Showing papers by "Suzanne Oparil published in 2009"
TL;DR: The results indicate that excessive dietary sodium ingestion contributes importantly to resistance to antihypertensive treatment and strategies to substantially reduce dietary salt intake should be part of the overall treatment of resistant hypertension.
Abstract: Observational studies indicate a significant relation between dietary sodium and level of blood pressure. However, the role of salt sensitivity in the development of resistant hypertension is unknown. The present study examined the effects of dietary salt restriction on office and 24-hour ambulatory blood pressure in subjects with resistant hypertension. Twelve subjects with resistant hypertension entered into a randomized crossover evaluation of low (50 mmol/24 hours×7 days) and high sodium diets (250 mmol/24 hours×7 days) separated by a 2-week washout period. Brain natriuretic peptide; plasma renin activity; 24-hour urinary aldosterone, sodium, and potassium; 24-hour ambulatory blood pressure monitoring; aortic pulse wave velocity; and augmentation index were compared between dietary treatment periods. At baseline, subjects were on an average of 3.4±0.5 antihypertensive medications with a mean office BP of 145.8±10.8/83.9±11.2 mm Hg. Mean urinary sodium excretion was 46.1±26.8 versus 252.2±64.6 mmol/24 hours during low- versus high-salt intake. Low- compared to high-salt diet decreased office systolic and diastolic blood pressure by 22.7 and 9.1 mm Hg, respectively. Plasma renin activity increased whereas brain natriuretic peptide and creatinine clearance decreased during low-salt intake, indicative of intravascular volume reduction. These results indicate that excessive dietary sodium ingestion contributes importantly to resistance to antihypertensive treatment. Strategies to substantially reduce dietary salt intake should be part of the overall treatment of resistant hypertension.
491 citations
TL;DR: Cellular/molecular mechanisms by which estrogen modulates injury-induced inflammation, growth factor expression, and oxidative stress in arteries and isolated vascular smooth muscle cells are reviewed, with emphasis on the role of estrogen receptors and the nuclear factor-kappaB (NFkappa B) signaling pathway.
Abstract: Estrogen has antiinflammatory and vasoprotective effects when administered to young women or experimental animals that appear to be converted to proinflammatory and vasotoxic effects in older subjects, particularly those that have been hormone free for long periods. Clinical studies have raised many important questions about the vascular effects of estrogen that cannot easily be answered in human subjects. Here we review cellular/molecular mechanisms by which estrogen modulates injury-induced inflammation, growth factor expression, and oxidative stress in arteries and isolated vascular smooth muscle cells, with emphasis on the role of estrogen receptors and the nuclear factor-κB (NFκB) signaling pathway, as well as evidence that these protective mechanisms are lost in aging subjects.
285 citations
TL;DR: The parallels between O-GlcNAc signaling and redox signaling, as an alternative paradigm for understanding the role of O- GlcNAcylation in regulating cell function, are explored.
Abstract: The posttranslational modification of serine and threonine residues of nuclear and cytoplasmic proteins by the O-linked attachment of the monosaccharide β-N-acetylglucosamine (O-GlcNAc) is a highly...
146 citations
TL;DR: Evidence from subsequent analyses of ALLHAT and other clinical outcome trials confirm that neither alpha-blockers, angiotensin-converting enzyme inhibitors, nor calcium channel blockers surpass thiazide-type diuretics (at appropriate dosage) as initial therapy for reduction of cardiovascular or renal risk.
