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2019年 夏季 期刊文獻精選

Long-term mortality after blood pressure-lowering and lipid-lowering treatment in patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy study: 16-year follow-up results of a randomised factorial trial.

Ajay Gupta MRCP, Judith Mackay MRCP, Andrew Whitehouse MBBS, Thomas Godec MSc, Tim Collier MSc, Stuart Pocock Prof, Neil Poulter Prof 及 Peter Sever Prof
Lancet, The, 2018-09-29, 卷 392, 期 10153, 頁面 1127-1137, Copyright © 2018 Elsevier Ltd



In patients with hypertension, the long-term cardiovascular and all-cause mortality effects of different blood pressure-lowering regimens and lipid-lowering treatment are not well documented, particularly in clinical trial settings. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy Study reports mortality outcomes after 16 years of follow-up of the UK participants in the original ASCOT trial.


ASCOT was a multicentre randomised trial with a 2 × 2 factorial design. UK-based patients with hypertension were followed up for all-cause and cardiovascular mortality for a median of 15.7 years (IQR 9.7–16.4 years). At baseline, all patients enrolled into the blood pressure-lowering arm (BPLA) of ASCOT were randomly assigned to receive either amlodipine-based or atenolol-based blood pressure-lowering treatment. Of these patients, those who had total cholesterol of 6.5 mmol/L or lower and no previous lipid-lowering treatment underwent further randomisation to receive either atorvastatin or placebo as part of the lipid-lowering arm (LLA) of ASCOT. The remaining patients formed the non-LLA group. A team of two physicians independently adjudicated all causes of death.


Of 8580 UK-based patients in ASCOT, 3282 (38·3%) died, including 1640 (38.4%) of 4275 assigned to atenolol-based treatment and 1642 (38.1%) of 4305 assigned to amlodipine-based treatment. 1768 of the 4605 patients in the LLA died, including 903 (39.5%) of 2288 assigned placebo and 865 (37.3%) of 2317 assigned atorvastatin. Of all deaths, 1210 (36.9%) were from cardiovascular-related causes. Among patients in the BPLA, there was no overall difference in cardiovascular mortality between treatments (adjusted hazard ratio [HR] 0.90, 95% CI 0.81–1.01, p=0.0776]), although significantly fewer deaths from stroke (adjusted HR 0.71, 0.53–0.97, p=0.0305) occurred in the amlodipine-based treatment group than in the atenolol-based treatment group. There was no interaction between treatment allocation in the BPLA and in the LLA. However, in the 3975 patients in the non-LLA group, there were fewer cardiovascular deaths (adjusted HR 0.79, 0.67–0.93, p=0.0046) among those assigned to amlodipine-based treatment compared with atenolol-based treatment (p=0.022 for the test for interaction between the two blood pressure treatments and allocation to LLA or not). In the LLA, significantly fewer cardiovascular deaths (HR 0.85, 0.72–0.99, p=0.0395) occurred among patients assigned to statin than among those assigned placebo.


Our findings show the long-term beneficial effects on mortality of antihypertensive treatment with a calcium channel blocker-based treatment regimen and lipid-lowering with a statin: patients on amlodipine-based treatment had fewer stroke deaths and patients on atorvastatin had fewer cardiovascular deaths more than 10 years after trial closure. Overall, the ASCOT Legacy study supports the notion that interventions for blood pressure and cholesterol are associated with long-term benefits on cardiovascular outcomes.

Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial.

David E Kandzari MD, Michael Böhm Prof, Felix Mahfoud Prof, Raymond R Townsend MD, Michael A Weber Prof, Stuart Pocock PhD, Konstantinos Tsioufis MD, Dimitrios Tousoulis MD, James W Choi MD, Cara East MD, Sandeep Brar MD, Sidney A Cohen MD, Martin Fahy MS, Garrett Pilcher MS 及 Kazuomi Kario Prof
Lancet, The, 2018-06-09, 卷 391, 期 10137, 頁面 2346-2355, Copyright © 2018 Elsevier Ltd



Previous catheter-based renal denervation studies have reported variable efficacy results. We aimed to evaluate safety and blood pressure response after renal denervation or sham control in patients with uncontrolled hypertension on antihypertensive medications with drug adherence testing.


