Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Research Articles

Applying Trial Emulation Methods to Population-Scale Linked Electronic Health Records for Individuals with Multiple Long-Term Conditions Whilst Adjusting for Informative Observations

Background & ObjectivesTrial Emulation methods can be applied to Population-Scale Linked Electronic Health Records (EHR) to generalise the results of Randomised Controlled Trials (RCTs) to a broader patient population. However, the Data Generating Mechanisms (DGMs) associated with EHR data mean that there is a need to adjust for informative observations, i.e. worse prognosis patients may have more observations. ApproachUsing the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) as a case study: a RCT of a calcium-channel blocker-based regimen versus a β-blocker-based regimen, an emulated trial was created from population-scale, individual-level, linked anonymized EHR data curated as part of the Wales Multimorbidity e-cohort (WMC) for individuals who would have been eligible for ASCOT-BPLA but who also had Multiple Long-Term Conditions (MLTCs). Outcomes were systolic and diastolic blood pressure estimated/predicted at treatment initiation, 6 weeks, 3 months, and 6 monthly until 4 years. Methods & Results Predictions were made using a fully probabilistic Bayesian joint model which allowed for dropout due to death and which either did or did not also adjust for the frequency of blood pressure observations available. In previous simulation studies such a joint modelling approach has been shown to out-perform other adjustment methods in terms of bias and coverage. Conclusions & ImplicationsWhilst EHR data offer an attractive platform in which to evaluate interventions in people living with MLTCs, the inherent DGMs associated with them need to be taken into account, and the use of a joint modelling approach is an attractive way to achieve this.

Predictors of visit-to-visit blood pressure variability in patients with hypertension: an analysis of trials with an amlodipine treatment arm

We conducted a post hoc analysis of blood pressure (BP) data from long-term antihypertensive trials to identify predictors of visit-to-visit BP variability (BPV). BPV was defined as the within-subject coefficient of variation in systolic BP from week 12 onward. BP data from the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, Comparison of Amlodipine Versus Enalapril to Limit Occurrences of Thrombosis, NY92011, and R-0510 trials were pooled and dichotomized into top 25th and bottom 75th percentiles because of positive skew. Significant (P < .001) predictors of BPV within the top 25th percentile were identified using logistic regression. The baseline characteristics of the pooled cohort (n = 47,558) were similar between patients who received amlodipine (n = 17,499) versus other antihypertensive drugs (n = 29,491). BPV in the top 25th percentile was lower with amlodipine versus other treatments (13.7 ± 3.2 vs. 14.3 ± 3.5), with single-study analyses of Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and Comparison of Amlodipine Versus Enalapril to Limit Occurrences of Thrombosis all showing BPV was the lowest with amlodipine. Baseline diastolic BP, estimated glomerular filtration rate, and smoking were predictors of BPV, with significant two-way interactions between smoking and both age and body mass index and between systolic BP or diastolic BP and being randomized to treatment other than amlodipine. In conclusion, analysis of BPV required transformation of BP data. After transformation, a number of baseline variables and combinations of variables were predictors of BPV.

