What antihypertensive (anti-hypertensive) medication has the least reported adverse effects?

From the Guidelines

Angiotensin II receptor blockers (ARBs) like losartan, valsartan, and olmesartan generally have the least reported side effects among antihypertensive medications. Typically started at lower doses (such as losartan 25-50 mg daily), these medications can be titrated upward as needed for blood pressure control. ARBs work by blocking the hormone angiotensin II from binding to receptors in blood vessels, allowing them to relax and widen, which lowers blood pressure. Their favorable side effect profile stems from their selective mechanism of action, which avoids many of the adverse effects seen with other antihypertensives. Unlike ACE inhibitors, ARBs rarely cause cough or angioedema 1. They also don't cause the fatigue, depression, or sexual dysfunction sometimes associated with beta-blockers, or the electrolyte disturbances and metabolic effects seen with diuretics. However, no antihypertensive is completely free of side effects - ARBs can occasionally cause dizziness, elevated potassium levels, and are contraindicated during pregnancy. The best medication choice should always be individualized based on a patient's specific health conditions, age, other medications, and comorbidities.

Some key points to consider when choosing an antihypertensive medication include:

• The patient's specific health conditions, such as kidney disease or heart failure
• The presence of other medications that may interact with the antihypertensive
• The patient's age and comorbidities
• The potential side effects of the medication, such as dizziness or elevated potassium levels

According to the 2018 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults, ARBs are a suitable choice for the initiation and maintenance of antihypertensive treatment 1. The 2013 ESH/ESC guidelines for the management of arterial hypertension also support the use of ARBs as a first-line treatment option 1.

It's worth noting that while ARBs have a favorable side effect profile, they may not be suitable for all patients. For example, patients with a history of angioedema or those who are pregnant or breastfeeding may need to avoid ARBs. In these cases, alternative antihypertensive medications may be necessary. Ultimately, the choice of antihypertensive medication should be based on a thorough evaluation of the patient's individual needs and health status.

From the FDA Drug Label

In controlled clinical trials directly comparing amlodipine (N=1730) at doses up to 10 mg to placebo (N=1250), discontinuation of amlodipine because of adverse reactions was required in only about 1. 5% of patients and was not significantly different from placebo (about 1%). In controlled clinical trials, discontinuation of therapy for adverse events occurred in 2. 3% of patients treated with losartan and 3. 7% of patients given placebo.

Comparison of Adverse Effects:

• Amlodipine: 1.5% discontinuation due to adverse reactions
• Losartan: 2.3% discontinuation due to adverse events
• Placebo: 1% (amlodipine study) and 3.7% (losartan study) discontinuation due to adverse events

Based on the provided information, amlodipine appears to have the least reported adverse effects, with a discontinuation rate of 1.5% due to adverse reactions, which is not significantly different from placebo (1%). However, it is essential to note that the evidence is not conclusive, and a conservative clinical decision would be to consult the FDA drug label and other reliable sources for the most up-to-date information. 2 2 3

From the Research

Antihypertensive Medications with Least Reported Adverse Effects

• Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, is well tolerated with few serious adverse effects being reported 4
• Thiazide diuretics, such as chlortalidone and hydrochlorothiazide, have been shown to have a similar adverse effect profile to other antihypertensive drugs, with the added risk of provoking hyperglycaemia and diabetes 5
• The combination of an ACE inhibitor and a calcium channel blocker has been suggested as an optimal combination for the treatment of hypertension, with a reduced probability of adverse effects related to the dose of antihypertensive 6
• The combination of losartan and hydrochlorothiazide has been shown to be effective and safe, with fewer adverse effects on uric acid and other metabolic parameters compared to diuretic monotherapy 7
• ACE inhibitors, such as lisinopril, have been found to have specific benefits in patients with diabetes, atherosclerosis, left ventricular dysfunction, and renal insufficiency, with a similar adverse effect profile to other antihypertensive drugs 8

Comparison of Antihypertensive Medications

• Lisinopril has been compared to other antihypertensive medications, including hydrochlorothiazide, atenolol, metoprolol, and nifedipine, and has been found to be at least as effective in lowering blood pressure 4
• Chlortalidone has been shown to be superior to lisinopril in preventing stroke, and to be more effective than amlodipine in preventing heart failure 5
• The combination of losartan and hydrochlorothiazide has been compared to the combination of candesartan and amlodipine, and has been found to be similarly effective in reducing blood pressure 7