We found predominantly moderate quality evidence that all-cause mortality is similar when first-line RAS inhibitors are compared to other first-line antihypertensive agents .
First-line thiazides caused less HF and stroke than first-line RAS inhibitors .
Compared with first-line CCBs , first-line RAS inhibitors reduced HF but increased stroke .
The magnitude of the reduction in HF exceeded the increase in stroke .
The small differences in effect on blood pressure between the different classes of drugs did not correlate with the differences in the primary outcomes
BACKGROUND Renin-angiotensin system ( RAS ) inhibitors are widely prescribed for treatment of hypertension , especially for diabetic patients on the basis of postulated advantages for the reduction of diabetic nephropathy and cardiovascular morbidity and mortality .
Despite widespread use of angiotensin converting enzyme ( ACE ) inhibitors and angiotensin receptor blockers ( ARBs ) for hypertension in both diabetic and non-diabetic patients , the efficacy and safety of RAS inhibitors compared to other antihypertensive drug classes remains unclear .
OBJECTIVES To evaluate the benefits and harms of first-line RAS inhibitors compared to other first-line antihypertensive drugs in patients with hypertension .
Mortality and morbidity during and after the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
A r and omized , double-blind , active-controlled , multicenter trial assigned 32,804 participants aged 55 years and older with hypertension and ≥ 1 other coronary heart disease risk factors to receive chlorthalidone ( n=15,002 ) , amlodipine ( n=8898 ) , or lisinopril ( n=8904 ) for 4 to 8 years , when double-blinded therapy was discontinued . Passive surveillance continued for a total follow-up of 8 to 13 years using national administrative data bases to ascertain deaths and hospitalizations . During the post-trial period , fatal outcomes and nonfatal outcomes were available for 98 % and 65 % of participants , respectively , due to lack of access to administrative data bases for the remainder . This paper assesses whether mortality and morbidity differences persisted or new differences developed during the extended follow-up . Primary outcome was cardiovascular mortality and secondary outcomes were mortality , stroke , coronary heart disease , heart failure , cardiovascular disease , and end-stage renal disease . For the post-trial period , data are not available on medications or blood pressure levels . No significant differences ( P<.05 ) appeared in cardiovascular mortality for amlodipine ( hazard ratio [ HR ] , 1.00 ; 95 % confidence interval [ CI ] , 0.93 - 1.06 ) or lisinopril ( HR , 0.97 ; CI , 0.90 - 1.03 ) , each compared with chlorthalidone . The only significant differences in secondary outcomes were for heart failure , which was higher with amlodipine ( HR , 1.12 ; CI , 1.02 - 1.22 ) , and stroke mortality , which was higher with lisinopril ( HR , 1.20 ; CI , 1.01 - 1.41 ) , each compared with chlorthalidone . Similar to the previously reported in-trial result , there was a significant treatment-by-race interaction for cardiovascular disease for lisinopril vs chlorthalidone .  Black participants had higher risk than non-black participants  taking lisinopril compared with chlorthalidone . After accounting for multiple comparisons , none of these results were significant . These findings suggest that neither calcium channel blockers nor angiotensin-converting enzyme inhibitors are superior to diuretics for the long-term prevention of major cardiovascular complications of hypertension
We found predominantly moderate quality evidence that all-cause mortality is similar when first-line RAS inhibitors are compared to other first-line antihypertensive agents .
First-line thiazides caused less HF and stroke than first-line RAS inhibitors .
Compared with first-line CCBs , first-line RAS inhibitors reduced HF but increased stroke .
The magnitude of the reduction in HF exceeded the increase in stroke .
The small differences in effect on blood pressure between the different classes of drugs did not correlate with the differences in the primary outcomes
BACKGROUND Renin-angiotensin system ( RAS ) inhibitors are widely prescribed for treatment of hypertension , especially for diabetic patients on the basis of postulated advantages for the reduction of diabetic nephropathy and cardiovascular morbidity and mortality .
Despite widespread use of angiotensin converting enzyme ( ACE ) inhibitors and angiotensin receptor blockers ( ARBs ) for hypertension in both diabetic and non-diabetic patients , the efficacy and safety of RAS inhibitors compared to other antihypertensive drug classes remains unclear .
OBJECTIVES To evaluate the benefits and harms of first-line RAS inhibitors compared to other first-line antihypertensive drugs in patients with hypertension .