In this international, randomised, single-blind, sham-control, proof-of-concept trial, patients with uncontrolled hypertension (aged 20–80 years) were enrolled at 25 centres in the USA, Germany, Japan, UK, Australia, Austria, and Greece. Eligible patients had an office systolic blood pressure of between 150 mm Hg and 180 mm Hg and a diastolic blood pressure of 90 mm Hg or higher; a 24 h ambulatory systolic blood pressure of between 140 mm Hg and 170 mm Hg at second screening; and were on one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned to undergo renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were masked to randomisation assignments. The primary efficacy endpoint was blood pressure change from baseline (measured at screening visit two), based on ambulatory blood pressure measurements assessed at 6 months, as compared between treatment groups. Drug surveillance was used to assess medication adherence. The primary analysis was done in the intention-to-treat population. Safety events were assessed through 6 months as per major adverse events. This trial is registered with , number NCT02439775 , and follow-up is ongoing.


Between July 22, 2015, and June 14, 2017, 467 patients were screened and enrolled. This analysis presents results for the first 80 patients randomly assigned to renal denervation (n=38) and sham control (n=42). Office and 24 h ambulatory blood pressure decreased significantly from baseline to 6 months in the renal denervation group (mean baseline-adjusted treatment differences in 24 h systolic blood pressure −7.0 mm Hg, 95% CI −12.0 to −2.1; p=0.0059, 24 h diastolic blood pressure −4.3 mm Hg, −7.8 to −0.8; p=0.0174, office systolic blood pressure −6.6 mm Hg, −12.4 to −0.9; p=0.0250, and office diastolic blood pressure −4.2 mm Hg, −7.7 to −0.7; p=0.0190). The change in blood pressure was significantly greater at 6 months in the renal denervation group than the sham-control group for office systolic blood pressure (difference −6.8 mm Hg, 95% CI −12.5 to −1.1; p=0.0205), 24 h systolic blood pressure (difference −7.4 mm Hg, −12.5 to −2.3; p=0.0051), office diastolic blood pressure (difference −3.5 mm Hg, −7.0 to −0.0; p=0.0478), and 24 h diastolic blood pressure (difference −4.1 mm Hg, −7.8 to −0.4; p=0.0292). Evaluation of hourly changes in 24 h systolic blood pressure and diastolic blood pressure showed blood pressure reduction throughout 24 h for the renal denervation group. 3 month blood pressure reductions were not significantly different between groups. Medication adherence was about 60% and varied for individual patients throughout the study. No major adverse events were recorded in either group.


Renal denervation in the main renal arteries and branches significantly reduced blood pressure compared with sham control with no major safety events. Incomplete medication adherence was common.

Angiotensin-Converting Enzyme Inhibitors in Hypertension.

Franz H. Messerli MD, Sripal Bangalore MD, MHA, Chirag Bavishi MD, MPH 及 Stefano F. Rimoldi MD
JACC (Journal of the American College of Cardiology), 2018-04-03, 卷 71, 期 13, 頁面 1474-1482, Copyright © 2018 American College of Cardiology Foundation


Most guidelines for the management of patients with cardiovascular disease recommend angiotensin-converting enzyme (ACE) inhibitors as first-choice therapy, whereas angiotensin receptor blockers (ARBs) are merely considered an alternative for ACE inhibitor–intolerant patients. The aim of this review was to compare outcomes and adverse events between ACE inhibitors and ARBs in patients. In patients with hypertension and hypertension with compelling indications, we found no difference in efficacy between ARBs and ACE inhibitors with regard to the surrogate endpoint of blood pressure and outcomes of all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. However, ACE inhibitors remain associated with cough and a very low risk of angioedema and fatalities. Overall withdrawal rates because of adverse events are lower with ARBs than with ACE inhibitors. Given the equal outcome efficacy but fewer adverse events with ARBs, risk-to-benefit analysis in aggregate indicates that at present there is little, if any, reason to use ACE inhibitors for the treatment of hypertension or its compelling indications.

Sex Differences of Patients With Systemic Hypertension (From the Analysis of the Systolic Blood Pressure Intervention Trial [SPRINT]).

