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 the NPPA T2238C genetic variant with cardiovascular disease outcomes in patients with hypertension.
CONTEXT The NPPA gene codes for the precursor of atrial natriuretic polypeptide , suggesting that NPPA may modulate the efficacy of some antihypertensive drugs . OBJECTIVE To test whether participants with minor NPPA alleles in the T2238C or G664A variants had different rates of cardiovascular disease or blood pressure (  BP ) changes than common allele homozygotes when treated with a diuretic vs other antihypertensive medications . DESIGN , SETTING , AND PATIENTS Post hoc analysis of 38,462 participants with hypertension from ALLHAT , a multicenter r and omized clinical trial conducted in the United States and Canada . Genotyping was performed from February 2004 to January 2005 . INTERVENTION Participants were r and omly assigned to receive a diuretic ( chlorthalidone ; n = 13,860 ) , a calcium antagonist ( amlodipine ; n = 8174 ) , an angiotensin-converting enzyme inhibitor ( lisinopril ; n = 8233 ) , or an alpha-blocker ( doxazosin ; n = 8195 ) . MAIN OUTCOME MEASURE The primary outcome measure was coronary heart disease ( CHD ) , defined as fatal CHD or nonfatal myocardial infa rct ion ( mean follow-up , 4.9 years ) . Secondary outcomes were stroke , all-cause mortality , combined cardiovascular disease outcomes , and 6-month systolic and diastolic BP changes . Genotype x treatment interactions were tested where genotypes were modeled additively and dominantly . RESULTS Depending on genotype , the event rates per 1000 person-years were 15.3 to 19.7 for CHO , 9.6 to 15.4 for stroke , and 27.4 to 30.7 for all-cause mortality . For the NPPA T2238C variant , lower event rates were found for the C allele carriers than for the TT homozygous individuals when comparing chlorthalidone and amlodipine ( CHD : CC = 0.86 ; TC = 0.90 ; TT = 1.09 ; P = .03 [ dominant model ] ; stroke : CC = 1.18 ; TC = 0.82 ; TT = 1.26 ; P = .01 [ additive and dominant models ] ; all-cause mortality : CC = 0.87 ; TC = 0.98 ; TT = 1.12 ; P = .05 [ dominant model ] ) . Combined end points yielded similar results . Consistent with these clinical findings , 6-month changes in systolic BP for those with the CC genotype showed larger reductions with chlorthalidone ( -6.5 mm Hg ) than with amlodipine ( -3.8 mm Hg ) , lisinopril ( -2.4 mm Hg ) , or doxazosin ( -3.8 mm Hg ) . Among those with the TT genotype , systolic BP differences between drugs were less ( range , -5.4 to -7.5 mm Hg ; P value , < .001 to .003 for interaction ) ; diastolic BP showed similar results . We found no pharmacogenetic associations with the NPPA G664A variant . CONCLUSIONS The NPPA T2238C variant was associated with modification of antihypertensive medication effects on cardiovascular disease and BP . Minor C allele carriers experienced more favorable cardiovascular disease outcomes when r and omized to receive a diuretic , whereas TT allele carriers had more favorable outcomes when r and omized to receive a calcium channel blocker
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 .