Antihypertensive Add-On Has Edge Over Boosting Doses

While adding an agent was a less common antihypertensive intensification strategy than boosting dose, it was slightly more effective, a large observational study showed.

Among some 178,000 veterans getting treatment intensified for uncontrolled hypertension, only 25% received a new antihypertensive, whereas the rest had the dose of existing medications maximized, found Carole E. Aubert, MD, of Bern University Hospital in Switzerland, and colleagues, reporting in the Annals of Internal Medicine.

As expected, fewer patients at 3 months adhered to the added agent — with its potentially greater pill burden and potential for new adverse events and drug interaction — versus those on the higher drug dose (49.8% vs 65.0%).

However, the extra antihypertensive cut systolic blood pressure significantly more, by an extra 0.8 mm Hg at 3 months and by 1.1 mm Hg more at 12 months than dose maximization (-5.6 vs -4.5 mm Hg).

That difference would be expected to cut relative risk of major cardiovascular events by approximately 2 percentage points, or by 5 percentage points if analyzed without adjusting for baseline systolic blood pressure — “an analysis that may be closer to that done in hypertension trials,” the researchers noted.

“Our findings are consistent with a strategy of targeting several concurrent mechanisms to counteract hypertension,” the team concluded.

Still, the investigators cautioned: “When adapting antihypertensive medication regimens, it is important to consider not only [blood pressure] control but also the risk–benefit ratio of each antihypertensive medication in light of all comorbid conditions and comedications and the added complexity of adding an additional medication, particularly in older patients with multiple comorbid conditions, who are more vulnerable to adverse effects of medication and frequently receive multiple medications.”

It’s no surprise that adding an antihypertensive drug would have a bigger impact than dose escalation, since a half dose is typically only 25% less potent than a full dose, noted Olivier Steichen, MD, PhD, of the Assistance Publique-Hôpitaux de Paris and Sorbonne Universite in Paris, writing in an accompanying editorial.

The key is just to intensify treatment when needed, he explained: “When intensification is indicated, we should not waste time with elaborate reasoning: Either add a drug or maximize the dose of existing drugs, whichever seems to fit best with the patient’s current treatment, clinical state, and preferences. We must try to keep the treatment as simple as possible but remember that increasing the dose of a single drug has a limited effect on the overall potency of a combination. We should use [single-pill combinations] whenever they simplify the treatment and explain any unavoidable complexity to the patient. A follow-up visit must be planned about 1 month later to assess adherence, tolerance, and effectiveness and to perform further adjustments if needed.”

The study emulated a clinical trial by treating its 178,562 patients as if randomized at the time of treatment intensification at a Veterans Affairs (VA) Health Services facility for a systolic blood pressure of 130 mm Hg or greater on an antihypertensive regimen in which at least one drug was not at maximal dose.

The researchers used VA pharmacy records, Medicare Part D medication files, and administrative and clinical data from encounters with VA primary care, geriatric care, cardiology, endocrinology, nephrology, and neurology specialists from July 2009 through June 2013.

Limitations of the study, the researchers said, included the largely elderly, male population (average age 75.8, 98% men), most of whom had at least one chronic condition comorbid to hypertension, as well as reliance on unstandardized office measurements.

Oliver added that the main shortcoming of the study was the diverse set of situations in which patients needed intensification in terms of baseline number and doses of antihypertensive drugs, number of pills per day, blood pressure level (systolic 130 mm Hg or higher), comorbid conditions, and fitness.

Further trials comparing dose intensification strategies “would ultimately provide the most definitive support for our findings, given that the possibility of confounding and bias cannot be completely eliminated even with our careful efforts to approximate the conditions of a trial,” Aubert’s group added.