Thiazides (Water Pills): Best Initial Treatment for High Blood Pressure, Study Finds

High blood pressure, or hypertension, affects an estimated 108 million adult Americans.[1] It is critical to control blood pressure to prevent or minimize its long-term complications, including heart disease, stroke and chronic kidney disease.

For initial therapy, the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for blood pressure treatment recommend the use of any oral medication from four main classes of antihypertensive (blood-pressure lowering) drugs.[2] These medication classes are thiazide or thiazide-like diuretics (known as water pills, such as chlorthalidone [generic only], hydrochlorothiazide [MICROZIDE], indapamide [generic only] and metolazone [ZAROXOLYN]), angiotensin-converting enzyme (ACE) inhibitors (such as captopril [generic only]), angiotensin receptor blockers (ARBs) (such as losartan [COZAAR]) and calcium channel blockers. Calcium channel blockers are divided into two categories: dihydropyridines (such as amlodipine [KATERZIA, NORVASC]) and nondihydropyridines (such as diltiazem [CARDIZEM, CARTIA XT, DILTZAC, TAZTIA XT]).

The ACC/AHA guidelines were based on evidence from randomized clinical trials, which compared a few individual drugs, rather than drug classes, with each other.

A recent very large observational study that addressed this gap showed that thiazides or thiazide-like diuretics appear to be the most effective and safest medications for initial treatment of hypertension. The study was published in the Nov. 16, 2019, issue of the Lancet and was partially funded with federal funding from Australia, the U.S. and South Korea.

The new Lancet study[3]

Using several administrative health insurance claims and electronic health record databases from the U.S., Germany, Japan and South Korea, the study researchers identified 4.9 million patients who initiated therapy with a single antihypertensive medication from July 1996 to March 2018 and had no evidence of using any blood pressure medications in the prior year.

The researchers found that the most commonly initiated medication class was ACE inhibitors (48%), followed by calcium channel blockers (19%), thiazide or thiazide-like diuretics (17%) and ARBs (15%). They compared these medication classes with respect to their effectiveness and safety after a median follow-up of at least two years for most of the databases, using sophisticated statistical analysis to adjust for observable differences (such as demographic characteristics, previous conditions and intake of other medications) between patients.

The researchers found that when patients remained on their initial antihypertensive drug, thiazide or thiazide-like diuretics were associated with approximately 15% lower rates of the study’s primary endpoints (acute heart attack, hospitalization for heart failure, and stroke) than ACE inhibitors. Thiazide or thiazide-like diuretics also were associated with lower rates of these endpoints than nondihydropyridine calcium channel blockers, but the rates for these diuretics did not differ from those for either dihydropyridine calcium channel blockers or ARBs.

In addition, thiazides or thiazide-like diuretics generally had a more favorable overall safety profile than all other antihypertensive drug classes based on an assessment of 46 adverse safety outcomes. Most notably, ACE inhibitors were associated with higher risk of death, angioedema (an allergic reaction characterized by swelling of the skin and mucus membranes), cough, transient ischemic attack (brief stroke-like symptoms), hyperkalemia (high blood levels of potassium), hypotension (low blood pressure), dementia and kidney disease than were thiazide or thiazide-like diuretics.

However, compared with other drug classes, thiazide or thiazide-like diuretics were associated with a higher risk of electrolyte imbalances: hypokalemia (low blood levels of potassium) and hyponatremia (low blood levels of sodium). Although potentially serious, hypokalemia and hyponatremia can be detected with routine blood tests and easily managed: Hypokalemia is managed by increasing the intake of potassium-rich foods and hyponatremia is managed by restricting water intake.

The researchers estimated that if the new users of ACE inhibitors in this study (2.4 million) had instead been started on a thiazide or thiazide-like diuretic, more than 3,100 major cardiovascular events (including heart attacks and strokes) potentially could have been avoided.

Notably, Public Citizen’s Health Research Group has previously recommended that thiazide-type diuretics generally should be the initial therapy for hypertensive patients (except those with chronic kidney disease) because of their superior ability to prevent acute heart failure events.[4]

What You Can Do

If you are newly diagnosed with high blood pressure and have no other medical conditions (such as diabetes or high cholesterol), you should try lifestyle modification first — reducing salt intake in your diet and exercising more. If these changes do not work and antihypertensive therapy is necessary, talk with your doctor about taking a low-dose thiazide or thiazide-like diuretic as a first-line treatment. During treatment with thiazide or thiazide-like diuretics, it is important that you monitor for signs of hypokalemia (including irregular pulse rate, palpitations and weakness) and hyponatremia (including abdominal pain, vomiting, dizziness and weakness) and undergo blood work before and after initiation of thiazide therapy to monitor your levels of sodium and potassium. If you develop these electrolyte imbalances while taking a certain thiazide drug, consult your doctor regarding switching to another thiazide because there is evidence that the risk of these adverse effects can vary across different thiazides.[5]

If you have diabetes, kidney disease or certain other conditions, you may need to take an ACE inhibitor, ARB or calcium channel blocker to manage your high blood pressure. Discuss these options with your doctor.
 

References

[1] Centers for Disease Control and Prevention. Facts about hypertension. January 28, 2020. https://www.cdc.gov/bloodpressure/facts.htm. Accessed March 4, 2020.

[2] Whelton PK, Carey RM, Aronow WS, et al. 2017 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: Executive summary. A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018;138(17):e426-e483.

[3] Suchard MA, Schuemie MJ, Krumholz HM, et al. Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis. Lancet. 2019;394(10211):1816-1826. >

[4] New blood pressure treatment guidelines released. Worst Pills, Best Pills News. September 2014. /newsletters/view/918. Accessed March 5, 2020.

[5] Hripcsak G, Suchard MA, Shea S, et al. Comparison of cardiovascular and safety outcomes of chlorthalidone vs hydrochlorothiazide to treat hypertension. JAMA Intern Med. doi:10.1001/jamainternmed.2019.7454. [published online ahead of print February 17, 2020]