Search

Aims: Resting heart rate (RHR) has been shown to be associated with cardiovascular outcomes in various conditions. It is unknown whether different levels of RHR and different associations with cardiovascular outcomes occur in patients with or without diabetes, because the impact of autonomic neuropathy on vascular vulnerability might be stronger in diabetes. Methods and results: We examined 30937 patients aged 55years or older with a history of or at high risk for cardiovascular disease and after myocardial infarction, stroke, or with proven peripheral vascular disease from the ONTARGET and TRANSCEND trials investigating ramipril, telmisartan, and their combination followed for a median of 56months. We analysed the association of mean achieved RHR on-treatment with the primary composite outcome of cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, the components of the composite primary outcome, and all-cause death as continuous and categorical variables. Data were analysed by Cox regression analysis, ANOVA, and chi2 test. These trials were registered with ClinicalTrials.gov.number NCT00153101. Patients were recruited from 733 centres in 40 countries between 1 December 2001 and 31 July 2008 (ONTARGET) and 1 November 2001 until 30 May 2004 (TRANSCEND). In total, 19450 patients without diabetes and 11487 patients with diabetes were stratified by mean RHR. Patients with diabetes compared to no diabetes had higher RHRs (71.8 ± 9.0 vs. 67.9 ± 8.8, P

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 ClinicalTrials.gov, 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. : Medtronic.

Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p

ispartof: Journal of Hypertension vol:35 issue:11 pages:2327-2328 ispartof: location:Netherlands status: published

Introduction: Combination therapy is needed to control blood pressure (BP) in a large number of hypertensive patients with diabetes mellitus. Adherence to treatment is a major clinical problem; therefore, the time duration of the antihypertensive action of a drug determines BP control when a dose is skipped. Objectives: The aim was to determine whether the fixed-dose combination of olmesartan/amlodipine provides equal efficacy and safety as the perindopril/amlodipine combination when a drug dose is missed. Methods: In this noninferiority trial with a randomized, double-blind, double-dummy parallel group, controlled design, 260 patients received either olmesartan 20-40 mg/amlodipine 5-10 mg or perindopril 4-8 mg/amlodipine 5-10 mg for 24 weeks. The main outcome was the sitting office DBP after 24 weeks of treatment at 48 h from last administration. Results: The olmesartan/amlodipine combination reached noninferiority criteria in reduction of office DBP after 24 weeks of treatment and after the missed dose, compared with the perindopril/amlodipine combination (-11.7 and -10.5 mmHg, respectively). Office SBP and pulse pressure were significantly lower in both groups after 24 weeks of treatment and 48 h after the missed dose, observing a trend to greater SBP reduction in the olmesartan/amlodipine group. Conclusions: The combination olmesartan/amlodipine is safe, well tolerated, and as effective as the combination of perindopril/amlodipine in the control of essential hypertension in patients with diabetes mellitus. A missed dose does not leave the patients unprotected in both treatments; however, a faster control with less dose increment is observed with olmesartan/amlodipine.

Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage.The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101.784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p0.0001) or combination therapy (-6.11 [17.9], p0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril.In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.

Background— Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers reduce left ventricular hypertrophy (LVH). The effect of these drugs on LVH in high-risk patients without heart failure is unknown. Methods and Results— In the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), patients at high vascular risk and tolerant of ACE inhibitors were randomly assigned to ramipril, telmisartan, or their combination (n=23 165). In the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND), patients intolerant of ACE inhibitors were randomized to telmisartan or placebo (n=5343). Prevalence of LVH at entry in TRANSCEND was 12.7%. It was reduced by telmisartan (10.5% and 9.9% after 2 and 5 years) compared with placebo (12.7% and 12.8% after 2 and 5 years) (overall odds ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P =0.0017). New-onset LVH occurred less frequently with telmisartan compared with placebo (overall odds ratio, 0.63; 95% CI, 0.51 to 0.79; P =0.0001). LVH regression was similar in the 2 groups. In ONTARGET, prevalence of LVH at entry was 12.4%. At follow-up, it occurred slightly less frequently with telmisartan (odds ratio, 0.92; 95% CI, 0.83 to 1.01; P =0.07) and the combination (odds ratio, 0.93; 95% CI, 0.84 to 1.02; P =0.12) than with ramipril, but differences between the groups were not significant. New-onset LVH was associated with a higher risk of primary outcome during follow-up (hazard ratio, 1.77; 95% CI, 1.50 to 2.07). Conclusions— In patients at high vascular risk, telmisartan is more effective than placebo in reducing LVH. New-onset LVH is reduced by 37%. The effect of combination of the 2 drugs on LVH is similar to that of ramipril alone.

BACKGROUND-: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers reduce left ventricular hypertrophy (LVH). The effect of these drugs on LVH in high-risk patients without heart failure is unknown. METHODS AND RESULTS-: In the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), patients at high vascular risk and tolerant of ACE inhibitors were randomly assigned to ramipril, telmisartan, or their combination (n=23 165). In the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND), patients intolerant of ACE inhibitors were randomized to telmisartan or placebo (n=5343). Prevalence of LVH at entry in TRANSCEND was 12.7%. It was reduced by telmisartan (10.5% and 9.9% after 2 and 5 years) compared with placebo (12.7% and 12.8% after 2 and 5 years) (overall odds ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.0017). New-onset LVH occurred less frequently with telmisartan compared with placebo (overall odds ratio, 0.63; 95% CI, 0.51 to 0.79; P=0.0001). LVH regression was similar in the 2 groups. In ONTARGET, prevalence of LVH at entry was 12.4%. At follow-up, it occurred slightly less frequently with telmisartan (odds ratio, 0.92; 95% CI, 0.83 to 1.01; P=0.07) and the combination (odds ratio, 0.93; 95% CI, 0.84 to 1.02; P=0.12) than with ramipril, but differences between the groups were not significant. New-onset LVH was associated with a higher risk of primary outcome during follow-up (hazard ratio, 1.77; 95% CI, 1.50 to 2.07). CONCLUSIONS-: In patients at high vascular risk, telmisartan is more effective than placebo in reducing LVH. New-onset LVH is reduced by 37%. The effect of combination of the 2 drugs on LVH is similar to that of ramipril alone. © 2009 American Heart Association, Inc.