AHA Highlights Single-Pill Combo Therapy for Hypertension

Single-pill combination (SPC) therapies containing two or more antihypertensive agents have the potential to provide more rapid and sustained blood pressure control compared with other approaches for managing hypertension, possibly improving persistently poor control rates and leading to greater reductions in cardiovascular events, according to a scientific statement from the American Heart Association (AHA).

Use of SPC therapies cuts pill burden, improves treatment adherence, and helps overcome clinical inertia in prescribing, writing group chair Jordan King, PharmD (University of Utah, Salt Lake City), and colleagues emphasize in the document, which was published online this week in Hypertension. This approach also has been shown to be cost-effective despite the higher price of the combination pills versus the individual drugs.

The authors estimate that about three-quarters of patients with hypertension will ultimately require at least two medications to get their BP to below 140/90 mm Hg.

And it’s likely, King told TCTMD, that that proportion is even greater when aiming for the more stringent goal of less than 130/80 mm Hg recommended in the latest hypertension guidelines from the AHA, the American College of Cardiology, and several other professional societies. Those guidelines, released earlier this year, give a preference for SPC therapies when initiating treatment for adults with stage 2 hypertension.

Despite the commercial availability of numerous SPC therapies for hypertension, the pills are underused.

The approach of starting with one antihypertensive agent, adjusting the dose, and then adding on more medications as needed doesn’t work, King said. In many cases, “patients don’t ever get onto that second medication. They don’t ever get onto an effective regimen. BP control is just stagnant. We just do not do a good enough job of getting patients onto the right regimen,” he said. “Starting with the two drugs, in a single-pill combo, gets us there faster, gets us onto a good regimen, and gets us there right away. It’s safe, it’s effective. It’s hard to justify nowadays the stepped-care approach, in my opinion.”

Positives and Limitations

The new scientific statement reviews the clinical evidence around SPC therapies for hypertension, with discussions of both the benefits and the potential limitations.

On the plus side, the accumulated literature shows that using SPC therapies improves BP control compared with prescribing the medications together individually, King said. There is a lack of randomized data showing that SPC therapies provide better cardiovascular outcomes, although observational studies suggest that that can be expected. “Blood pressure’s such a strong surrogate endpoint that I don’t think anyone would question whether improving someone’s blood pressure control is going to translate into better outcomes,” King said.

SPC therapies do cost more than the constituent medications on their own, but nearly all studies examining their cost-effectiveness indicate that they have the potential to be cost-saving in the long run.

It’s not, however, “all butterflies and rainbows” when it comes to use of SPC therapies, King said, noting that prior research has revealed declining use of these treatments over time.

Some of the reasons cited by physicians for not using fixed-dose combination pills are the inability to identify which component might be causing side effects, the lack of availability of an SPC therapy with a preferred combination of BP-lowering drugs, and spotty insurance coverage, among others.

Single-pill combinations can be a great opportunity to take someone who’s on not a very good regimen and put them onto a more effective guideline-concordant regimen. Jordan King

Some of the issues raised by prescribing physicians “may be more perceived than real,” King said.

Regarding the side-effect issue, most antihypertensive agents have well-described adverse event profiles and that managing unexpected effects wouldn’t differ much whether treatment was given with an SPC therapy or the individual drugs, he said.

While not all combinations of BP-lowering drugs are available in single-pill forms, there should be a comparable combination on the market that can fill any need, King said. “There are some regimens that don’t exist, but the major ones, the ones that are guideline-recommended, do exist,” he said, adding that physicians should ask themselves whether the regimen they’re trying to prescribe, if it’s not available in a single pill, is really the right one to use. “Single-pill combinations can be a great opportunity to take someone who’s on not a very good regimen and put them onto a more effective guideline-concordant regimen.”

He acknowledged that inconsistent insurance coverage for SPC therapies plays a role in their use. “For the vast majority of patients, this is a slam dunk, assuming you can get it paid for,” King added.

Focusing on Implementation

The scientific statement reviews strategies for increasing use of SPC therapies in clinical practice and highlights issues, such as the limited availability of SPC therapies containing three or more drugs, that should be addressed moving forward.

Implementation studies are where the field needs to move next, King said, pointing to the potential for team-based or protocolized care or electronic health record-based changes to increase uptake of fixed-dose combinations. That, he said, “can go a long way in improving population blood pressure control.”

SPC therapies for hypertension represent something of a behavioral intervention for physicians in that their use can lead to reconsideration of how they’re managing patients with high BP, King added.

“I hope that people take maybe a fresh look at their own use of these medications and try to prioritize [SPC therapies], given their superiority to prescribing individual medications,” he said.