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AFFIRM
no statistical difference in mortality between rate and rhythm control, however, increased mortality in rhythm control in older pts, those with CAD, those without CHF; 2002
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RACE II
Lenient ( resting <110) vs. strict (resting < 80 ) HR control in pts with AFib - lenient rate control was as effective as strict and required fewer office visits; 2010
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RE-LY
In pts with Afib, Both doses of Dabigatran are non-inferior to warfarin in preventing stroke and systemic embolism with lower major bleeding profile; slight increase in GI bleeding; 2009
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ESPS-2, ESPRIT
Aggrenox BID is more effective for secondary prevention of stroke in pts with ischemic stroke/TIAs; 1996, 2006
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SPAF I, SPAF II, SPAF III
Warfarin > ASA > placebo in reducing stroke events in AFib. For high risk patients with Afib, Warfarin INR 2-3 is more effective than low intensity warfarin (INR 1.2-1.5) dosing plus ASA 325 (1.9% vs. 7.9% stroke rates respectively). For low risk patients, ASA 325 has acceptable low risk of stroke < 3%. Sub-study of SPAF III established high risk factors of the CHADS2 risk score; 1991, 1994, 1996
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ARISTOTLE
apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.; 2011
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COGENT
use of plavix in pts with ACS, DES placed, on PPI who have risk of GI bleeding related to NSAID use or positive for H. pylori - When used with plavix, PPI reduces rate of GI outcomes without change in cardiovascular events. Weak recommendation in pts without risk of GI bleed; Important to note that the study didnot have adequate power, didnot include patients with high risk bleeding; 2010
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TRITON-TIMI 38
Used universal definition of MI. In pts with moderate-severe unstable angina, NSTEMI, and STEMI, Prasugrel (loading 60 then 10 daily) reduced CV death, nonfatal MI, nonfatal stroke compared to clopidogrel (loading 300 then 75 daily) at 1, 6, and 15 months; additionally, there's reduced stent thrombosis in prasugrel group. Similar bleeding profiles; 2007 - 19% reduction in CV death, MI or stroke compared with clopidogrel in patients undergoing PCI for ACS.
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PLATO
Pts with ACS, with or without ST elevation, ticagrelor reduces death from vascular, MI, and CVAs; slight increase non-procedural related, i.e. fatal intracranial bleeding, but fewer other types of fatal bleeding; 2009
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GUSTO-I
In pts with acute MI, Accelerated t-PA plus IV Heparin has lower mortality although higher bleeding than streptokinase and standard therapy. Older age, Anterior MI, increased Killip class lower systolic BP ( < 110) and increased HR (> 90) predictive of 4 time more higher 30 day mortality ; also, lower TIMI flow grade in infarct artery, renal dysfunction, arrhythmias are factors; 1995
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CAPRIE
In pts with CAD, plavix was slightly better than aspirin in reducing primary endpoints of MI, CVA, and vascular death; conferred benefit for CVA and PAD; no benefit in pts with previous MI; 1996
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CAST
flecanide and encanide increased mortality (relative risk 2.5) in pts with post-MI asymptomatic or mildly symptomatic ventricular arrhythmias; 1989
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ISIS II
ASA lowers CV death, Recurrent MI, CVA when given to patients with acute MI; 1988
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COMMIT
Plavix plus ASA reduces 30 day mortality (0.6% ARR), BB good after MI if pts do not have heart failure/cardiogenic shock; 2005
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HORIZONS AMI
Bivalirudin reduced bleeding and death compared to Heparin plus Glycoprotein IIb/IIIa inhibitor in 30 days; increased <24 hr in stent thrombosis with bivalirudin but offsetted between 24 hrs to 30 days; 2009
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TACTICS - TIMI 18
GpIIb/IIIa inhibitor plus invasive strategy in pts with moderate-high risk UA/NSTEMI is better than conservative management; 2001
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CURE
plavix in addition to aspirin in patients with non-STEMI ACS reduces risk of CV death, MI, and CVAs by 20%; 2002
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CLARITY - TIMI 28
In STEMI patients, plavix in addition to aspirin plus thrombolysis reduced CV death, occlusion of infarct-related artery, re-MI and by 20% at 30 days; 2005
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ISIS-4
In pts with suspected or acute MI, Captopril reduced all cause mortality at 5 wks and long term follow up; increased rate of hypotension and/or renal dysfunction in pts with captopril warranting termination; no benefit conferred by magnesium sulfate or isordil; 1995
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GISSI 3
Lisinopril, when given < 24 hrs in pts with acute MI, reduced mortality and severe LV diastolic dysfunction (EF < 35%); 1994
