Summary of Relevant Clinical Studies and Landmark Trials


Courses	Phar 6122

Summary of Relevant Clinical Studies

NOTE: Landmark Trials are those trials which are of substantive influence on the clinical practice of cardiovascular medicine. Trials under the heading of Enrichment are to supplement information. As a student of Phar. 6122, you should be quite familiar with their Objectives, Methods, Results and Interpretation of those trials. Additional trials are added which may augment the student's understanding of the area but may not have been as influential as others in contemporary practice.
Topic/Reference Status	html Version	Description
Hypertension
*Landmark Trials for Hypertension*
pdf	html	Study Description
ACCOMPLISH	NA	Benazepril plus Amlodipine or Hydrochlorothiazide for Hypertension in High-Risk Patients: the B-A combination was superior to B-HCT in reducing CV events in hypertensives at high risk for such events.
a.ASCOT-BPLA Article b. ASCOT-BPLA editorial	NA	(Blood pressure arm of ASCOT. Thearzede and β-blockers vs CCBA and ACE)
HYVET		Treatment of Hypertension in Patients 80 Yeasr of Age or Older: Treatment of the old-old, remains beneficial with diuretic with or without ACE inhibitor.
a. ON Target b. ON Target Editorial		Telmisartan, Ramipril or Both in patients with high risk for vascular Events: Double blind randomized study with primary outcome of CV death, MI, Stroke or hospitalization for HF. Telmisartan equal to ramipril in pts with vascular disease or high risk diabetes but was associated with less angioedema. The combination was associated with more AE's without increase in benefit.
VALUE Trial VALUE editorial	NA	(valsartan vs. amlodipine for prompt blood pressure control)
*Enrichment Trials for Hypertension*
pdf	html	Study Description
a. AASK b. article c. editorial	AASK Trial	(ISH, nitrendipine + others vs PL)
ABCD Trial	ABCD Trial	(nisoldipine vs enalapril in preventing type 2 DM complications)
ACCF/AHA 2011 HTN in Elderly		Expert consensus on hypertension in the elderly, ACC 2011
ANBP2	NA	(Australia National Blood Pressure-2 Trial)
ALLHAT	ALLHAT Trial	(chlorthalidone vs lisinopril, and amlodipine)
BENEDICT
Blood Pressure Trialists' collaboration		Effects of different blood-pressure-lowering regimens on major cardiovascular events
CAMELOT	NA
DETAIL
DREAM Trial	NA	Ramapril vs. Placebo in patients with either IFG or IGT but not diabetes for reduction in CV events
a. EUROPA Trial b. EUROPA Correspondence	a. NA b. NA	(felodipine + ASA + goal BP)
Haffner Study	NA	(Type 2 Diabetes and CV Risk)
a. HOPE ACE b. Micro-HOPE c. HOPE Vitamin E d. HOPE Ambulatory vs. Office BP	a. HOPE ACE Trial b. Micro-HOPE c. HOPE Vitamin E Trial d. NA	a. Ramapril vs. Placebo in High Risk Patients b. HOPE for type 2 diabetics only c. HOPE with Vitamin E component d. Comparative Effects of Ramipril on Ambulatory and Office Blood Pressures
HOT Trial	HOT Trial
Hydrochlorthiazide Meta-Analysis	Frans Messerli	Antihypertensive Efficacy of HCTZ evaluated by ABM (meta-analysis of randomized trials)
IDNT	IDNT Trial	(PL, irbesartan, amlodipine in type 2 DM nephropathy)
INVEST	NA	A Calcium Antagonist vs a Non–Calcium Antagonist Hypertension Treatment Strategy for Patients With Coronary Artery Disease
IRMA II	IRMA II Trial	(irbesartan in type 2 DM + microalbuminuria)
a. LIFE b. LIFE Trial Commentary c. LIFE Trial Diabetes Patients	LIFE Trial	(losartan vs. atenolol)
NA	MIDAS Trial	(isradipine vs HCTZ in progression of mean max IMT)
Navigator		Valsartan vs. Placebo
NORDIL	NA	Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension
a. PEACE Trial b. PEACE Editorial	a. NA b. NA	a. b.
