A prospective evaluation of persistence on antihypertensive treatment with different antihypertensive drugs in clinical practice South African hypertension guideline 2011. Antihypertensive medications and C-reactive protein in the multi-ethnic study of atherosclerosis. ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy. Genome-wide response to antihypertensive medication using home blood pressure measurements: a pilot study nested within the HOMED-BP study. Effect of different antihypertensive drug classes on central aortic pressure. Choices, persistence and adherence to antihypertensive agents: evidence from RAMQ data. Efficacy of various antihypertensive agents as evaluated by indices of vascular stiffness in elderly hypertensive patients. Effects of antihypertensive agents, alpha receptor blockers, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers, on oxidative stress 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). Background and design of the new U.S. trial on diet and drug treatment of "mild" hypertension (TOMHS). Long-Term Use of Angiotensin Receptor Blockers and the Risk of Cancer Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? Differences in antihypertensive drug persistence associated with drug class and gender: a PHARMO study. Effects of the Oral Direct Renin Inhibitor Aliskiren in Patients With Symptomatic Heart Failure Angiotensin-converting enzyme inhibitors and aortic rupture: a population-based case-control study Medical treatment of hypertension in Switzerland. The 2009 Swiss Hypertension Survey (SWISSHYPE). Renoprotective Effect and Cost-Effectiveness of Using Benidipine, a Calcium Channel Blocker, to Lower the Dose of Angiotensin Receptor Blocker in Hypertensive Patients with Albumiuria Angiotensin II Type 1 Receptor Blockers Reduce Urinary Oxidative Stress Markers in Hypertensive Diabetic Nephropathy Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure.
Persistence on treatment affects the efficacy of antihypertensive treatment . We prospect ively investigated the persistence on therapy and the extent of  blood pressure ( BP ) control  in 347 hypertensive patients ( age 59.4 ± 6 years ) r and omly allocated to a first-line treatment with : angiotensin-converting enzyme ( ACE ) inhibitors , calcium-channel blockers ( CCBs ) , ß-blockers , angiotensin-II receptor blockers ( ARBs ) , or diuretics and followed-up for 24-months . Persistence on treatment was higher in patients treated with ARBs ( 68.5 % ) and ACE inhibitors ( 64.5 % ) vs CCBs ( 51.6 % ; p < 0.05 ) , β-blockers ( 44.8 % , p < 0.05 ) , and diuretics ( 34.4 % , p < 0.01 ) . No ARB , ACE inhibitor , β-blocker , or diuretic was associated with a higher persistence in therapy compared with the other molecules used in each therapeutic class . The rate of persistence was significantly higher in patients treated with lercanidipine vs others CCBs ( 59.3 % vs 46.6 % , p < 0.05 ) . Systolic and diastolic BP was decreased more successfully in patients treated with ARBs ( −11.2/−5.8 mmHg ) , ACE inhibitors ( −10.5/−5.1 mmHg ) , and CCBs ( −8.5/−4.6 mmHg ) compared with ß-blockers ( −4.0/−2.3 mmHg p < 0.05 ) and diuretics ( −2.3/−2.1 mmHg , p < 0.05 ) . No ARB , ACE inhibitor , β-blocker , or diuretic was associated with a higher BP control compared with the other molecules used in each therapeutic class . A trend toward a better BP control was observed in response to lercanidipine vs other CCBs ( p = 0.059 ) . The present results confirm the importance of persistence on treatment for the management of hypertension in clinical practice OUTCOMES Extensive data from r and omised controlled trials have shown the benefit of treating hypertension . The target blood pressure ( BP ) for antihypertensive management is systolic < 140 mmHg and diastolic < 90 mmHg with minimal or no drug side-effects ; however , stricter BP control is required for patients with end-organ damage , co-existing risk factors and co-morbidity , e.g. diabetes mellitus . The reduction of BP in the elderly and in those with severe hypertension should be achieved gradually over 1 month . Co-existent risk factors should also be controlled . BENEFITS Benefits of management include reduced risks of stroke , cardiac failure , chronic kidney disease and coronary heart disease . RECOMMENDATIONS The correct BP measurement procedure is described , and evaluation of cardiovascular risk factors and recommendations for antihypertensive therapy are stipulated . The total cardiovascular disease risk profile should be determined for all patients to inform management strategies . Lifestyle modification and patient education are cornerstones in the management of every patient . Major indications , pre caution s and contra-indications to each recommended antihypertensive drug are listed . Combination therapy should be considered ab initio if the BP is ≥ 20/10 mmHg . First-line drug therapy for uncomplicated hypertension includes low-dose thiazide-like diuretics , calcium channel blockers ( CCBs ) or angiotensin-converting enzyme inhibitors ( ACE-Is ) ( or ARBs - angiotensin II receptor blockers ) . If the target BP is not obtained , a second antihypertensive should be added from the aforementioned list . If the target BP is still not met , the third remaining antihypertensive agent should be used . In black patients  either thiazide-like diuretics or CCBs can be used initially , because response rates are better than with ACE-Is or β-blockers . In treating resistant hypertension , a central ly acting drug , vasodilator , α-blocker , spironolactone or β-locker should be added . This guideline includes management of specific situations , i.e. hypertensive emergency and urgency , severe hypertension with target organ damage , hypertension in diabetes mellitus , resistant hypertension , fixed drug combinations , new trials in hypertension , and interactions of antihypertensive agents with other drugs . VALIDITY The guideline was developed by the Southern African Hypertension Society BACKGROUND The effects of different antihypertensive medication classes on C-reactive protein ( CRP ) levels are still not well characterized , and might be of relevance to treatment choices . METHODS We studied the association between antihypertensive medication class and CRP levels among participants with treated hypertension in the Multi-Ethnic Study of Atherosclerosis . We performed a cross-sectional study of hypertensive participants free of clinical cardiovascular disease who were taking one or more of the following medication classes : beta-blockers , calcium channel blockers , diuretics , and angiotensin-converting enzyme ( ACE ) inhibitors , or angiotensin II type I receptor blockers ( ARB ) .  