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Norwegian Timolol Study
In pts who survive acute MI, Beta blockers reduce all cause mortality, sudden death, and reinfarction; 1981
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Tele-HF
Follow up with telemonitoring in pts with CHF, doesnot improve mortality or readmission rate; only 55% 6-month pt compliance rate for using the telemonitoring system; 2010
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AIRE
In pts with non severe HF, significant relative reduction in all cause mortality by 23% when ramipril started 3-10 days after MI, benefit noticeable as early as 30 days, reduction in progression to heart failure; no reduction in reinfarction or stroke; 1993
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CAPRICORN
Carvedilol decreases cardiovascular and all cause mortality in post- infarction pts with EF < 40% ; 2001
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MERIT-HF
Metoprolol XL when used on top of ACE-I reversed ventricular remodeling as shown by decreased LV- EDV and ESV by cardiac MRI and decreases all cause mortality when started in pts with CHF; 2000
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SAVE (captopril, 1992), TRACE (trandolapril, 1995), SOLVD (enalapril, 1991)
ACEI reduces all cause mortality (~ 20%), remodeling, and decreased risk of worsening heart failure (37%) when started 2-10 days after MI, and in pts with CHF (EF < 35%)
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VALIENT (valsartan, 22)
ARBs have mortality equivalent to ACEI; side note: Angiotensin type 1 receptor blockers ( ARBs) have increased stimulation of angiotensin type 2 receptors, which have protective effect of decreased remodeling
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RESOLVD
enalapril plus candesartan combination was more beneficial in preventing LV dysfunction (reduced ESV and EDV), compared to either drug alone ; 1999
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CHARM Overall
candesartan addition to concurrent BB and/or ACEI therapy - trend toward significance in reducing all cause mortality; significant reduction in CV death or hospital admission for CHF (16%); NNT is 23 in 1 year
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OPTIMAAL
ARB vs. ACEI - In pts with acute MI or heart failure/LV dysfunction, Losartan had no additional benefit compared to captopril, but was better tolerated; 2002
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CIBIS II
in pts with EF < 35% and NYHA class III or IV, B1 blocker bisoprolol significantly reduced all cause mortality, sudden death, and all cause hospitalizations from CHF; 1999
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CONSENSUS
in pts with severe CHF (class IV), addition to diuretics and digoxin, enalapril reduces mortality by 27% and reduces progression of CHF; no change in sudden death; 1987
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V-HEFT (Vasodilator (enalapril vs. hydralazine/nitrate)-Heart Failure Trial)
pts with CHF on digoxin and diuretic; enalapril has greater reduction mortality compared to combination for at least 2 years, likely due to lower incidence of sudden death; both increase LV EF, combination > enalapril, combination increased O2 consumption at peak exercise at 1 year; 1991
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I-PRESERVE
Irbesartan did not improve mortality or CV outcomes in pts with HF symptoms (Class II-IV) and preserved EF > 45%; Most pts (63%) had HF due to hypertensive heart disease; 2008
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COPERNICUS
Pts with severe HF (EF < 25%) and Class III-IV, Coreg in addition to diuretic plus ACE/ARB reduces all cause mortality and hospitalization; 2001
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RALES
Aldactone 25 mg in addition to standard therapy reduces mortality and risk of sudden death in pts with severe CHF (EF < 35, Class 3-4); RRR 30%; 1999
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EPHESUS
Eplerenone in addition to standard therapy reduces mortality in pts with severe CHF; 2001
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JUPITER
Rosouvastatin reduced primary endpoint (CV death, MI, CVA, unstable angina, revascularization) in women > 60 and men > 50, LDL < 130 - low normal, elevated hsCRP > 2 by 44%, 20% reduction in total mortality, NNT is 95 in 2 yrs, slightly higher incidence of diabetes; 17K total number of patients; 2008 CRP Genetic loci analysis in pts with CAD - mendelian randomization study showed no effect of CRP levels and loci on CAD; JAMA July 2009
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TNT
Intense lipid lowering therapy in pts with CAD (prior MI +/- revascularization, stable angina) - high dose (80 mg) vs. low dose (10 mg) Lipitor - high dose has significantly lowerLDL and total cholesterol levels, and reduced risk of major CV event and death from coronary heart disease and stroke; 2005
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A to Z - NSTEMI, STEMI
2% reduction in CV death, MI and readmission for ACS reduced in pt receiving aggressive zocor (40 initially then 80 mg) vs. placebo then 20 mg zocor after 2 years. Effects occur primarily after 4 months of treatment. Significant decrease in CV death and CHF; 2004
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CARDS
