Thiazide and Thiazide-like Diuretics reduce morbidity outcomes and withdrawal symptoms in Hypertension

New research revealed that Thiazide and thiazide-like drugs reduced cardiovascular events, morbidity outcomes, and withdrawal due to various adverse effects compared to beta‐blockers, calcium channel blockers, ACE inhibitors, and alpha‐blockers. The study was published in the journal Cochrane Database of Systematic Reviews. 

Different first-line medication classes for patients with hypertension are frequently thought to have comparable efficacy in lowering blood pressure and reducing mortality and morbidity outcomes. When compared to a placebo or no treatment, first-line low-dose thiazide diuretics have previously been proven to have the best mortality and morbidity evidence. So, researchers compared Thiazides and other blood pressure-lowering medication classes side by side to see whether there were any significant differences. The effects of thiazide-diuretic drugs were compared with other classes of antihypertensive drugs on mortality, morbidity, and withdrawals due to adverse effects in patients with hypertension. 

The information specialist for Cochrane Hypertension looked through the trial registers, CENTRAL, MEDLINE, and Embase up until March 2021. To find other research, references and contacted study authors were also checked. In June 2022, a top-up search of the Specialised Register was conducted. Randomized active comparison trials that lasted at least a year were included. A first-line diuretic (thiazide, thiazide-like, or loop diuretic) was compared to another first-line drug class in clinical trials, such as beta-blockers, calcium channel blockers, alpha-adrenergic blockers, angiotensin II receptor blockers, direct renin inhibitors, or other antihypertensive drug classes. The following mortality and morbidity outcomes were measured in studies:

• Significant adverse events,
• Total cardiovascular events,
• Stroke, coronary heart disease (CHD),
• Congestive heart failure, and
• Withdrawals due to ill effects. 

Key findings: 

• Nearly twenty trials with twenty-six comparator arms randomizing over 90,000 participants having older male and female hypertensive patients (aged 50 to 75) with multiple co‐morbidities, including type 2 diabetes were included. 
• There was little to no difference in total mortality and stroke between first-line thiazide and first‐line beta‐blockers, first‐line calcium channel blockers, and first‐line ACE inhibitors and first‐line alpha‐blockers. 
• There was a reduction in total cardiovascular events and withdrawals due to adverse effects in the first-line thiazide group compared to first‐line beta‐blockers. 
• There was a decrease in total cardiovascular events, heart failure, and withdrawals due to the adverse effects of first-line thiazide compared to first‐line calcium channel blockers.
• When compared to the first‐line ACE inhibitors, there were reductions in stroke, withdrawals due to adverse effects in the first-line thiazide group. 
• There was a reduction in total cardiovascular events, stroke, and withdrawals due to adverse effects in the first-line thiazide group when compared to first‐line alpha‐blockers. 

Thus, in comparison to first-line thiazides, no antihypertensive medication class has shown any clinically significant advantages. 

Further reading: First‐line diuretics versus other classes of antihypertensive drugs for hypertension. https://doi.org/10.1002/14651858.CD008161.pub3