meta-regression analysis, the risk of stroke decreased by 13% (95% CI 5-20, P = 0.002) for each 5-mmHg reduction in SBP, and by 11.5% (95% CI 5-17, P < 0.001) for each 2-mmHg reduction in DBP. In contrast, the risk of MI did not show any association with the extent of BP reduction (SBP: P = 0.793; DBP: P = 0.832). In patients with diabetes, protection from stroke increases with the magnitude of BP reduction. We were unable to detect such a relation for MI.

Lowering blood pressure with β-blockers in peripheral artery disease: the importance of comorbidity

Lowering blood pressure with β-blockers in peripheral artery disease: the importance of comorbidity

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial

BackgroundBlood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.MethodsThis is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.DiscussionThe early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.Trial RegistrationClinical Trials NCT00970931.

Trends in utilization of lipid- and blood pressure-lowering agents and goal attainment among the U.S. diabetic population, 1999-2008

BackgroundFor patients with diabetes, clinical practice guidelines recommend treating to a low-density lipoprotein cholesterol (LDL-C) goal of <2.59 mmol/L (100 mg/dL) and a blood pressure (BP) target of <130/80 mmHg. This analysis assessed recent trends in the utilization of lipid-lowering and BP-lowering agents, as well as LDL-C and BP goal attainment, in the U.S. adult diabetic population.Methods9,167 men and nonpregnant women aged ≥20 years were identified from the fasting subsample of the 1999-2008 National Health and Nutritional Examination Survey. Diabetes was identified in 1,214 participants by self report, self-reported use of insulin or oral medications for diabetes, or fasting glucose ≥6.99 mmol/L (126 mg/dL).ResultsThe prevalence of diagnosed or undiagnosed diabetes increased significantly over the past decade, from 7.4% in 1999-2000 to 11.9% in 2007-2008 (P = 0.0007). During this period, the use of lipid-lowering agents by participants with diabetes increased from 19.5% to 42.2% (P < 0.0001), and the proportion at LDL-C goal increased from 29.7% to 54.4% (P < 0.0001). Although there was a significant increase in antihypertensive medication use (from 35.4% to 58.9%; P < 0.0001), there was no significant change in the proportion of participants at BP goal (from 47.6% to 55.1%; P = 0.1333) or prevalence of hypertension (from 66.6% to 74.2%; P = 0.3724).ConclusionsThe proportion of diabetic individuals taking lipid- and BP-lowering agents has increased significantly in recent years. However, while there has been a significant improvement in LDL-C goal attainment, nearly one-half of all U.S. adults with diabetes are not at recommended LDL-C or BP treatment goals.

Prehypertension: the Rationale for Early Drug Therapy

Blood pressure within prehypertensive levels confers higher cardiovascular risk by two means. At first, these levels are associated with higher risk for cardiovascular events, starting at BP values as low as 115/75 mmHg, and doubling at each 20 mmHg for systolic or 10 mmHg for diastolic BP. Prehypertension is also an intermediate stage for full hypertension, which develops in an annual rate of 7 out 100 individuals with 40-50 years of age. The precocious drug intervention in patients with prehypertension is therefore appealing. In individuals with previous cardiovascular disease or diabetes the use of BP-lowering agents is compulsory, since the 18-42% reduction of major cardiovascular events demonstrated in randomized clinical trials translates in palpable clinical benefit. In the absence of higher baseline risk, the absolute benefit of treatment is presumably small and was not demonstrated to date. These individuals could be candidate to treatment with the aim to prevent the development of full hypertension. The long-lasting effectiveness of non-drug therapies is low outside the controlled conditions of randomized clinical trials, and there are evidences that the use of BP-lowering drugs reduces the incidence of hypertension in individuals with prehypertension by more than 60%. Clinical trials testing the efficacy and safety of BP agents to prevent hypertension in a population-based perspective are required. In the meantime, it is worthy to present the option to start low doses of BP agents for individuals with prehypertension without co-morbidities who do not respond to the prescription of lifestyle modification.

