ARB antihypertensive drugs: Understanding their multiple protective benefits for the heart, brain, and kidneys.

What are the advantages of angiotensin receptor blockers (ARBs)?

Angiotensin receptor blockers (ARBs) can be considered similar to ACEIs because they act on the AT2 receptor, the receptor for angiotensin II. ARBs competitively bind to the AT2 receptor, making it difficult for angiotensin II to exert its effects. Since ARBs completely inhibit the RAAS (renin-angiotensin-aldosterone system), they have stable efficacy, good tolerability, and few adverse reactions. The US JNC7, European, and Chinese guidelines for hypertension prevention and treatment all list these drugs as initial and maintenance medications for hypertension. Their indications and contraindications are similar to those of ACEIs. Because ARBs do not affect bradykinin metabolism, they do not cause the cough associated with ACEIs. Therefore, some even call ARBs "ACEIs without cough."

ARBs have excellent cardioprotective, renal, and vascular protective effects. In hypertension studies, ARBs can reduce cardiovascular events, mortality, and stroke, while also reducing left ventricular hypertrophy and the incidence of atrial fibrillation and heart failure. Regarding renal protection, ARBs can reduce microalbuminuria and have a long-term protective effect. In type 2 diabetes, they can improve insulin resistance and reduce cardiovascular events. They can also reduce the number of new-onset diabetes cases in hypertensive patients.

However, in the primary and secondary prevention of heart failure and coronary artery disease, the overall efficacy of ARBs is similar to or inferior to that of ACEIs. Therefore, relevant guidelines in Europe and the United States consider ACEIs to be the first-line and cornerstone of treatment for heart failure, acute myocardial infarction, and post-infarction.

What are the differences between several ARB drugs?

Although these drugs have different half-lives, because they bind to receptors, once-daily administration can achieve or exceed 24 hours of effect. However, due to different development and market launch times, those launched later seem to be more effective than those launched earlier.

(1) Losartan was the first drug to be marketed, and its binding to the receptor is the weakest; followed by valsartan. Irbesartan's receptor affinity is 10 times that of losartan, while candesartan's is 50-80 times that of losartan, exhibiting the highest receptor binding affinity. Candesartan and telmisartan have the slowest dissociation rates from their receptors.

(2) A meta-analysis has shown that among the five drugs—losartan, valsartan, irbesartan, telmisartan, and candesartan—valsartan has the smallest average reduction in both systolic and diastolic blood pressure. Irbesartan and telmisartan may be more effective than losartan and valsartan.

(3) The antihypertensive efficacy of losartan at 80 mg/day is comparable to that of enalapril at 20 mg/day and amlodipine at 5 mg/day.

(4) In controlling morning blood pressure spikes, telmisartan provides the best control, followed by amlodipine and valsartan. (5) Irbesartan is effective in improving insulin sensitivity and glucose metabolism in diabetic patients with metabolic syndrome. Telmisartan appears to be even better.

ARBs, except for not causing irritating cough, have the same adverse reactions as ACEIs, such as possible hyperkalemia, transient increase in creatinine, and decrease in blood pressure.

Contraindications are also present in bilateral renal artery stenosis, hyperkalemia, and gestational hypertension.