New Analysis Questions Higher JNC 8's SBP Target for Patients Over 60

Shelley Wood

August 19, 2014

NEW YORK, NY — The decision to "ease up" on systolic blood pressure (SBP) targets in people over age 60 was one of the most hotly contested recommendations in the guidelines released by the Eighth Joint National Committee (JNC 8) last year.

Now the International Verapamil-Trandolapril Study (INVEST) investigators are adding their voice to a chorus of complaints over this decision with an analysis showing that patients over age 60 in that trial who achieved an SBP target of >150 mm Hg had more deaths and cardiovascular events than those whose systolic blood pressure was reduced to below 140 mm Hg[1].

"These data provide important information to focus the risk/benefit discussion for patients with on-treatment BP in the 140-to-150-mm-Hg range clearly on cardiovascular mortality and stroke prevention and on overall reduction of mortality for patients with on-treatment BP >150 mm Hg," INVEST investigators, led by Dr Sripal Bangalore, write in the August 26, 2014 issue of the Journal of the American College of Cardiology.

As previously reported by heartwire , the JNC 8 writing group published their recommendations in the Journal of the American Medical Association last December, but five members of the committee subsequently published a second paper spelling out their concerns with that report. Central to their complaints was the decision to increase the target SBP in patients older than 60—a key departure from the JNC 7 recommendations. The higher target in this age group is also different from that recommended in recent European, Canadian, UK, American College of Cardiology/American Heart Association , and American Society of Hypertension/International Society of Hypertension guidance.

In the post hoc analysis published Monday, Bangalore et al zeroed in on INVEST patients 60 years or older in the 2003 study, which compared a calcium-channel blocker and a beta-blocker in subjects with both hypertension and coronary artery disease. For the purposes of the new analysis, patients were grouped according to whether they achieved on-treatment SBPs of <140 mm Hg, 140 to <150 mm Hg, or >150 mm Hg.

Among the more than 8350 patients included in the analysis, patients who achieved SBPs lower than 140 mm Hg over two years of follow-up had the lowest rates of the primary outcome (first occurrence of all-cause death, CV mortality, total MI, nonfatal MI, total stroke, nonfatal stroke, heart failure, or revascularization).

In multivariate analyses, rates of the primary composite outcome among patients in the middle-target SBP range were no different from those in the lowest range, but those with blood pressures of 150 mm Hg or greater were significantly more likely to experience the primary outcome. Patients in both the middle-target group, as well as those with target SBPs of 150 or greater, were more likely to die of cardiovascular causes or to experience a stroke, compared with those in the lowest SPB target group.

Target-Organ Focus

In interviews with heartwire , both Bangalore as well as senior author Dr Franz Messerli stressed that their INVEST analysis adds to the evidence that the higher SBP target chosen by the JNC 8 writing group will put many hypertensive patients at risk. This is particularly true in the 60-70 age group, where some of the greatest gains have been made in reducing cardiovascular events.

Bangalore and Messerli both urge physicians to treat on a patient-by-patient basis, with particular attention to the J-curve phenomenon and what they call "target-organ heterogeneity."

"We should remember the nadir of this J-curve—ie, the optimal BP—varies from study to study, from population to population, from drug to drug, and perhaps most important for the clinician, from target organ to target organ in the same patient," Messerli explained. "The risk of stroke may still not be optimally reduced at a BP level that already could be too low for preventing coronary artery disease."

"Lower is better for stroke prevention, but that is not true for cardiac death prevention," Bangalore elaborated. "If a patient is at high risk of stroke, trying to get the blood pressure lower, maybe lower than 130, is likely best." In ACCORD , lowering systolic blood pressure to 119 in high-stroke-risk patients was associated with the best outcomes. But for a patient at high risk of MI, "as of now, the data would suggest a target level of around 130 to 140 mm Hg," he said.

JNC 8: A Long Road With Many Destinations

The National Heart, Lung, and Blood Institute (NHLBI) originally commissioned the JNC 8 guidelines and appointed the commission members in 2008. In 2013, the federal agency announced that it was handing off the task of guideline writing to the ACC/AHA. The JNC 8 members then decided to submit their document separately to JAMA. As such, the JNC 8 document (as stated explicitly in the document) is "not an NHBLI-sanctioned report and does not reflect the views of NHLBI."

Some answers to persistent questions may come from the ongoing National Heart, Lung, and Blood Institute–sponsored SPRINT trial, randomizing patients over age 50 to an SBP target of <120 mm Hg vs <140 mm Hg, but those likely won't shed much light on the question of 140 mm Hg vs 150 mm Hg in patients over 60, Bangalore observed.

In an accompanying editorial[2], Dr Alan Gradman (Temple University, Philadelphia, PA) points out that there is little, if any, randomized controlled trial evidence that treating older adults with SBPs between 140 and 150 "actually reduces cardiovascular events."

The JNC 8 writing group put rigorous restrictions on the kinds of data they could review for their recommendations, using only randomized controlled trials that specifically had blood pressure as an end point of interest.

As such, for the recommendation in patients over 60, just two small trials were used to support that recommendation, while others were excluded. A minority of JNC 8 members have already published their concerns about this decision making.

But Gradman also points out that INVEST was designed with specific BP goals, with patients stratified by whether they were "uncomplicated" or had other comorbidities. That complicates efforts to interpret this post hoc analysis, he writes. Going out on a limb, Gradman concludes, "My overall sense is that the JNC 8 panel recommendations are reasonable for patients with hypertension and CAD." These include the advice (not based on trial evidence) that if drug treatment "results in lower systolic blood pressure, without adverse effects on health or quality of life, treatment does not need to be adjusted," he quotes the guidance.

ACC president Dr Patrick O'Gara (Brigham and Women's Hospital, Boston, MA) and AHA president Dr Elliott Antman (Harvard Medical School, Boston, MA) also weighed in, releasing a statement to coincide with the INVEST paper's release. The study "supports the concerns raised by many stakeholders, including the American College of Cardiology, the American Heart Association, and a number of the individual members of the JNC 8 panel," they said.

"This new research suggests that raising the threshold for treatment of hypertension in patients 60 years of age or older with coronary artery disease may be detrimental to the best interest of patients and the public. It underscores ongoing concerns about adopting the unofficial 2013 targets as proposed by the panel originally appointed to write JNC 8. The ACC and AHA, working with the NHLBI, are in the process of assembling the writing panel that will evaluate evidence from a variety of sources and provide a comprehensive update of the hypertension guideline."

Bangalore disclosed serving on advisory boards for Daiichi Sankyo, Boehringer Ingelheim, Abbott, Gilead, and Abbott Vascular. Messerli disclosed being an ad hoc consultant for Daiichi Sankyo, Pfizer, Takeda Pharmaceuticals, Abbott Laboratories, AbbVie, Servier, Medtronic, and Ipca Laboratories. Disclosures for the coauthors are listed in the article. Gradman had no conflicts of interest.

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