Age Management Medicine News: September 2021 – #2

4-in-1 hypertension treatment may be better than standard care

Jessica Norris

Sept. 3, 2021 (Medical News Today) — Hypertension is highly prevalent. In the United States, an estimated 45% of adults have high blood pressure.

Due to the health risks associated with the condition, scientists are constantly researching and developing new treatment options to lower blood pressure effectively.

A new study, which appears in The Lancet, tests a novel medication regimen. Specifically, the researchers tested a single pill that contains ultra-low doses of four different blood pressure-lowering medications.

The authors conclude that this four-in-one pill may be more effective than a single medication in lowering blood pressure.

Hypertension and health

As the National Heart, Lung, and Blood Institute notes, blood pressure is the measurement of the pressure of blood flowing through the arteries of the body. Blood pressure is measured using two readings: the systolic and diastolic pressures.

The systolic pressure is the blood pressure when the heart ventricles contract to pump blood out to the body. The blood pressure when the ventricles of the heart relax to fill up with blood is called diastolic pressure.

normal systolic blood pressure reading is less than 120 millimeters of mercury (mm Hg), and a normal diastolic reading is below 80 mm Hg. Doctors define hypertension as involving a systolic reading of 130 mm Hg or higher, or a diastolic reading of 80 mm Hg or above.

Hypertension treatment often includes both lifestyle modifications and medication. Research is ongoing to develop the best medication options to treat high blood pressure, including combinations of medications.

Combined medications

Typically, when someone has hypertension, a doctor prescribes only one type of medication. Then, if this is ineffective, they may add another medication or switch to a different single medication.

The authors of the recent study hypothesized that starting people on a single pill that contained low doses of four different blood pressure-lowering medications might be more effective than them using only one type of medication.

Study author Prof. Clara K. Chow explained to Medical News Today:

“This randomized controlled trial questioned the paradigm of how we start in our management of people with hypertension. Instead of the common approach of starting with one drug at full dose and adding tablets, we started patients on a single pill containing four medicines each at a quarter of standard dose.”

It was a randomized, double-blind, active-controlled trial. This means that the assignation of participants to the control and experimental groups was random and that neither the participants nor the researchers knew who was in which group during data collection.

Importantly, rather than the control group receiving no treatment, they received standard care.

At the start of the trial, the participants either had untreated high blood pressure or were only taking one type of hypertension medication.

The study included 591 participants, with 300 participants in the intervention group and 291 participants in the control group. Those in the intervention group received a “quadpill,” which contained low doses of four medications that doctors use to treat high blood pressure: irbesartan, amlodipine, indapamide, and bisoprolol.

The control group received irbesartan starting at 150 milligrams.

If blood pressure remained high for participants in either group, there was the option to add other medications to their treatment regimen, starting with amlodipine.

The researchers evaluated the groups over a 12-week period. In addition, they followed a small number from each group over 12 months to examine the longer term effects.

The results of the study revealed more significant blood pressure improvements in the intervention group than in the control group. The authors reported the following differences between the two groups:

  • In the intervention group, 15% of participants needed additional medication to control blood pressure compared with 40% in the control group.
  • Overall, systolic blood pressure readings were lower in the intervention group compared with the control group.
  • The rates of blood pressure control were higher, at 76%, in the intervention group than in the control group, at 58%.
  • During the 12-month observation period, it was necessary to increase medication dosing more in the control group than in the intervention group.
  • Average systolic blood pressure readings remained lower overall for the intervention group compared with the control group over the 12-month observation period.

The researchers also found that adverse effects related to the quadpill treatment were comparable to adverse effects related to standard care.

They note that “[t]here was no excess in serious adverse events or acute kidney injury associated with the quadpill, but there were no types of adverse effects that occurred less frequently in the quadpill group compared with standard care.”

Study limitations and moving forward

The study demonstrates the effectiveness of combined medication in treating high blood pressure. Prof. Chow noted to MNT:

“The ‘quadpill’ approach was superior to the common approach. The BP [blood pressure] differences were sustained even at 12 months, that is we didn’t see ‘catch-up’ between the arms of the trial. It demonstrates that early low dose combination is a quick, more effective, and much simpler way of getting patients to BP control safely.”

The study did have limitations. The researchers did not reach their desired sample size because of the COVID-19 pandemic, and this limits the overall strength of the results.

Also, because of the relatively short time frame, the researchers could not measure long-term cardiovascular outcomes.

MNT also spoke with Prof. Bernard M. Y. Cheung from the Department of Medicine at the University of Hong Kong. Speaking about the limitations of the study, he reiterated that the study is relatively small. He also made a point about demographics:

“Eighty-two percent of the study participants were white. The results should, therefore, be interpreted with a degree of caution for other ethnic groups. For instance, in Chinese people, a calcium channel blocker alone achieves good blood pressure lowering, and in Black people, a diuretic may be better than irbesartan or other drugs in its class.”

The authors also note that doctors in the community would probably be slower to increase the dosages of medicines than the doctors involved in this study. This means that the results may actually underestimate the benefits of the quadpill.

They also encourage continued evaluation of the efficacy and tolerability of the quadpill treatment in comparison with other treatment regimens.

Nevertheless, this medication combination may offer another treatment option to people with high blood pressure.

When asked to comment on the study, cardiologist and vice president of medical at K Health, Dr. Edo Paz, offered an optimistic response to the study and his thoughts on further research:

“This study aligns with a few concepts we know to be true regarding blood pressure management. For one, multiple medications at lower doses likely have higher effectiveness and lower side effects than higher doses of a single medication. In addition, people with blood pressure significantly above goal will often require multiple medications.”

However, Dr. Paz added a note of caution: “Using so many different medications may actually increase [the] risk of side effects, and there was such a signal in this study. Overall, the study is small, so it is not likely to change practice significantly. But this overall strategy does merit further study, as a single pill may increase patient compliance with medications.”


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