Abstract: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is reevaluated considering information from new clinical trials, meta-analyses, and recent subgroup and explanatory analyses from ALLHAT, especially those regarding heart failure (HF) and the association of drug treatment with new-onset diabetes mellitus (DM) and its cardiovascular disease (CVD) consequences. Chlorthalidone was superior to (1) doxazosin mesylate in preventing combined CVD (CCVD) (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.13-1.27), especially HF (RR, 1.80; 95% CI, 1.40-2.22) and stroke (RR, 1.26; 95% CI, 1.10-1.46); (2) lisinopril in preventing CCVD (RR, 1.10; 95% CI, 1.05-1.16), including stroke (in black persons only) and HF (RR, 1.20; 95% CI, 1.09-1.34); and (3) amlodipine besylate in preventing HF, overall (by 28%) and in hospitalized or fatal cases (by 26%). Central independent blinded reassessment of HF hospitalizations confirmed each comparison. Results were consistent by age, sex, race (except for stroke and CCVD), DM status, metabolic syndrome status, and renal function level. Neither amlodipine nor lisinopril was superior to chlorthalidone in preventing end-stage renal disease overall, by DM status, or by renal function level. In the chlorthalidone arm, new-onset DM was not significantly associated with CCVD (RR, 0.96; 95% CI, 0.88-2.42). Evidence from subsequent analyses of ALLHAT and other clinical outcome trials confirm that neither α-blockers, angiotensin-converting enzyme inhibitors, nor calcium channel blockers surpass thiazide-type diuretics (at appropriate dosage) as initial therapy for reduction of cardiovascular or renal risk. Thiazides are superior in preventing HF, and new-onset DM associated with thiazides does not increase CVD outcomes.
100 citations
TL;DR: It is concluded that their complex design precludes a simple interpretation, that several important questions remain unanswered and that direct evidence – particularly in support of lowering systolic BP below 140 or 130 mmHg – is urgently needed.
Abstract: A large body of clinical trial data indicates that a given difference in blood pressure (BP), as measured in the clinic, results in a given difference in outcome. This correlation underpins current US and European guidelines for the management of hypertension. However, findings from recent comparative trials may appear inconsistent with a fixed relationship between BP lowering and outcome benefit, at least at all BP ranges, at all levels of total cardiovascular risk and with all drug combinations. We review the findings of six of these recent trials and conclude that their complex design precludes a simple interpretation, that several important questions remain unanswered and that direct evidence - particularly in support of lowering systolic BP below 140 or 130 mmHg - is urgently needed.
71 citations
TL;DR: The hypothesis that hypoxia, by reducing Thy-1, increases TGF-beta activation, and thereby inhibits normal alveolar development is supported.
Abstract: Transforming growth factor (TGF)-β mediates hypoxia-induced inhibition of alveolar development in the newborn lung. TGF-β is regulated primarily at the level of activation of latent TGF-β. Fibrobla...
67 citations
TL;DR: Patients diagnosed with this triad should be treated with low-salt diet, weight-loss counseling, and continuous positive airway pressure, as well as aggressive antihypertensive therapy, usually with multiple agents, including a mineralocorticoid receptor antagonist.
63 citations
TL;DR: Combination antihypertensive therapy with AML+OM±HTCZ, up‐titrated as necessary, allowed a majority of patients to achieve BP goal, and study medication was safe and well tolerated.
Abstract: J Clin Hypertens (Greenwich). 2009;11:475-482. (c) 2009 Wiley Periodicals, Inc.The authors report on the 44-week open-label extension of the 8-week, double-blind Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure (COACH) trial in 1684 patients. Initial therapy was amlodipine (AML) plus olmesartan medoxomil (OM) 5+40 mg/d, up-titrated to AML+OM 10+40 mg/d plus hydrochlorothiazide (HCTZ) 12.5 mg then 25 mg if patients did not achieve blood pressure (BP) goal (<140/90 mm Hg or <130/80 mm Hg in patients with diabetes). Baseline mean BP decreased from 164/102 mm Hg to 131/82 mm Hg at end of study, with an overall 66.7% of patients, including those with diabetes, achieving BP goal. The BP goal achievement was 80% for AML+OM 5+40 mg/d, 70.6% for AML+OM 10+40 mg/d, 66.6% for AML+OM+HCTZ 10+40+12.5 mg/d, and 46.3% for AML+OM+HCTZ 10+40+25 mg/d. Study medication was safe and well tolerated. Combination antihypertensive therapy with AML+OM+/-HTCZ, up-titrated as necessary, allowed a majority of patients to achieve BP goal.
57 citations
TL;DR: Aliskiren, the first in a new class of orally effective direct renin inhibitors (DRIs), is approved for the treatment of hypertension and has renoprotective, cardioprotective and anti-atherosclerotic effects in animal models that appear to be independent of BP lowering.
