First-line low-dose thiazides reduce all morbidity and mortality outcomes .
First-line ACE inhibitors and calcium channel blockers may be similarly effective but the evidence is less robust .
First-line high-dose thiazides and first-line beta-blockers are inferior to first-line low-dose thiazides
BACKGROUND Sustained elevated blood pressure , unresponsive to lifestyle measures , leads to a critically important clinical question : What class of drug to use first-line ?
This review answers that question .
OBJECTIVES PRIMARY OBJECTIVE To quantify the benefits and harms of the major first-line anti-hypertensive drug classes : thiazides , beta-blockers , calcium channel blockers , angiotensin converting enzyme ( ACE ) inhibitors , alpha-blockers , and angiotensin II receptor blockers ( ARB ) .
Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study
Abstract Objective : To compare the effectiveness and tolerability of hydrochlorothiazide , atenolol , nitrendipine , and enalapril in patients with mild to moderate hypertension . Design : R and omised multicentre trial over 48 weeks with double blind comparison of treatments . Setting : 48 centres in four countries . Patients : 868 patients with essential hypertension ( diastolic blood pressure 95 - 120 mm Hg ) Interventions : Initial treatment ( step 1 ) consisted of 12.5 mg hydrochlorothiazide ( n=215 ) , 25 mg atenolol ( n=215 ) , 10 mg nitrendipine ( n=218 ) , or 5 mg enalapril ( n=220 ) once daily . If diastolic blood pressure was not reduced to < 90 mm Hg within four weeks , doses were increased to 25 mg , 50 mg , 20 mg , 10 mg , respectively , once daily ( step 2 ) and after two more weeks to twice daily ( step 3 ) . The eight week titration phase was followed by an additional 40 weeks for patients who had reached the target diastolic pressure . Main outcome measure : Blood pressure by means of an automatic device with repeated measurements . Results : After eight weeks the response rate for  atenolol  ( 63.7 % ) was significantly higher than for enalapril ( 50.0 % ) , hydrochlorothiazide ( 44.7 % ) , or nitrendipine ( 44.5 % ) . After one year atenolol was still more effective ( 48.0 % ) than hydrochlorothiazide ( 35.4 % ) and nitrendipine ( 32.9 % ) , but not significantly better than enalapril ( 42.7 % ) . The treatment related dropout rate was higher ( P<0.001 ) in the nitrendipine group ( n=28 ) . Conclusions : There is no evidence of superiority for antihypertensive effectiveness or tolerability of the “ new ” classes of antihypertensives ( calcium channel blockers and angiotensin converting enzyme inhibitors ) . As these drugs are now widely used as treatment of first choice , our results further emphasise the need for studies confirming that they also reduce morbidity and mortality , as has been shown for diuretics and ß blockers . Key messages Calcium channel blockers and angiotensin converting enzyme inhibitors as initial monotherapy in the treatment of hypertension Reduction in mortality has been shown only with established ß blockers and diuretics Comparison of treatment with hydrochlorothiazide , atenolol , nitrendipine , and enalapril showed no superiority of the new drug classes Atenolol was the most effective drug , while nitrendipine showed the highest drop out rat  Elderly patients  respond better to hydrochlorothiazide and nitrendipine , and women better to enalapril , although in both subgroups the highest rate of response was with
First-line low-dose thiazides reduce all morbidity and mortality outcomes .
First-line ACE inhibitors and calcium channel blockers may be similarly effective but the evidence is less robust .
First-line high-dose thiazides and first-line beta-blockers are inferior to first-line low-dose thiazides
BACKGROUND Sustained elevated blood pressure , unresponsive to lifestyle measures , leads to a critically important clinical question : What class of drug to use first-line ?
This review answers that question .
OBJECTIVES PRIMARY OBJECTIVE To quantify the benefits and harms of the major first-line anti-hypertensive drug classes : thiazides , beta-blockers , calcium channel blockers , angiotensin converting enzyme ( ACE ) inhibitors , alpha-blockers , and angiotensin II receptor blockers ( ARB ) .