Understanding Visit‐to‐Visit Blood Pressure Variability

Office blood pressure (BP) is considered the gold standard to estimate the risk accompanying an elevation in BP. In daily clinical practice, iterative determinations of office BP constitute the method to consider whether the control of BP is adequate, and frequently the value obtained in an isolated visit is used to modify the treatment of the patient without paying due attention to the values of BP obtained in previous visits. According to the new guidelines of the European Society of Hypertension and the European Society of Cardiology, adequate control is considered when office BP is <140/90 mm Hg for practically the whole population with hypertension.1 Values above this value have been typically considered as uncontrolled but without any reference to differences among visits. It is well known that BP is characterized by marked short-term fluctuations occurring within a 24-hour period. These short-term variations have been shown to be the result of complex interactions between extrinsic environmental and behavioral factors and intrinsic cardiovascular regulatory mechanism.2 Short-term BP variability has been analyzed using ambulatory BP monitoring and has been shown to increase with the development, progression, and severity of cardiac, vascular, and renal damage.2 Recently, the concept of visit-to-visit variability (VVV) obtained through the analysis of systolic BP (SBP) in the repetitive visits in a well-known trial, the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), allowed Rothwell and colleagues3 to conclude in their post-hoc analysis that VVV in SBP and maximum SBP are strong predictors of stroke, independent of mean SBP. It is well established that adverse cardiovascular consequences of hypertension largely depend on absolute BP values and the concept of BP variability along the different visits to the doctor's office has added a new factor to be considered in order to obtain an adequate evaluation of risk and to pharmacologic therapy once this is started and maintained in hypertensive patients. After the initial publication, other groups have come to confirm, in post-hoc analyses, the relevance of VVV for the prediction of cardiovascular events and mortality in hypertensive patients and using data obtained in the general population.4-6 In the present issue of the Journal, Kostis and colleagues7 investigated the relevance of VVV during the very long-term follow-up (up to 17 years) of patients initially included in the Systolic Hypertension in the Elderly Program (SHEP). They confirmed that VVV was associated with cardiovascular death after 17 years of follow-up and after adjustment for confounding variables. This study had two other important advantages over previously published data. First, it was a placebo-controlled trial, which allowed the analysis of VVV in the placebo-treated group. Second, the influence of long-term adherence was considered, which allowed the investigation of the influence of this enormously important parameter on VVV. The relationship between VVV and cardiovascular outcome was significantly stronger in the active treatment group compared with the placebo. This could contribute, partly in agreement with previous data published in this Journal,8 to the hypothesis launched by the authors that inconsistent adherence to active therapy may be causally related to VVV as well as to the occurrence of cardiovascular death. Inconsistent adherence to placebo would be expected to have less influence on BP variability than active therapy. These findings expand the knowledge about the mechanisms underlying the existence of an increased VVV promoted either directly or through coexistent risk factors.3, 9 Another interesting aspect of the influence of active medication on VVV consists of its variation with time,6 with variability being more intense during the first year of follow-up, in which frequent changes in antihypertensive therapy take place and fluctuations in BP can be expected to occur before attaining the adequate amount of treatment required for sustained control of BP. With respect to the medication class effects on VVV, recent data10 have shown that diuretic therapy, as that used in SHEP, lowers BP variability, albeit the magnitude of the effect of antihypertensive medication class explained <10% of the VVV of BP. In summary, the data published in the study by Kostis and colleagues7 come to extend the understanding of VVV in BP, demonstrating that it is more important when active therapy is compared with placebo and introducing inconsistent adherence as a new factor that contributes to the understanding of this phenomenon, which has been shown to be relevant for the prognosis of hypertensive patients.

Fluctuation

Effective drug treatment of hypertension for the prevention of fatal and nonfatal cardiovascular disease passed its 50th anniversary 2 years ago.1 Until recently, the most consistent observation among trials had been that stroke risk was directly related to the fall in blood pressure on treatment.2 Older trials established the value of antihypertensive drug treatment and generally recruited disease-free participants at their outset. Recent trials have focused on less healthy participants. Recruitment has been extended to those with a prior stroke, recent myocardial infarction, coronary artery disease, chronic renal disease (with or without diabetes mellitus), heart failure, and combined high-risk states and the elderly (old-old). The benefit of antihypertensive drug treatment is still related to the reduction in blood pressure.3 Differences between drug classes have been found in some but not all trials; the differences are generally small, even if statistically significant. Antihypertensive drug treatment is effective in reducing risk for those with a higher disease burden, but risk is never lowered to levels equal to those who have lower pressure without antihypertensive drug treatment and lack prior cardiovascular disease. The hands of the cardiovascular clock may slow, but they never stop or reverse. It is a challenge to unmask traits that might account for the limited effectiveness of antihypertensive drug treatment in its present form. Article see p 569 In a retrospective look at blood pressure patterns in several stroke trials and the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering (ASCOT BP) …