RESULTS Among 2340 participants taking one or more antihypertensive medications , the mean serum CRP level was lower among participants taking a beta-blocker than among those not taking a beta-blocker ( 2.13 v 2.54 mg/L , P = .002 ) . This difference persisted after multivariate adjustment ( P = .021 ) . There were no other statistically significant differences in multivariate models . Among 1314 participants receiving monotherapy , the multivariate adjusted mean CRP level among participants taking a beta-blocker was lower ( 1.97 mg/L ) than those taking a diuretic ( 2.72 mg/L , P < .001 ) . In this monotherapy group , participants taking an ACE inhibitor or ARB also had a lower adjusted mean CRP ( 2.25 mg/L ) than those taking a diuretic ( P = .046 ) . African-American race/ethnicity did not modify any of those relationships . CONCLUSIONS The beta-blocker use was associated with lower CRP levels overall and among participants on monotherapy , whereas ACE inhibitor and ARB use was associated with lower CRP levels among participants on monotherapy . These findings warrant further evaluation in r and omized trials The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure ( SBP ) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy . Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits . Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each . The study was a balanced , r and omized crossover design with five periods : placebo ; angiotensin converting enzyme inhibitors ; beta-blocking drugs ; calcium-blocking drugs ; and thiazide diuretics .  Blood pressure ( BP ) was measured 24 to 26 h after the previous dose . A question naire for side effects was administered at each visit . Seventy-four patients entered the study . beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods . There were 9 of 66 patients on P , 9 of 46 on beta-blockers , 4 of 65 on calcium-blocking drugs , 4 of 65 on diuretic , and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects . Decreases in SBP compared to r and omized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg . Blood pressure decrease correlated with placebo BP ( P < .0005 , r = 0.53 to 0.70 ) . When corrected for placebo , target SBP ( < 140 mm Hg ) was reached in between 6 % to 15 % of patients on monotherapy . Sequential monotherapy achieved target in 29 % . Angiotensin converting enzyme inhibitors , calcium-blocking drugs , and diuretics had no more side effects than placebo . Patients on beta-blockers had more side effects and the well-being score was reduced . Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure . beta-Blockers were relatively ineffective , were frequently contraindicated , and had more side effects . Monotherapy achieved control in only a small number of patients . In elderly people with essential hypertension , therapy should be instituted with diuretics or calcium-blocking drugs , but combination therapy will usually be required to achieve goal OBJECTIVE To provide up date d , evidence -based recommendations for the prevention and management of hypertension in adults . OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions , evidence was review ed from r and omized controlled trials and systematic review s of trials . Changes in cardiovascular morbidity and mortality were the primary outcomes of interest . However , for lifestyle interventions , blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field . For treatment of patients with kidney disease , the progression of kidney dysfunction was also accepted as a clinical ly relevant primary outcome . EVIDENCE A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to up date the 2006 Canadian Hypertension Education Program recommendations . In addition , reference lists were scanned and experts were contacted to identify additional published studies . All relevant articles were review ed and appraised independently by both content and method ological experts using prespecified levels of evidence . RECOMMENDATIONS Dietary lifestyle modifications for prevention of hypertension , in addition to a well-balanced diet , include a dietary sodium intake of less than 100 mmol/day . In hypertensive patients , the dietary sodium intake should be limited to 65 mmol/day to 100 mmol/day . Other lifestyle modifications for both normotensive and hypertensive patients include : performing 30 min to 60 min of aerobic exercise four to seven days per week ; maintaining a healthy body weight ( body mass index of 18.5 kg/m2 to 24.9 kg/m2 ) and waist circumference ( less than 102 cm in men and less than 88 cm in women ) ; limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women ; following a diet reduced in saturated fat and cholesterol , and one that emphasizes fruits , vegetables and low-fat dairy products , dietary and soluble fibre , whole grains and protein from plant sources ; and considering stress management in selected individuals with hypertension . For the pharmacological management of hypertension , treatment thresholds and targets should