Roberto Ochoa-Jimenez MD, Karolina Viquez-Beita MD, Chathuri Daluwatte PhD 及 Robbert Zusterzeel MD, PhD, MPH
American Journal of Cardiology, The, 2018-09-15, 卷 122, 期 6, 頁面 985-993, Copyright © 2018


There are differences in the incidence, pathophysiology, and long-term effects of hypertension between women and men. We assessed sex-specific benefit-risk tradeoffs of different blood pressure (BP) goals in patients enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT) after propensity score matching those with standard therapy (systolic BP <140 mm Hg) to those with intensive therapy (systolic BP <120 mm Hg; n = 9,106). Cox regression was conducted to compare standard versus intensive therapy in women and men with the composite outcome of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. Women were generally healthier at baseline and had a lower cardiovascular risk. Men on intensive therapy had a lower risk of the composite outcome compared to those on standard therapy (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.57 to 0.86, p = 0.001) while in women no differences between therapy groups were observed (HR 0.82 [0.60 to 1.12], p = 0.206) . For safety outcomes, women and men had increased risk of related serious adverse events with intensive treatment (HR 1.52 [1.06 to 2.18], p = 0.023 and HR 2.07 [1.55 to 2.77], p < 0.001, respectively). In conclusion, our study demonstrated that women did not benefit from intensive compared to standard BP control. A potential explanation for this may be the lower baseline cardiovascular risk in women.

Anti-hypertensive treatment in peripheral artery disease.

Costas Tsioufis, Ioannis Andrikou, Gerasimos Siasos, Konstantinos Filis 及 Dimitrios Tousoulis
Current Opinion in Pharmacology, 2018-04-01, 卷 39, 頁面 35-42, Copyright © 2018 Elsevier Ltd


Peripheral artery disease (PAD) affects more than 200 million people worldwide. Hypertension has been related to increased risk of PAD. The treatment of elevated blood pressure (BP) in these patients is indicated to lower the cardiovascular risk with a BP goal of less than 130/80 mmHg. Although there is no evidence that one class of antihypertensive medication or strategy is superior for BP lowering in PAD, the use of renin-angiotensin-system (RAS) inhibitors can be effective to reduce the cardiovascular risk. Beta-blockers (BBs) are not contraindicated. In the presence of carotid atherosclerosis, calcium-channel blockers (CCBs) and angiotensin-converting-enzyme inhibitors are recommended. In fibromuscular dysplasia the treatment of choice is percutaneous renal angioplasty. In renal artery disease optimal medical therapy includes RAS inhibitors, CCBs, BBs and diuretics.

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Optimal Systolic Blood Pressure Target in Resistant and Non-Resistant Hypertension: A Pooled Analysis of Patient-Level Data from SPRINT and ACCORD.

Steven M. Smith PharmD, MPH, Matthew J. Gurka PhD, David A. Calhoun MD, Yan Gong PhD, Carl J. Pepine MD 及 Rhonda M. Cooper-DeHoff PharmD, MS
American Journal of Medicine, The, 2018-12-01, 卷 131, 期 12, 頁面 1463-1472.e7, Copyright © 2018



Prior studies suggest benefits of blood pressure lowering on cardiovascular risk may be attenuated in patients with resistant hypertension compared with the general hypertensive population, but prospective data are lacking.


We assessed intensive (<120 mm Hg) versus standard (<140 mm Hg) systolic blood pressure targets on adverse outcome risk according to baseline resistant hypertension status, using Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Systolic Blood Pressure Intervention Trial (SPRINT) patient-level data. Patients were categorized as having baseline apparent resistant hypertension (blood pressure ≥130/80 mm Hg while using 3 antihypertensive drugs or use of ≥4 drugs regardless of blood pressure) or non-resistant hypertension (all others). Cox regression was used to assess effects of treatment assignment, resistant hypertension status, their interaction, and other covariates, on first occurrence of 2 outcomes: myocardial infarction, stroke, cardiovascular death ± heart failure, and the same outcomes plus all-cause death, individually.


Among 14,094 patients, 2710 (19.2%) had baseline apparent resistant hypertension. In adjusted models, an intensive target reduced risk of both outcomes (myocardial infarction/stroke/cardiovascular death: hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.71-0.93; myocardial infarction/stroke/heart failure/cardiovascular death: HR 0.78; 95% CI, 0.69-0.88) as well as stroke (HR 0.72; 95% CI, 0.55-0.94) and heart failure (HR 0.73; 95% CI, 0.59-0.91). An intensive target also appeared to reduce myocardial infarction, cardiovascular death, and all-cause death risk. Benefits were observed irrespective of baseline resistant hypertension status.


Our findings provide the first evidence to support guidance to treat resistant hypertension to the same blood pressure goal as non-resistant hypertension.