Implementing Home Blood Pressure Into Practice

See related article, pp 1081–1086 The growing worldwide epidemic of high blood pressure in both developed and developing nations is a challenge on many levels.1 The need for better prevention of cardiovascular disease through control of hypertension is clear.2 Public awareness of the need to treat hypertension is partly reflected by the widespread purchases of home blood pressure devices in several of the developed countries. In the United States, Japan, and Finland, the estimates are that 55% to 75% of hypertensive patients already have a home device.3 Research studies have provided a robust epidemiological basis for supporting the greater accuracy of home blood pressure monitoring (HBPM) compared with clinic pressures for prognosis of fatal and nonfatal cardiovascular disease in long-term follow-up surveys and in cross-sectional designs.4 There is a general consensus that HBPM is more convenient, available, and less costly than ambulatory blood pressure monitoring, but the superiority of ambulatory blood pressure monitoring for special clinical problems (ie, detection of nondippers or need for sleep pressures in chronic renal disease, autonomic neuropathies, and sleep apnea) is also clearly recognized.5 Surveys of both physicians6 and patients7 suggest that HBPM is both appreciated and recognized as a valuable strategy. Several experts in the field of hypertension research and care have published appeals to expand the use of HPBM for routine care and to have it supported by health care …

Impact of amlodipine-based therapy among older and younger patients in the Anglo-Scandinavian Cardiac Outcomes Trial−Blood Pressure Lowering Arm (ASCOT-BPLA)

Older patients experience higher rates of cardiovascular disease than younger patients, but studies have suggested that relative risk reductions due to antihypertensive therapy are lower in older than younger patients. The Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) allowed an evaluation of the efficacy and safety of an amlodipine versus an atenolol-based antihypertensive regimen among older (≥ 65 years) and younger (<65 years) patients. In ASCOT-BPLA 19 257 patients (8137 aged ≥ 65 years and 11 020 <65 years) were randomly assigned to receive amlodipine or atenolol-based antihypertensive therapy. The primary endpoint (nonfatal myocardial infarction and fatal coronary heart disease) and seven secondary endpoints were consistent with the original trial design. All cardiovascular endpoints evaluated favoured the amlodipine-based regimen, significantly so in seven of the 16 age-stratified endpoints. Compared with the atenolol-based regimen, the amlodipine-based regimen reduced the relative risk of cardiovascular events by 17% in older and 15% in younger patients (P < 0.01). Overall, older patients experienced more cardiovascular events [n = 1625 (20%)] than younger patients [n = 1339 (12%)]. Discontinuations due to serious adverse events were low in both age groups and less frequent in the amlodipine-based versus atenolol-based regimen: 0.6 versus 1.1% among older patients and 0.4 versus 0.8% among younger patients. The amlodipine-based regimen reduced the relative risk of cardiovascular events more effectively than the atenolol-based regimen in both older and younger patients. However, because event rates were higher among older patients, the absolute benefits were greater for older compared with younger patients.

Blood Pressure Variability

A series of articles1–4⇓⇓⇓ published recently in The Lancet and Lancet Neurology raise an interesting issue that has implications for both the clinical management of hypertension and future research in hypertension, particularly in the development and use of different classes of blood pressure (BP)–lowering drugs. These studies, which were led by Peter Rothwell at the John Radcliffe Hospital in Oxford, United Kingdom, suggest that, whereas there is undoubted and well-proven benefit in the current practice of reducing mean BP to prevent cardiovascular events, there may be additional benefit in also reducing BP variability (BPV), especially to prevent stroke. The studies suggest, moreover, that different classes of drugs are superior to others in reducing BPV (calcium channel blockers being best and the β-blocker atenolol being worst). However, these articles, by virtue of their sheer volume (≈50 pages of printed text and many pages of supplementary web appendix data), could overwhelm all but the most stoic readers, and misinterpretation of the data could lead to confusion and have an adverse effect on clinical practice. It is important, therefore, to assess the scientific reality and determine how attention to BPV might benefit patients with hypertension. In the first analysis, systolic BPV between visits and maximum BP reached in 4 cohorts of patients with previous transient ischemic attacks were strong predictors for subsequent stroke.1 In treated hypertensive patients in the Anglo-Scandinavian Cardiac Outcome Trial-Blood Pressure Lowering Arm systolic BPV between visits was also a strong predictor of stroke and coronary events independent of mean clinic or ambulatory BP measurement (ABPM). BPV on ABPM was a weaker predictor overall but was related to visit-to-visit variability. Traditional measures of variability, such as SD and coefficient of variation (CV), were used in these analyses, but one of the problems encountered in the …