take into account each individual 's global atherosclerotic risk , target organ damage and any comorbid conditions : blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease . Most patients require more than one agent to achieve these blood pressure targets . In adults without compelling indications for other agents , initial therapy should include thiazide diuretics ; other agents appropriate for first-line therapy for diastolic and /or systolic hypertension include angiotensin-converting enzyme ( ACE ) inhibitors ( except in black patients ) , long-acting calcium channel blockers ( CCBs ) , angiotensin receptor blockers ( ARBs ) or beta-blockers ( in those younger than 60 years of age ) . First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs . Certain comorbid conditions provide compelling indications for first-line use of other agents : in patients with angina , recent myocardial infa rct ion , or heart failure , beta-blockers and ACE inhibitors are recommended as first-line therapy ; in patients with cerebrovascular disease , an ACE inhibitor plus diuretic combination is preferred ; in patients with nondiabetic chronic kidney disease , ACE inhibitors are recommended ; and in patients with diabetes mellitus , ACE inhibitors or ARBs ( or , in patients without albuminuria , thiazides or dihydropyridine CCBs ) are appropriate first-line therapies . All hypertensive patients with dyslipidemia should be treated using the thresholds , targets and agents outlined in the Canadian Cardiovascular Society position statement ( recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease ) . Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy . Once blood pressure is controlled , acetylsalicylic acid therapy should be considered . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence -Based Recommendations Task Force . All recommendations reported here achieved at least 95 % consensus . These guidelines will continue to be up date d annually OBJECTIVE To provide up date d , evidence -based recommendations for the therapy of hypertension in adults . OPTIONS For patients with hypertension , a number of antihypertensive agents may control blood pressure . R and omized trials evaluating first-line therapy with thiazides , beta-adrenergic antagonists , angiotensin-converting enzyme inhibitors , calcium channel blockers , alpha-blockers , central ly acting agents or angiotensin II receptor antagonists were review ed . OUTCOMES The health outcomes that were considered were changes in blood pressure , cardiovascular morbidity , and cardiovascular and /or all-cause mortality rates . Economic outcomes were not considered due to insufficient evidence . EVIDENCE MEDLINE was search ed for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension . Reference lists were scanned , experts were polled , and the personal files of the subgroup members and authors were used to identify other published studies . All relevant articles were review ed and appraised , using prespecified levels of evidence , by content experts and method ological experts . VALUES A high value was placed on the avoidance of cardiovascular morbidity and mortality . BENEFITS , HARMS AND COSTS Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension . In certain setting s , and for specific classes of drugs , blood-pressure lowering has been associated with reduced cardiovascular morbidity and /or mortality . RECOMMENDATIONS The present document contains detailed recommendations pertaining to treatment thresholds , target blood pressures , and choice of agents in various setting s in patients with hypertension . The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus , the amalgamation of the previous sections on treatment of hypertension in the young and old into one section , increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke . Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk , the presence and /or absence of target organ damage , and comorbidities . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group . Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation . Only those recommendations achieving high levels of consensus are reported here . These guidelines will continue to be up date d annually BACKGROUND Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were r and omly allocated to first-line treatment with a calcium channel blocker ( CCB ) , angiotensin-converting enzyme inhibitor ( ACEI ) or angiotensin II receptor blocker ( ARB ) . METHODS We recruited 265 ( 93 for CCB , 71 for ACEI and 101 for ARB ) patients who completed the genomic study .  Home blood pressure was measured for 5 days off-treatment before r and omization and for 5 days after 2 - 4 weeks of r and omized drug treatment . Genotyping was performed by 500 K DNA microarray chips . The blood pressure responses to the three drugs were analyzed separately as a quantitative trait . For replication of SNPs with p < 10(-4 ) , we used the multicenter GEANE study , in which patients were r and omized to valsartan or amlodipine . RESULTS SNPs in PICALM , TANC2 , NUMA1 and APCDD1 were found to be associated with CCB responses and those in ABCC9 and YIPF1 were found to be associated with ARB response with replication . CONCLUSION Our approach , the first based on high-fidelity phenotyping by home blood pressure measurement , might be a step in moving towards the personalized treatment of hypertension Central aortic systolic blood pressure ( BP ) is an important determinant of cardiac workload and cardiac hypertrophy . The relationship of central aortic systolic BP and brachial BP varies depending on the stiffness of blood vessels . It is not certain whether the different drug classes affect the brachial and aortic systolic BP in a similar manner . In a double-blind crossover study , we measured the effects of the four major drug classes compared with placebo on central aortic pressure . Central aortic pressure and various indices were determined using the Sphygmo Cor apparatus . The study was undertaken in patients aged 65 to 85 years with systolic BP > 150 mm Hg at study entry . Results are reported for 32 patients who had satisfactory applanation tonometry in all five periods .  