Effects of exercise training on endothelial function in individuals with hypertension: a systematic review with meta-analysis.

Marinei L. Pedralli MSc, Bruna Eibel PhD, Gustavo Waclawovsky MSc, Maximiliano I. Schaun PhD, Walter Nisa-Castro-Neto PhD, Daniel Umpierre PhD, Linda S. Pescatello PhD, Hirofumi Tanaka PhD 及 Alexandre Machado Lehnen PhD
Journal of the American Society of Hypertension, 2018-12-01, 卷 12, 期 12, 頁面 e65-e75, Copyright © 2018 American Heart Association


A slight increase (1%) in endothelial function is associated with reduction of cardiovascular risks by 13% in individuals with cardiovascular disease risk, including those with hypertension. Thus, we conducted a systematic review and meta-analysis to assess the efficacy of exercise training on endothelial function in individuals with hypertension.We included randomized clinical trials (RCTs) with adult participants diagnosed with hypertension undergoing exercise training (≥4 weeks), and the primary outcome was endothelial function, measured by flow-mediated dilatation (FMD). Five studies comprising a total of 362 participants (252 exercise and 110 controls; 59.3 years old, ranged from 52.0 to 67.2 years) were included in the meta-analysis. The pooled mean estimate indicated increased FMD after exercise training of 1.45 ( P = .001), and 95% confidence interval −0.11 to 3.00 compared with control comparators. The studies were characterized by significant heterogeneity (χ2 = 23.34, P < .001, I 2 = 70%). The present results are consistent with the notion that aerobic exercise training elicits favorable adaptations in endothelial function in individuals with hypertension. However, more studies are needed to make more definitive conclusions.

Simple dietary advice reduces 24-hour urinary sodium excretion, blood pressure, and drug consumption in hypertensive patients.

Natale Musso MD, Beatrice Carloni MD, Maria C. Chiusano RD 及 Massimo Giusti MD
Journal of the American Society of Hypertension, 2018-09-01, 卷 12, 期 9, 頁面 652-659, Copyright © 2018 American Heart Association

Sodium intake should be restricted to 100 mEq, that is, about 2.3 grams per day. Strict diets, however, are often cumbersome and seldom matched by rigorous compliance. We studied 291 patients on antihypertensive treatment, 240 of whom were instructed to avoid salty foods, such as cheese and cured meats, and to switch from regular bread to salt-free bread. The remaining 51 matched patients constituted a control group and received only generic dietary advice. Na[U]/24h, K[U]/24h, and office BP (automated repeated measurements) were recorded before dieting started and after 9 ± 1 weeks of dieting. Our intervention group showed a significant decrease in body weight (71.75 ± 14.0 to 70.54 ± 13.33 kg, P < .0001), sodium excretion (153.1 ± 44.61 to 133.5 ± 37.1 mEq/24h, P < .05), systolic and diastolic BP (134.16 ± 16.0 to 126.5 ± 10.53 mm Hg, P = .014 and 80.59 ± 11.47 to 75.9 ± 8.72 mm Hg, P = .026, respectively), and drug consumption (1.71 ± 0.91 to 1.49 ± 0.84 DDD, P < .05). The rate of responders to antihypertensive therapy increased (51.4% to 79.5%). In the control group neither significant nor substantial changes were seen. Our data suggest that even a minimal reduction in the apparent sodium intake (∼0.5 grams per day) can improve both BP values and responder rates in treated hypertensive patients, while reducing the consumption of antihypertensive drugs.

Efficacy and Safety of Triple Therapy With Telmisartan, Amlodipine, and Rosuvastatin in Patients With Dyslipidemia and Hypertension: The Jeil Telmisartan, Amlodipine, and Rosuvastatin Randomized Clinical Trial.

Soon Jun Hong MD, PhD, Han Saem Jeong MD, Jin-Man Cho MD, PhD, Kiyuk Chang MD, PhD, Wook Bum Pyun MD, PhD, Youngkeun Ahn MD, PhD, Min Su Hyon MD, PhD, Woong Chol Kang MD, PhD, Jae-Hwan Lee MD, PhD 及 Hyo-Soo Kim MD, PhD
Clinical Therapeutics, 2019-02-01, 卷 41, 期 2, 頁面 233-248.e9, Copyright © 2018



Fixed-dose combination therapy with telmisartan, amlodipine, and rosuvastatin is needed in patients with hypertension and dyslipidemia for better adherence and cost-effectiveness than free–equivalent combination therapies. This study aimed to compare the efficacy and safety of combination therapy with telmisartan, amlodipine, and rosuvastatin versus telmisartan plus amlodipine or telmisartan plus rosuvastatin in patients with hypertension and dyslipidemia.


