Substantial BP Reductions Appear to Lower Stroke Risk Safely in CAD Patients

Steep reductions in blood pressure (BP) to as low as 118/68 mm Hg appear to lower the likelihood of stroke without imparting greater risk of myocardial infarction (MI) among patients with documented coronary artery disease (CAD), according to a post hoc analysis of the ONTARGET trial published online October 20, 2014, ahead of print in Hypertension.

“The present study is reassuring as to the safety of blood pressure reduction over the explored range, even for achieved blood pressure values < 130/80 mm Hg,” Paolo Verdecchia, MD, of the Hospital of Assisi (Assisi, Italy), and colleagues write.

Methods
The researchers examined the relationship between BP changes from baseline and the risks of stroke and MI using data from the 19,102 patients in ONTARGET who had CAD but not congestive heart failure (mean age 66.4; 22% female). Because the main trial results did not show a difference in outcome between the 3 study arms—in which patients received the ACE inhibitor ramipril, the angiotensin receptor blocker telmisartan, or a combination—the patients were pooled for this analysis, in which the average baseline BP was 141/82 mm Hg and the average reduction during a median follow-up of 4.7 years was 7/6 mm Hg.

 

After adjustment for possible determinants of reverse causality, including randomized allocation, reductions in BP from baseline were associated with lower stroke risk and unchanged MI risk, whereas increases in systolic BP were associated with increased risks for both outcomes.

Reducing systolic BP by 34 mm Hg (equal to the 10th percentile of measures or an achieved pressure of 118 mm Hg), for example, was associated with a 16% lower risk for stroke (HR 0.84; 95% CI 0.71-0.99) compared with a reduction of just 7 mm Hg. The HR for MI was 1.05 (95% CI 0.91-1.21).

On the other hand, increasing systolic BP by 20 mm Hg (equal to the 90th percentile of measures or an achieved pressure of 160 mm Hg) was associated with a 42% greater stroke risk (HR 1.42; 95% CI 1.23-1.63) and a 20% increase in MI risk (HR 1.20; 95% CI 1.06-1.35) compared with a reduction of just 7 mm Hg.

Similar patterns were seen in the relationships between changes in diastolic pressure and each outcome.

When looking at achieved BP rather than changes from baseline, there was no relationship between systolic or diastolic readings and MI risk. For stroke, however, both high and low values of achieved systolic and diastolic pressure were associated with risk.

Minor BP Changes Influence Risk

“Our data suggest that a [systolic BP] target of < 140 mm Hg is appropriate for the prevention of stroke in patients at high vascular risk with previous evidence of CAD,” Dr. Verdecchia and colleagues write, citing the finding that even minor changes in BP were associated with lower or higher stroke risk.

The results also support a recent scientific statement from the American Heart Association/American Stroke Association stating that “the decrease in BP with antihypertensive drugs seems to be the major determinant for the reduction in the risk of stroke,” they add.

In addition, the data bolster “the position of a 'minority group' of the JNC 8 panel who believe that a systolic BP target of 150 mm Hg in people aged > 60 is too high,” Dr. Verdecchia told TCTMD in an email. “This study showed a significant rise in the risk of stroke for an achieved systolic BP of 150 mm Hg compared with a reference of 140 mm Hg, thereby supporting a more stringent BP target of 140 mm Hg for the prevention of stroke.”

“Future guidelines should emphasize the different effect of a tighter BP control on the risk of stroke and MI,” the authors conclude. “The present analysis should be considered as hypothesis generating and as a further stimulus to randomized controlled trials to test the effect of different BP goals on the risks of stroke and MI taken separately.”

Suzanne Oparil, MD, of the University of Alabama at Birmingham (Birmingham, AL), agreed that further trials are needed to establish appropriate BP goals, particularly in patients with established CAD. She noted that about 20% of the patients fit this description in the ongoing SPRINT trial, which is comparing systolic BP goals of < 120 mm Hg vs < 140 mm Hg for cardiovascular risk reduction. The first results are expected in 2017.

In the meantime, Dr. Oparil said, the results of this study should ease concerns about a potential increased risk of MI with treatment to very low BP levels.

“I don’t think it should drive recommendations,” she said, “but it should make practitioners comfortable that getting the blood pressure to the normal range—120/70 mm Hg—is probably reasonably safe.”



Source:
Verdecchia P, Reboldi G, Angeli F, et al. Systolic and diastolic blood pressure changes in relation with myocardial infarction and stroke in patients with coronary artery disease. Hypertension. 2014;Epub ahead of print.

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Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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Disclosures
  • The ONTARGET trial was funded by Boehringer Ingelheim.
  • Dr. Verdecchia reports receiving consulting and lecture fees and research grants from Boehringer Ingelheim and other companies manufacturing ARBs and support from the Fondazione Umbra Cuore e Ipertensione-ONLUS in Italy.
  • Dr. Oparil reports being the principal investigator of 1 of the 5 SPRINT trial regions.

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