In this large trial, denervation of the kidneys with use of a radiofrequency ablation catheter in the renal arteries had no significant effect on blood pressure in patients with resistant ...hypertension. This contradicts results of smaller trials that did not include a sham control.
Because of the aging of the population and rising rates of obesity, hypertension is increasing in prevalence worldwide.
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Approximately 10% of patients with diagnosed hypertension have resistant hypertension, defined as a systolic blood pressure of 140 mm Hg or higher despite adherence to at least three maximally tolerated doses of antihypertensive medications from complementary classes, including a diuretic at an appropriate dose.
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Patients with resistant hypertension who are receiving appropriate medical therapy have high rates of cardiovascular complications, with few treatment options.
The sympathetic nervous system — in particular, sympathetic cross-talk between the kidneys and the brain — appears . . .
Background The optimal treatment for critical limb ischemia remains controversial owing to conflicting conclusions from previous studies. Methods and Results We obtained administrative claims on ...Medicare beneficiaries with initial critical limb ischemia diagnosis in 2011. Clinical outcomes and healthcare costs over 4 years were estimated among all patients and by first treatment (endovascular revascularization, surgical revascularization, or major amputation) in unmatched and propensity-score-matched samples. Among 72 199 patients with initial primary critical limb ischemia diagnosis in 2011, survival was 46% (median survival, 3.5 years) and freedom from major amputation was 87%. Among 9942 propensity-score-matched patients (8% rest pain, 26% ulcer, and 66% gangrene), survival was 38% with endovascular revascularization (median survival, 2.7 years), 40% with surgical revascularization (median survival, 2.9 years), and 23% with major amputation (median survival, 1.3 years; P<0.001 for each revascularization procedure versus major amputation). Corresponding major amputation rates were 6.5%, 9.6%, and 10.6%, respectively ( P<0.001 for all pair-wise comparisons). The cost per patient year during follow-up was $49 700, $49 200, and $55 700, respectively ( P<0.001 for each revascularization procedure versus major amputation). Conclusions Long-term survival and cost in critical limb ischemia management is comparable between revascularization techniques, with lower major amputation rates following endovascular revascularization. Primary major amputation results in shorter survival, higher risk of subsequent major amputation, and higher healthcare costs versus revascularization. Results from this observational research may be susceptible to bias because of the influence of unmeasured confounders.
The SYMPLICITY HTN-3 randomized, blinded, sham-controlled trial confirmed the safety of renal denervation (RDN), but did not meet its primary efficacy endpoint. Prior RDN studies have demonstrated ...significant and durable reductions in blood pressure. This analysis investigated factors that may help explain these disparate results.
Patients with resistant hypertension were randomized 2 : 1 to RDN (n = 364) or sham (n = 171). The primary endpoint was the difference in office systolic blood pressure (SBP) change at 6 months. A multivariable analysis identified predictors of SBP change. Additional analyses examined the influence of medication changes, results in selected subgroups and procedural factors. Between randomization and the 6-month endpoint, 39% of patients underwent medication changes. Predictors of office SBP reduction at 6 months were baseline office SBP ≥ 180 mmHg, aldosterone antagonist use, and non-use of vasodilators; number of ablations was a predictor in the RDN group. Non-African-American patients receiving RDN had a significantly greater change in office SBP than those receiving sham; -15.2 ± 23.5 vs. -8.6 ± 24.8 mmHg, respectively (P = 0.012). Greater reductions in office and ambulatory SBP, and heart rate were observed with a higher number of ablations and energy delivery in a four-quadrant pattern.
Post hoc analyses, although derived from limited patient cohorts, reveal several potential confounding factors that may partially explain the unexpected blood pressure responses in both the sham control and RDN groups. These hypothesis-generating data further inform the design of subsequent research to evaluate the potential role of RDN in the treatment of resistant hypertension. CLINICALTRIALS.GOV IDENTIFIER: NCT01418261.
