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Elderly CAD patients benefit from a systolic value below 140 mm Hg

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Analysis limited by caveats

The findings reported by Dr. Bangalore and his coauthors support a lower blood pressure target, specifically in patients with hypertension and coronary artery disease. The implication is that the appropriate systolic blood pressure target should be less than 140 mm Hg for patients aged 60 or older with coronary artery disease.

However, the evidence they present does not firmly refute a systolic pressure goal of less than 150 mm Hg for patients aged 60 or older, as recommended by the panel originally constituted as the Eighth Joint National Committee (JNC 8) (JAMA 2014;311:507-20). That’s because all patients included in the analysis – those patients who entered the INVEST trial with a systolic pressure greater than 150 mm Hg – would qualify for treatment based on the recommendations of the former JNC 8 panel. But little, if any, evidence from randomized clinical trials supports the idea that antihypertensive treatment reduces cardiovascular events in older adults who start treatment with a systolic blood pressure of 140-160 mm Hg.

Another limitation of the new analysis is that the INVEST design called on physicians to treat all patients to a goal pressure of less than 140/90 mm Hg or less than 130/85 mm Hg for patients with diabetes or renal impairment using either of two prespecified treatment regimens (JAMA 2003;290:2805-16). Although patients received either one or the other regimen based on the treatment arm to which they were randomized, the intensity of treatment that all patients in INVEST received was roughly the same. After 2 years, 57% of all patients in the subgroup studied in the post-hoc analysis responded with a systolic pressure that achieved the target. Although the 43% who did not meet the target had worse outcomes than the 57% who achieved a lower systolic pressure, it is not clear that the less responsive patients in the 43% group would have done better with intensified treatment that might have driven their systolic pressure down further, below 140 mm Hg.

In other words, the new analysis compared the outcomes of responders with nonresponders. To compare a target of less than 140 mm Hg with a target in the 140-150 mm Hg range among the nonresponder patients in INVEST would require a prospective trial in which the nonresponder patients are randomized to additional antihypertensive treatment or to placebo to test the benefit of intensified treatment to reach the sub–140 mm Hg goal. More aggressive treatment of these elderly nonresponders could increase the number of treatment-related adverse events. Without data like these, there is no right answer to the question of which systolic target to use.

I believe that the blood pressure target recommendations of the former JNC 8 panel are reasonable for patients with hypertension and coronary artery disease. Their recommendations continue to use a diastolic target pressure of less than 90 mm Hg, which helps insure that most patients with significant hypertension will receive appropriate treatment regardless of their systolic pressure. Clinicians need to use their clinical judgment about treatment for patients with isolated systolic hypertension in the 140-149 mm Hg range. Patients at increased risk for stroke should probably receive more intensive treatment. An important corollary recommendation from the former JNC-8 panel was that when treatment drops a patient’s systolic pressure below 140 mm Hg without causing adverse effects, the treatment can be maintained and the patient’s pressure kept at this lower level.

Dr. Alan H. Gradman is a cardiologist who practices in Pittsburgh. He had no relevant disclosures. He made these comments in an editorial that accompanied the report by Dr. Bangalore and coauthors (J. Amer. Coll. Cardiol. 2014;64:794-6).


 

FROM JACC

References

Elderly hypertensive patients who had coronary artery disease and a baseline systolic blood pressure greater than 150 mm Hg had significantly fewer cardiovascular deaths and strokes if they achieved a systolic pressure of less than 140 mm Hg, compared with similar patients who achieved a systolic pressure of 140-149 mm Hg.

The findings were noted in a post-hoc analysis of data collected from more than 8,000 patients in an international treatment study. The researchers compared outcomes for patients who achieved these two different levels of systolic pressure as a way to assess the new hypertension treatment goal of a systolic pressure less than 150 mm Hg in patients aged 60 years or older as recommended by the group originally appointed as the Eighth Joint National Committee (JNC 8) (JAMA 2014;311:507-20). Their finding that the patients who achieved the lower systolic pressure level of less than 140 mm Hg had a significantly lower rate of cardiovascular death and stroke as compared with patients whose systolic pressure remained in the 140-149 mm Hg range provided "important information to focus the risk-benefit discussion for patients who had on-treatment blood pressure in the 140-150 mm Hg range," wrote Dr. Sripal Bangalore, a cardiologist at New York University and his associates in an article published online on August 18 (J. Amer. Coll. Cardiol. 2014;311:784-93).

Dr. Sripal Bangalore

At least one expert questioned the ability of such a post-hoc analysis to address blood pressure goals in a meaningful way. "To adjudicate between a target of 140 mm Hg and 150 mm Hg it would be necessary to perform a prospective trial in which the population was randomized to these targets," commented Dr. Alan H. Gradman in an editorial that accompanied the new study (J. Amer. Coll. Cardiol. 2014;311:794-6). More aggressive blood pressure lowering could result in increased adverse events, he warned.

Despite these limitations, other experts hailed the new finding as important evidence against the recommendations of the former JNC 8 committee. "This study supports the concerns raised by many stakeholders, including the American College of Cardiology [ACC], the American Heart Association [AHA], and a number of the individual members of the JNC 8 panel (Ann. Intern. Med. 2014;160:499-503.), about the panel’s 2013 recommendations to raise blood pressure targets in older patients," said Dr. Patrick T. O’Gara, ACC president, and Dr. Elliott Antman, AHA president, in a joint written statement released to coincide with the new report’s publication.

"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," Dr. O’Gara and Dr. Antman said in their statement. Their statement added that "the ACC and AHA, working with the NHLBI [National Heart, Lung, and Blood Institute] 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."

The post-hoc analysis focused on a subgroup of 8,354 patients from among the 22,576 total patients enrolled in the (International Verapamil SR Trandolapril Study (INVEST), which enrolled patients aged 50 years or older with hypertension and pre-existing coronary artery disease at 862 centers in 14 countries (JAMA 2003;290:2805-16). Patients had been randomized to receive treatment with either a combination of verapamil sustained release plus trandolapril and hydrochlorothiazide if needed, or a combination of atenolol plus hydrochlorothiazide and trandolapril if needed, with a goal blood pressure on treatment of less than 140/90 mm Hg or less than 130/85 mmHg in patients with diabetes, renal impairment, or both. The primary, combined outcome of INVEST showed no significant difference in efficacy or safety between the two regimens compared in the study, and roughly 70% of patients in both treatment subgroups reached their goal blood pressures.

The new analysis selected the 8,354 patients who enrolled in INVEST at age 60 years or older and had a systolic blood pressure of at least 150 mm Hg at baseline. This subgroup included 4,787 patients (57%) who achieved a systolic pressure of less than 140 mm Hg after 24 months on study treatment, 1,747 patients who achieved a systolic pressure of 140-149 mm Hg after 24 months, and 1,820 patients whose systolic pressure failed to fall below 150 mm Hg.

In multiple propensity score – adjusted analyses, the rate of cardiovascular death was a relative 34% higher among patients with an achieved systolic pressure of 140-149 mm Hg, compared with those whose pressures fell below 140 mm Hg. Also, the total rate of stroke was 89% higher among patients whose pressures stayed in the 140-149 mm Hg range, compared with patients who achieved lower pressures. The rate of nonfatal stroke was 70% higher among the 140-149 mm Hg subgroup. All three of these differences were statistically significant.

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