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Congress Report: the European Society of Cardiology (ESC) Congress, Barcelona, Spain, 26–30 August, 2017

Congress Report: the European Society of Cardiology (ESC) Congress, Barcelona, Spain, 26–30 August, 2017
  • Cardiometabolic
  • Hypertension

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International meeting
Hypertension
SPRINT study
screening
arthritis

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A number of innovative trials were presented at ESC 2017, coinciding with their publication. Of particular note was the SPYRAL HTN-OFF MED study of renal denervation in treatment-naïve hypertensive patients; the PRECISION-ABPM sub-study, looking at changes in ambulatory blood pressure in patients with osteoarthritis or rheumatoid arthritis who were at increased risk of coronary artery disease and who received celecoxib, ibuprofen or naproxen for 4 months; The VIVA (Viborg Vascular) trial, which assessed the benefits of combined screening for abdominal aortic aneurysm, peripheral artery disease and hypertension in a large male cohort; and a new subgroup analysis of the SPRINT study looking at the effect of intensive blood pressure reduction in those with a high starting systolic blood pressure (≥160 mm Hg) and divided according to their 10-year Framingham risk score.

SPYRAL HTN-OFF MED

The SPYRAL HTN-OFF MED study of renal denervation in hypertensive patients not taking medication was presented by Professor Michael Boehm (University of Saarland, Homburg/Saar, Germany) and published simultaneously in the Lancet.1 Following the failure of the SYMPLICITY HTN-3 trial to demonstrate a significant reduction in blood pressure with renal denervation compared with a sham procedure,2 SPYRAL HTN-OFF MED was designed to overcome some of the potential problems with the earlier study.  In the new study, patients were not taking antihypertensive drugs at the time of randomization and cessation of drug therapy was confirmed by testing serum and urine thus avoiding interference of drug effects on assessment of the procedure effect. In addition, patients with isolated systolic hypertension (ISH) were excluded from the trial as it was thought they may be less responsive to renal denervation. The denervation procedure was performed by highly experienced operators and was also more extensive and used a four-electrode, simultaneous ablation system to assure circumferentiality, in contrast to the mono-electrode, sequential ablation system used previously. It also involved additional treatments to branches of the main renal arteries so that an average of 5.2 branches per patient were treated with an average number of ablations of 25.9 in branches and 17.9 in the main arteries giving an average of 43.8 ablations per patient, as compared with an average of 11.2 ablations per patient in the SYMPLICITY HTN-3 trial.

The study included 80 patients who were drug-naïve or had discontinued antihypertensive maintenance therapy. After 3 months, there were significant reductions in the office and 24 hour (24-h) systolic blood pressure (SBP) and diastolic blood pressure (DBP) after renal denervation but no significant changes in the sham-control group (Figure 1). The mean difference between the groups were 24-h SBP -5.0 mm Hg (95% CI -9.9 to -0.2; P=0.0414), 24-h DBP -4.4 mm Hg (-7.2 to -1.6; P=0.0024), office SBP -7.7 mm Hg (-14.0 to -1.5; P=0.0155), and office DBP -4.9 mm Hg (-8.5 to -1.4; P=0.0077). The baseline-adjusted analyses showed similar findings and there were no major adverse events in either group.

It should be noted there was a very wide range of responses and both office and ambulatory BPs increased in some patients after both renal denervation and sham procedures. In discussion, it was noted that the average changes in blood pressure were relatively small, that renal denervation is unlikely to be used as a first line procedure before trying medication and that the study excluded patients with ISH which can be difficult to treat. However, these results do provide biologic proof of principle that renal denervation can reduce blood pressure and should provide a new starting point for further investigations.

Figure 1

PRECISION-ABPM

The Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen Or Naproxen - Ambulatory Blood Pressure Measurement study (PRECISION-ABPM) was presented by Dr Frank Ruschitzka (University Heart Centre, Zurich, Switzerland) and has been published in the European Heart Journal.3 PRECISION-ABPM is a pre-specified sub-study of the PRECISION trial, which compared treatment with the selective cyclo-oxygenase-2 (COX-2) inhibitor celecoxib, to the nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen and naproxen for a primary composite outcome of cardiovascular death (including haemorrhagic death), nonfatal myocardial infarction or nonfatal stroke in over 24,000 patients and showed that moderate doses of celecoxib were non-inferior to ibuprofen or naproxen with regard to cardiovascular safety.4

The PRECISION-ABPM study involved ambulatory blood pressure measurement in 444 patients with osteoarthritis (92%) or rheumatoid arthritis (8%) and who had evidence of, or were at increased risk for coronary artery disease and who received celecoxib (100–200 mg BID), ibuprofen (600–800 mg TID) or naproxen (375–500 mg BID) for 4 months. The change in mean 24-h SBP with celecoxib was -0.3 mm Hg (95% CI, −2.25, 1.74), with ibuprofen was 3.7 mm Hg (95% CI, 1.72, 5.58) and with naproxen was 1.6 mm Hg (95% CI, −0.40, 3.57). The difference between celecoxib and ibuprofen was significant (P=0.0009) but differences between celecoxib and naproxen, and between naproxen and ibuprofen were not significant. Similar differences between the drugs were observed for DBP. In addition, the percentage of patients with normal baseline BP who developed hypertension (mean 24-h SBP ≥130 and/or DBP ≥80 mm Hg) was less with celecoxib (10.3%) than with ibuprofen (23.2%) or naproxen (19.0%) (odds ratio 0.39, P=0.004 and odds ratio 0.49, P=0.03 versus ibuprofen and naproxen, respectively).