Abstract: The renin-angiotensin-aldosterone system (RAAS) is an important mediator of blood pressure (BP) and volume regulation in both normotensive and hypertensive persons and is a major contributor to hypertension-related target organ damage. The concept of renin inhibition for managing hypertension by blocking the RAAS pathway at its point of activation is very attractive since the renin-angiotensinogen reaction is the first and rate-limiting step in the generation of angiotensin II (Ang II). Aliskiren, the first in a new class of orally effective direct renin inhibitors (DRIs), is approved for the treatment of hypertension. It is effective in reducing BP in the general population of hypertensive patients and in special patient groups such as obese persons, and has a tolerability and safety profile similar to placebo. Aliskiren has renoprotective, cardioprotective and anti-atherosclerotic effects in animal models that appear to be independent of BP lowering. It reduces proteinuria in diabetic patients and has favorable neurohumoral effects in patients with symptomatic heart failure. Additional outcome trials are needed to establish the role of this novel class of antihypertensive medication in the therapeutic armamentarium.
50 citations
TL;DR: The concomitant intake of certain medications that counter the effects of antihypertensive drugs and the frequent occurrence of orthostatic hypotension complicate treatment in older patients and drive down blood pressure control rates.
36 citations
TL;DR: Risk scores developed from patient characteristics, including albuminuria, strongly predicted outcomes and may improve risk assessment of patients with hypertension and LVH and planning of clinical trials.
Abstract: Objective. We assessed readily available patient characteristics, including albuminuria (not included in traditional cardiovascular risk scores), as predictors of cardiovascular events in hypertens ...
TL;DR: The rationale for using CCB/ARB combinations in patients with hypertension is discussed, which has been recently investigated in clinical trials wherein amlodipine was combined with olmesartan medoxomil or valsartan.
Abstract: Hypertension is a leading contributor to the burden of cardiovascular disease. The importance of lowering blood pressure (BP) to reduce the risk of cardiovascular events has been demonstrated in numerous clinical trials. Most patients require combination antihypertensive therapy utilizing agents from complementary drug classes to achieve BP goals. A calcium channel blocker (CCB)/angiotensin receptor blocker (ARB) combination is a rational approach for such an antihypertensive strategy. Benefits of CCB/ARB combination therapy include additive BP-lowering effects and lower incidences of adverse events (AEs). These agents demonstrate benefits associated with their respective drug classes. The ARBs confer stroke protection, renal protection, and tolerability similar to placebo, without dose-related symptomatic and metabolic AEs, while CCBs are beneficial in reducing stroke and treating angina and cardiac ischemia. The efficacy of this combination has been recently investigated in clinical trials wherein amlodipine was combined with olmesartan medoxomil or valsartan. This article discusses the rationale for using CCB/ARB combinations in patients with hypertension.
TL;DR: After 8 weeks of treatment, the combination of amlodipine + OM is safe and efficacious, irrespective of baseline hypertension stage or prior antihypertensive medication use, and produced the greatest mean BP reductions in patients with baseline SeSBP ≥180 mm Hg.
Abstract: :This report includes a prespecified secondary analysis of the COACH study (Combination of Olmesartan medoxomil and Amlodipine besylate in Controlling High blood pressure) based on baseline hypertension severity and prior antihypertensive medication use and a post hoc efficacy analysis of th
TL;DR: Losartan blunted the decrease in HDL cholesterol during antihypertensive treatment in the LIFE study, and higher intreatment HDL cholesterol was associated with fewer composite endpoints and may partly explain the better outcome of losartan-based treatment.
Abstract: Objective: Beta-blockers and angiotensin II receptor blockers have different effects on lipids.
Methods: We examined lipid levels in the Losartan Intervention For Endpoint reduction in hypertension ...
TL;DR: After adjusting for other risk factors, relatively low, but not high, hemoglobin during antihypertensive treatment was associated with higher incidence of all-cause mortality and the composite end point.
TL;DR: Combination therapy using an antagonist of the renin-angiotensin-aldosterone system and a calcium-channel blocker has potential advantages over monotherapy and is being explored in several ongoing clinical trials.