Baseline Heart Rate, Antihypertensive Treatment, and Prevention of Cardiovascular Outcomes in ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial)

The aim of this study was to evaluate the effect of baseline heart rate on the efficacy of atenolol-based compared with amlodipine-based therapy in patients with hypertension uncomplicated by coronary heart disease in the ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm). Heart rate is an established risk factor for cardiovascular events. Consequently, it is a widely held belief that beta-blockers should be prescribed for management of hypertension in patients with higher heart rates. Patients with atrial fibrillation or taking rate-limiting antihypertensive drugs at baseline were excluded. Primary analyses used Cox models to investigate the potential attenuation of the treatment effect with higher baseline heart rate on total cardiovascular events and procedures (TCVP) via introduction of an interaction term. Secondary analyses assessed coronary and total stroke outcomes. Primary unadjusted analyses included 12,759 patients and 1,966 TCVP. At the final visit, mean heart rate reduction from baseline was 12.0 (SD 13.7) and 1.3 (SD 12.1) beats/min in atenolol- and amlodipine-based groups, respectively. There was a reduction in TCVP in those allocated amlodipine-based therapy compared with atenolol-based therapy (unadjusted hazard ratio: 0.81, p < 0.001). This benefit was unattenuated at higher heart rates (interaction p value = 0.81). Similar results were obtained for coronary and total stroke outcomes. There was no evidence that the superiority of amlodipine-based over atenolol-based therapy for patients with hypertension uncomplicated by coronary heart disease was attenuated with higher baseline heart rate. These data suggest that, in similar hypertensive populations without previous or current coronary artery disease, higher baseline heart rate is not an indication for preferential use of beta-blocker-based therapy.

Ambulatory blood pressure monitoring predicts cardiovascular events in treated hypertensive patients – an Anglo-Scandinavian cardiac outcomes trial substudy

Results of the Anglo-Scandinavian cardiac outcomes trial-blood pressure lowering arm (ASCOT-BPLA) showed significantly lower rates of coronary and stroke events in individuals allocated an amlodipine-perindopril combination drug regimen than in those allocated an atenolol-thiazide combination drug regimen. The aims of the ambulatory blood pressure (ABP) substudy of ASCOT were to examine the impact of the two blood pressure (BP)- lowering regimens on ambulatory pressures, test to what extent the between-treatment differences in cardiovascular outcome could be attributed to differences in ABP and assess whether ABP provides predictive information additional to that of clinic blood pressure (CBP) in treated hypertensive patients. One thousand, nine hundred and five patients from four ASCOT centres had repeated ABPs performed over a median follow-up period of 5.5 years. As in the whole ASCOT population, CBP values were lower in amlodipine-perindopril-treated patients compared with those treated with atenolol-thiazide [between-regimen difference [95% confidence intervals (CIs)]]: [-1.5 (-2.4 to -0.5)/-1.2 (-1.8 to +0.5) mmHg]. Daytime BP during follow-up was higher in patients treated with amlodipine-perindopril therapy [+1.1 (0.1-2.1)/+1.6 (0.8-2.3) mmHg]; night-time systolic, but not diastolic BP, was lower in patients treated with amlodipine-perindopril therapy [-2.2 (-3.4 to +0.9)/+0.8 (0.0-1.6) mmHg]. The relative risk of a cardiovascular event associated with a 1 SD increment in accumulated mean BP was 1.35 (1.18-1.53) for clinic systolic BP, 1.30 (1.14-1.49) for daytime systolic BP and 1.42 (1.24-1.62) for night-time systolic BP. With adjustment for baseline variables, treatment regimen and clinic systolic BP, the hazard ratios were 1.17 (1.00-1.36) and 1.25 (1.08-1.47) for daytime and night-time systolic BP, respectively. The between-regimen adjusted hazard ratio for cardiovascular events (amlodipine-perindopril therapy versus atenolol-thiazide therapy) was 0.74 (0.55-1.01) and increased to 0.81 (0.60-1.10) after further adjustment for clinic systolic BP. Further, adjustment for night-time systolic BP increased the hazard ratio to 0.85 (0.62-1.16). The amlodipine-perindopril and atenolol-thiazide regimens had different effects on daytime and night-time ABP, which may have contributed to the lower rates of events in patients treated with amlodipine-perindopril therapy. Both CBP and ABP were significantly associated with rates of cardiovascular events. ABP nocturnal pressures provided complimentary and incremental utility over CBP in the prediction of cardiovascular risk in treated hypertensive patients. These data support the use of ABP to assess the effect of antihypertensive treatment in clinical practice.

