Hypertension Highlights from the European Society of Cardiology Congress 2017
By Alex Kasiakogias and Costas Tsioufis
The attention grabbers
The first late-breaking clinical trial presented was RACE 3, a multicentre, randomized, open-label study designed to test the hypothesis that upstream therapy of risk factors is superior to conventional therapy for sinus rhythm maintenance at 12 months, in 250 patients with early symptomatic persistent atrial fibrillation and early mild to moderate heart failure. Cardiac rehabilitation, mineralocorticoid receptor antagonists, statins and angiotensin-converting enzyme inhibitors comprised the upstream therapy applied. At one year follow-up, continuous seven day holter revealed that sinus rhythm was maintained in 75% of the upstream therapy group versus 63% in the control group (p=0.021). The study results support that thorough management of risk factors at the early stages of combined persistent atrial fibrillation and heart failure is effective for sinus rhythm maintenance. (M Rienstra, AH Hobbelt, M Alings, J Tijssen, MD Smit, J Brügemann, B Geelhoed, RG Tieleman, HL Hillege, R Tukkie, DJ Van Veldhuisen, H Crijns, IC Van Gelder, for the RACE 3 Investigator. The routine versus aggressive upstream rhythm control for prevention of early persistent atrial fibrillation in heart failure study).
Interesting results have also emerged from further analyses of the SPRINT trial. In a post-hoc analysis of patient-level data, researchers from Taiwan reported that aggressive blood pressure lowering may not suit all patients in terms of prognosis. The group of patients with systolic BP greater than 160mmHg and a less than 31% 10-year Framingham risk score –comprising 5% of the study population- presented with a three times greater risk of all cause death with the intensive blood pressure approach (HR:3.12, 95% CI: 1.00-9.69). The nature of a subgroup analysis, the small number of patients and accordingly the limited number of events should definitely not be overlooked. Nevertheless, the extension of the J-curve concept in hypertension from an absolute BP value to a BP reduction threshold, along with an interaction with baseline blood pressure and cardiovascular risk, are aspects that may be targeted in future research. (TD Wang, HJ Lin, WJ Chen, TC Weng, WY Shau. Increased all-cause mortality with intensive blood-pressure control in patients with a baseline systolic blood pressure of >=160 mmHg and a Lower Framingham risk score: a cautionary note from SPRINT).
In another report from data derived from 97% of the SPRINT original participants, the association of changes in systolic blood pressure over time with the primary outcome was examined with a joint analysis utilizing a longitudinal mixed model and Cox proportional model. The researchers from the Netherlands found that the benefits of intensive treatment are not observed in patients with chronic kidney disease, cardiovascular disease, age <75 years, a female gender, black race and an initial blood pressure greater than 132mmHg. This was attributed primarily due to serious adverse events such as hypotension and syncope, kidney dysfunction and hyponatremia. (OL Rueda-Ochoa, LZ Rojas Sanchez, OH Franco, D Rizopoulos, M Kavousi. Changes in systolic blood pressure over time as predictor of major cardiovascular events: a joint model analysis of the SPRINT trial).
The PRECISION-ABPM randomized double-blind substudy investigated the effects on ambulatory blood pressure of treatment with COX-2 inhibitor celecoxib versus the non-selective NSAIDs naproxen and ibuprofen. The final study population consisted of 444 patients with osteoarthritis or rheumatoid arthritis and of increased cardiovascular risk that were followed for four months. Ibuprofen was associated with the greatest increase in 24-hour systolic blood pressure of more than 3 mmHg. Celecoxib did better compared to ibuprofen and naproxen regarding development of hypertension and compared to ibuprofen regarding time to first hospitalization for hypertension. All-cause mortality was also lower in the celecoxib group. The moderate dose of celecoxib used in the trial and the inability to include a placebo arm should be kept in mind when interpreting the results, but the study overall provides further evidence for an adverse impact on the cardiovascular system of NSAIDs, particularly ibuprofen. (F Van de Werf, E V Shlyakhto, F Ruschitzka. The PRECISION-ABPM (Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement) – Trial).