Calcium channel blockers and diuretics caused a greater fall in brachial artery systolic BP than angiotensin-converting enzyme ( ACE ) inhibitors or beta-blocking drugs . On placebo , central aorta augmentation pressure and index were 23 mm Hg and 33.3 % ; on ACE inhibitors the values were 18 mm Hg and 30 % ; on beta-blockers , 26 mm Hg and 38.5 % ; on calcium channel blockers , 16 mm Hg and 28 % ; and on diuretics , 17 mm Hg and 28.8 % . The augmentation pressure on beta-blocking drugs was greater than on the other three drug classes ( P < .05 ) , and augmentation pressures on ACE inhibitors , calcium channel blockers , and diuretics were less than on placebo ( P < .05 ) . The lowest central aortic pressures were achieved with calcium blocking drugs and diuretics . Therapy based on brachial artery recordings may thus overestimate the effect of beta-blocking drugs on central aortic systolic BP and underestimate the effectiveness of ACE inhibitors and calcium blocking drugs . The clinical importance of this discrepancy needs to be evaluated BACKGROUND Most treatment recommendations for hypertension are based on criteria that consider efficacy , safety and cost . Given the need for long-term use of antihypertensive agents , treatment compliance should also be taken into consideration in the selection process . OBJECTIVE The purpose of the present study was to estimate persistence and adherence to  antihypertensive agents in a real-life setting . METHODS Persistence and adherence to treatment were estimated using data from the Regie de l'assurance maladie du Quebec . RESULTS Data from a r and om sample of 4561 subjects with a diagnosis of hypertension covered by the Regie de l'assurance maladie du Quebec drug plan and using one of the antihypertensive agents reimbursed by the drug plan for the first time between January 2000 and December 2001 were analyzed . The persistence rate observed after a two-year period with diuretics was significantly lower ( 52.8 % ) than with any other classes of antihypertensive agent ( P<0.01 ) . Persistence rates for beta-blockers , calcium channel blockers , angiotensin-II receptor blockers and angiotensin-I converting enzyme inhibitors were 69.3 % , 64.3 % , 60.9 % and 58.9 % , respectively . After two years , the proportion of patients who were 80 % adherent to their treatment was 64.9 % for angiotensin-I converting enzyme inhibitors , 65.0 % for angiotensin-II receptor blockers , 64.2 % for calcium channel blockers , 60.3 % for beta-blockers and 50.9 % for diuretics . The proportion of patients who were 80 % adherent to their treatment was significantly lower for diuretics than with any other antihypertensive agents ( P<0.01 ) . CONCLUSION Persistence and adherence to treatment are essential to treatment success . Results of the present study indicate that , in a real-life setting , patients are significantly less compliant to diuretics than to any other antihypertensive agents When observed in elderly hypertensive patients , increased pulse pressure ( PP ) and arterial stiffness are known to be independent risk factors for cardiovascular diseases . Increased systolic blood pressure ( SBP ) leads to left ventricular hypertrophy , while decreased diastolic blood pressure ( DBP ) results in decreased coronary circulation . It is known that increased arterial stiffness is the major cause of increased PP . Thus basic morbid states of cardiac failure or ischemic heart diseases are more likely to develop in elderly hypertensive patients with increased PP and arterial stiffness , and there is need of antihypertensive drugs that decrease these effects in elderly hypertensives . In this study , we compared the effects of an angiotensin-receptor blocker ( ARB : valsartan ) , an angiotensin-converting enzyme inhibitor ( ACE-I : temocapril ) , and long-acting Ca antagonists ( L- and N-type Ca channel blocker : cilnidipine ; and L-type Ca channel blocker : nifedipine CR ) on PP and arterial stiffness measured by pulse wave velocity in elderly hypertensive patients for 3 months . The ARB yielded the largest reductions in PP and brachial-ankle pulse wave velocity ( baPWV ) , followed by the ACE-I and L- and N-type Ca channel blocker , while the L-type Ca channel blocker yielded no improvement . The effects on arterial stiffness and PP thus varied among the drug characteristics . Although ARB achieved the largest reduction in baPWV , this decrease was not associated with any reductions in PP , SBP , DBP , or mean blood pressure , as were the baPWV-decreases achieved by the other drugs , suggesting that ARB may further reduce the risk of arteriosclerosis in elderly hypertensive patients by decreasing arterial stiffness in addition to its antihypertensive effect Background Free oxygen radicals and insufficiency of antioxidant enzymes have been implicated in the pathogenesis of hypertension disease ( HD ) . Trace elements function as a co-factor in antioxidant enzymes . The antioxidant system and trace elements have been investigated in many different studies including HD , but these subjects have not been investigated as a whole in these patients . Objective The aim of the present study was to investigate the antioxidative system and trace elements in hypertensive patients given different antihypertensive therapy .  