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Risk-based hypertension treatment cuts cardiovascular events

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Intriguing results – more questions remain

An unusual methodology adds both strengths and a potential weakness to the study by the Blood Pressure Lowering Treatment Trialists’ Collaboration.

The risk categories that the investigators constructed employed a parsimonious set of covariables, and omitted blood lipids, to balance model fit with the availability of risk factor data.

Thereafter, considering only the patients with an event, they defined three cut-off points of estimated risk that would divide the individuals into four equal-size groups. Finally, they applied these cut-off points to the overall trial population to define the four main risk strata.

Although a laudable attempt to maximize the power and precision of the estimated treatment effects in each of the four risk strata, the method does beg the question of external validation.

For the proof-of-principle shown in this study, internal validation might be adequate, and important measures of that – the observed versus expected event rates – are graphically presented in the study’s appendix. However, although the authors are not explicitly promoting these equations for general use, the absence of external validation somewhat limits the generalizability of the findings.

Before a completely risk-based approach should be implemented, more questions require answers.

First, the accuracy and external validity of the prediction models should be tested in contemporary cohorts of patients. Second, whether treatment decisions based mainly on total cardiovascular risk outperform decisions mostly based on blood pressure should be clarified. Patients at relatively low risk of cardiovascular events, such as younger patients with hypertension or those with low phenotypic expression of risk factors, should not be denied treatment with the argument that the expected absolute benefit is small.

Dr. Paolo Verdecchia and Dr. Gianpaolo Reboldi are affiliated with the University of Perugia, Italy. These remarks are taken from their accompanying editorial (Lancet 2014;384:562-4).


 

FROM THE LANCET

References

As cardiovascular risks increase, so does the protection offered by antihypertensive medications, a large meta-analysis has determined.

The review of 52,000 patients has also found that the number needed to treat decreased as risk levels increased. For those at lowest risk, treatment would prevent 14 cardiovascular events over 5 years; for those at highest risk, treatment would prevent 38 events/1,000 patients.

"This finding provides support for the notion that blood pressure–lowering treatment should target those at greatest cardiovascular risk, not just those with the highest blood pressure levels," Dr. Johan Sundström and his colleagues in the Blood Pressure Lowering Treatment Trialists’ Collaboration reported in the Aug. 16 issue of the Lancet. "A risk-based approach is likely to be more cost effective than a blood pressure-based approach and could simultaneously reduce the numbers of patients needing treatment, and control drug costs while increasing the numbers of averted strokes and heart attacks."

Dr. Sundström of Uppsala University, Sweden, and his team analyzed 11 studies that comprised 26 groups randomized to placebo or various antihypertensive medications. These included ACE inhibitor–based treatment; calcium channel blocker–based treatment; diuretic-based treatment; and more-intensive vs. less-intensive blood pressure–lowering regimens.

The final analysis included full 5-year data on about 52,000 patients. These were separated into four increasing risk groups, which the authors created based on age, sex, body mass index, systolic and diastolic blood pressures, other antihypertensive treatment, current smoking, diabetes, and history of cardiovascular disease. Interaction analyses for age and sex, age and smoking, age and diabetes, age and history of cardiovascular disease, and age and other antihypertensive treatment were also included. However, lipid measurements were not.

Those 5-year risk groups were less than 11%; 11%-15%; 15%-21%; and more than 21%.

The primary outcome was a composite of total major cardiovascular events (nonfatal stroke; death from cerebrovascular disease; coronary heart disease, including myocardial infarction; heart failure; and cardiovascular morbidity.) Secondary outcomes were stroke, coronary heart disease, heart failure, cardiovascular mortality, and total mortality.

Over the 5-year follow-up period, there were 4,167 cardiovascular events (8%). The number of events varied from low- to high-risk groups: 4.1% in the low-risk group, followed by 8.3%, 12.6%, and 18.6%.

"However," the investigators said, "in absolute terms, treating 1,000 patients in each group with blood pressure–lowering treatment for 5 years would prevent 14, 20, 24, and 38 cardiovascular events, respectively," a significant preventive effect (Lancet 2014 Aug. 16;384:591-8).

Inversely, the number needed to treat for 5 years to avoid 1 cardiovascular event decreased with increasing baseline risk, from 71 in the lowest-risk group, to 51 and 41 in the second and third risk groups, and down to 26 in the highest-risk group.

The drugs continued to exert a significant effect despite several subanalyses that controlled for a variety of factors. Indeed, when they examined the relationship between cardiovascular events and the magnitude of both systolic and diastolic blood pressure reduction, the authors found even greater absolute event reduction.

For example, in the highest-risk group when systolic blood pressure of at least 140 mm Hg declined by 16 points, 69 events would be prevented over 5 years. When diastolic pressure of at least 90 mm Hg declined in that group by 8 points, 76 events would be prevented.

Even a 4 mm Hg reduction in systolic and diastolic pressures in the high-risk would reduce events by 19 and 22, respectively.

Despite the findings of prior studies also showing the benefit of risk managing blood pressure, the technique has fallen out of favor, the authors noted. "In part at least, this reluctance to use absolute risk as a basis for decision making might be a result of the absence of direct evidence of effectiveness, which this study should go some way toward addressing."

As members of the Blood Pressure Lowering Treatment Trialists’ Collaboration, the authors received individual funding for their work. Dr. Sundström declared that he is on the advisory board for Itrim. A number of the other authors declared financial relationships with pharmaceutical companies.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

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