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 .
Pharmacogenetic Association of NOS3 Variants with Cardiovascular Disease in Patients with Hypertension: The GenHAT Study
Nitric oxide synthase 3 ( NOS3 ) catalyzes production of NO in the endothelium and may play a role in cardiovascular disease ( CVD ) . We assessed the pharmacogenetic associations of three NOS3 polymorphisms and three antihypertensive drugs with CVD outcomes . Hypertensive subjects ( n = 30,280 ) from a multi-center , double-blind clinical trial were r and omized to chlorthalidone , amlodipine , or lisinopril treatment ( mean follow up , 4.9 years ) . Outcomes included coronary heart disease ( CHD : fatal CHD and nonfatal myocardial infa rct ion ) ; stroke ; heart failure ( fatal , requiring hospitalization , or outpatient treatment ) ; all-cause mortality ; and end-stage renal disease ( ESRD ) . Main effects of NOS3 variants on outcome and genotype-treatment interactions were tested . For NOS3 −690 C > T ( rs3918226 ) , a higher hazard ratio ( HR ) was found in minor allele carriers for CHD ( CC = 1.00 , CT+TT = 1.12 ( 95 % confidence interval ( CI ) = 1.00–1.26 ) , P = 0.048 ) . For NOS3 −922 A > G ( rs1800779 ) , a higher HR was found in minor allele carriers for heart failure ( AA = 1.00 , AG+GG = 1.10 ( CI = 1.00–1.21 ) , P = 0.046 ) . Significant pharmacogenetic findings were observed for stroke and all-cause mortality . For −690 C > T , a lower HR was observed for stroke in minor allele carriers when treated with amlodipine versus lisinopril ( CC = 0.85 ( CI = 0.73–0.99 ) , CT+TT = 0.49 ( CI = 0.31–0.80 ) , P = 0.04 ) . For glu298asp G > T ( rs1799983 ) , a lower HR was observed for all-cause mortality in minor allele carriers when treated with amlodipine versus lisinopril ( GG = 1.01 ( CI = 0.91–1.13 ) , GT+TT = 0.85 ( CI = 0.75–0.97 ) , P = 0.04 ) . We observed significant associations with NOS3 variants and CHD and heart failure and significant pharmacogenetic effects for stroke and all cause mortality . This suggests that NOS3 variants may potentially provide useful clinical information with respect to treatment decisions in the future
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 .