Abstract: A large number of patients who present with signs or symptoms of heart failure (HF) do not have evidence of left ventricular systolic dysfunction. As a result, HF in the presence of normal or preserved ejection fraction, or diastolic HF, is increasingly recognized as a health care challenge. Guidelines have been issued for the classification, diagnosis, and prevention of HF from diastolic dysfunction, but treatment of this condition remains problematic. Antihypertensive agents that have been proven in clinical trials to improve outcomes in HF with systolic dysfunction, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers, have not yet demonstrated comparable benefits in patients with diastolic dysfunction. Combination therapy using an antagonist of the renin-angiotensin-aldosterone system and a calcium-channel blocker has potential advantages over monotherapy and is being explored in several ongoing clinical trials.
TL;DR: Aliskiren, the first in a new class of orally effective direct renin inhibitors (DRIs), is approved for the treatment of hypertension and has renoprotective, cardioprotective and anti-atherosclerotic effects in animal models that appear to be independent of BP lowering.
Abstract: The renin–angiotensin–aldosterone system (RAAS) is a key mediator of blood pressure (BP) and volume regulation in both normotensive and hypertensive persons. Stimulation of RAAS also contributes to hypertension-related target organ damage. The renin–angiotensinogen reaction is the first and rate-limiting step in the generation of angiotensin II (Ang II) and has been a target of antihypertensive drug development for decades. Aliskiren is the first in a new class of orally effective direct renin inhibitors (DRIs) and is approved for the treatment of hypertension in humans. It effectively reduces BP in the general population of hypertensive patients and has a tolerability and safety profile similar to placebo. Aliskiren has favorable effects on vascular inflammation and remodeling, on neurohumoral mediators of various forms of cardiovascular disease, including heart failure, and on proteinuria in diabetic patients. Additional outcome trials are needed to establish the role of this novel class of antihypertensive medication in preventing cardiovascular disease morbidity and mortality.
TL;DR: The controversy related to the J-curve, coined by Cruickshank in 1987, has continued for more than 40 years, and a new debate erupted when data from the prospective, randomized Hypertension Optimal Treatment (HOT) study became available.
Abstract: Early observational BP data from untreated persons undergoing insurance physicals demonstrated that mortality was directly proportional to BP, even in the normal range. However, some argued that tr...
TL;DR: Despite more rapid and aggressive BP lowering, initial fixed-dose irbesartan/HCTZ demonstrated a comparable AE profile to irbesARTan monotherapy in patients with severe hypertension.
Abstract: This prospective, double-blind, multicenter trial compared the safety and tolerability of irbesartan/hydrochlorothiazide (HCTZ) fixed-dose combination therapy with irbesartan monotherapy in patients with severe hypertension (seated diastolic blood pressure (SeDBP) >or=110 mm Hg, mean BP 172/113 mm Hg at baseline). Patients were randomized 2:1 to 7 weeks' irbesartan/HCTZ 150/12.5 mg to 300/25 mg (n = 468) or irbesartan 150 mg to 300 mg (n = 227). The incidence of treatment-related adverse events (AEs) was similar with combination and monotherapy (11.3% and 10.1%), and most AEs were mild-to-moderate. The combined incidence of prespecified AEs was lower with irbesartan/HCTZ than with irbesartan (8.8% vs. 11.5%). There were no treatment-related serious AEs or deaths. At week 5, more patients achieved SeDBP < 90 mm Hg compared to irbesartan (47% vs. 33%; P = 0.0005). Despite more rapid and aggressive BP lowering, initial fixed-dose irbesartan/HCTZ demonstrated a comparable AE profile to irbesartan monotherapy in patients with severe hypertension.
TL;DR: The purpose of this review is to discuss resistant hypertension, its recognition and diagnostic workup and management, and to present current data about the disease from the latest research.
Abstract: Background: Resistant hypertension is a common clinical problem, and patients with resistant hypertension have increased cardiovascular risk. It is a subset of the hypertensive population that is little studied and poorly characterized. Objective: The purpose of this review is to discuss resistant hypertension, its recognition and diagnostic workup and management, and to present current data about the disease from the latest research. Methods: We define resistant hypertension and differentiate it from pseudoresistance. We identify diagnostic tests that may be done on patients with resistant hypertension. Last, we discuss therapeutic approaches to resistant hypertension, focusing on pharmacological treatment, and present an algorithm that may be used by the clinician in treating a patient with resistant hypertension. Conclusion: Resistant hypertension is a significant clinical problem commonly encountered by clinicians. Patients with resistant hypertension have increased cardiovascular risk. In evaluating ...