Influence of blood pressure reduction on composite cardiovascular endpoints in clinical trials

The use of a composite cardiovascular endpoint (CCEP) is frequent in clinical trials. However, the relation between the reduction in blood pressure (BP) and the risk of CCEP is poorly known. We conducted a meta-analysis of trials, which compared different BP-lowering agents with placebo or active treatments in patients with hypertension or composite features of high cardiovascular risk. The outcome measure was a triple (myocardial infarction, stroke and cardiovascular death) or quadruple (those mentioned above and congestive heart failure) CCEP. Thirty trials fulfilled the inclusion criteria, for a total of 221 024 patients. Experimental treatments reduced the risk of CCEP by 9% (P < 0.0001). In a multivariable meta-regression analysis, for each 5-mmHg reduction in SBP, there was a 13% less risk of CCEP (95% confidence interval 8-19, P = 0.001) and, for each 2-mmHg reduction in DBP, there was a 12% less risk of CCEP (95% confidence interval 7-16, P = 0.001). Use of triple or quadruple CCEP (P = 0.150), its definition as primary or nonprimary endpoint (P = 0.305) and use of placebo or active control as comparators (P = 0.552) did not influence the estimates. A different BP reduction of at least 4.6 mmHg in SBP or at least 2.2 mmHg in DBP was required to achieve a 95% prediction interval entirely lying below the unity. BP reduction is important to reduce the risk of CCEP in clinical trials. A significant difference between two treatment groups in the risk of CCEP may be anticipated for a SBP/DBP reduction differing by 4.6/2.2 mmHg or more.

INFLUENCE OF CIRCADIAN TIME OF ANTIHYPERTENSIVE TREATMENT ON CARDIOVASCULAR RISK: RESULTS OF THE MAPEC STUDY: PP.16.102

Objectives: Clinical studies have documented morning-evening, administration-time differences in antihypertensive efficacy, duration of action, safety profile and/or effects on the circadian blood pressure (BP) pattern of several different classes of BP-lowering medications. Despite these findings, most hypertensive subjects ingest all their BP-lowering agents in a single morning dose. The MAPEC study investigated if chronotherapy of hypertension has any influence in cardiovascular morbidity and mortality. Methods: This prospective study investigated 3344 subjects (1718 men), 52.6 ± 14.5 years of age. At baseline, BP was measured every 20-min intervals 07:00 to 23:00 h and every 30-min at night for 48 h. Physical activity was simultaneously monitored every minute by wrist actigraphy. The same evaluation procedure was scheduled yearly or more frequently (quarterly) if treatment adjustment was required to improve BP control. The Cox proportional-hazard model was used to estimate relative risks of cardiovascular events associated with use of antihypertensive treatment and circadian time of treatment. Results: At the last evaluation, 625 subjects were normotensive and 606 untreated hypertensives according to ambulatory BP criteria. Among the remaining subjects, 1068 were receiving all antihypertensive medication on awakening, and 1045 were ingesting some antihypertensive agent at bedtime. Compared with normotensive subjects, the relative risk of cardiovascular events was highest for patients ingesting all drugs on awakening (3.84 [2.48–5.95]) and lowest for those receiving all medication at bedtime (0.95 [0.44–2.07]; P = 0.907 compared to normotensive subjects; P < 0.001 compared to all other groups). Compared with untreated subjects, cardiovascular risk was significantly higher with increasing number of drugs on awakening, but consistently lower, independently of the number of drugs, when medication was ingested at bedtime. Non-dipping was significantly lower (28 vs. 61%) among subjects treated at bedtime. Conclusions: In subjects with essential hypertension, pharmacologic therapy should take into account when to treat with respect to the rest-activity pattern of each patient. Treatment at bedtime not only improves BP control and decreases the prevalence of non-dipping, but also significantly reduces cardiovascular risk to the level of normotension.