The huge PURE trial triggered new debate regarding dietary measures by reporting a series of interesting findings. This multicentre study performed in 18 countries on 135000 participants and with more than four years follow-up showed that an increased fat intake was associated with decreased mortality (HR: 0.77, CI: 0.67-0.87). The most controversial finding is that even saturated fat consumption was associated with fewer deaths, standing in contrast to most current recommendations. On the other hand, high carbohydrate intake, processed or not, was associated with an increased mortality. Another finding was that maximum benefit from consumption of fruits and vegetables was with a three to four servings daily and in a raw form. Limitations of the study include the use of a self-reported food questionnaire, the non-randomized nature of the trial and non-discrimination of carbohydrates to processed or not. Physicians may feel uncomfortable advising patients to lose the carbohydrates and favour all kinds of fats but for the time being the study results remind us that a balanced diet including moderate fat consumption and reasonable amounts of vegetables are enough to keep people healthy. (M Dehghan on behalf of the PURE investigators. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from 5 continents: The PURE study).
An interim analysis of the SPYRAL HTN-OFF MED study on 80 patients with untreated mild to moderate hypertension provided data of a significant decrease in blood pressure after renal denervation. Having a randomized, sham-procedure (angiography)- controlled design with careful blinding, the study showed that after 3 months there was a relative 7.7/5.0 mmHg reduction in office/ambulatory systolic blood pressure in the renal denervation group compared to the control group. The study boasts of certain novelties differentiating it from the deal-breaking at that time SYMPLICITY-HTN3 trial: the inclusion of untreated patients with moderate hypertension (office blood pressure 150-180/>90mmHg) confirmed with 24-hr monitoring, the exclusion of patients with isolated systolic hypertension ,the thorough assessment of adherence with drug testing, the procedure being performed by very experienced operators and the more than 40 ablations applied per patient extending from the main artery to the branches using a multi-electrode catheter. The study investigators noted that the study was not powered for statistical significance but provided proof-of-principle to continue with a pivotal trial. (M Böhm, D Kandzari, R Townsend, F Mahfoud, K Kario, S Pocock, M Weber, S Ewen, K Tsioufis, D Tousoulis, A Sharp, T Watkinson, R Schmieder, A Schmid, J Choi, C East, A Walton, I Hopper, D Cohen, R Wilensky, D Lee, A Ma, C Devireddy, J Lea, P Lurz, K Fengler, J Davies, N Chapman. Investigation of catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications: Three-month results from the randomized, sham-controlled, proof of concept SPYRAL HTN-OFF MED Trial).
3-point quick picks
- Sodium retention is the main mechanism of drug resistant hypertension and diuretics such as spironolactone and amiloride stand as the most effective treatments, as shown in substudies of the PATHWAY-2 trial that utilized non-invasive measurements of cardiac output, vascular resistance and total body water volume. (B Williams et al. Mechanisms for benefit of spironolactone in resistant hypertension in the PATHWAY-2 study)
- A high-salt intake (more than 13.7gr) compared to a low salt intake (less than 6.8gr) is associated with a double risk of heart failure after adjustment for age and gender, as reported in a 12-year study of 4630 randomly selected participants. (P Jousilahti et al. Salt intake and the risk of heart failure)
- Visit-to-visit blood pressure variability (defined as the blood pressure standard deviation across visits) is associated with a greater risk of cerebrovascular accident, myocardial infarction and death, as reported in a retrospective analysis of the medical records of more than 312,000 patients. (CH Yeh et al. Visit-to-visit variability of systolic and diastolic blood pressure has different prognostic significance on death and cardiovascular events for hypertensive patients)
- The unilateral implantation of the Mobius HD endovascular baroreflex amplification device has acceptable safety and a 75% responder rate, as reported in a multicentre, first-in-human, non-randomized trial on 40 patients with resistant hypertension. (W Spiering et al. Efficacy and safety results of endovascular baroreflex amplification (EBA) for resistant hypertension (CALM-FIM studies): a safety and proof-of-principle cohort study)
The monthly ESH guide through publications
Edited by Prof. Costas Tsioufis, ESH Secretary and Dr Alex Kasiakogi
This montly collection features concise summaries of recently published articles dedicated to the most current research on hypertension and related diseases.