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 .
Antihypertensive pharmacogenetic effect of fibrinogen-beta variant −455G>A on cardiovascular disease, end-stage renal disease, and mortality: the GenHAT study
Objective The FGB gene codes for fibrinogen-&bgr ; , a polypeptide of the coagulation factor fibrinogen , which is positively associated with cardiovascular diseases . Studies show that angiotensin-converting enzyme ( ACE ) inhibitors lower plasma fibrinogen concentrations , whereas diuretics and calcium-channel blockers do not . As carriers of the FGB-455 minor ‘ A ’ allele have higher levels of fibrinogen while ACE inhibitors lower it , we hypothesize that ‘ A ’ allele carriers benefit more from antihypertensive treatment with ACE inhibitors than calcium-channel blockers or diuretics , relative to ‘ GG ’ genotype individuals . Methods The Genetics of Hypertension Associated Treatment ( GenHAT ) study [ ancillary to Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) ] genotyped hypertensive participants for several hypertension-related c and i date genes , making this a post-hoc analysis of a r and omized trial . In total , 90.1 % of the ALLHAT population was successfully genotyped for FGB-455 . We included participants ( n=30 076 ) r and omized to one of three antihypertensive medications ( lisinopril , amlodipine , chlorthalidone )  , with two treatment comparisons : lisinopril versus chlorthalidone and lisinopril versus amlodipine . The primary outcome of ALLHAT/GenHAT was coronary heart disease , defined as fatal coronary heart disease or non-fatal myocardial infa rct ion , and secondary outcomes included stroke , heart failure , all-cause mortality , and end-stage renal disease ( ESRD ) with mean follow-up time of 4.9 years . Genotype-by-treatment interactions ( pharmacogenetic effects ) were tested with the Cox regression . Results Stroke : common ‘ GG ’ homozygotes had higher risk on lisinopril versus amlodipine [ hazard ratio (HR)=1.38 , P<0.001 ] , whereas minor ‘ A ’ allele carriers had slightly lower risk ( HR=0.96 , P=0.76 ; P value for interaction=0.03 ) . Mortality : ‘ GG ’ homozygotes had higher risk on lisinopril versus amlodipine ( HR=1.12 , P=0.02 ) or chlorthalidone ( 1.05 , P=0.23 ) , whereas ‘ A ’ allele carriers had slightly lower risk ( HR=0.92 , P=0.33 for lisinopril versus amlodipine ; HR=0.88 , P=0.08 for lisinopril versus chlorthalidone ; P value for interactions 0.04 and 0.03 , respectively ) . ESRD : ‘ GG ’ homozygotes had higher risk on lisinopril versus chlorthalidone ( HR=1.27 , P=0.08 ) , whereas ‘ A ’ allele carriers had lower risk ( HR=0.64 , P=0.12 ; P value for interaction=0.03 ) . Conclusion There was evidence of pharmacogenetic effects of FGB-455 on stroke , ESRD , and mortality , suggesting that relative to those homozygous for the common allele , variant allele carriers of the FGB gene at position −455 have a better outcome if r and omized to lisinopril than chlorthalidone ( for mortality and ESRD ) or amlodipine ( for mortality and stroke ) . For the models in which a pharmacogenetic effect was observed , the outcome rates among ‘ GG ’ homozygotes were higher in those r and omized to lisinopril versus amlodipine or chlorthalidone , whereas minor ‘ A ’ allele carriers had lower event rates when r and omized to lisinopril versus the other medications
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 .