The emerging role of high-density lipoprotein cholesterol in hypertension trials

Population Health Research Institute,McMaster University, Hamilton Health Sciences, Hamilton, CanadaCorrespondence to Fabio Angeli, MD, Department of Cardiology, ClinicalResearch Unit ‘Preventive Cardiology’, Hospital Santa Maria della Misericordia,06156 Perugia, ItalyTel: +39 075 5782213; fax: +39 075 5782214; e-mail: fangeli@cardionet.it

Which patients would benefit the most from the perindopril-amlodipine combination?

In the recent Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm trial, the amlodipine ± perindopril strategy resulted in fewer deaths and cardiovascular events than an atenolol ± thiazide strategy. Because of the intrinsic properties of both angiotensin-converting enzyme inhibitors, particularly in terms of secondary prevention of ischaemic heart disease, and calcium-channel blockers, in terms of anti-anginal properties, the combination of amlodipine and perindopril should prove particularly beneficial in patients with coronary artery disease and either hypertension or anginal symptoms. In addition, both classes of medications have a favourable metabolic profile and have been shown to reduce the occurrence of new-onset diabetes mellitus in a variety of clinical situations. Finally, the impact of the amlodipine ± perindopril combination on central aortic pressure suggests a particular relevance in situations of increased central pulse pressure, such as elderly populations or patients with chronic kidney disease. Therefore, the amlodipine ± perindopril combination is likely to offer important clinical benefits in a number of fairly common clinical conditions.

Effect of Doxazosin Gastrointestinal Therapeutic System as Third-Line Antihypertensive Therapy on Blood Pressure and Lipids in the Anglo-Scandinavian Cardiac Outcomes Trial

The role of doxazosin in treatment of hypertension remains controversial. We evaluated the effects on blood pressure (BP) and biochemical parameters of doxazosin GITS (gastrointestinal therapeutic system) as a third-line antihypertensive agent among 10,069 participants in the Anglo-Scandinavian Cardiac Outcomes Trial--Blood Pressure Lowering Arm (ASCOT-BPLA) whose BP remained above 140/90 mm Hg (130/80 mm Hg in those with diabetes mellitus). Among those who received doxazosin, mean age was 63 years (SD 9 years), 79% were male, and 32% had diabetes. Doxazosin was initiated a median of 8 months (interquartile range 3 to 24 months) after randomization and was added to a mean of 2.0 (SD 0.3) other antihypertensive drugs; the mean starting and final doses were 4.1 (SD 0.6) and 7.0 (SD 3.1) mg, respectively. During a median of 12 months (interquartile range 4 to 31 months) of uninterrupted doxazosin treatment, during which other antihypertensive treatments remained unchanged, mean BP fell 11.7/6.9 mm Hg (SD 18.8/9.6 mm Hg, P<0.0001) from 158.7/89.2 mm Hg (SD 18.3/10.6 mm Hg). After the addition of doxazosin, 29.7% of participants achieved target BP. There was no apparent excess of heart failure among doxazosin users. There were associated modest favorable effects on plasma lipid profiles, but a small rise in fasting plasma glucose was observed. Doxazosin was generally well tolerated, with 7.5% of participants discontinuing the drug because of adverse events, most frequently dizziness, fatigue, headache, and edema. alpha-Blockers are no longer recommended as add-on therapy in some hypertension guidelines. However, although they are nonrandomized and were not placebo-controlled, the present findings suggest that doxazosin is a safe and effective third-line antihypertensive agent.

