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A Review of the Key Clinical Trials of 2014.

McKavanagh P, McCune C, Menown IB - Cardiol Ther (2015)

Bottom Line: Over the last year, multiple, potentially practice-changing, cardiology trials or studies have been published or presented at international meetings including the American College of Cardiology, European Association for Percutaneous Cardiovascular Interventions, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, Heart Failure Congress, Heart Rhythm Society, Heart Failure Society of America, American Society of Hypertension and the American Heart Association.In this paper, the authors describe and place in clinical context, new HF, data including neprilysin inhibitors, intravenous ferric carboxymaltose, potassium-absorbing compounds, quadripolar leads for cardiac resynchronization therapy and intraventricular device intervention.New trial data are also described for acute coronary syndromes (clopidogrel, prasugrel, ticagrelor), stable coronary artery disease (ivabradine), percutaneous coronary intervention (the role of thrombectomy or treatment of non-culprit lesions during primary intervention, pressure wire studies and outcomes of new stent designs), transcatheter aortic valve intervention data, atrial fibrillation (anticoagulation and direct current cardioversion), electrophysiology (leadless pacemaker devices, use of quinidine in Brugada syndrome) and coronary prevention (landmark Ezetimibe outcome data, PCSK9 clinical trials, childhood prevalence of hypertension, renal denervation for resistant hypertension and the role of cardiac computerized tomography in cardiovascular screening).

View Article: PubMed Central - PubMed

Affiliation: Craigavon Cardiac Centre, Southern Trust, Craigavon, BT63 5QQ, Northern Ireland, UK, mckavanagh@doctors.org.uk.

ABSTRACT

Introduction: Over the last year, multiple, potentially practice-changing, cardiology trials or studies have been published or presented at international meetings including the American College of Cardiology, European Association for Percutaneous Cardiovascular Interventions, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, Heart Failure Congress, Heart Rhythm Society, Heart Failure Society of America, American Society of Hypertension and the American Heart Association.

Methods: Clinical trial results presented at major cardiology conferences during 2014 were reviewed by the authors. Search terms included heart failure (HF), acute coronary syndrome, stable coronary disease, interventional cardiology, atrial fibrillation, electrophysiology and coronary prevention. Selection criteria were trials of broad relevance to the cardiology community, those with potential to change current practice and those with potential to guide further phase III research.

Results: In this paper, the authors describe and place in clinical context, new HF, data including neprilysin inhibitors, intravenous ferric carboxymaltose, potassium-absorbing compounds, quadripolar leads for cardiac resynchronization therapy and intraventricular device intervention. New trial data are also described for acute coronary syndromes (clopidogrel, prasugrel, ticagrelor), stable coronary artery disease (ivabradine), percutaneous coronary intervention (the role of thrombectomy or treatment of non-culprit lesions during primary intervention, pressure wire studies and outcomes of new stent designs), transcatheter aortic valve intervention data, atrial fibrillation (anticoagulation and direct current cardioversion), electrophysiology (leadless pacemaker devices, use of quinidine in Brugada syndrome) and coronary prevention (landmark Ezetimibe outcome data, PCSK9 clinical trials, childhood prevalence of hypertension, renal denervation for resistant hypertension and the role of cardiac computerized tomography in cardiovascular screening).

Conclusion: This paper summarizes key clinical trials during 2014 and should be of practical interest to clinicians and cardiology researchers.

No MeSH data available.


Related in: MedlinePlus

The primary end point of cardiovascular death or HF hospitalization taken with permission from PARADIGM-HF. Reproduced with permission from [2]. HR hazard ratio
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Fig1: The primary end point of cardiovascular death or HF hospitalization taken with permission from PARADIGM-HF. Reproduced with permission from [2]. HR hazard ratio

Mentions: For the past two decades, angiotensin-converting enzyme (ACE) inhibitors have been considered the cornerstone of HF therapy. Neprilysin is a neutral endopeptidase which degrades potentially beneficial natriuretic and vasoactive peptides. The prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in HF (PARADIGM-HF) study (ClinicalTrials.gov #NCT01035255) randomized 8442 patients with reduced left ventricular (LV) ejection fraction and New York Heart Association (NYHA) class II–III symptoms to LCZ696 (a combination of the neprilysin inhibitor sacubitril and valsartan) or to standard treatment with enalapril [2]. The trial was stopped early after a mean follow-up of 27 months, at which point LCZ696 compared with enalapril resulted in a 20% decrease in primary end point of CV death or HF hospitalization [hazard ratio (HR) in the LCZ696 group, 0.80; 95% confidence interval (CI), 0.73–0.87; p < 0.001) (Fig. 1) [2], a 20% reduction in CV death (HR 0.80; 95% CI 0.71–0.89; p < 0.001) and a 16% reduction in the pre-specified key single end point of all-cause mortality [HR 0.84 (95% CI 0.76–0.93); p < 0.001]. LCZ696 also reduced the risk of HF hospitalization by 21% (p < 0.001) and decreased the symptoms and physical limitations of HF (p = 0.001). It is worth noting that the dose of enalapril used may have been suboptimal (maximum 10 mg twice daily vs. the maximum valsartan dose of 320 mg daily). The incidence of numerically greater, but non-significant excess of angioedema with LCZ696 may have been underestimated by use of a careful run-in period to exclude intolerant patients. Nevertheless, assuming LCZ696 receives a license, it is likely to be quickly included in clinical HF guidelines given its highly significant reduction in CV mortality and all-cause mortality.Fig. 1


A Review of the Key Clinical Trials of 2014.

