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 .
Heart Failure With Preserved and Reduced Left Ventricular Ejection Fraction in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
Background — Heart failure ( HF ) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction ( PEF [ ≥50 % ] or REF [ < 50 % ] ) . In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , 42 418 high-risk hypertensive patients were r and omized to chlorthalidone , amlodipine , lisinopril , or doxazosin , providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF . Methods and Results — HF diagnostic criteria were prespecified in the ALLHAT protocol . EF estimated by contrast ventriculography , echocardiography , or radionuclide study was available in 910 of 1367 patients ( 66.6 % ) with hospitalized events meeting ALLHAT criteria . Cox regression models adjusted for baseline characteristics were used to examine treatment differences for HF ( overall and by PEF and REF ) . HF case fatality rates were examined . Of those with EF data , 44.4 % had HFPEF and 55.6 % had HFREF . Chlorthalidone reduced the risk of HFPEF compared with amlodipine , lisinopril , or doxazosin ; the hazard ratios were 0.69 ( 95 % confidence interval [ CI ] , 0.53 to 0.91 ; P=0.009 ) , 0.74 ( 95 % CI , 0.56 to 0.97 ; P=0.032 ) , and 0.53 ( 95 % CI , 0.38 to 0.73 ; P<0.001 ) , respectively . Chlorthalidone  reduced the risk of HFREF compared with amlodipine or doxazosin ; the hazard ratios were 0.74 ( 95 % CI , 0.59 to 0.94 ; P=0.013 ) and 0.61 ( 95 % CI , 0.47 to 0.79 ; P<0.001 ) , respectively . Chlorthalidone was similar to lisinopril with regard to incidence of HFREF ( hazard ratio , 1.07 ; 95 % CI , 0.82 to 1.40 ; P=0.596 ) . After HF onset , death occurred in 29.2 % of participants ( chlorthalidone/amlodipine/lisinopril ) with new-onset HFPEF versus 41.9 % in those with HFREF ( P<0.001 ; median follow-up , 1.74 years ) ; and in the chlorthalidone/doxazosin comparison that was terminated early , 20.0 % of HFPEF and 26.0 % of HFREF patients died ( P=0.185 ; median follow-up , 1.55 years ) . Conclusions — In ALLHAT , with adjudicated outcomes , chlorthalidone significantly reduced the occurrence of new-onset hospitalized HFPEF and HFREF compared with amlodipine and doxazosin . Chlorthalidone also reduced the incidence of new-onset HFPEF compared with lisinopril . Among high-risk hypertensive men and women , HFPEF has a better prognosis than HFREF
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 .