Methods We examined  malondialdehyde and superoxide dismutase activities together with copper and zinc levels in plasma of 102 patients with HD and in 51 healthy controls . Results It was found that in patients with HD , plasma malondialdehyde was significantly higher than those of controls , while plasma superoxide dismutase activities were significantly lower in patients with HD . Plasma zinc levels were significantly higher than those of controls and plasma copper levels were significantly lower in patients with HD . Plasma lipid levels and oxidative state were analyzed in five different treatment groups given antihypertensive drug therapy before and after a 3-month treatment period . Conclusions In conclusion , our clinical study shows that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have notable effects on oxidative stress , and are an essential step in managing essential hypertension by the way of improvement of endothelial dysfunction . Although it has been shown that calcium channel blockers , beta blockers and alpha receptor blockers have antioxidant effects in in vitro conditions , we did not demonstrate these effects in our clinical study Hypertension is the most common condition seen in primary care and leads to myocardial infa rct ion , stroke , renal failure , and death if not detected early and treated appropriately . Patients want to be assured that blood pressure ( BP ) treatment will reduce their disease burden , while clinicians want guidance on hypertension management using the best scientific evidence . This report takes a rigorous , evidence -based approach to recommend treatment thresholds , goals , and medications in the management of hypertension in adults . Evidence was drawn from r and omized controlled trials , which represent the gold st and ard for determining efficacy and effectiveness . Evidence quality and recommendations were grade d based on their effect on important outcomes . There is strong evidence to support treating hypertensive persons aged 60 years or older to a  BP goal  of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg ; however , there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal , or in those younger than 30 years for a diastolic goal , so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion . The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease ( CKD ) as for the general hypertensive population younger than 60 years . There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor , angiotensin receptor blocker , calcium channel blocker , or thiazide-type diuretic in the nonblack hypertensive population , including those with diabetes . In the black hypertensive population , including those with diabetes , a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy . There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes . Although this guideline provides evidence -based recommendations for the management of high BP and should meet the clinical needs of most patients , these recommendations are not a substitute for clinical judgment , and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient A multicenter , r and omized , controlled , double-blind U.S. trial is comparing the combined effects of diet treatment and 1 of 5 active drug regimens with diet treatment alone , for the long-term management of middle-aged adults with " mild " hypertension . Factors stimulating this trial are data documenting the high prevalence of mild hypertension in the adult population ; mild hypertension 's responsibility for a high proportion of morbidity and mortality attributable to hypertension overall ; data from long-term hypertension intervention trials showing reduced morbidity and mortality of people with mild hypertension with use of either diuretics or beta blockers as step-1 therapy , and other trials that failed to demonstrate beneficial impact on morbidity and mortality , possibly due to residual questions concerning aspects of benefit to risk ratios with these medications ; recent data from trials showing long-term control of mild hypertension and other risk factors by nutritional means ; lack of data from long-term trials on benefit to risk ratios with newer drugs such as selective alpha 1 inhibitors , angiotensin converting enzyme inhibitors and calcium channel blockers ; paucity of data from trials on long-term combined effects of diet and drug therapy , and of diet alone , for people with mild hypertension . During the next few years , phase 1 of the trial will study 6 groups of drugs . The step-1 drugs are angiotensin converting enzyme inhibitor ( enalapril ) , alpha 1 inhibitor ( doxazosin ) , beta blocker ( acebutolol ) , calcium channel blocker ( amlodipine ) , diuretic ( chlorthalidone ) and placebo . All participants are to receive vigorous sustained nutritional counseling to reduce obesity , moderate sodium intake and avoid heavy use of alcohol . Key endpoints for phase 1 of the study are the need for additional medication to control mild hypertension , side effects ( i.e. , clinical and biochemical ) and consequent need to discontinue drug and quality of life . Phase-1 data are to be used to complete the phase-2 design , with the ultimate aim to assess effects on morbidity and mortality The association between angiotensin receptor blockers ( ARBs ) and cancer is controversial with meta-analyses of r and omized controlled trials and observational studies reporting conflicting results . Thus , the objective of this study was to determine whether ARBs are associated with an overall increased risk of the four most common cancers , namely , lung , colorectal , breast and prostate cancers , and to explore these effects separately for each cancer type . We conducted a retrospective cohort study using a nested case-control analysis within the United Kingdom ( UK ) General Practice Research Data base . We assembled a cohort of patients prescribed antihypertensive agents between 1995 , the year the first ARB ( losartan ) entered the UK market , and 2008 , with follow-up until December 31 , 2010 . Cases were patients newly-diagnosed with lung , colorectal , breast and prostate cancer during follow-up . We used conditional logistic regression to estimate adjusted rate ratios ( RRs ) and 95 % confidence intervals ( CIs ) of cancer incidence , comparing ever use of ARBs with ever use of diuretics and /or beta-blockers .  