McKavanagh P, McCune C, Menown IB - Cardiol Ther (2015)

The primary end point of cardiovascular death or HF hospitalization taken with permission from PARADIGM-HF. Reproduced with permission from [2]. HR hazard ratio
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4472645&req=5

Fig1: The primary end point of cardiovascular death or HF hospitalization taken with permission from PARADIGM-HF. Reproduced with permission from [2]. HR hazard ratio
Mentions: For the past two decades, angiotensin-converting enzyme (ACE) inhibitors have been considered the cornerstone of HF therapy. Neprilysin is a neutral endopeptidase which degrades potentially beneficial natriuretic and vasoactive peptides. The prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in HF (PARADIGM-HF) study (ClinicalTrials.gov #NCT01035255) randomized 8442 patients with reduced left ventricular (LV) ejection fraction and New York Heart Association (NYHA) class II–III symptoms to LCZ696 (a combination of the neprilysin inhibitor sacubitril and valsartan) or to standard treatment with enalapril [2]. The trial was stopped early after a mean follow-up of 27 months, at which point LCZ696 compared with enalapril resulted in a 20% decrease in primary end point of CV death or HF hospitalization [hazard ratio (HR) in the LCZ696 group, 0.80; 95% confidence interval (CI), 0.73–0.87; p < 0.001) (Fig. 1) [2], a 20% reduction in CV death (HR 0.80; 95% CI 0.71–0.89; p < 0.001) and a 16% reduction in the pre-specified key single end point of all-cause mortality [HR 0.84 (95% CI 0.76–0.93); p < 0.001]. LCZ696 also reduced the risk of HF hospitalization by 21% (p < 0.001) and decreased the symptoms and physical limitations of HF (p = 0.001). It is worth noting that the dose of enalapril used may have been suboptimal (maximum 10 mg twice daily vs. the maximum valsartan dose of 320 mg daily). The incidence of numerically greater, but non-significant excess of angioedema with LCZ696 may have been underestimated by use of a careful run-in period to exclude intolerant patients. Nevertheless, assuming LCZ696 receives a license, it is likely to be quickly included in clinical HF guidelines given its highly significant reduction in CV mortality and all-cause mortality.Fig. 1

Bottom Line: Over the last year, multiple, potentially practice-changing, cardiology trials or studies have been published or presented at international meetings including the American College of Cardiology, European Association for Percutaneous Cardiovascular Interventions, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, Heart Failure Congress, Heart Rhythm Society, Heart Failure Society of America, American Society of Hypertension and the American Heart Association.In this paper, the authors describe and place in clinical context, new HF, data including neprilysin inhibitors, intravenous ferric carboxymaltose, potassium-absorbing compounds, quadripolar leads for cardiac resynchronization therapy and intraventricular device intervention.New trial data are also described for acute coronary syndromes (clopidogrel, prasugrel, ticagrelor), stable coronary artery disease (ivabradine), percutaneous coronary intervention (the role of thrombectomy or treatment of non-culprit lesions during primary intervention, pressure wire studies and outcomes of new stent designs), transcatheter aortic valve intervention data, atrial fibrillation (anticoagulation and direct current cardioversion), electrophysiology (leadless pacemaker devices, use of quinidine in Brugada syndrome) and coronary prevention (landmark Ezetimibe outcome data, PCSK9 clinical trials, childhood prevalence of hypertension, renal denervation for resistant hypertension and the role of cardiac computerized tomography in cardiovascular screening).

View Article: PubMed Central - PubMed

Affiliation: Craigavon Cardiac Centre, Southern Trust, Craigavon, BT63 5QQ, Northern Ireland, UK, mckavanagh@doctors.org.uk.

ABSTRACT

Introduction: Over the last year, multiple, potentially practice-changing, cardiology trials or studies have been published or presented at international meetings including the American College of Cardiology, European Association for Percutaneous Cardiovascular Interventions, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, Heart Failure Congress, Heart Rhythm Society, Heart Failure Society of America, American Society of Hypertension and the American Heart Association.

Methods: Clinical trial results presented at major cardiology conferences during 2014 were reviewed by the authors. Search terms included heart failure (HF), acute coronary syndrome, stable coronary disease, interventional cardiology, atrial fibrillation, electrophysiology and coronary prevention. Selection criteria were trials of broad relevance to the cardiology community, those with potential to change current practice and those with potential to guide further phase III research.

Results: In this paper, the authors describe and place in clinical context, new HF, data including neprilysin inhibitors, intravenous ferric carboxymaltose, potassium-absorbing compounds, quadripolar leads for cardiac resynchronization therapy and intraventricular device intervention. New trial data are also described for acute coronary syndromes (clopidogrel, prasugrel, ticagrelor), stable coronary artery disease (ivabradine), percutaneous coronary intervention (the role of thrombectomy or treatment of non-culprit lesions during primary intervention, pressure wire studies and outcomes of new stent designs), transcatheter aortic valve intervention data, atrial fibrillation (anticoagulation and direct current cardioversion), electrophysiology (leadless pacemaker devices, use of quinidine in Brugada syndrome) and coronary prevention (landmark Ezetimibe outcome data, PCSK9 clinical trials, childhood prevalence of hypertension, renal denervation for resistant hypertension and the role of cardiac computerized tomography in cardiovascular screening).

Conclusion: This paper summarizes key clinical trials during 2014 and should be of practical interest to clinicians and cardiology researchers.

No MeSH data available.


Related in: MedlinePlus