Management of Blood Pressure for Acute and Recurrent Stroke

Marc Fisher MD Kennedy Lees MD Section Editors: Hypertension is the most important modifiable risk factor for stroke.1,2 It is estimated that 25% or more of strokes may be attributable to hypertension. Because many patients with stroke have mild hypertension or prehypertension, we have shifted our focus and now think of stroke on a continuum of risk based on blood pressure (BP) level rather than on a threshold effect.3 Because high BP may not exist in isolation, a wider definition of hypertension has been proposed that also takes into account the absolute risk of cardiovascular events and associated metabolic factors or early disease markers.3 Lowering BP reduces the risk of stroke. Epidemiological studies have shown that for each 10 mm Hg lower systolic blood pressure (SBP), there is a decrease in risk of stroke of approximately one third in persons aged 60 to 79 years. This association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, stroke subtypes, and for fatal and nonfatal events.4 Lowering diastolic blood pressure (DBP) was once the main target to achieve stroke and other cardiovascular event reduction, but SBP has now become the target.3 As recently shown, even the elderly with sustained SBP elevation may gain from BP reduction in relation to less fatal or nonfatal stroke, death, and heart failure.5 Although the role of longer-term BP control to improve outcomes in patients with stroke is undisputed, BP management immediately after a stroke remains controversial. In an effort to resolve this controversy, several pilot clinical trials have been initiated. In this review, we discuss the results of some of these trials and available evidence-based guidelines for BP control in the settings of acute ischemic and hemorrhagic stroke (excluding subarachnoid hemorrhage) and …

Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS) – a randomised controlled trial

To assess the effects of acute pressor and depressor blood pressure (BP) manipulation on 2-week death and dependency following acute stroke and investigate the safety and efficacy of such treatments. A multicentre, prospective, randomised, double-blind, placebo-controlled titrated-dose trial. Five hospitals in England. Patients over 18 years admitted to hospital with a clinical diagnosis of suspected stroke and either (1) symptom onset < 36 hours and hypertension, defined as systolic BP (SBP) < 160 mmHg (depressor arm), or (2) symptom onset < 12 hours and hypotension, defined as SBP < or = 140 mmHg (pressor arm). Patients were allocated to either the pressor or the depressor arm depending on blood pressure at randomisation. The ratio of allocation to active intervention versus matched placebo was 2:1 for the depressor arm and 1:1 for the pressor arm. The primary end point was death and dependency at 2 weeks, with dependency defined as a modified Rankin score < 3. Secondary end points were the safety of acute pressor (0-12 hours post stroke) and depressor (0-36 hours post stroke) BP manipulation in stroke patients; whether effects of BP reduction are influenced by stroke type (ischaemic versus haemorrhagic); whether alternative routes for administration of antihypertensive therapy (including sublingual and intravenous) are effective in dysphagic stroke patients; whether effects of BP manipulation are influenced by the time to treatment; and the short- and medium-term cost-effectiveness of such therapy in the acute post-stroke period on subsequent disability or death. 180 patients were recruited over the 36-month trial period, 179 in the depressor arm and one in the pressor arm (who received placebo). No significant difference was found in death or dependency at 2 weeks between those receiving active depressor treatment with lisinopril or labetalol and those receiving placebo, although numbers recruited to the trial were lower than projected. Active treatment was not associated with an increase in early neurological deterioration despite significantly greater reductions in BP at 24 hours and 2 weeks with active therapy compared with placebo. Active treatment was generally well tolerated and treatment discontinuation rates were similar in active and placebo groups. Survival analysis showed that the active treatment group had a lower mortality at 3 months than the placebo group (p = 0.05). The pressor arm was closed early because of problems with recruitment, so no conclusions can be drawn regarding this therapy. Oral and sublingual lisinopril and oral and intravenous labetalol are effective BP-lowering agents in acute cerebral infarction and haemorrhage and do not increase the likelihood of early neurological deterioration. The study was not sufficiently powered to detect a difference in disability or death at 2 weeks. However, the 3-month difference in mortality in favour of active treatment is of interest, although care must be taken in interpretation of the results. Further work is needed to confirm this and to assess whether there are differences in the effectiveness of labetalol compared with lisinopril in terms of reducing death or dependency after acute stroke, and whether the introduction of treatment post stroke earlier than was achieved here would be of greater benefit.