PROGRESS PROGRESS editorial	NA	(peridndopril and indapamide to lower BP which had a larger risk reduction of recurrent stroke or TIA)
RENAAL Trial	RENAAL Trial	(losartan in type 2 DM + nephropathy)
SHEP Stroke	SHEP Trial	(captopril vs atenolol in type 2 DM)
Sodium Reduction to Prevent CVD and Stroke		The Importance of Population-Wide Sodium Reduction as a Means to Prevent Cardiovascular Disease and Stroke: A Call to Action From the American Heart Association
Syst-China Trial	SYST-China Trial	(doxazocin vs chlorthalidone)
Syst-Eur Trial	SYST-EUR Trial	(ISH, nitrendipine + others vs PL)
NA	TOMHS Trial	(ramipril vs amlodipine vs metoprolol in African Americans) (Management of High Blood Pressure in African Americans
UKPDS 39 Trial	UKPDS 39 Trial	(chlorthalidone + atenolol in ISH)
B-Blocker meta-analysis	NA	Beta-blocker meta-analysis Lancet 2005
Lipids
*Landmark Trials for Lipids*
pdf	html	Study Description
a. ACCORD trial- on simvistatin b. Editorial c. Correspondence	NA NA	Fenofibrate Vs. Placebo Added to T2 DM patients Correspondence
AIM-High Article AIM-High Editorial		Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensie Statin Therapy:
ENHANCE	NA	Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia: In patients with FH, the addition of ezetimibe to simvastatin did not result in significant differences in the change in intima-media thickness vs. simvastatin alone.
FIELD Study (Keech 2006) FIELD Study (Scott 2009)	NA	Effects of long-term fenofibrate therapy on type 2 diabetes and CV events.
a. HPS b. HPS Diabetes Substudy c. HPS Antioxidant d. HPS Cost-Effectiveness in US	HPS	a. Simvastatin vs Placebo b. c. d. Statin Cost-Effectiveness in the United States for People at Different Vascular Risk Levels
JUPITER - Main Trial For Jupiter editorials see below		Rosuvastatin to prevent vascular events in men and women with elevated CRP: In this trial of apparently healthy people without hyperlipidemia but elevated hsCRP, rosuvastatin significantly reduced major CV events.
a. PROVE-IT b. PROVE-IT Editorial c. PROVE-IT Post-Hoc	PROVE IT	(Atorvastatin 80 mg vs. Pravastatin 40 mg in ACS)
TNT Editorial	NA	Atorvastatin 10mg vs Atorvastatin in stable coronary disease
TNT Study	NA	The evaluation of intensive vs. moderate lipid lowering by statins for patients with chronic CAD (atorvastatin 80 vs. 10mg)
a.VA-HIT b VA-Hit study analysis based on HDL vs TG c.VA-Hit substudy of patients with DM	VA-HIT	Overall results (gemfibrozil vs PL secondary prevention) Analysis of the study based on HDL vs. TG as the driver of improved outcomes sub study of those participating in the study who were diabetics
a. Grundy 2004 White Paper: Circulation b. Grundy 2005 Metabolic Syndrome	NA NA	Proposed revision to NCEP ATP III guidelines -new targets Diagnosis and Management of the Metabolic Syndrome
WOSCOPS	WOSCOPS	(Pravastatin primary Prevention)
*Enrichment Trials for Lipids*
pdf	html	Study Description
AFSCAPSTexCAPS	AFSCAPS/TexCAPS	(Lovastatin primary Prevention)
ALLHAT-LLT	ALLHAT-LLT	(pravastatin vs usual care)
ASCOT-LLT	NA	(Lipid lowering arm. Atorvastatin 10 mg vs PL)
Phase Z of the A to Z trial		(Early Intensive vs. a Delayed Conservative Simvistatin Strategy in Patients With Acute Coronary Syndromes)
Asteroid Trial		(Effect of Very High-Intensity statin Therapy on Regression of Coronary Atherosclerosis)
ARBITER-6-HALTS: ER Niacin v Ezetimibe and CIMT		Comparison between ER Niacin and Ezetimibe added to statins using CIMT. (Taylor NEJM 2009)
BIP Trial	BIP Study	(Benzfibrate secondary Prevention)
Brugts:Key Meta-analysis of Statins in patients without CVD		Statin Meta-analysis of contemporary benefit of statins in patients without established CV disease
CARDS	NA	Atorvastatin 10mg vs. placebo in Type 2 diabetes.
Cholesterol Treatment Trialists' (CTT) Collaboration		Meta-analysis of intensive LDL lowering in 170,000 participants in 26 trials.