TL;DR: Ovarian hormones play an important role in women’s health, providing the most reliable and convenient means of contraception and of relieving menopausal symptoms, and hormone therapy of women with ovarian failure continues to be a topic of active debate in the scientific and popular literature.
Abstract: Ovarian hormones play an important role in women’s health, providing the most reliable and convenient means of contraception and of relieving menopausal symptoms.1,2 Hormone therapy also has other benefits, eg, regulation of menstrual irregularities and relief of dysmenorrhea in menstruating women and prevention of vulvovaginal atrophy and osteoporosis/fractures in postmenopausal women. In addition, natural estrogens, principally 17β-estradiol, and natural progesterone (but not synthetic progestins) have biological effects that protect the vasculature from oxidative and inflammatory injury and prevent cardiovascular disease.3 These functions have been adduced by some to account for the 10- to 15-year delay in presentation of clinical cardiovascular disease and events in women compared with men.
In contrast to the unquestioned benefits of endogenous ovarian hormones, hormone therapy of women with ovarian failure, whether naturally occurring or surgically induced, continues to be a topic of active debate in the scientific and popular literature. Although observational studies have shown substantial (≈50% reduction in coronary heart disease) benefit of menopausal hormone therapy (also referred to as “menopausal hormone replacement therapy” or “hormone replacement therapy”) in women who choose to take them (usually beginning treatment in the perimenopausal or early postmenopausal period), randomized, controlled trials have not confirmed a cardioprotective effect and have even shown evidence of harm. Accordingly, current guidelines do not recommend use of menopausal hormone therapy for the prevention or treatment of cardiovascular disease in women.
Important limitations of the available randomized, controlled trials are that they typically enrolled women who were >60 years of age and, thus, were ≥10 years postmenopause and that they typically used nonphysiological hormone preparations, eg, conjugated equine estrogen and the synthetic progestin medroxyprogesterone …
TL;DR: When clinic blood pressure is greater than 140/90 mmHg, the condition is referred to as hypertension as mentioned in this paper, and it is referred as hypertension when the condition occurs in patients with high blood pressure.
Abstract: When clinic blood pressure is greater than 140/90 mmHg, the condition is generally referred to as hypertension. However, as we learn more about blood pressure and its measurement, including the pro...
TL;DR: BP-lowering efficacy of the three agents was similar at 3 months, with OM having the greatest early efficacy, with numerically greater mean reductions in DBP and SBP, and a higher proportion of Black and non-Black patients achieving goal BP of 140/90mm Hg at week 8.
Abstract: Blacks appear to have a more modest blood pressure (BP) response to angiotensin receptor blocker (ARB) monotherapy than non-Blacks. This post-hoc analysis compared the BP-lowering efficacy of olmesartan medoxomil (OM), losartan potassium (LOS), and valsartan (VAL) in Black versus non-Black participants in a randomized, forced-titration study. Patients were randomized to OM 20, LOS 50, and VAL 80mg/day or placebo for 4 weeks and uptitrated to 40, 100, and 320mg/day doses, respectively, by study end. The primary end point was the mean change from baseline in diastolic BP (DBP) at week 8. All treatments produced significant reductions in mean DBP and systolic BP (SBP) in Blacks (n=150; P
TL;DR: Despite exclusion of patients with known ACEI intolerance from the trial, ARB treatment was better tolerated, with fewer drug discontinuations and adverse effects than ramipril treatment, and the data were consistent through all pre-specifi ed subgroups with no differences in any cardiovascular endpoint.