Perindopril: Beyond Lowering Blood Pressure

Perindopril, a prodrug ester of perindoprilat, is an angiotensin-converting enzyme inhibitor that lowers angiotensin II and potentiates bradykinin. This agent has proven efficacy in a wide range of cardiovascular diseases. Its efficacy, safety and tolerability are well established in the treatment of hypertension. Beyond pharmacodynamic effects shown in lowering blood pressure, perindopril was also involved in the improvement of endothelial function and the normalization of vascular and cardiac structure and function. Large morbidity-mortality trials, such as the European Trial on Reduction of Cardiac Events with Perindopril in Patients with Stable Coronary Artery Disease (EUROPA), Perindopril Protection Against Recurrent Stroke Study (PROGRESS) and Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), have shown that treatment with perindopril reduces and prevents cardiovascular disease in a large range of patients with vascular diseases (including stable coronary disease), whether or not they are hypertensive.

Determinants of New-Onset Diabetes Among 19,257 Hypertensive Patients Randomized in the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm and the Relative Influence of Antihypertensive Medication

The purpose of this study was to determine the baseline predictors of new-onset diabetes (NOD) in hypertensive patients and to develop a risk score to identify those at high risk of NOD. Among 19,257 hypertensive patients in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) who were randomly assigned to receive one of two antihypertensive regimens (atenolol +/- thiazide or amlodipine +/- perindopril), 14,120 were at risk of developing diabetes at baseline. Of these, 1,366 (9.7%) subsequently developed NOD during median follow-up of 5.5 years. A multivariate Cox model was developed to identify the independent predictors of NOD and individual risk scores. NOD was significantly associated with an increase in baseline fasting plasma glucose (FPG), BMI, serum triglycerides, and systolic blood pressure. In contrast, amlodipine +/- perindopril in comparison with atenolol +/- thiazide treatment (hazard ratio 0.66 [95% CI 0.59-0.74]), high HDL cholesterol, alcohol use, and age >55 years were found to be significantly protective factors. FPG was the most powerful predictor with risk increasing by 5.8 times (95% CI 5.23-6.43) for each millimole per liter rise >5 mmol/l. The risk of NOD increased steadily with increasing quartile of risk score, with a 19-fold increase (95% CI 14.3-25.4) among those in the highest compared with those in the lowest quartile. The model showed excellent internal validity and discriminative ability. Baseline FPG >5 mmol/l, BMI, and use of an atenolol +/- diuretic regimen were among the major determinants of NOD in hypertensive patients. The model developed from these data allows accurate prediction of NOD among hypertensive subjects.

