Indications for Combination Therapy
Summary: For Grade 2 high-risk patients (see hypertension grading for details), start directly with two-drug combination therapy; for less severe cases, combine as appropriate. If the two-drug combination is ineffective, gradually increase dosage or add drug types.
Patients with Grade 2 or higher hypertension (≥160/100 mmHg), cardiovascular high or very high risk with blood pressure exceeding target by 20/10 mmHg, can initiate treatment with two antihypertensive drugs. Patients with Grade 1 hypertension may also consider initial treatment with low-dose combination therapy. If target blood pressure is not reached, increase dosage on original low doses or add a third or even fourth antihypertensive drug.
Methods of Combination Therapy
Summary: Combine different types
, avoid combining the same type but different drugs
(For mechanisms of different types of antihypertensive drugs, see 
https://forum.beginner.center/t/topic/2098 )
When combining two drugs, their antihypertensive mechanisms should be complementary, providing additive blood pressure reduction while offsetting or alleviating adverse reactions. For example, adding a low dose of thiazide diuretics to ACEI or ARB therapy can achieve blood pressure reduction equal to or greater than doubling the ACEI or ARB dose. ACEI or ARB combined with dihydropyridine CCB also shows similar effects.
Combination Regimens of Two Drugs
Summary:
- ACEI/ARB (potassium-increasing) + diuretics (potassium-decreasing)
- ACEI/ARB (vasodilation of arteries and veins) + CCB (arterial vasodilation)
- CCB + diuretics: reduce stroke risk (Don’t all antihypertensives lower blood pressure and thus reduce stroke risk? What is special about this combination?)
- CCB (vasodilation increasing heart rate) + β-blockers (vasoconstriction decreasing heart rate)
① ACEI or ARB + thiazide diuretics: ACEI and ARB may slightly increase blood potassium levels and antagonize adverse effects such as hypokalemia caused by long-term use of thiazide diuretics. This combination has synergistic effects and enhances blood pressure reduction.
② Dihydropyridine CCB + ACEI or ARB: CCB directly dilates arterial vessels; ACEI or ARB dilate both small arteries and veins, resulting in synergistic antihypertensive effects. Dihydropyridine CCB often causes ankle edema, which ACEI or ARB can alleviate or counteract. The Chinese Hypertension Intervention Efficacy Study (CHIEF) showed that low-dose long-acting dihydropyridine CCB + ARB initial treatment significantly improves blood pressure control rates.
③ Dihydropyridine CCB + thiazide diuretics: The FEVER study confirmed that this combination reduces the risk of stroke in hypertensive patients.
④ CCB + β-blockers: Dihydropyridine CCB dilates blood vessels and mildly increases heart rate, counteracting β-blockers’ vasoconstriction and heart rate slowing effects. Combined use reduces adverse effects.
Fixed-dose combination preparations composed of these drugs should have complementary antihypertensive mechanisms, additive effects, and mutual mitigation of adverse reactions.
Combination Regimens of Three Drugs
Summary: CCB + ACEI/ARB + diuretics are most commonly used (Mechanism? Why are these three the most used?)
Adding another antihypertensive drug to the above two-drug combinations forms a three-drug regimen. The most common is the combination of dihydropyridine CCB + ACEI (or ARB) + thiazide diuretics.
Combination Regimens of Four Drugs
Summary: When blood pressure cannot be controlled, use all
Mainly for resistant hypertension patients, a fourth drug can be added on the basis of the above three-drug regimen, such as β-blockers, aldosterone receptor antagonists, aliskiren, clonidine, or α-blockers.
SPC (Single-Pill Combination)
Summary: A convenience package for combination therapy
SPC: An effective means of implementing combined antihypertensive treatment. Usually composed of two or more antihypertensive drugs with different mechanisms of action. Compared with random combination therapy, it offers convenience, improves treatment adherence, and enhances antihypertensive efficacy. Attention should be paid to contraindications and possible adverse reactions of each component during use.
New SPCs: Generally composed of 2 or 3 antihypertensive drugs with different mechanisms of action, mostly taken once daily. They improve adherence. Currently marketed new SPCs in China mainly include: ACEI + thiazide diuretics, ARB + thiazide diuretics; dihydropyridine CCB + ARB, dihydropyridine CCB + ACEI, dihydropyridine CCB + β-blockers, thiazide diuretics + potassium-sparing diuretics, etc.
Traditional SPCs in China: Include compound reserpine (compound antihypertensive tablets), compound reserpine aliskiren tablets, Zhenju antihypertensive tablets, etc., mainly composed of commonly used reserpine, hydrochlorothiazide, hydralazine hydrochloride, or clonidine at the time. These compound preparations are still widely used, especially the long-acting compound reserpine aliskiren tablets.
References
Chinese Hypertension Prevention and Treatment Guidelines Revision Committee, Hypertension Alliance (China), Hypertension Branch of China International Exchange and Promotive Association for Medical and Health Care, et al. Chinese Hypertension Prevention and Treatment Guidelines (2024 Revised Edition) [J]. Chinese Journal of Hypertension, 2024, 32(7): 603-700. DOI:10.16439/j.issn.1673-7245.2024.07.002.