4S Trial	4S Trial 4S	(Simvastatin secondary Prevention)
a. CARE b. CARE Diabetes	CARE	(Pravastatin primary Prevention)
Fish Oils (Omega 3 Fatty Acid Research)	Various Contemporary Trials and Papers	Some Reviews, some recent research studies
HPS-2 THRIVE	http://www.mercknewsroom.com/press-release/prescription-medicine-news/merck-announces-hps2-thrive-study-tredaptive-extended-relea	Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events, study of extended-release niacin/laropiprant, did not meet primary endpoint. This independently conducted study enrolled >25,000 patients at high risk for CV events. (14,741 from Europe and 10,932 from China) followed for 3.9 yrs comparing Niacin and larapiprant plus statin to statin alone therapy. Intervention did not reduce risk of combined coronary deaths and events but was also saw a SSign. Increase in of some types of non-fatal SAE’s for those on the combo product.
a. IDEAL b. IDEAL editorial	NA	Comparison between High Dose Atorvastatin (80mg) vs. moderate dose Simvastatin (20mg) for secondary prevention of Coronary events
Jupiter Enrichment a. JUPITER - Lorgeril b. JUPITER - Kaul c. JUPITER - Ray		a.)Cholesterol Lowering, Cardiovascular Diseases and the JUPITER controversy b.) By Jove! What Is a Clinician to Make of JUPITER? c.) Statins and All-Cause Mortality in High-Risk Primary Prevention
a. LIPID b. LIPID Trial Follow-up	LIPID	(Pravastatin primary Prevention)
MIRACL	MIRACL	(atorvastatin vs post ACS)
Post Bypass Trial	Post-Bypass Study	(Pravastatin secondary prevention)
PROSPER	PROSPER Trial	(Pravastatin in elderly CVD)
REVERSAL	REVERSAL	(Atorvastatin 80 mg vs. Pravastatin 40 mg for coronary artery atheroma burden)
SPARCL		(Statins reduce the incidence of strokes among patients at increased risk for cardiovascular disease; whether they reduce the risk of stroke after a recent stroke or transient ischemic attack (TIA) remains to be established)
McKenny American Journal of Cardiology 2006 NLA Statin Safety Assesment	NLA Statin Safety Assesment by McKenney et al. American Journal of Cardiology 2006; 97: 89-94	(Final Conclusions and Recommendations of the National Lipid Association Statin Safety Assessment Task Force) Read both tables and recommendations
Anticoagulation and Thrombolytic Studies
*Landmark Trials for Antiplatelets (Asprin)*
pdf	html	Study Description
ATT Collaboration (Lancet 2009)		Asprin in the primary and secondary prevention of vascular disease
Beradis (BMJ 2009)		Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trial
Calvin (Diab Care2009)		Asprin for primary prevention
Redberg (Circ 2009)		Primary prevention performance measures
USPSTF Statement (2009)		This paper describes the use of Asprin for primary prevention. Key figures are Figure 2 (men) and Figure 4 (women) as wells as risk calculators for men and women. Summary slide: USPSTF Summary
Pigone (Circ 2010)		Asprin for primary prevention
Aspirin use in Women		Aspirin in Primary Prevention for Women
*Landmark Trials for Antiplatelets (Clopidogel)*
pdf	html	Study Description
Holmes (JACC 2010)		ACCF AHA Clopidogrel clinical allert
Fuster (JAMA_2010)		Clopidogrel and CYP2C19 Editorial
Mega (JAMA_2010)		CYP2C19 reduced function genotype and PCI adverse outcomes clopidogrel
Abraham_(JACC 2010)		ACC PPI Thienopyridine Consensus Document
Anticoagulation and Thrombolytic Studies
*Selected Landmark Trials for Anticoagulation and Thrombolytic Studies*
pdf	html	Study Description
ASSENT-3	ASSENT-3	(TNK ase + Enoxaparin vs TNK + UFH, vs TNKase + abciximab + UFH)
NA	CAPRIE Trial CAPRIE abstract	(clopidogel vs ASA)
CREDO	NA	Early combination therapy (Clopedigril + ALA with PCI)
CURE Trial	CURE Trial	(clopedigrel + ASA vs. ASA)
ESSENCE	ESSENCE	(Enoxaparin vs UFH)
GUSTO IV	GUSTO IV	ACS (PL vs abciximab 24 hrs vs abciximab 48 hrs)
SYNERGY SYNERGY editorial		Enoxaparin vs. UFH in high-risk NSTEMI patients.
