Study Questions Role of BP Meds in Patients With Hypertension but No Other CVD Risk Factors

New observational data hint that antihypertensive therapy may not cut mortality and CV disease in patients who have blood pressures ranging from 140/90 to 159/99 mm Hg but no other cardiovascular disease or CV risk factors. What’s more, over the course of nearly 6 years, treated patients had more adverse events than those left untreated.

“The present data provide no evidence to suggest that new [American College of Cardiology/American Heart Association (ACC/AHA)] guidelines will reduce CVD events in low-risk patients with mild hypertension,” write James P. Sheppard, PhD (University of Oxford, United Kingdom), and colleagues.

In their study, published online October 29, 2018, in JAMA Internal Medicine, the investigators looked specifically at patients with no history of CVD and no CVD risk factors, but with blood pressure levels in the range now considered to be stage 2 hypertension under the most recent US hypertension guidelines that were deemed “mild” in earlier iterations. In the new European guidelines, this same range would be considered grade 1 hypertension warranting lifestyle interventions before medication is considered.

Sheppard and colleagues’ study used observational data from the Clinical Practice Research Datalink, zeroing in on patients with no history of CVD, left ventricular hypertrophy, A-fib, diabetes, chronic kidney disease, or family history of premature heart disease. In all, 19,143 patients received a prescription for antihypertensive medication, while the same number of patients did not.

Mortality was 4.08% in the untreated group and 4.49% in the treated group (that is, the group that received a prescription), amounting to a risk difference of 0.41% (95% CI 0.02%-0.85%). There was no significant difference between groups in time to death (HR 1.02; 95% CI 0.88-1.17) or for stroke, MI, heart failure, or non-MI acute ACS.

Patients in the treatment group had a higher likelihood than untreated patients of developing hypotension, electrolyte abnormalities, syncope, and acute kidney injury. There were no increased risks of falls or bradycardia associated with antihypertensive therapy.

Asked to comment on the findings for TCTMD, Paul Whelton, MD (Tulane University School of Public Health and Tropical Medicine, New Orleans, LA), who chaired the ACC/AHA hypertension guideline writing committee, highlighted the difficulties in interpreting observation data.

“We can look at the same data here and come to different conclusions, none of which will have a high degree of certainty,” he said.

Low-risk patients pose a challenge, since the majority of evidence in support of lower cutoffs for treatment come from trials in high-risk patients, Whelton noted. “So you try to come up with best evidence on imperfect data.” Despite the lower level of evidence, the ACC/AHA guidelines do recommend initiating pharmacologic therapy for all individuals with a BP of 140/90 mm Hg or higher regardless of risk. Whelton said the committee is not likely to change that recommendation anytime soon.  

"We used several lines of reasoning to come up with a recommendation for use of drugs [in low-risk patients] if [a nonpharmaceutical strategy] on its own didn't work,” Whelton noted. “Other reasonable people can say the evidence is not there, just as the Canadians have.”

The Canadian guidelines separate out recommendations based on level of risk.

Caution for the Truly Low Risk

“It’s very important to remember there have been landmark clinical trials demonstrating the benefits of blood pressure reduction with medication below 140/90 for most adults, and particularly in higher-risk [patients] getting the most benefit from it. I think we need to trust clinical trials,” said Erin D. Michos, MD (Johns Hopkins University School of Medicine, Baltimore, MD), also commenting on the study for TCTMD. “But I do agree that there should be caution for exactly this type of population of truly low-risk individuals because there is a lack of randomized clinical trials in this patient population.”

Michos also expressed skepticism about the strength of observational data on treatment effects. “This observational data is really focusing on a very unique low-risk population with no risk factors and their follow-up time was only 5.8 years. In individuals with no cardiovascular disease and no risk factors, I would be surprised to see any kind of cardiovascular outcome that quickly,” she said. Another important issue is whether the patients truly had hypertension to begin with, something that Michos said would have been helpful to have confirmed.

Whelton agreed, adding that the ACC/AHA guidelines do include a caution about the importance of excluding white-coat hypertension before embarking on drug therapy. “On the other side of the coin, you want to be pretty sure about risk profiling before you say somebody is low risk, because unfortunately it’s unusual in adults in our setting,” he observed.

In an email, Sheppard agreed that the results should be interpreted cautiously. “We did our best to take things such as age and previous medical history into account in our analysis, since these could have caused differences between our treatment groups which may have affected the results,” he said. “Whilst the patients were similar in the characteristics which we could measure, we cannot rule out the possibility that some unmeasurable characteristics may have been different, causing patients in the treatment group to be at higher risk than those in the control group.”

Sheppard added, however, that the benefits of treating patients at low risk for cardiovascular disease and mild hypertension are not clear-cut. “It is possible that some patients may suffer more harm than good, so doctors should be cautious when considering treatment in this population,” he noted.

Of note, the authors could not ascertain whether the prescriptions were ultimately filled or whether patients took the medication as prescribed.

Individualized Care and Discussion

For high-risk individuals, the magnitude of the survival benefits of lowering BP to the newer goal has been estimated in terms of hundreds of thousands of lives saved per year.

“I believe our analysis demonstrates that extrapolation of data from trials to different, often lower-risk populations may not always be appropriate,” Sheppard told TCTMD. “Ultimately, the decision to initiate treatment in this population should come after a discussion between the patient and their doctor, in which the benefits and harms of therapy are considered.”

Michos agreed, adding that there is no “one size fits all” when approaching antihypertensive therapy.

“Trials are based on averages, and people are individuals,” she said. “We should do a personalized approach that considers individual risk, the patient’s preferences, the benefits in choosing targets, and an intense focus on lifestyle changes and medication adherence.”

As for the generalizability of the study, Whelton said it’s important that it doesn’t cause confusion, especially since the authors chose to use the outdated term “mild” hypertension.

“It’s really unusual to call it mild,” he said. “If you match that [BP range] with high risk, there’s nothing mild about it at all.”