Hypertension represents a significant global public health concern, contributing to vascular and renal morbidity, cardiovascular mortality, and economic burden. The opportunity to influence clinical ...outcomes through hypertension management is therefore paramount. Despite adherence to multiple available medical therapies, a significant proportion of patients have persistent blood pressure elevation, a condition termed resistant hypertension. Recent recognition of the importance of the renal sympathetic and somatic nerves in modulating blood pressure and the development of a novel procedure that selectively removes these contributors to resistant hypertension represents an opportunity to provide clinically meaningful benefit across wide and varied patient populations. Early clinical evaluation with catheter‐based, selective renal sympathetic denervation in patients with resistant hypertension has mechanistically correlated sympathetic efferent denervation with decreased renal norepinephrine spillover and renin activity, increased renal plasma flow, and has demonstrated clinically significant, sustained reductions in blood pressure. The SYMPLICITY HTN‐3 Trial is a pivotal study designed as a prospective, randomized, masked procedure, single‐blind trial evaluating the safety and effectiveness of catheter‐based bilateral renal denervation for the treatment of uncontrolled hypertension despite compliance with at least 3 antihypertensive medications of different classes (at least one of which is a diuretic) at maximal tolerable doses. The primary effectiveness endpoint is measured as the change in office‐based systolic blood pressure from baseline to 6 months. This manuscript describes the design and methodology of a regulatory trial of selective renal denervation for the treatment of hypertension among patients who have failed pharmacologic therapy. Clin. Cardiol. 2012. doi: 10.1002/clc.22008
Dr. Kandzari receives research/grant support and consulting honoraria from Medtronic CardioVascular, Abbott Vascular and Boston Scientific; Dr. Bhatt receives honoraria from WebMD and research grants from Amarin, AstraZeneca, Bristol‐Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company. Dr. Oparil receives research/grant support from Merck and Co., NHLBI, Novartis, and Takeda, honoraria from Daiichi Sankyo and Pfizer, and is a consultant for Bayer, Medtronic, Novartis, Pfizer, and Daiichi Sankyo. Dr. Rocha‐Singh is a consultant for Medtronic, Covidien, and Cardiosonic. Dr. Flack receives grant/research support from NIH, Daiichi Sankyo, sanofi aventis, and Novartis. He is on the Speaker Bureau for Novartis, Daiichi Sankyo, and Boehringer Ingleheim, and is a consultant for Glaxo‐Smith‐Kline, Novartis, NIH, Daiichi Sankyo, and Boehringer Ingleheim, Medtronic, and Back Beat Hypertension. Dr. Katzen is a consultant for Abbott, CRBard, Boston Scientific, WL Gore, and Medtronic. Dr. Massaro is a member of the Data Safety Monitoring Board and will no longer participate as a member of the SYMPLICITY HTN‐3 Steering Committee. Dr. Leon, Dr. O'Neill, and Dr. Esler have nothing to disclose. Dr. Negoita, Dr. Sobotka, and Craig Straley are employees of Medtronic, Inc. Dr. Bakris receives grant/clinical trial support (paid directly to University of Chicago) from Forest Laboratories, Medtronic, and Relapysa, and is a consultant to Takeda, Abbott, CVRx, Johnson & Johnson, Eli Lilly, and the Food and Drug Administration. Dr. Bakris is on the Speaker Bureau for Takeda, and the Boards of the National Kidney Foundation and the American Society of Hypertension. He is Editor for the American Journal of Nephrology and Associate Editor for Diabetes Care and Nephrology Dialysis and Transplantation.
Patients with severe carotid-artery stenosis, who are at high risk for stroke, usually undergo endarterectomy. This clinical trial compared endarterectomy and carotid stenting with the use of a stent ...with an emboli-protection device in patients with severe carotid-artery stenosis. Stenting was found to be not inferior to endarterectomy with respect to clinical outcome. Therefore, the less invasive approach may be an acceptable alternative among patients with high-risk carotid-artery stenosis.
The less invasive approach may be an acceptable alternative among patients with high-risk carotid-artery stenosis.
Several trials have shown carotid endarterectomy to be superior to medical management for the prevention of stroke in patients with symptomatic or asymptomatic carotid-artery stenosis.
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The patients in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and those in the Asymptomatic Carotid Atherosclerosis Study (ACAS) were carefully selected and had low rates of surgical complications.
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Many patients for whom surgery poses a high risk, however, routinely undergo carotid endarterectomy in clinical practice and were excluded from these trials, and such patients have outcomes that are substantially worse than those reported in these trials.
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During the past decade, carotid . . .