The Jeil Telmisartan, Amlodipine, and Rosuvastatin Randomized Clinical Trial (J-TAROS-RCT) was an 8-week, multicenter, randomized, double-blind, parallel, Phase III clinical trial conducted at 9 hospitals in Korea. After a run-in period of >4 weeks, patients who fulfilled the criteria of the National Cholesterol Education Program Adult Treatment Panel III guidelines were eligible for randomization to receive 1 of 3 treatments for 8 weeks: (1) telmisartan/amlodipine 80 mg/10 mg plus rosuvastatin 20 mg, (2) telmisartan/amlodipine 80 mg/10 mg, or (3) telmisartan 80 mg plus rosuvastatin 20 mg. The primary end point was efficacy evaluation of combination therapy with telmisartan/amlodipine/rosuvastatin by comparing the change in mean sitting systolic blood pressure (msSBP) and mean percentage change in LDL-C from baseline after 8 weeks of treatment. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients.


Among 148 patients, the changes in msSBP from baseline after 8 weeks of treatment were a mean (SD) of −24.41 (2.38) versus −9.31 (2.36) mm Hg in the telmisartan/amlodipine/rosuvastatin and telmisartan/rosuvastatin groups, respectively. Significantly more participants achieved the target BP at week 8 in the telmisartan/amlodipine/rosuvastatin group (41 patients [87.2%]) than in the telmisartan/rosuvastatin group (24 [50.0%], P < 0.001). The changes in mean (SD) LDL-C at 8 weeks compared with baseline values were −57.59% (11.59%) versus 6.08% (20.98%) in the telmisartan/amlodipine/rosuvastatin and telmisartan/amlodipine groups, respectively. The percentages of patients who achieved the target LDL-C according to their risk factors after 8 weeks of treatment were 97.87% vs 6.12% in the telmisartan/amlodipine/rosuvastatin and the telmisartan/amlodipine groups ( P < 0.0001), respectively. No significant differences were found in the incidence of overall AEs and adverse drug reactions, and serious AEs were comparable among 3 groups.


Fixed-dose combinations of telmisartan, amlodipine, and rosuvastatin decreased BP and LDL-C in patients with hypertension and dyslipidemia. The safety and tolerability profiles of fixed-dose telmisartan, amlodipine, and rosuvastatin combination therapy were comparable with those of telmisartan plus amlodipine or telmisartan plus rosuvastatin. identifier: NCT03088254 .

Resistant hypertension: Renal denervation or intensified medical treatment?

Alberto Morganti 及 Giuseppe Mancia
European Journal of Internal Medicine, 2018-04-01, 卷 50, 頁面 6-11, Copyright © 2017 European Federation of Internal Medicine

Resistant hypertension (RH) can be diagnosed if blood pressure (BP) is not controlled with the combination of three antihypertensive drugs, including a diuretic, all at effective doses. Patients affected by this condition exhibit a marked increase in the risk of cardiovascular and renal morbid and fatal events. They also exhibit an increased activity of the sympathetic nervous system which is likely to importantly contribute at the renal and other vascular levels to the hypertensive state. Almost 10 years ago renal denervation (RDN) by radiofrequency thermal energy delivery to the walls of the renal arteries was proposed for the treatment of RH. Several uncontrolled studies initially reported that this procedure substantially reduced the elevated BP values but this conclusion has not been supported by a recent randomized control trial, which has almost marginalized this therapeutic approach. A revival, however, is under way because of recent positive findings and technical improvement that hold promise to make renal denervation more complete. The antihypertensive efficacy and overall validity of RDN will have to be tested against drug treatment of RH. Several studies indicate that an excess of aldosterone production contributes to RH and recent evidence documents indisputably that anti-aldosterone agents such as spironolactone can effectively control BP in many RH patients, although with some side effects that require close patients' monitoring. At present, it is advisable to treat RH with the addition of an anti-aldosterone agent. If BP control is not achieved or serious side effects become manifest RDN may then be considered.