The cohort included 1,165,781 patients , during which 41,059 patients were diagnosed with one of the cancers under study ( rate 554/100,000 person-years ) . When compared to diuretics and /or beta-blockers , ever use of ARBs was not associated with an increased rate of cancer overall ( RR : 1.00 ; 95 % CI : 0.96–1.03 ) or with each cancer site separately . The use of angiotensin-converting enzyme inhibitors and calcium channel blockers was associated with an increased rate of lung cancer ( RR : 1.13 ; 95 % CI : 1.06–1.20 and RR : 1.19 ; 95 % CI : 1.12–1.27 , respectively ) . This study provides additional evidence that the use of ARBs does not increase the risk of cancer overall or any of the four major cancer sites . Additional research is needed to further investigate a potentially increased risk of lung cancer with angiotensin-converting enzyme inhibitors and calcium channel blockers BACKGROUND Previous studies have reported an increased risk of cancer with calcium-channel blockers in man . Other work in animals suggests that inhibitors of angiotensin-I-converting enzyme ( ACE ) protect against cancer . We aim ed to assess the risk of cancer in hypertensive patients receiving ACE inhibitors or other antihypertensive drugs .  METHODS Our retrospective cohort study was based on the records of 5207 patients who attended the Glasgow Blood Pressure Clinic between Jan 1 , 1980 , and Dec 31 , 1995 . The patients ' records are linked with the Registrar General Scotl and and the West of Scotl and Cancer Registry . FINDINGS Compared with the West of Scotl and controls , the relative risks of incident and fatal cancer among the 1559 patients receiving ACE inhibitors were 0.72 ( 95 % CI 0.55 - 0.92 ) and 0.65 ( 0.44 - 0.93 ) . Among the 3648 patients receiving antihypertensive drugs other than ACE inhibitors ( calcium-channel blockers 1416 , diuretics 2099 , beta-blockers 2681 ) , the corresponding relative risks were 110 ( 0.97 - 1.22 ) and 1.03 ( 0.87 - 1.20 ) . The relative risk of cancer was lowest in women on ACE inhibitors : 0.63 ( 0.41 - 0.93 ) for incident cancer ; 0.48 ( 0.23 - 0.88 ) for fatal cancer ; and 0.37 ( 0.12 - 0.87 ) for female-specific cancers . The reduced relative risk of cancer in patients on ACE inhibitors was greatest with follow-up of longer than 3 years . Calcium-channel blockers , diuretics , and beta-blockers had no apparent effect on risk of cancer . INTERPRETATION Long-term use of ACE inhibitors may protect against cancer . The status of this finding is more that of hypothesis generation than of hypothesis testing ; r and omised controlled trials are needed OBJECTIVE The objective of the study is to investigate factors related to treatment persistence among users of antihypertensive ( AHT ) drugs in daily practice . METHODS Data for this study were obtained from the PHARMO data base including pharmacy records and hospitalizations in the Netherl and s ( n=950,000 ) . Patients who newly received AHT therapy ( n=17,113 ) between 1997 and 2001 were selected . Of these patients , r and om sample s of 500 patients per drug class were drawn . One-year persistence was defined as ( 1 ) the percentage of patients using AHTs at least 270 days and receiving AHT in 3 months after the 1-year follow-up period , and ( 2 ) Catalan method ( Kaplan-Meier curves ) . Gender specific persistence rates per drug class were adjusted for significant factors including age , use of antidiabetics and lipid lowering drugs , and prior cardiovascular hospitalizations ( OR and 95%CI ) . RESULTS Persistence was highest in users of angiotensin II receptor blockers ( ARBs ) ( 62.0 % ) , progressively lower in users of angiotensin converting enzyme inhibitors ( ACE-inhibitors , 59.7 % ) , betablockers ( 35.0 % ) , calcium channel blockers ( 34.7 % ) , and diuretics ( 33.0 % ) , result ing in the highest OR of 3.4 [ 95%CI : 2.6 - 4.5 ] for ARBs compared to diuretics . The persistence of AHT use in women was substantially lower ( 40.1 % vs. 50.2 % , OR 0.7 [ 95%CI : 0.6 - 0.8 ] ) and differences between drug classes were larger than in men . CONCLUSIONS These results demonstrate marked differences in persistence between AHT classes , with the highest persistence for ARBs and lowest for diuretics . Women were less persistent with their AHT compared to men . This low persistence leads to suboptimal treatment with a potential for substantial clinical consequences . Especially in women , more attention paid to AHT persistence patterns could improve their cardiovascular outcome Background —Loss of negative feedback inhibition of renin release during chronic treatment with an angiotensin-converting enzyme ( ACE ) inhibitor leads to a compensatory rise in renin secretion and downstream components of the renin-angiotensin-aldosterone ( RAAS ) cascade . This may overcome ACE inhibition but should be blocked by a direct renin inhibitor . We studied the effects of adding the direct renin inhibitor aliskiren to an ACE inhibitor in patients with heart failure . Methods and Results — Patients with New York Heart Association class II to IV heart failure , current or past history of hypertension , and plasma brain natriuretic peptide ( BNP ) concentration > 100 pg/mL who had been treated with an ACE inhibitor ( or angiotensin receptor blocker ) and β-blocker were r and omized to 3 months of treatment with placebo  ( n=146 ) or aliskiren 150 mg/d ( n=156 ) . The primary efficacy outcome was the between-treatment difference in N-terminal pro-BNP ( NT-proBNP ) . Patients ’ mean age was 68 years , mean ejection fraction was 31 % , and mean±SD