Background This study presents the short-term and midterm results of direct percutaneous sac injection (DPSI) for postoperative endoleak treatment after endovascular aortic aneurysm repair (EVAR). ...Methods Between March 1994 and November 2011, EVAR was performed in 986 patients. The median follow-up was 63 ± 45 months (range, 0-211 months). A retrospective analysis was performed. DPSI was used in 21 patients for 19 type II endoleaks and two endoleaks of undefined origin (EOUO), of which 12 (57%) were after failure of a previous endovascular treatment attempt. Results DPSI using thrombin (n = 16), coils (n = 7), gelfoam (n = 6), or glue (n = 3), or a combination, was technically feasible in all patients. Saccography during DPSI revealed a previously undetected type I endoleak in three patients. Immediate DPSI success was achieved in 16 of 18 procedures (88.9%), with two complications. Glue incidentally intravasated in the inferior vena cava, causing a clinically nonsignificant subsegmental pulmonary artery embolism in one patient, and the temporary development of a type III endoleak, possibly from graft puncture, in another. During a median follow-up of 39 months (interquartile range, 13-88 months) after DPSI, recurrent endoleaks were observed in nine patients (50.0%), one type I endoleak due to graft migration, five type II endoleaks, and three EOUO. The occurrence of a re-endoleak during follow-up was significantly associated with dual-antiplatelet medication (0% in patients without re-endoleak vs 44.4% in patients with re-endoleak; P = .023) and with a nonsignificant trend for the use of aspirin alone (33.3% in patients without re-endoleak vs 80% in patients with re-endoleak; P = .094). Re-endoleak occurred in 33.3% of the patients without antiplatelet medication and in 100% of patients with dual-antiplatelet medication ( P = .026). Thrombin was used as the sole embolic agent during the initial DPSI in all patients with dual-antiplatelet therapy. No other factor was significantly associated with re-endoleaks. Reintervention was deemed necessary in six patients within a median of 10 months (interquartile range, 4-16 months) after DPSI, including six additional DPSI treatments in four patients with type II re-endoleaks, cuff placements in one type I endoleak, and endograft relining in one EOUO. Conclusions This initial experience suggests that DPSI is feasible as a technique for endoleak treatment after EVAR. However, complications and endoleak recurrence remain a concern. The role of antiplatelet therapy and different embolic agents on long-term embolization success needs to be studied in more detail.
Prior studies of catheter-based renal artery denervation have not systematically performed ambulatory blood pressure monitoring (ABPM) to assess the efficacy of the procedure.
SYMPLICITY HTN-3 (Renal ...Denervation in Patients With Uncontrolled Hypertension) was a prospective, blinded, randomized, sham-controlled trial. The current analysis details the effect of renal denervation or a sham procedure on ABPM measurements 6 months post-randomization.
Patients with resistant hypertension were randomized 2:1 to renal denervation or sham control. Patients were on a stable antihypertensive regimen including maximally tolerated doses of at least 3 drugs including a diuretic before randomization. The powered secondary efficacy endpoint was a change in mean 24-h ambulatory systolic blood pressure (SBP). Nondipper to dipper (nighttime blood pressure BP 10% to 20% lower than daytime BP) conversion was calculated at 6 months.
The 24-h ambulatory SBP changed -6.8 ± 15.1 mm Hg in the denervation group and -4.8 ± 17.3 mm Hg in the sham group: difference of -2.0 mm Hg (95% confidence interval CI: -5.0 to 1.1; p = 0.98 with a 2 mm Hg superiority margin). The daytime ambulatory SBP change difference between groups was -1.1 (95% CI: -4.3 to 2.2; p = 0.52). The nocturnal ambulatory SBP change difference between groups was -3.3 (95 CI: -6.7 to 0.1; p = 0.06). The percent of nondippers converted to dippers was 21.2% in the denervation group and 15.0% in the sham group (95% CI: -3.8% to 16.2%; p = 0.30). Change in 24-h heart rate was -1.4 ± 7.4 in the denervation group and -1.3 ± 7.3 in the sham group; (95% CI: -1.5 to 1.4; p = 0.94).
This trial did not demonstrate a benefit of renal artery denervation on reduction in ambulatory BP in either the 24-h or day and night periods compared with sham (Renal Denervation in Patients With Uncontrolled Hypertension SYMPLICITY HTN-3; NCT01418261).
In the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial of 334 patients with carotid-artery disease, carotid-artery stenting was not inferior to ...endarterectomy at 30 days or at 1 year. Most patients were followed for an additional 2 years. There was no significant difference between the two groups in the composite end point of death, stroke, or myocardial infarction within 30 days or death or ipsilateral stroke between 31 days and 3 years.
In the SAPPHIRE trial of patients with carotid-artery disease, carotid-artery stenting was not inferior to endarterectomy at 30 days or at 1 year. In this follow-up study, there was no significant difference between the two groups in the composite end point of death, stroke, or myocardial infarction within 30 days or death or ipsilateral stroke between 31 days and 3 years.
There is a direct relationship between the degree of carotid artery stenosis and the risk of ipsilateral stroke.
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Carotid revascularization by means of carotid endarterectomy has proved highly successful in reducing the incidence of stroke among patients with moderate-to-severe symptomatic carotid stenosis
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as well as among those with severe asymptomatic carotid stenosis.
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Although carotid endarterectomy has been considered the gold standard for the treatment of carotid stenosis for decades, carotid artery stenting has emerged as an alternative type of treatment for this common disorder.
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The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) . . .
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