Category Archives: Cardiology

Systolic Blood Pressure Intervention Trial (SPRINT) – Discuss your views here

A Randomized Trial of Intensive versus Standard Blood-Pressure Control – The SPRINT Trial

This exciting paper has shaken the entire medical world and prompts the question whether BP targets should be radically changed (from 140 mm Hg to 120 mm Hg systolic*in many patients with increased cardiovascular risk).*


The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain.


We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes.


At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group.


Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; number, NCT01206062.)

Posted from WordPress for Android – Google Nexus 5


Novel agent outperforms ACE inhibitor in large HF trial

The investigational agent LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNI), has demonstrated superior efficacy to a widely used ACE inhibitor in the treatment of patients with chronic heart failure, according to a study presented at the recent European Society of Cardiology (ESC) Congress in Barcelona, Spain.

In the PARADIGM-HF* trial, LCZ696, a combination of the ARB valsartan and neprilysin inhibitor sacubitril, showed a significant 20 percent greater effect over enalapril 20 mg/day in reducing cardiovascular death or hospitalization for heart failure (21.8 vs 26.5 percent; p=0.0000002). [N Engl J Med 2014, e-pub 30 Aug, DOI: 10.1056/NEJMoa1409077]

When components of the composite primary endpoint were analyzed separately, LCZ696 demonstrated a 20 percent greater reduction in cardiovascular death (13.3 vs 16.5 percent; p=0.00004) and a 21 percent greater reduction in hospitalization for heart failure (12.8 vs 15.6 percent; p=0.0004) compared with enalapril.

“The trial was stopped early in April, after a median follow-up of 27 months, for an overwhelming benefit of LCZ696 on cardiovascular mortality,” said co-principal investigator Dr. Milton Packer of the Southwestern Medical Center in Dallas, Texas, US.

The ARNI also reduced all-cause mortality, a secondary endpoint of the trial, by an incremental 16 percent compared with enalapril (17 vs 19.8 percent; p<0.0001).

Symptoms and physical limitations of heart failure, measured on the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 8 months, significantly improved in patients receiving LCZ696 vs enalapril (KCCQ score, -2.99 vs -4.63; p=0.001).

“Enalapril 20 mg/day is the current gold-standard therapy in CHF. Results of the PARADIGM-HF trial provide compelling evidence that LCZ696 should replace current use of ACEIs and ARBs in the management of patients with mild to moderately severe CHF,” said Packer.

“The major benefit of LCZ696 is that it changes the natural course of CHF,” he pointed out. “It doubles the benefit of current cornerstone treatment with ACEIs, which reduce cardiovascular death by 18 percent vs placebo.”

The PARADIGM-HF trial included 8,399 patients with class II to IV heart failure and an ejection fraction of 40 percent or below. The patients were randomized to receive LCZ696 200 mg twice daily (n=4,187) or enalapril 10 mg twice daily (n=4,212), in addition to recommended therapy.

“LCZ696 was better tolerated than enalapril,” reported Packer. “It was less likely than enalapril to cause cough, hyperkalemia or renal impairment, and less likely to be discontinued due to an adverse event.”

“Although more symptomatic hypotension was reported with LCZ696, this rarely required treatment discontinuation,” he continued. “Importantly, LCZ696 was not associated with an increased risk of serious angioedema, which was the main safety concern observed with a related medication known as omapatrilat in another trial.”

The survival advantage demonstrated in the trial has prompted the US FDA to grant Fast Track status to LCZ696. Its developer Novartis expects the FDA review to be completed by the end of 2014.

*PARADIGM-HF: Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure.

Posted from WordPress for Android – Google Nexus 5