systolic blood pressure was 129±17.4 mm Hg . Sixty-two percent of the patients were in New York Heart Association functional class II , and 33 % were taking an aldosterone antagonist . Plasma NT-proBNP rose by 762±6123 pg/mL with placebo and fell by 244±2025 pg/mL with aliskiren  ( P=0.0106 ) . BNP and urinary ( but not plasma ) aldosterone were also reduced by aliskiren . Clinical ly important differences in blood pressure and biochemistry were not seen between aliskiren and placebo . Conclusions —Addition of aliskiren to an ACE inhibitor ( or angiotensin receptor blocker ) and β-blocker had favorable neurohumoral effects in heart failure and appeared to be well tolerated BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors prevent the expansion and rupture of aortic aneurysms in animals . We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms . METHODS We did a population -based case-control study of linked administrative data bases in Ontario , Canada . The sample included consecutive patients older than 65 ( n=15,326 ) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1 , 1992 , and April 1 , 2002 . FINDINGS Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm ( odds ratio [ OR ] 0.82 , 95 % CI 0.74 - 0.90 ) than those who did not receive ACE inhibitors . Adjustment for demographic characteristics , risk factors for rupture , comorbidities , contraindications to ACE inhibitors , measures of health-care use , and aneurysm screening yielded similar results ( 0.83 , 0.73 - 0.95 ) . Consistent findings were noted in subgroups at high risk of rupture , including patients older than 75 years and those with a history of hypertension . Conversely , such protective associations were not observed for beta blockers ( 1.02 , 0.89 - 1.17 ) , calcium channel blockers ( 1.01 , 0.89 - 1.14 ) , alpha blockers ( 1.15 , 0.86 - 1.54 ) , angiotensin receptor blockers ( 1.24 , 0.71 - 2.18 ) , or thiazide diuretics ( 0.91 , 0.78 - 1.07 ) . INTERPRETATION ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm , unlike other antihypertensive agents . R and omised trials of ACE inhibitors for prevention of aortic rupture might be warranted OBJECTIVES Despite a broad and efficient pharmacological antihypertensive armamentarium , blood pressure ( BP ) control is suboptimal and heterogeneous throughout Europe . Recent representative data from Switzerl and are limited . The goal of the present survey was therefore to assess the actual control rate of high BP in Switzerl and in accordance with current guidelines . The influence of risk factors , target organ damage and medication on BP levels and control was also evaluated . METHODS A cross-sectional visit-based survey of ambulatory hypertensive patients was performed in 2009 in Switzerl and . 281 r and omly selected physicians provided data on 5 consecutive hypertensive patients attending their practice s for BP follow-up . Data were anonymously collected on demographics , comorbidities and current medication , and BP was recorded . Subsequent modification of pharmacological antihypertensive therapy was assessed . RESULTS Data from 1376 patients were available . Mean age was 65 ± 12 years , 53.9 % were male subjects . 26.4 % had complicated hypertension . Overall , BP control ( < 140/90 mm Hg for uncomplicated and < 130/80 mm Hg for complicated hypertension ) was achieved in 48.9 % . Compared to patients with complicated hypertension , BP control was better in patients with uncomplicated hypertension ( 59.4 % vs. 19.2 % , p < 0.001 ) . As a monotherapy the most prescribed drug class were angiotensin receptor blockers ( ARB , 41 % ) , followed by angiotensin converting enzyme ( ACE ) inhibitors ( 21.5 % ) , betablockers ( 20.8 % ) and calcium channel blockers ( CCB , 10.8 % ) . The most prescribed drug combinations were ARB + diuretic ( 30.1 % ) and ACE inhibitors + diuretic ( 15.3 % ) . 46 % were receiving a fixed drug combination . In only 32.7 % of patients with uncontrolled hypertension was a change in drug therapy made . CONCLUSION This representative survey on treated adult hypertensive patients shows that , compared to earlier reports , the control rate of hypertension has improved in Switzerl and for uncomplicated but not for complicated , particularly diabetes-associated hypertension . ARBs and ACE inhibitors are the most prescribed antihypertensive drugs for monotherapy , whereas diuretics and ARBs were the most used for combination therapy In hypertensive patients with chronic renal disease ,  angiotensin receptor blockers ( ARBs ) are among the first-line drugs , and calcium channel blockers ( CCBs ) are recommended as a second line . We examined the effects of two therapeutic strategies using ARBs and benidipine , a CCB , on blood pressure ( BP ) , urinary albumin excretion ( UAE ) , and cost-effectiveness in hypertensive patients with albuminuria . Patients whose BP was 140/90 mmHg or higher despite treatment with low- or medium-dose ARBs were assigned r and omly to two groups . In Group A ( n=14 ) , the ARB dose was maximized and then benidipine was added until BP targets were reached ( < 130/85 mmHg ) . In Group B ( n=18 ) , benidipine was administered first and then the ARB dose was increased until BP targets were reached . The BP targets were achieved by ARB alone in 36 % of Group A patients and by the addition of benidipine in 83 % of Group B patients . Finally , BP decreased in each group , reaching the targets in 93 % of Group A patients and 94 % of Group B patients after a 4-month therapeutic period . UAE was decreased in both groups after a 4-month therapeutic period compared to the allocation period ( −33±6 % in Group A , −31±6 % in Group B ; p<0.001 , respectively ) . The monthly drug cost was higher ( 11,426±880 vs. 8,955±410 yen , p=0.012 ) and the cost-effectiveness of antihypertensive treatment was lower ( p=0.003 ) in Group A