CHICAGO -- Tackling blood pressure without also addressing lipids doesn't help in primary cardiovascular prevention for people not at high risk, the HOPE-3 trial showed.
The likelihood of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke over a median 5.6 years of follow-up was similar whether such intermediate-risk patients without preexisting cardiovascular disease took candesartan and hydrochlorothiazide (Atacand) or placebo (4.1% versus 4.4%, hazard ratio 0.93, P=0.40), Eva M. Lonn, MD, of McMaster University in Hamilton, Ontario, and colleagues found.
Including resuscitated cardiac arrest, heart failure, and revascularization events along with the hard endpoints in a second co-primary composite endpoint likewise showed no advantage to blood pressure-lowering treatment (4.9% versus 5.2% on placebo, HR 0.95, P=0.51).
The findings were reported here at the American College of Cardiology meeting and simultaneously online in the New England Journal of Medicine.
The HOPE-3 trial also included a statin versus placebo comparison in a 2x2 factorial design -- both statin alone and statin plus blood pressure lowering significantly lowered risks for the primary prevention population enrolled. See MedPage Today's coverage of those findings here.
"The overall null results of the blood-pressure-lowering component of HOPE-3 could be due to insufficient dosing of antihypertensive medications, treatment of a relatively low-risk group, or chance," William C. Cushman, MD, and David C. Goff, Jr., MD, PhD, in an editorial in NEJM.
"Neither of the drugs for blood-pressure lowering that were used in the trial have been shown to reduce the risk of cardiovascular events at such low doses," they added. "If higher doses had been used, the risk of cardiovascular events might have been significantly reduced, whether from greater blood-pressure lowering, additional effects of the antihypertensive drugs, or both."
For the blood pressure arm, the trial enrolled 12,705 participants at intermediate risk who did not have cardiovascular disease and randomized them to 16-mg candesartan plus 12.5-mg hydrochlorothiazide per day or placebo.
The mean baseline blood pressure was 138.1/81.9 mm Hg, and this declined by 6.0/3.0 mm Hg more with treatment than with placebo.
That editorialists noted that the 95% confidence interval for benefit did not exclude the magnitude of an effect one might expect from this small differential in blood pressure.
Most antihypertensive trials have used higher-risk populations to boost trial efficiency and demonstrated cardiovascular benefit for lowering blood pressure in people with an average systolic above 130 mm Hg and either known cardiovascular disease or predicted 5-year risk of cardiovascular events of at least 6.5%, Cushman and Goff noted. In SPRINT, people without baseline cardiovascular disease had to have either subclinical cardiovascular disease or 10-year cardiovascular risk of more than 15%.
Notably, in HOPE-3 there was one prespecified subgroup who did appear to benefit -- people with the highest baseline blood pressures, above 143.5 mm Hg, which would put them in line for antihypertensive treatment under current guidelines.
In that group only, antihypertensive treatment reduced risk of both co-primary composite endpoints (P=0.02 and P=0.009, respectively, for trend in the two outcomes).
Neither benefit nor harm was seen in the lower baseline blood pressure tertiles.
Thus, the editorials concluded: "These results may help to define the combined threshold of systolic blood pressure (<140 mm Hg) and cardiovascular risk (<5.0%) below which the use of blood-pressure–lowering medications may not be useful in the short term.
"However, these results do not rule out the possibility of a benefit with longer-term treatment in a portion of this relatively low-risk population."
The trial was funded by the Canadian Institutes of Health Research and AstraZeneca.
Lonn disclosed relationships with both those organizations and Bayer, GlaxoSmithKline, Merck Schering, Eli Lilly, Amgen, Sanofi, and Novartis.
Cushman reported grant support from Merck and Eli Lilly outside the submitted work. He is also an uncompensated member of the steering committee for the Takeda-sponsored EXAMINE diabetes CV outcome trial, and he provides uncompensated consulting to Takeda related to hypertension clinical trials.
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