Getting to Goal Blood Pressure: Why Reserpine Deserves a Second Look

Getting to Goal Blood Pressure: Why Reserpine Deserves a Second Look

Hypertension Treatment Guidelines: Is It Time for an Update?

Hypertension Treatment Guidelines: Is It Time for an Update?

Update on the management of hypertension to prevent stroke

Hypertension is the leading modifiable risk factor for stroke, including first-ever and recurrent stroke. The association between blood pressure (BP) and stroke risk is continuous and may be documented as low as 115/75 mm Hg. Because of this continuum of risk, and because most strokes occur in individuals with mild hypertension or even normal BP values, we are now beginning to recognize "prehypertension" as a stage in which early recognition and intervention may confer benefit. In addition to increased risk for ischemic and hemorrhagic stroke, hypertension may be associated with increased risk of cognitive impairment. Reductions in BP are reliably associated with reduced stroke risk. Some evidence suggests that certain agents, including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, may have protective effects beyond BP lowering. Overall, the degree of BP lowering is key, and therefore most classes of BP-lowering agents may be recommended at this point. Many patients with hypertension will require more than one BP-lowering agent to control BP. Lifestyle modification is appropriate at all levels of intervention. Further studies are needed to ascertain the mechanisms of benefit of different classes of antihypertensive agents in the reduction of stroke and cardiovascular disease risk.

Importance of renin in blood pressure regulation and therapeutic potential of renin inhibition

Despite improvements in its detection and treatment, hypertension remains a significant public health problem worldwide. In recent years, many international hypertension societies and organisations have set increasingly rigorous blood pressure (BP) targets, with the aim of reducing cardiovascular complications, and this has in turn necessitated the use of more antihypertensive medications to reach these targets in individual patients. There is therefore an ongoing need to develop antihypertensive drugs with new mechanisms of action. Renin inhibitors represent a novel class of compounds which offer considerable promise as BP-lowering agents. Here, we review the rationale for renin inhibition as a therapeutic target and examine the preclinical and clinical evidence for the antihypertensive effectiveness of the renin inhibitors.

Early Detection of Progressive Chronic Kidney Disease

The Multiple Risk Factor Intervention Trial (MRFIT) Research Group presents in this issue of JASN data on the value of a single measurement of dipstick proteinuria and estimated GFR for prediction of end-stage renal disease (ESRD) over a 25-yr period ([1][1]). These data were obtained in middle-aged

Past, present, and future clinical trials of cardiovascular risk reduction—the hypertension perspective

The relationship between blood pressure (BP) and risk of cardiovascular (CV) events is continuous, consistent, and independent of other risk factors—the higher the BP, the greater the CV risk. Over the past few decades, numerous clinical trials have shown that reducing BP can reduce the risk of CV events. A wide variety of different antihypertensive drugs were examined in these trials, including “older” BP-lowering agents such as diuretics and β-blockers, and “newer” agents, including ACE inhibitors and calcium channel blockers. The recent ALLHAT trial compared the effects of older with newer antihypertensive agents on CV events in hypertensive patients. Although it remains uncertain whether one antihypertensive drug has superiority over another for CV protection, it is clear that monotherapy is not sufficient to attain currently recommended BP targets in the majority of patients with hypertension; in ALLHAT, for example, a combination of at least two antihypertensive agents was necessary to produce the largest reductions in CV risk. The question of which combination of antihypertensive drugs is most effective will be addressed by the next generation of randomized controlled trials, including the ASCOT trial.

Safety and efficacy of combination ace inhibitor/calcium channel blocker therapy versus ace inhibitor monotherapy in african american patients with hypertension and type 2 diabetes

P-401 Key Words: Combination Therapy, Diabetes, Hypertension