Analysis of Recent Papers in Hypertension

Analysis of Recent Papers in Hypertension

Pulsology Reloaded

The Losartan Intervention For Endpoint reduction in hypertension (LIFE) Study,1 the Second Australian National Blood Pressure Trial (ANBP2),2 and the Anglo-Scandinavian Cardiovascular Outcome Trials3 have shown that different antihypertensive treatments may have different impacts on the rate of events in hypertension while achieving comparable brachial blood pressure (BP) reduction. Thus, although brachial BP estimation by classic Riva–Rocci cuff sphygmomanometer and the Korotkoff auscultatory technique have provided almost all of our knowledge on epidemiology, prognosis, and treatment of hypertension,4,5 recent trials1–3 are revealing intrinsic limitations of the conventional approach, because the real goal of treatment in hypertension is the reduction in the number and the rate of untoward events. More recently, the Conduit Artery Function Evaluation (CAFE) Study6 described higher central BP as a key factor explaining the greater number and rate of events with atenolol than with amlodipine plus perindopril. Central pressure waveform and BP values can be estimated by applanation tonometry, a method supported by solid theoretical principles and modeling studies in experimental settings.7 Analysis of the systolic portion of the carotid pressure waveform allows for obtaining indices of the arterial viscous-elastic properties that correlate with end-organ damage and clinical outcomes in hypertension.8 Therefore, the indices of arterial waveform reflection and mechanics and central BP assessed by applanation tonometry have the potential to add significant information for risk stratification beyond and above brachial BP. In fact, the conclusions of the CAFE Study were well received.9 In addition, applanation tonometry has also been associated with 2D-guided M-mode vascular ultrasonography to assess simultaneously the viscous-elastic properties of the carotid artery, the intima–media thickness, and quantification of atherosclerosis.8 Assessment of cardiovascular target organ damage is curial for a global risk assessment …

First-Line Therapy for Hypertension

Letters17 April 2007First-Line Therapy for HypertensionMohsen S. Eledrisi, MDMohsen S. Eledrisi, MDFrom King Abdulaziz National Guard Medical Center, Alahsa, Saudi Arabia.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-146-8-200704170-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: In the recent Update in Cardiology (1), Rapaport draws conclusions from the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) (2) and recommends that physicians consider “using amlodipine as a first-line antihypertensive in patients with ≥3 other cardiovascular risk factors.” This should be interpreted carefully. The ASCOT-BPLA investigators found no difference in the study's primary outcome and observed the reported benefits in secondary end points. In addition, several issues were raised about the design of the trial. First is the choice of a β-blocker as a comparator for first-line therapy versus amlodipine. Ever since the Medical Research ...

Effect of Spironolactone on Blood Pressure in Subjects With Resistant Hypertension

Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication. We evaluated the effect among 1411 participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm who received spironolactone mainly as a fourth-line antihypertensive agent for uncontrolled blood pressure and who had valid BP measurements before and during spironolactone treatment. Among those who received spironolactone, the mean age was 63 years (SD: +/-8 years), 77% were men, and 40% had diabetes. Spironolactone was initiated a median of 3.2 years (interquartile range: 2.0 to 4.4 years) after randomization and added to a mean of 2.9 (SD: +/-0.9) other antihypertensive drugs. The median duration of spironolactone treatment was 1.3 years (interquartile range: 0.6 to 2.6 years). The median dose of spironolactone was 25 mg (interquartile range: 25 to 50 mg) at both the start and end of the observation period. During spironolactone therapy, mean blood pressure fell from 156.9/85.3 mm Hg (SD: +/-18.0/11.5 mm Hg) by 21.9/9.5 mm Hg (95% CI: 20.8 to 23.0/9.0 to 10.1 mm Hg; P<0.001); the BP reduction was largely unaffected by age, sex, smoking, and diabetic status. Spironolactone was generally well tolerated; 6% of participants discontinued the drug because of adverse effects. The most frequent adverse events were gynecomastia or breast discomfort and biochemical abnormalities (principally hyperkaliemia), which were recorded as adverse events in 6% and 2% of participants, respectively. In conclusion, spironolactone effectively lowers blood pressure in patients with hypertension uncontrolled by a mean of approximately 3 other drugs. Although nonrandomized and not placebo controlled, these data support the use of spironolactone in uncontrolled hypertension.

Hypertension Treatment Guidelines: Is It Time for an Update?

Hypertension Treatment Guidelines: Is It Time for an Update?

Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial

Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial