Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial—the Losartan Heart Failure Survival Study ELITE II

https://courses.washington.edu/pharm550/Week2/supp%20reading%20wk%202%20Pitt%201.pdf

Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE)

Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004—BHS IV

Background After the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial ended in February 1997, randomized patients were offered active study medication for a further period of observation. Objective To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia. Methods Eligible patients had no dementia and were at least 60 years old. Their systolic blood pressure at entry was 160 to 219 mm Hg, with diastolic blood pressure below 95 mm Hg. Antihypertensive therapy was started immediately after randomization in the active treatment group, but only after termination of the double-blind trial in the control patients. Treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d), hydrochlorothiazide (12.5-25 mg/d), or both add-on drugs. Results Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall. The incidence of dementia doubled from 32 to 64 cases, 41 of whom had Alzheimer disease. Throughout follow-up, systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects randomized to active treatment. At the last examination, the blood pressure difference was still 4.2/2.9 mm Hg; 48.1%, 26.4%, and 11.4% of the control patients were taking nitrendipine, enalapril, and/or hydrochlorothiazide, whereas in the active treatment group these proportions were 70.2%, 35.4%, and 18.4%, respectively. Compared with the controls, long-term antihypertensive therapy reduced the risk of dementia by 55%, from 7.4 to 3.3 cases per 1000 patient-years (43 vs 21 cases, P P Conclusion The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure–lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/213524/ioi10730.pdf

The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(99)10365-9.pdf

Angiotensin II receptor antagonists

ObjectiveTo compare the incidence of cough in patients with a history of angiotensin converting enzyme (ACE) inhibitor-related cough who received losartan [a type 1 angiotensin II (Ang II) receptor antagonist], lisinopril (an ACE inhibitor) or hydrochlorothiazide (a diuretic).DesignAn international,

Effects of modulators of the renin-angiotensin-aldosterone system on cough. Losartan Cough Study Group.

Background: Losartan potassium, the first nonpeptide selective blocker of angiotensin II at the ATI receptor, has been shown to exhibit clinical antihypertensive effects. The aim of the present study was to characterize the efficacy and duration of action of losartan by ambulatory blood pressure monitoring. Methods: The study was performed in nonblack hypertensive patients whose baseline untreated clinical diastolic blood pressures were 95 mm Hg or higher and whose average 24-hour ambulatory diastolic blood pressures were 85 mm Hg or higher. Patients were randomized, double-blind, into four treatment groups: placebo (n=32) or losartan, 50 mg once daily (n=29), 100 mg once daily (n=30), or 50 mg twice daily (n=31). Clinical and 24-hour ambulatory blood pressures were measured at baseline (off treatment for at least 4 weeks) and after 4 weeks of treatment. Results: By clinical sphygmomanometer measurements at the end of the 24-hour or 12-hour dosing intervals (trough), all three losartan dosages were significantly more effective than placebo at decreasing systolic and diastolic blood pressures. By average 24-hour ambulatory systolic/ diastolic blood pressure measurements, the decreases produced were 0.0/0.2 mm Hg for placebo and 9.2/6.9, 9.9/6.4, and 13.2/8.5 mm Hg, respectively, for losartan, 50 mg once daily, 100 mg once daily, and 50 mg twice daily. All drug effects were different from placebo ( P P Conclusion: Ambulatory blood pressure monitoring, which virtually eliminated antihypertensive placebo responses, demonstrated clear 24-hour efficacy for losartan, 50 mg once daily, as well as for higher doses of 100 mg once daily and 50 mg twice daily. This ATI receptor blocker had antihypertensive effects that appeared additive when combined with low-dose diuretic therapy. Losartan was generally well tolerated. (Arch Intern Med. 1995;155:405-411)

Blood pressure effects of the angiotensin II receptor blocker, losartan.

Background A common adverse experience in hypertensive patients treated with angiotensin converting enzyme (ACE) inhibitors is a tickling dry cough. Objectives The aim of the present study was to review clinical observations and mechanisms of cough associated with ACE inhibitors. In addition, since the AT1-type angiotensin II antagonists (represented by losartan, MK954, DuP753) are not expected to influence other systems (kinins, prostaglandins) affected by ACE inhibitors, we explored the hypothesis that antihypertensive therapy with these agents will not be associated with cough at a similar frequency or quality to that seen with ACE inhibitors. Design and methods Patients with a history of an ACE inhibitor-associated dry cough confirmed by a second challenge with lisinopril were enrolled into an international, multicenter, randomly allocated, double-blind, parallel-group, controlled trial, to be treated with losartan, lisinopril or hydrochlorothiazide. The presence and severity of cough were assessed by a self-administered questionnaire and a visual analog scale, respectively. Conclusions It is expected that the new class of antihypertensive agents, angiotensin II antagonists, will not be associated with the high incidence of dry cough associated with the use of ACE inhibitors. It appears that this cough is not related to alterations in the renin-angiotensin system but to kininase II effects.

Association between cough and angiotensin converting enzyme inhibitors versus angiotensin II antagonists: the design of a prospective, controlled study.

Two hundred eighty-six patients with mild to moderate hypertension who had untreated diastolic blood pressure while seated of 95 to 115 mm Hg were randomized to receive placebo or once-daily doses of 2.5, 5, or 10 mg of the dihydropyridine calcium channel blocker felodipine extended release (ER). Blood pressure was measured 24 hours after dosing (at trough). Mean reductions in diastolic blood pressure after 8 weeks of double-blind treatment were significantly greater in each of the ER felodipine treatment groups (2.5, 5, and 10 mg ER felodipine: -7.8, -9.5, and -11.3 mm Hg, respectively) than in the placebo group (-5.3 mm Hg). The effect was dose dependent for both diastolic and systolic blood pressure. Moreover, much of the peak antihypertensive effect was still present at trough, confirming the 24-hour efficacy of the drug. Felodipine was well tolerated.

E B Nelson

Papers

Effects of modulators of the renin-angiotensin-aldosterone system on cough. Losartan Cough Study Group.

Blood pressure effects of the angiotensin II receptor blocker, losartan.

Association between cough and angiotensin converting enzyme inhibitors versus angiotensin II antagonists: the design of a prospective, controlled study.

Extended‐release felodipine in patients with mild to moderate hypertension