There was some discussion as to whether the doses of the three drugs had equipotent analgesic effects and it was noted the dose of celecoxib was at the lower end of the therapeutic range but the others were at the higher end. It was also noted that all NSAIDs are likely to raise blood pressure especially in predisposed individuals and this is usually a dose-dependent effect. A statement from the American Heart Association (AHA) by Dr Elliott Antman (Brigham and Women's Hospital, Harvard University, USA) released in response to PRECISION-ABPM5 suggested there were some concerns with the study and recommended that the 2007 Scientific Statement from the AHA was still a useful resource on the use of NSAIDs and cardiovascular risk.6

The Viborg Vascular (VIVA) trial

The Viborg Vascular (VIVA) trial was presented by Professor Jes Lindholt (Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Denmark) and published in the Lancet.7 This was a prospective, randomized, controlled trial involving 50,156 men aged 65 to 74 years from the Central Denmark region, with half of the subjects being invited to combined screening for abdominal aortic aneurysm (AAA), peripheral artery disease (PAD) and hypertension and the other half being controls. Out of those screened, 22% had positive results with 3% having AAA, 11% PAD and 10% had unknown hypertension; 11·5% of those with a positive test had

more than one condition. Those who tested positive for AAA and/or PAD had a confirmatory test and were advised on lifestyle modifications, with 33% started on low-dose aspirin and/or statin. Those with an aneurysm >50 mm in diameter were referred to a vascular surgeon and half of those with aneurysms >55 mm underwent repair within 5 years. Men with suspected hypertension were referred to their GP and antihypertensive treatment was initiated in one-third.

Triple vascular screening reduced overall mortality by 7% with a hazard ratio of 0·93 (95% CI, 0·88–0·98; P=0·01) at the end of 5 years and was considered highly cost-effective as it resulted in one life saved for every 169 men screened without causing any serious harm. Men in the screening group also reported moderately higher quality of life than those in the control group.

SPRINT study – new analysis

The SPRINT study8 continued to be a hot topic of debate in several sessions at the ESC Congress. A new analysis of patient-level data from the SPRINT study was presented at a clinical trial update session by Dr Tzung-Dau Wang (National Taiwan University, Taipei City, Taiwan).9 His group undertook a stepwise subgroup analysis according to patient baseline SBP. Patients with baseline SBP ≥160 mm Hg (n=976) showed no benefit in all-cause mortality from intensive BP reduction; when the subgroups were divided according to the 10-year Framingham risk score (FRS), those with baseline SBP ≥160 mm Hg, FRS ≤ the median (31.3%, n=480) and a lower blood pressure target of 120 mm Hg had a significantly increased all-cause mortality with a hazard ratio of 3.12 (95% CI, 1.00–9.69; P=0.049). The presenter and discussants suggested this finding should be interpreted with caution as it was a post-hoc analysis and numbers in this subgroup were small (representing only 5% of the study population) and there were only 14 deaths in this subgroup. However, it would be reasonable to conclude that not all hypertensive patients would benefit from intensive blood pressure reduction, an individualized approach to blood pressure control is desirable and identifying those who may be harmed by large reductions in BP is important.

References

1.         Townsend RR, et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017 http://www.ncbi.nlm.nih.gov/pubmed/28859944

2.         Bhatt DL, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370:1393-1401. http://www.ncbi.nlm.nih.gov/pubmed/24678939

3.         Ruschitzka F, et al. Differential blood pressure effects of ibuprofen, naproxen, and celecoxib in patients with arthritis: the PRECISION-ABPM (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement) Trial. Eur Heart J. 2017 ehx508-ehx508. http://dx.doi.org/10.1093/eurheartj/ehx508

4.         Nissen SE, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med. 2016;375:2519-2529. http://www.ncbi.nlm.nih.gov/pubmed/27959716

5.         Antman E. American Heart Association. Chronic NSAID use and ambulatory blood pressure:  PRECISION-ABPM in Perspective. Available at: https://professional.heart.org/professional/EducationMeetings/MeetingsLi.... 2017

6.         Antman EM, et al. Use of nonsteroidal antiinflammatory drugs. An update for clinicians: A scientific statement from the American Heart Association. 2007;115:1634-1642. http://circ.ahajournals.org/content/circulationaha/115/12/1634.full.pdf

7.         Lindholt JS, Søgaard R. Population screening and intervention for vascular disease in Danish men (VIVA): a randomised controlled trial. The Lancet. 2017 http://www.sciencedirect.com/science/article/pii/S014067361732250X

8.         Wright JT, Jr., et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2116. http://www.ncbi.nlm.nih.gov/pubmed/26551272

9.         Wang TD, et al. 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. European Society of Cardiology 2017 Congress. Clinical Trials Update. August 28, 2017, Barcelona, Spain. Abstract 3828. Available at: http://congress365.escardio.org/Session/22259#.Wd3tpluCyUl.

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