Ultra-long-term efficacy and safety of catheter-based renal denervation in resistant hypertension: 10-year follow-up outcomes.

BACKGROUND: Randomized sham-controlled trials have confirmed the efficacy and safety of catheter-based renal denervation in hypertension. Data on the very long-term effects of renal denervation are scarce. AIMS: This study evaluates the 10-year safety and efficacy of renal denervation in resistant hypertension. METHODS: This prospective single-center study included patients with resistant hypertension undergoing radio-frequency renal denervation between 2010 and 2012. Office blood pressure, 24-h ambulatory blood pressure, antihypertensive medication, color duplex sonography, and renal function were assessed after 1-, 2- and 10-years. RESULTS: Thirty-nine patients completed the 10-year follow-up (mean follow-up duration 9.4 ± 0.7 years). Baseline office and 24-h ambulatory systolic blood pressure were 164 ± 23 mmHg and 153 ± 16 mmHg, respectively. After 10 years, 24-h ambulatory and office systolic blood pressure were reduced by 16 ± 17 mmHg (P < 0.001) and 14 ± 23 mmHg (P = 0.001), respectively. The number of antihypertensive drugs remained unchanged from 4.9 ± 1.4 to 4.5 ± 1.2 drugs (P = 0.087). The estimated glomerular filtration rate declined within the expected range from 69 (95% CI 63 to 74) to 60 mL/min/1.73m2 (95% CI 53 to 68; P < 0.001) through 10-year follow-up. Three renal artery interventions were documented for progression of pre-existing renal artery stenosis in two patients and one patient with new-onset renal artery stenosis. No other adverse events were observed during the follow-up. CONCLUSION: Renal denervation was safe and sustainedly reduced ambulatory and office blood pressure out to 10 years in patients with resistant hypertension.

Comparison of three creatinine-based equations to predict adverse outcome in a cardiovascular high-risk cohort: an investigation using the SPRINT research materials.

Background: Novel creatinine-based equations have recently been proposed but their predictive performance for cardiovascular outcomes in participants at high cardiovascular risk in comparison to the established CKD-EPI 2009 equation is unknown. Method: In 9361 participants from the United States included in the randomized controlled SPRINT trial, we calculated baseline estimated glomerular filtration rate (eGFR) using the CKD-EPI 2009, CKD-EPI 2021, and EKFC equations and compared their predictive value of cardiovascular events. The statistical metric used is the net reclassification improvement (NRI) presented separately for those with and those without events. Results: During a mean follow-up of 3.1 ± 0.9 years, the primary endpoint occurred in 559 participants (6.0%). When using the CKD-EPI 2009, the CKD-EPI 2021, and the EKFC equations, the prevalence of CKD (eGFR <60 ml/min/1.73 m2 or >60 ml/min/1.73 m2 with an ACR ≥30 mg/g) was 37% vs. 35.3% (P = 0.02) vs. 46.4% (P < 0.001), respectively. The corresponding mean eGFR was 72.5 ± 20.1 ml/min/1.73 m2 vs. 73.2 ± 19.4 ml/min/1.73 m2 (P < 0.001) vs. 64.6 ± 17.4 ml/min/1.73 m2 (P < 0.001). Neither reclassification according to the CKD-EPI 2021 equation [CKD-EPI 2021 vs. CKD-EPI 2009: NRIevents: -9.5% (95% confidence interval (CI) -13.0% to -5.9%); NRInonevents: 4.8% (95% CI 3.9% to 5.7%)], nor reclassification according to the EKFC equation allowed better prediction of cardiovascular events compared to the CKD-EPI 2009 equation (EKFC vs. CKD-EPI 2009: NRIevents: 31.2% (95% CI 27.5% to 35.0%); NRInonevents: -31.1% (95% CI -32.1% to -30.1%)). Conclusion: Substituting the CKD-EPI 2009 with the CKD-EPI 2021 or the EKFC equation for calculation of eGFR in participants with high cardiovascular risk without diabetes changed the prevalence of CKD but was not associated with improved risk prediction of cardiovascular events for both those with and without the event.

Radio frequency-based renal denervation: a story of simplicity?

