In recent years, the paradigm of hypertension treatment has shifted toward aggressive blood pressure management to prevent serious cardiovascular complications. This shift has led to the growing importance of combination therapy in treating hypertension. Combination therapy has the advantage of providing more effective blood pressure control in treating hypertension.

With the rising significance of combination therapy, pharmaceutical companies are introducing new medications for hypertension. Recently, Aprovasc, co-developed by Sanofi and Handok, is expected to enter the prescription race. Aprovasc is a two-drug combination that combines Sanofi's irbesartan-based monotherapy Aprovel with amlodipine.

Korea Biomedical Review sat down with Dr. Lee Hae-young, professor of cardiology at Seoul National University Hospital, to learn more about recent trends in hypertension treatment and how introducing new combinations will impact the hypertension treatment landscape.

Question: Why has the timing for considering combination therapy in hypertension treatment advanced recently?

Answer: Blood pressure control is essential, as every 2 mm Hg increase in blood pressure is associated with a 10 percent higher risk of stroke. Antihypertensive medications typically lower blood pressure by 10 to 20 mm Hg Hypertension is diagnosed when blood pressure is 140 mm Hg or higher. Still, the majority of people with hypertension have a blood pressure of 160-170 mm Hg at their first visit to the doctor, making it difficult to achieve normal blood pressure levels with a single medication. Studies have shown that less than 40 percent of patients can control their blood pressure with a single medication, and more than 60 percent require a combination of two or more medications with different mechanisms to achieve normalized blood pressure.

However, the problem with adding new medications is that patients' adherence is often poor. For example, if a patient with a blood pressure of 142 mm Hg is advised to take an additional medication, they may be reluctant to do so, saying that they will manage it with lifestyle habits, such as exercise.

Conversely, if you start them on a combination of two medications from the start and then taper them off once their blood pressure is under control, most patients will comply. In light of this, European guidelines recommend starting combination therapy strategically to achieve effective blood pressure lowering and adherence. Although Korean guidelines do not yet specify the initial use of combination therapy, they are favorable to the use of combination therapy in patients who are expected to have poor adherence or difficulty controlling blood pressure when adding additional medications.

Q: Can you elaborate on the common combinations used in therapy?

A: Diuretics are recommended for combination therapy. Diuretics work by removing excess sodium from the body, but they can have side effects, including sodium deficiency and constipation, if they are overdosed.

The combination of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs), on the other hand, is relatively free from the risk of these overcorrection side effects. In the case of ARBs, the hormone angiotensin is not normally activated in the body, so blocking it with medication does not affect the body and is relatively safe. In the case of CCB, it helps to control blood pressure by blocking the calcium pathway and expanding blood vessels, just like adding lanes to a city road with heavy traffic congestion.

In other countries, it isn't easy to use the combination of these two drugs due to the cost of the drugs. However, thanks to the government's and pharmaceutical companies' efforts, the cost of drugs is relatively low in Korea, making it easy to use this combination. According to a hypertension fact sheet published by the Korean Society of Hypertension, the combination of ARBs and CCBs has overtaken the combination of ARBs and diuretics as the main combination therapy in recent years.

When I go to overseas conferences, I notice a lot of interest in hypertension management in Korea. Korea has one of the world's highest blood pressure control rates, and I think it is because ARB and CCB combinations are available at a low cost.

Q: Why is combination therapy more helpful than single agents?

A: Adherence drops by more than 10 percent with each additional medication. This means that doctors prescribe medications, but patients don't take them. When reducing medications, less important ones are removed from the prescription, and patients don't know which ones so that they may miss important ones. Another problem is splitting medications. When ARBs are halved, they remain 90 percent effective but last for a shorter period. This means they lose their effectiveness at 4 or 5 a.m., a time when many strokes occur, leaving you defenseless. Combination medications are preferred over single medications because of the increased risk associated with poor adherence.

Q: What is your opinion on the consideration of agents like diuretic chlorothalidone?

A: Chlorothalidone has the advantage of having a strong effect lasting 24 hours. However, as mentioned above, it has a strong sodium excretion effect, so there is a risk of overdose. When adding chlorothalidone, serum electrolyte levels should be checked in the first two weeks and periodically afterward. This drug can be maximally effective if you follow these steps. However, if this is difficult to manage, the risk of side effects is high.

Q: What are the potential advantages of releasing the combination therapy of irbesartan and amlodipine on the market?

A: Up to 90 percent of the effectiveness of antihypertensive medications is in lowering blood pressure. The blood pressure-lowering effect is responsible for 90 percent of a drug's benefit, and the remaining 10 percent is the difference between the blood pressure-lowering effect and other benefits. Aprovel, an ARB, is effective in protecting kidney, leading to treatment guidelines recommending ARBs in patients with poor renal function. The combination is also recommended for monotherapy, a strategy of switching from one drug to another. I think the biggest advantage of having a drug that can be used after Aprovel is that it expands the treatment options.

Q: If so, what are some considerations for prescribing this combination?

A: There are two things to consider. The first is kidney damage, and the second is left ventricular hypertrophy, a thickening of the heart. Patients with left ventricular hypertrophy can improve their symptoms by managing their blood pressure. Based on the evidence above of Aprovel's ability to protect the kidneys and manage left ventricular hypertrophy in patients with hypertension, we recommend Aprovel for patients with these two conditions. We may consider a combination if they fail to achieve blood pressure control with Aprovel.

Q: What advice do you have for patients managing hypertension throughout their lives?

A: As Korea is emerging as a nation with longevity, the Korean medical environment is very well equipped. Now, we should aim for a long, healthy life, not just a long life. Korea has a gap of more than nine years between healthy and actual life expectancy. This gap is due to stroke, myocardial infarction, and dementia. And the only preventive treatment for dementia is blood pressure control. Most patients start controlling their blood pressure between the ages of five and 60 when the blood vessels break down in the 40s and 50s.

Koreans are now experiencing an explosive increase in aortic valve stenosis and atrial fibrillation, both of which are caused by high blood pressure. The difference in blood pressure health is made in the 40s and 50s, so the Korean Society of Hypertension will try to treat young hypertensive patients quickly.