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 .
The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) Trial: Outcomes in Patients Receiving Monotherapy
In the main Valsartan Antihypertensive Long-Term Use Evaluation ( VALUE ) report , we investigated outcomes in 15 245 high-risk hypertensive subjects treated with valsartan- or amlodipine-based regimens .  In this report , we analyzed outcomes in 7080 patients ( 46.4 % ) who , at the end of the initial drug adjustment period ( 6 months ) , remained on monotherapy .  Baseline characteristics were similar in the  valsartan ( N=3263 ) and amlodipine ( N=3817 ) groups . Time on monotherapy was 3.2 years ( 78 % of treatment exposure time ) . The average in-trial blood pressure was similar in both groups . Event rates in the monotherapy group were 16 % to 39 % lower than in the main VALUE trial . In the first analysis , we censored patients when they discontinued monotherapy ( “ censored ” ) ; in the second , we counted events regardless of subsequent therapy ( intention-to-treat principle ) . We also assessed the impact of duration of monotherapy on outcomes . No difference was found in primary composite cardiac end points , strokes , myocardial infa rct ions , and all-cause deaths with both analyses . Heart failure in the valsartan group was lower both in the censored and intention-to-treat analyses ( hazard ratios : 0.63 , P=0.004 and 0.78 , P=0.045 , respectively ) . Longer duration of monotherapy amplified between-group differences in heart failure . New-onset diabetes was lower in the valsartan group with both analyses ( odds ratios : 0.78 , P=0.012 and 0.82 , P=0.034 ) . Thus , despite lower absolute event rates in monotherapy patients , the relative risks of heart failure and new-onset diabetes favored valsartan . Moreover , these findings support the feasibility of comparative prospect i ve trials in lower-risk hypertensive patients
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 .