Radio frequency-based renal denervation is a safe and effective way of lowering blood pressure, a common condition associated with high cardiovascular risk. Several catheters have been developed to administer energy to the renal arteries and their side branches, thereby modulating sympathetic renal activity. The Symplicity Flex™ and Symplicity Spyral™ are first- and second-generation devices, respectively, for radio frequency-based renal denervation. There is a continuous need to further improve and adjust interventional antihypertensive therapies. Several randomized controlled trials have been conducted to investigate the safety and efficacy of these catheters and most were able to show radio frequency-based renal denervation to be feasible, safe and effective in lowering blood pressure in hypertensive patients with and without concomitant antihypertensive medication. Herein, the authors discuss the pathophysiologic concepts of renal denervation and its procedural approaches, report catheter designs, summarize clinical trials outcomes and, finally, discuss real-world evidence.

High blood pressure causes illness and death worldwide. Treatment of high blood pressure is usually based on lifestyle modification and blood pressure-lowering drugs. Renal denervation represents a minimally invasive approach to lower blood pressure by interrupting the nerves surrounding the renal arteries. These nerves are involved in the body's fight-or-flight and rest-and-digest systems, the so-called autonomous nervous system. The Spyral™ catheter system uses radio frequency energy to modulate renal nerve activity. Trials have consistently shown that renal denervation is safe. The first-generation catheter was a monoelectrode catheter called Symplicity Flex™ and several points in the renal artery had to be treated. The second-generation device called the Symplicity Spyral™ catheter, on the other hand, has a multielectrode design and consequently fewer ablation points are sufficient for complete denervation. Caused by the positive effects on blood pressure and the consistent safety reports, renal denervation is considered by current guidelines as an alternative and additive treatment approach in patients with high blood pressure.

A randomized, placebo-controlled, trial to assess the photosensitizing, phototoxic and carcinogenic potential of hydrochlorothiazide in healthy volunteers.

BACKGROUND AND AIMS: Pharmacovigilance reports, associating hydrochlorothiazide (HCT) with skin cancer, resulted in a significant decrease of HCT prescriptions for hypertension and heart failure. Whether HCT exhibits phototoxic properties thereby causing skin cancer remains unknown. This study aimed to examine the photosensitizing, phototoxic and carcinogenic potential of HCT in a randomized, placebo-controlled, double-blind trial in vivo and also in vitro . METHODS: The trial assigned 30 healthy, normotensive adult volunteers in a 2:1 ratio to either HCT 25 mg/day or placebo for 15 days. Photosensitivity of the skin with and without the effect of HCT treatment were assessed. Following whole-body ultraviolet A (UVA) and B (UVB, 311 nm) irradiation, phototoxic and carcinogenic reactions by measuring urinary excretion of pyrimidine dimers were evaluated. For the in-vitro studies, human keratinocytes (HaCaT) were incubated with HCT, irradiated with UVB, and analysed for markers of inflammation, apoptosis and carcinogenesis. RESULTS: Skin photosensitivity following exposure to UVA and UVB remained unchanged from baseline to 15-day follow-up in both groups (UVA change HCT 0.0 J/cm 2 vs. placebo 0.0 J/cm 2 ; P  = 0.99; UVB change HCT 0.0 J/cm 2 vs. placebo -0.2 J/cm 2 ; P  = 0.06). Pyrimidine dimers were not detected in either group. In vitro , combination of HCT and UVB irradiation did not induce the expression of oxidative stress marker proteins, inflammatory proteins, apoptotic proteins or activation of oncoproteins. CONCLUSION: HCT did not increase photosensitivity for UVA or UVB in healthy volunteers compared with placebo, and was not associated with phototoxic or carcinogenic reactions. In vitro , HCT was also not associated with phototoxicity or carcinogenesis (NCT04654312).

Interventional therapies for pulmonary embolism.

Pulmonary embolism (PE) is the leading cause of in-hospital death and the third most frequent cause of cardiovascular death. The clinical presentation of PE is variable, and choosing the appropriate treatment for individual patients can be challenging. Traditionally, treatment of PE has involved a choice of anticoagulation, thrombolysis or surgery; however, a range of percutaneous interventional technologies have been developed that are under investigation in patients with intermediate-high-risk or high-risk PE. These interventional technologies include catheter-directed thrombolysis (with or without ultrasound assistance), aspiration thrombectomy and combinations of the aforementioned principles. These interventional treatment options might lead to a more rapid improvement in right ventricular function and pulmonary and/or systemic haemodynamics in particular patients. However, evidence from randomized controlled trials on the safety and efficacy of these interventions compared with conservative therapies is lacking. In this Review, we discuss the underlying pathophysiology of PE, provide assistance with decision-making on patient selection and critically appraise the available clinical evidence on interventional, catheter-based approaches for PE treatment. Finally, we discuss future perspectives and unmet needs.