than in Group B. We conclude that the addition of benidipine to low- or medium-dose ARB is , in light of the renal protection and the cost-effectiveness of this approach , a useful therapeutic strategy for controlling BP in hypertensive patients with albuminuria We tested the hypothesis that blockade of angiotensin II type 1 receptors reduces oxidative stress markers in parallel with urinary albumin and type IV collagen excretions . Sixty-six diabetic patients with nephropathy were r and omly assigned to either the angiotensin II receptor blocker ( ARB ; n=33 ) or trichlormethiazide ( n=33 ) group . The majority of patients had been treated with angiotensin-converting enzyme inhibitors or calcium channel blockers for ≥1 year before the present study . Reduction of blood pressure was not different between the 2 groups , and HbA1c levels did not change over the study period ( 8 weeks ) . Treatment with ARB ( c and esartan 8 mg/day , n=11 or valsartan 80 mg/day , n=22 ) for 8 weeks reduced the levels of plasma monocyte chemoattractant protein 1 , interleukin 6 , urinary 8-epi-prostagl and in F2&agr ; , 8-hydroxydeoxyguanosine , albumin , and type IV collagen , whereas the levels of these markers were not altered with trichlormethiazide ( 2 mg/day ) . Significant correlation was observed between the reduction of the urinary 8-epi- prostagl and in F2&agr ; and 8-hydroxydeoxyguanosine and those of the urinary albumin and type IV collagen . Subjects with large oxidative stress had large reduction rates because of ARB administration and showed large urinary albumin suppression . These results suggest that ARBs  reduce oxidative stress and inflammation in diabetic patients independent of their effects on blood pressure . In addition , increases in oxidative stress caused by angiotensin II may play an important role in the progression of diabetic nephropathy . Our results may help to explain the clinical observation that ARB reduces urinary albumin excretion very efficiently in some patients but not in others BACKGROUND Angiotensin II type 1 receptor blockers have favourable effects on haemodynamic measurements , neurohumoral activity , and left-ventricular remodelling when added to angiotensin-converting-enzyme ( ACE ) inhibitors in patients with chronic heart failure ( CHF ) . We aim ed to find out whether these drugs improve clinical outcome . METHODS Between March , 1999 , and November , 1999 , we enrolled 2548 patients with New York Heart Association functional class II-IV CHF and left-ventricular ejection fraction 40 % or lower , and who were being treated with ACE inhibitors .  We r and omly assigned patients c and esartan ( n=1276 , target dose 32 mg once daily ) or placebo ( n=1272 ) . At baseline , 55 % of patients were also treated with beta blockers and 17 % with spironolactone . The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF . Analysis was done by intention to treat . FINDINGS The median follow-up was 41 months . 483 ( 38 % ) patients in the c and esartan group and 538 ( 42 % ) in the placebo group experienced the primary outcome ( unadjusted hazard ratio 0.85 [ 95 % CI 0.75 - 0.96 ] , p=0.011 ; covariate adjusted p=0.010 ) . C and esartan reduced each of the components of the primary outcome significantly , as well as the total number of hospital admissions for CHF . The benefits of c and esartan were similar in all predefined subgroups , including patients receiving baseline beta blocker treatment . INTERPRETATION The addition of c and esartan to ACE inhibitor and other treatment leads to a further clinical ly important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction BACKGROUND Actions of angiotensin II may contribute to the progression of heart failure despite treatment with currently recommended drugs . We therefore evaluated the long-term effects of the addition of the angiotensin-receptor blocker valsartan to st and ard therapy for heart failure . METHODS A total of 5010 patients with heart failure of New York Heart Association ( NYHA ) class II , III , or IV were r and omly assigned to receive 160 mg of valsartan or placebo twice daily . The primary outcomes were mortality and the combined end point of mortality and morbidity , defined as the incidence of cardiac arrest with resuscitation , hospitalization for heart failure , or receipt of intravenous inotropic or vasodilator therapy for at least four hours . RESULTS Overall mortality was similar in the two groups . The incidence of the combined end point , however , was 13.2 percent lower with valsartan than with placebo ( relative risk , 0.87 ; 97.5 percent confidence interval , 0.77 to 0.97 ; P=0.009 ) , predominantly because of a lower number of patients hospitalized for heart failure ; 455 ( 18.2 percent ) in the placebo group and 346 ( 13.8 percent ) in the valsartan group ( P<0.001 ) . Treatment with valsartan also result ed in significant improvements in NYHA class , ejection fraction , signs and symptoms of heart failure , and quality of life as compared with placebo ( P<0.01 ) . In a post hoc analysis of the combined end point and mortality in subgroups defined according to base-line treatment with angiotensin-converting-enzyme ( ACE ) inhibitors or beta-blockers , valsartan had a favorable effect in patients receiving neither or one of these types of drugs but an adverse effect in patients receiving both types of drugs . CONCLUSIONS Valsartan significantly reduces the combined end point of mortality and morbidity and improves clinical signs and symptoms in patients with heart failure , when added to prescribed therapy . However , the post hoc observation of an adverse effect on mortality and morbidity in the subgroup receiving valsartan , an ACE inhibitor , and a beta-blocker raises concern about the potential safety of this specific combination
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 ) .