Abstract: 0.004), and also the hypothesis of the combination being superior to ramipril, which was rejected with about the same precision (1). A total of 25 620 participants averaging 66 years of age, including 27% women, 74% with known stable coronary and 21% cerebrovascular disease, 37% with diabetes and 69% with known hyperten-sion (blood pressure averaging 142/82 mmHg) were treated for more than 4 years, with only 43 persons lost to follow-up. Numbers of participants reaching the primary cardiovascular endpoint were 1412 and 1423, respectively, on ramipril and telmisartan, and 1386 on the combination. Blood pressures were lowered by 6.0/4.6, 6.9/5.2 and 8.4/6.0 mmHg, respectively in the three groups, as expected in high-risk people, of whom 57% were taking beta-blockers and about 30% were taking both diuretics and calcium-channel blockers (CCB) at the beginning of the trial. A large proportion of participants were also taking aspirin and statins. The data were consistent through all pre-specifi ed subgroups with no differences in any cardiovascular endpoint. Despite exclusion of patients with known ACEI intolerance from the trial, ARB treatment was better tolerated, with fewer drug discontinuations and adverse effects than ramipril treatment.TRANSCEND included 5926 patients similar to those in ONTARGET, but with proven intolerance to ACEIs. These patients were randomized to either telmisartan or placebo on top of pre-existing therapy (2). Although on-treatment mean blood pressure was 4.0/2.2 mmHg lower in the telmisartan group, these patients did not show any signifi cant reduction in the primary cardiovascular outcome (cardiovascular death, stroke, myocardial infarction and heart failure; RR 0.92, 0.81–1.05,
TL;DR: Previously, the reliability of patient self-assessed blood pressures was questioned based on poor accuracy and reproducibility of the available automated blood pressure monitoring devices, but modern technology has largely solved such problems, as demonstrated by Germano and coworkers in their assessment of four automatic devices for selfmeasurement of blood pressure.
Abstract: Because of the high prevalence of hypertension in most societies, the economic aspects of hypertension diagnosis and treatment becomes critical to modern medicine. In formal health economic assessments, costs and consequences of medical diagnostic and treatment interventions are weighed against outcome benefi ts and value for patients and society ( 1,2). In such assessments, it is clear that the medical, economic and human costs of untreated and inadequately controlled hypertension are enormous ( 3). From such a perspective, a rational detection, treatment and follow-up strategy requires that intrinsic outcome values be delivered to the individual at risk as well as to the society. Since most experts individually or collectively consider that adequate blood pressure control is critical for the achievement of desired outcome benefi ts for individual patients and for the hypertensive population as a whole ( 1), procedures and methods for diagnostic assessment as well as guidelines for treatment and follow-up become important in health economic assessments of hypertension. Thus, the standard methods used for diagnosis as well as for non-pharmacological and pharmacological treatment of hypertensive patients clearly impact on the cost and cost/utility of diagnosing and treating hypertension in the population ( 3). The assessment of blood pressure has to be reliable, affordable and easy. Compared with classical clinic measurements, patient self-assessment of blood pressure has advantages, i.e. it is affordable and easy. Further, self-measurements may be repeated over time more easily than offi ce measurements, thus providing a better background for proper risk assessment and choice of intervention strategies. Before the emergence of enabling technologies such as microelectronics and information technology, costs for collecting, organizing, processing and storing information for assessment of blood pressure were comparatively high. However, since the price for effi cient information processing has fallen considerably, this can now be done on a much larger scale than before. In the light of these developments, the use of patient self-assessment in hypertension diagnosis and treatment has to be re-evaluated. Also of importance is that the increasing use of patient blood pressure self-assessment in hypertension diagnosis and follow-up shifts the costs of the assessment procedure from healthcare providers to the patients. Previously, the reliability of patient self-assessed blood pressures was questioned based on poor accuracy and reproducibility of the available automated blood pressure monitoring devices. However, modern technology has largely solved such problems, as demonstrated by Germano and coworkers ( 4) in their assessment of four automatic devices for selfmeasurement of blood pressure. Clearly, valid technologies have emerged, which enable a wide range of patients to assess correctly their own blood pressures. Important barriers that previously blocked the diffusion and wider dissemination of such techniques to larger groups of patients have largely been removed. However, the healthcare profession has been slow to adopt and incorporate such developments into the routine management of hypertensive patients. This is likely to change, since it is increasingly clear that hypertension experts, health providers, manufacturers and patients share a common interest in working for the wider dissemination and acceptance of validated devices and techniques for patient blood pressure self-assessment. With respect to lowering costs and optimizing cost-utility, the management of patients with high blood pressure has to provide value to the individual patient as well as to society as a whole. Safe, effi cacious and easy to manage antihypertensive therapies, both monotherapies and fi xed dose combinations, are currently available. In this issue of Blood Pressure, Hermans et al., in an openlabel assessment study ( 5), demonstrate that the beta-blocker nebivolol interacts with several blood pressure regulating systems and provides a high
TL;DR: ARBs appear to be effective in the primary prevention of AF, at least in hypertensive patients, and results of the large ONTARGET Trial suggest that ARBs and ACEIs are probably equally effective in preventing AF in a high-risk population.