Association of hydrochlorothiazide treatment compared with alternative diuretics with overall and skin cancer risk: a propensity-matched cohort study.

INTRODUCTION: Hydrochlorothiazide (HCT) has been suggested to induce photosensitivity, thereby increasing the incidence of skin cancers. After a pharmacovigilance alert, HCT was frequently withdrawn or substituted by other diuretics. The aim of this study was to compare the association of exposure to HCT with cancer risk versus alternative diuretics. METHODS: A retrospective cohort study was conducted based on data from the AOK PLUS, a large German statutory health insurance fund. Patients with HCT treatment were propensity score matching to patients using non-HCT diuretics. Incidence of cancer of any kind and, specifically, skin cancer was assessed in both groups. Time-to-incident cancer diagnosis was evaluated and compared between the groups. RESULTS: A total of 199 708 patients were included in the final analysis ( n  = 76 855 in the HCT group; n  = 122 853 in the non-HCT-diuretics group). After propensity score matching, 122 554 patients remained in the sample ( n  = 61 277 for both groups, of which >96% had hypertension, mean age 73 years, 61% female). HCT treatment was associated with a lower incidence of cancer of any kind compared with non-HCT diuretics (incidence rate ratio per 100 patient years 0.84 95% confidence interval: 0.82-0.87). HCT treatment was associated with a small albeit significantly higher incidence rate ratio of skin cancer (1.15 95% confidence interval: 1.06-1.24) with significant variances over time. Although numerically higher, the difference accounts to only 0.05 more skin cancer diagnoses in 100 patient-years. CONCLUSION: HCT treatment compared with alternative diuretics was associated with a lower all-cancer risk and a numerically small increased skin cancer risk in a large German population. Risk-benefit evaluation should be executed in patients with increased skin cancer risk and treatment with HCT. Furthermore, advice for skin protection is warranted in all patients taking thiazide or thiazide-like diuretics.

Arterial hypertension - clinical trials update 2022.

Hypertension is the most prevalent cardiovascular risk factor worldwide and is associated with increased cardiovascular morbidity and mortality. Despite the availability of multimodal therapeutic approaches, a large number of patients do not achieve guideline-recommended blood pressure targets, which reiterates the importance of continued research in the field. This article summarizes and discusses the most relevant clinical trials in hypertension research published in 2021 and 2022. The topics include new insights into treatment targets in the elderly, novel findings of salt consumption and lifestyle interventions in resistant hypertension, new evidence about early antihypertensive combination therapy and the use of angiotensin II receptor blocker neprilysin inhibitors in resistant hypertension, as well as data regarding the safety of antihypertensive drugs with respect to cancerogeneity and regarding the impact of acetaminophen, a commonly used pain medication, on blood pressure. Finally, we provide an update on recent evidence on renal denervation and its role in current hypertension management.

Photoinduced skin reactions of cardiovascular drugs-a systematic review.

This systemic review aims to provide a practical overview of the prevalence, clinical manifestation, and management of adverse photoinduced skin reactions caused by frequently used cardiovascular drugs and to assess their potential relevance for skin cancer development. Data search included PubMed, Web of Science, and the Cochrane Library. A systematic review of peer-reviewed studies reporting the photosensitizing and/or skin cancer-inducing properties of common cardiovascular drugs was performed and a guide to clinical management of photoinduced skin eruptions by cardiovascular drugs was provided. Study quality was assessed for major methodological biases. A total of 58 studies were identified (i.e. 23 case reports, 14 observational studies, 10 review articles, 10 experimental studies, and 1 meta-analysis). Most commonly, drug-associated adverse photoinduced cutaneous reactions were caused by phototoxic and photoallergic mechanisms. There is evidence suggesting that amiodarone and dronedarone, thiazide diuretics, thiazide-like diuretics, angiotensin receptor blockers, dihydropyridine-type calcium channel blockers, and certain angiotensin-converting enzyme inhibitors and statins may cause photoinduced adverse cutaneous reactions. Other drugs such as anticoagulants, antiplatelets, aldosterone antagonists, and fibrates have not been linked with photosensitizing reactions or adverse cutaneous reactions. Some drugs, i.e. thiazides and thiazide-like diuretics, were associated with an increased risk of non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma). Certain commonly used cardiovascular drugs have been associated with adverse photoinduced cutaneous reactions. If they occur, further diagnosis and treatment might be needed, depending on the severity and progress. Whether photosensitizing drugs increase the risk of skin cancer remains elusive and further randomized controlled trials are required.