Lipitor 10 mg daily reduces risk of major cardiovascular events including stroke in pts with DM2; relative risk reduction of 37% and benefits emerge after 1 yr on therapy, favorable trend with regards all cause mortality; 2004
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CARE
pravastatin reduces risk of major cardiovascular events in pts (both gender and over and under 60) with average cholesterol and previous MI by 24%; lowers total cholesterol, LDL, and triglycerides by 20%, 285, and 14% respectively, and increases HDL by 5%; 1996
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WOSCOPS
pts hyperlipidemia and no hx of MI, pravastatin reduced CV deaths (RRR 30%) and need for revascularization (RRR 37%); 1995
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CURVES
Atorvastatin of all doses is more potent in reducing cholesterol levels than simvastatin, pravastatin, lovastatin and fluvastatin; 1998
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LIPID
Pravastatin reduced mortality from all causes and CV events in pts with acute MI or unstable angina and cholesterol 155-271; 1998
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4S
in pts with high cholesterol 210-310 and stable angina or previous MI ( > 6 months), simvastatin reduced all cause mortality, future coronary events and need for CABG/PCI; 1994
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PARTNER cohort A
699 elderly patients (median age 84.1) with severe aortic stenosis were randomized to either TAVI or surgery. TAVI was just as good as surgery in surgery-eligible patients for the primary end point of mortality. More stroke/TIA, vascular complications seen in TAVI group but more major bleeds in surgery group. Better symtomatic improvement in TAVI. 2011
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NORDISTEMI
Early invasive strategy in pts with STEMI has significant reductions in primary outcomes (death, stroke, reinfarction) at 30 days, but at 12 months, reductions were nonsignificant, but trended towards significance as invasive group had less incidence of death, strokes, reinfarction at 12 months; 2010
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BARI 2D
In pts with DM2, stable CAD, no significant difference in mortality between prompt revascularization ( surgery or angioplasty) vs. medical therapy; or between insulin sensitization (metformin, TZDs) vs. insulin provision therapy (sulfonylurea, insulin); 2009
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CURRENT - OASIS 7
double dose plavix loading dose plus 150 a day for 1 week then 75 daily is beneficial mainly in subgroup of pts undergoing PCI by reducing stent thrombosis; 2008
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GUSTO -IIB
PTCA has better outcomes than thrombolysis in pts with AMI. lowest 30 day mortality when D2B time < 60 minutes (1%), 60-90 minutes (4%), > 90 minutes (6.5%)
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SYNTAX
PCI vs. CABG in pts with severe CAD - At 1 yr, CABG group had lower rates of major cardiac or cerebrovascular events (12% vs. 18%) and repeat revascularization (6% vs. 14%); however, there was increase in rate of strokes (2.2% vs. 0.6%). Conclusion - CABG should be standard of care in pts with severe 3 vessel or left main disease; 2009
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SHOCK
In pts with cardiogenic shock due to acute MI, early revascularization vs. medical stabilization does not improve 30 day mortality but does improve 6-month and 12-month mortality, especially in pts < 75; 1999
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COURAGE
Compared with optimal medial therapy(OMT), PCI plus OMT in stable CAD did not reduce all cause mortality, non-fatal MI, and other major CV events; however, there was reduction in reoccurrences of angina symptoms in PCI + OMT group; 2008
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CARP
In patients with stable CAD, coronary artery revascularization prior to elective major vascular surgery, s.a. expanding AAA, PVOD of legs, does not improve outcomes; 2004
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ERACI, GABI, BARI, CABRI, RITA, EAST
PTCA and CABG have similar rates of survival and avoidance of MI and similar long term health care costs; PTCA group had increased rates of recurrent angina and revascularization; nearly 1/4 of PTCA patients required CABG; At 10 year follow up some studies showed that Diabetics and pts > 65 yrs have slightly decreased mortality with CABG; Subset of CABRI trial - pts with multi-vessel or chronically occluded major vessel disease had better outcomes with CABG; 1994, 1994, 1996, 1995, 1998, 1999
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SoS (Stent or Surgery)
PCI is associated with higher rates of repeat revascularization compared to CABG; similar incidence of q-wave MI; fewer deaths in CABG group; 2002
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FRISC-II, RITA-3
At 5 year follow up, in moderate-high risk pts with ACS without ST elevation, early invasive intervention strategy has improved outcomes in terms of death/MI; 2005, 2006
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MADIT-CRT
defibrillator along with BiV ICD (CRT-ICD therapy )is associated with 41% heart failure events when compared to ICD alone in pts with ischemic or nonischemic heart failure (EF < 30%, NYHA Class I or II) and wide QRS > 130ms; most benefit in reducing HF events in pts with QRS > 150; Echo evidence of decreased LV EDV /ESV and improved EF at 1 year; 2009
