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ekgcircle3.gif (1164 bytes) 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
Tachycardias Part 2   Primer on Broad Complex Tachycardia Part 2
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