Abstract: Atrial fi brillation (AF) is by far the most frequent sustained cardiac arrhythmia. Hypertension – because of its high prevalence – accounts for more cases of AF than any other risk factor ( 1 ). Furthermore, angiotensin II has been suggested as a contributor to the atrial remodelling that predisposes to the development of AF, and blockers of the renin-angiotensin system (RAS), including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin IIreceptor blockers (ARBs), have shown promise in reducing the incidence of AF in heart failure and hypertension trials ( 2,3 ). However, the recent GISSI-AF study did not demonstrate preventive effects of the ARB valsartan on recurrent AF, calling into question the ability of RAS blockade to prevent this common arrhythmia ( 4 ). GISSI-AF randomized 1442 patients with a history of symptomatic AF and underlying cardiac disease, hypertension or diabetes, who were in sinus rhythm at baseline to the ARB valsartan in a dose of up to 320 mg/day or placebo. After 12 months, AF had recurred in 371 patients in the valsartan group and in 375 patients in the placebo group ( p 0.84). Thus, GISSI-AF confi rmed that an ARB alone – i.e. not combined with amiodarone – is ineffective in preventing recurrent AF ( 5 ). However, in combination with amiodarone, various RAS inhibitors may be effective ( 6 – 8 ), and in hypertensive patients, ARB or ACEI treatment may be particularly effective ( 9 ). Results of the large ONTARGET Trial suggest that ARBs and ACEIs are probably equally effective in preventing AF in a high-risk population ( 10 ). One caveat is that ONTARGET was not a typical hypertension trial, since it enrolled many patients who were at high cardiovascular risk but were not hypertensive ( 10 ). New-onset AF in randomized controlled trials of antihypertensive therapy is generally detected by systematic electrocardiogram (ECG) recordings (11,12 ). Though ECG recording is less sensitive than telemetry and trans-telephonic ECG monitoring for capturing asymptomatic AF ( 4 ), trials with large numbers of participants have adequate statistical power to overcome that defi ciency. Thus, in the large LIFE Study and VALUE Trial with more than 9000 and 15 000 participants, respectively, ARBs prevented new-onset AF signifi cantly better than the comparators, a beta-blocker and a calcium antagonist. Losartan was better than atenolol in LIFE ( 11) , and valsartan was better than amlodipine in VALUE ( 12 ). At present, while awaiting ongoing proper meta-analyses, ARBs appear to be effective in the primary prevention of AF, at least in hypertensive patients. No prospective hypertension trial has investigated the effect of RAS blockade on development of AF as a primary endpoint ; all have been directed to the serious goal of testing the best ways of preventing myocardial infarction, stroke, heart failure and cardiovascular death in hypertensive persons. New AF is thus an appropriate secondary endpoint for randomized controlled trials of anti-hypertensive treatment. Future clinical trials may improve upon ECG methods of detecting AF by use of telemetry and trans-telephonic ECG monitoring. This is particularly appropriate in the trials that will follow the successful HYVET study ( 13) ; we will likely have randomized clinical trials that will investigate the potential benefi ts and risks of treating hypertension in the elderly at lower threshold pressures and to lower goal pressures, as well as compare more aggressive vs less aggressive treatment strategies. These questions were not investigated in HYVET but are important for a majority of the elderly population. Capturing patients with new AF in these studies will be highly interesting in light of the current controversy ( 4,11,12 ). B lo od P re ss D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y U ni ve rs ity o f T or on to o n 01 /1 3/ 15