NA	TIMI IIB	(enoxaprin vs UFH)
AMI Therapy
*Landmark Trials for AMI*
pdf	html	Study Description
CAPRICORN	CAPRICORN	Carvedilol post AMI in patients with low EF
EPHESUS	NA	(eplerenone vs PL post AMI)
a. VALIANT b. VALIANT Editorial	NA	Valsartan, captopril or both
*Enrichment Trials for AMI*
pdf	html	Study Description
NA	Summary of ACE Inhibitors Post AMI	Table of Studies with ACE inhibitors Post AMI
NA	B-Blockers Meta analysis	B-blockers post AMI-meta analysis
NA	Summary of Beta-blockers Post AMI	(Tables of beta-blockers Post MI)
HART II Study	NA	LMWH and Lytics with AMI
OPTIMAAL Trial	OPTIMAAL Trial	Losartan-captopril post MI
Antiarrhythmics
*Selected Landmark Trial for Antiarrhythmics*
pdf	html	Study Description
a. AFFIRM TRIAL b. AFFIRM FOLLOW UP	AFFIRM Trial	(Rate control vs Rhythm control in AF patients)
ARREST TRIAL	ARREST Trial	(amiodarone in cardiac arrest)
NA	CAST and CAST II Trials I	(Flecainide, encainide, morcizine post MI)
NA	AVID	(ICD vs amiodarone and sotalol in VAs)
NA	CAMIAT	(amiodarone post MI)
Drug Induced QT Prolongation Review		(Roden NEJM 2004)
NA	EMIAT	(amiodarone post MI)
NA	ESVEM	(Sotalol and Holter Monitoring vs EPS)
LIFE -Trial-Afib analysis	NA	(LIFE trial analysis for endpoints of related to Afib. Angiotensin II Receptor Blockade Reduces New-Onsset Atrial Fibrillation and Subsequent Stroke Compared to Atenolol.)
NA	MADIT	(ICD w/ventricular arrhythmias (VAs)
SCD HeFT Trial	NA	(conventional therapy and placebo vs. conventional therapy and amiodarone vs. convention therapy and ICD in HF patients with NYHA II or II and EF <35%)
NA	Summary Table of Key Trials
NA	SWORD	(sotalol in post MI and LVD)
Congestive Heart Failure
*Landmark Trials for Congestive Heart Failure*
pdf	html	Study Description
a. CHARM Overall b. CHARM Added c. CHARM Alternative d. CHARM Preserve	CHARM Series	Added, Overall, Preserved, Alleviate
COMET	NA	(IR metoprolol vs. carvedilol in CHF)
COPERNICUS	COPERNICUS	(cavedilol vs PL)
a.The DIG Study b.Serum DIG Conc. V. Outcome	The Dig Study	(Digoxin vs PL) (Serum Concentration + Outcomes from DIG study)
EPHESUS	NA	(eplerenone vs PL post AMI)
MERIT-HF	MERIT-HF	(metroprolol CR-XL vs. PL)
RALES	RALES	(spironolactone vs. PL)
SOLVD	SOLVD	(enalapril vs PL)
Val-HEFT	Val-HEFT	valsartan vs standard therapy)
VHeFT II	VHeFT II	(enalapril vs hydralazine + ISDN in HF patients)
*Enrichment Trials for Congestive Heart Failure*
pdf	html	Study Description
A-HeFT Trial A-HefT editorial	NA	(ISDN + hydralazine in African American NYHA III and IV HF patients)
ATLAS	ATLAS Trial	(Lisinopril high dose vs low dose)
Bisoprolol and Enalapril for CHF	NA	Initiating Treatment for Chronic Heart Failure With Bisoprolol Followed by Enalapril, as Compared With the Opposite Sequence
NA	Carvedilol Studies in CHF
CIBIS-II Trial	CIBIS- II	(bisoprolol vs PL)
CONSENSUS	CONSENSUS	(enalapril vs PL)
a. ELITE b. ELITE II	ELITE	a. Losartan vs captopril in patients with HF where Losartan appeared to have benefits, b. Losartan vs. captopril in HF patients where no difference existed
PRAISE	PRAISE	(amlodipine vs standard therapy)
Stains- Survival in HF	NA
VMAC	NA	IV Nesiritide vs. IV nitroglycerine for decompensated acute heart failure
Miscellaneous Studies
*Enrichment* *Trials for Miscellaneous Studies*
pdf	html	Study Description
APC study		Study Description: CV risk with Celecoxib
Atrial Arrhythmia		Primer on Atrial Arrhythmia
Cardiac Art 1 Cardiac Art 2 Cardiac Art 3 Cardiac Art 4 Cardiac Art 5 Cardiac Art 6		Primers on Cardiac function at cellular level
Cardiovascular effects and interactions with Herbals		Cardiovascular effects and interactions with Herbals
ECG Introduction		Primer on rhythm strip recognition and ECG information
ECG Terminology		Primer on ECG Terminology
	ESPS2
Generic Atorvastatin and Health Care Costs Jackivicious NEJM 2011		This paper looks at the effects that generic atorvastatin will have on both health care costs as well as market share of alternative statins.
Genomics		Antihypertensives
Genomics of Cardiovascular Disease O'Donnell NEJM 2011		Review of genetic and genomic studies in cardiovascular medicine over the past decade.
Inheritance and Drug Response		Genomics and Medicine NEJM 2003
Pharmacogenomics		- Drug Disposition, Drug Targets, and Side Effects
Tachycardias Part 1		Primer on Broad Complex Tachycardia Part 1
T achycardias Part 2		Primer on Broad Complex Tachycardia Part 2

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