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SCD-HeFT
Amio vs. placebo, ICD vs. placebo for CHF - In pts with mild-moderate CHF, EF <35, shock only ICD reduced risk of death (ARR 7.2% at 5 years), main effects in pts with Class II symptoms, minimal effect in Class III; Amio showed no benefit in Class II, but reduced survival in Class III; 2005
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REVERSE
CRT reverses remodeling in systolic LV dysfunction, pts with asymptomatic to mild HF or wide QRS, EF < 40 - significant improvement in reverse LV remodeling seen by measures of LVESV and LVEDV along with EF after 6 months in pts with CRT with further improvement overtime; there was significant decrease in morbidity and mortality; 2009
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AVID
ICD is more effective than antiarrythmic drugs in reducing arrhythmia related cardiac deaths. 1999
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ACCORD
increased mortality from any cause with aggressive glycemic control hgba1c < 6 vs. 7-7.9 in diabetic pts, NNH is 95 in 3.5 yrs; 2008
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ACCORD BP
intensive bp control < 120 vs. < 140 systolic in diabetics did not reduce fatal and nonfatal CV events; 2010
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BEAUTIFUL
ivabradine (selective sinus node inhibitor - reduced SA node pacemaker current (If)) addition to standard therapy of BB, etc. in pts with CAD and LVF < 40% showed no reduction in mortality or admissions for new onset of HF, however, in pts with HR > 70 bpm, reduction in fatal and nonfatal MI 36%, coronary revascularization by 30%, and HR reduction by 6 bpm ; 2009
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SHIFT
ivabradine outcomes in chronic HF stage 2 -4, HR > 77 bpm - reduction in hospitalization or CV death from heart failure. Drug side effects, bradycardia and visual side effects; 2010
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WHI (Women's Health Initiative)
post menopausal women on combined hormonal therapy is associated with increased risk of CAD, PE, CVA and invasive breast cancer but decreased risk of hip fractures and colorectal cancer; absolute risk excess was 19 per 100,000 person-years; 2002
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VALUE
Valsartan vs. Amlodipine in HTN control: Amlodipine has better HTN control in first few months, but equal efficacy at 6 years; Valsartan group had greater incidence of MI and Amlodipine group had greater incidence of new onset diabetes; 2004
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UKPDS (HTN in Diabetes study)
BP control < 150/85 in pts with HTN and Diabetes with ACEI or BB, plus additional meds if needed, reduces risk of diabetic related complications and death related to diabetes (MI, PV0D, renal disease, CVA, sudden death) along with decrease in progression of neuropathy and retinopathy; 1998
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ONTARGET
ARB vs. ARB plus ACEI - Pts with CAD/MI high risk diabetes, without heart failure - Telmisartan is equally efficacious as ramipril, but better tolerated, yet had higher rates of hypotension; combination therapy conferred no benefit in preventing cardiovascular mortality/morbidity; 2008
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HOPE
in patients with known vascular disease or diabetes plus at least one cardiovascular risk factor, ramipril reduced risk of death, MI, stroke, and revascularization, along with diabetic complications; new diagnosis of diabetes significantly lower in ramipril group; Vitamin E did not lower the risk of CAD; 2000
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GISSI-HF
polyunsaturated fatty acids (PUFA) 1g/day associated with decreased mortality and hospital admission in pts with symptomatic HF( Class II-IV); NNT 56 over 4 years; Rosouvastatin in pts with symptomatic HF does not improve mortality or hospital admissions, etc. it may be prescribed for pts with indication for statin i.e. CAD, but not just for HF; 2008
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ALLHAT
thiazide vs. CCB vs. ACEI - No significant difference in all cause mortality, fatal or nonfatal coronary heart disease (CHF). Thiazide type diuretics (chlorthalidone) are superior at preventing 1 or more forms of CVD and should be first line of therapy; amlodipine higher 6 yr rate of HF and lisinopril had higher 6 yr rates of CHD, stroke, and HF; 2002
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Framingham Heart study
high levels of LDL, Hypertension, cigarette smoking, obesity, elevated blood sugar levels, stress, lack of exercise, menopause, ECG abnormalities increase risk of coronary heart disease; 1984
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LIFE
Losartan vs. atenolol - losartan shows reduction in CV deaths (MI and stroke) compared to atenolol, and losartan in better tolerated with similar BP reduction; reduction in new onset diabetes in losartan group; 2002
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ELITE I, ELITE II
Losartan was not superior to captopril, only better tolerated. 1997, 2000
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