Which diuretic for which hypertensive patient?

We have read with great interest the editorial by Mishra. Diuretics represent a heterogeneous class of drugs, differing from each other by structure, site and mechanism of action. They are largely prescribed in different cardiovascular diseases, particularly in hypertension and heart failure. However, despite the available data on their efficacy, diuretics are still underused in the management of hypertension.

Formerly, diuretics were considered to be one of the most potent antihypertensive treatments. Nowadays, after the onset of new efficient anti-hypertensive drugs, diuretics may be no longer considered the most privileged first-line strategy.2, 1 Indeed, most of the current guidelines downgraded the place of thiazide diuretics in the management of hypertension from the preferential initial therapy to one of the possible first-line alternatives among a large armamentarium of anti-hypertensive drugs.3, 4, 5, 6, 7

Interestingly, thiazide and thiazide like diuretics are those recommended as first-line strategy for primary hypertensive treatment in different guidelines.3, 4, 5, 6, 7 Thiazide and thiazide like diuretics neither have the same structure nor the same site of action, and that would explain the huge disparities concerning their efficiency and side effects. However, despite their differences, the recommendations generally do not favor any agent on the other.3, 4, 5, 6 Whereas, other types of diuretics are barely mentioned in different guidelines and thereby are ever more underutilized in daily practice.

Hence, although recommendations encouraged a treatment approach based on considering patient's characteristics, the majority of guidelines are based on evidence for drug classes rather than individual drugs.3, 4, 5, 6 Only NICE recommendations encourage when initiating or changing treatment, to prescribe a thiazide-like diuretic, such as chlorthalidone or indapamide in preference to a conventional thiazide diuretics.

For the above reasons, we should not think any more if patient with hypertension needs or not a diuretic. Indeed, a new question should arise in light: which diuretic for which patient?

Much evidence support the inferiority of hydrochlorothiazide compared to other thiazide like agents. In fact, hydrochlorothiazide duration of antihypertensive action is less than 24 h, while indapamide has even in the immediate release form, at least 24-h duration of action for blood pressure reduction.8, 9 In addition, a network analysis demonstrated that hydrochlorothiazide was less effective in preventing cardiovascular events as compared with chlorthalidone and the association hydrochlorothiazide-amiloride. Moreover, it is inferior to indapamide in improving endothelial function and longitudinal strain in patients with hypertension and diabetes. Hydrochlorothiazide is also inferior to spironolactone in improving coronary flow reserve.

Many authors suggest that indapamide is by far the most efficient and tolerable diuretic for hypertensive patients. Compared to hydrochlorothiazide, it was demonstrated to be more efficient in improving micro-albuminuria (in diabetics), reducing left ventricular mass index, inhibiting platelet aggregation, and reducing oxidative stress. Indapamide was also shown to reduce left ventricular hypertrophy more than enalapril.13, 14 Importantly, indapamide do not share with thiazide diuretics their adverse effects on lipid and glucide metabolism, thereby it can be safely prescribed in diabetic patients.

However, despite this strong evidence, one of the reasons explaining the huge disparities of thiazide/thiazide like diuretics prescription may be due to that chlorthalidone is only commercialized with atenolol and azilsartan. Likewise, indapamide is only combined with perindopril. The only advantages of hydrochlorothiazide seem to be its extensive availability in formulations with other classes of antihypertensive drugs and its low price.

Otherwise, while spironolactone did not show an appropriate evidence for reducing cardiovascular events in hypertensive patients, its place in reducing total mortality in advanced heart failure is well known. Moreover, its efficiency in resistant hypertension is well established. Similarly, eplerenone was shown to have greater impact on systolic blood pressure and to improve endothelial function in hypertensive patients with similar rates of hyperkalemia.17, 18

Finally, loop diuretics could be of benefit in case of chronic kidney disease with serum creatinine >1.5 mg/dL or eGFR <30 mL/min/1.73 m2. Their antihypertensive effect might be improved with nighttime administration.

To conclude, diuretics are efficient and quite safe antihypertensive drugs with several decades of clinical application. The concept to replace “one size fits all” (class effect) paradigm to a more tailored approach in prescribing diuretics seems to be rational and appropriate not only to increase their prescription by clinicians, but also to achieve better clinical outcome for patients.

Conflicts of interest

The authors have none to declare.