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(1) Few negative trials teach us as much as the sham-controlled, prospective, single-blinded, randomized clinical trial of renal denervation called SYMPLICITY-HTN-3.One can see its potential value in small cohorts of patients with diseases of catecholamine excess, such as ventricular tachycardia storm.

Bhatt DL, Kandzari DE, O"Neill WW, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370:1393-1401. Abstract

 (2) The impressive results of the PARADIGM-HF trial may be the first breakthrough in drug therapy for heart failure in more than two decades.

Investigators compared the novel combination drug LCZ696 (valsartan/sacubitril; Novartis still has not given it a brand name) with standard-dose enalapril in a multicenter clinical trial. The idea behind angiotensin-neprilysin inhibition (ARNI) drugs is that the addition of the neprilysin inhibitor (sacubitril) to the angiotensin-receptor blocker (ARB) will help counter the unfavorable vasoconstriction, sodium retention, and negative remodeling seen with neurohormonal activation in heart failure patients.The results of PARADIGM-HF were clear. LCZ696 lowered the rate of the primary endpoint, a composite of cardiovascular (CV) death or first hospital admission for heart failure, by 4.7%. The novel drug also lowered the most important endpoint, premature death from any cause, by 2.8%. Functional status and quality-of-life measures favored LCZ696. Renal function remained stable with the study drug.

McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004. Abstract

(3) This was a good year for novel cardiac monitoring technologies.The CRYSTAL AF trial[5] showed that an implantable loop recorder (ILR) was six times more likely than conventional monitoring to detect atrial fibrillation (AF) in patients who had just suffered ischemic stroke. The majority of ILR-detected cases of AF were asymptomatic. The EMBRACE trial,[6] published alongside CRYSTAL-AF in the same issue of the New England Journal of Medicine, confirmed the value of extended monitoring after cryptogenic stroke or transient ischemic attack. In that study, Canadian researchers detected new AF in one in six patients using 30-day ambulatory ECG recorders.

Sanna T, Diener H-C, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014;370:2478-2486. Abstract

(4) An analysis of the SPRINT-AF. Canadian registry revealed that 40% of AF patients treated with oral anticoagulants were taking antiplatelet drugs without an indication. I see this often. In the absence of recent stent placement, acute coronary syndrome, or the presence of a mechanical valve, there are no data to support combining these classes of drugs. In fact, the combination increases the risk of bleeding.

Japanese research group presented a trial of 14,464 high-risk patients in which aspirin failed to prevent CV events.

Gupta M, Singh N, Cox JL, et al. High rates of concomitant antiplatelet use in patients with atrial fibrillation treated with oral anticoagulation: Insights from the Stroke Prevention and Rhythm Intervention in Atrial Fibrillation (SPRINT-AF) registry. Program and abstracts of the American Heart Association 2014 Scientific Sessions; November 15-19, 2014; Chicago, Illinois. Abstract 25612.

Ikeda Y, Shimada K, Teramoto T, et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: A randomized clinical trial. JAMA. 2014 Nov 17. [Epub ahead of print]

(5) Four in five heart attacks are preventable. These were the beautiful findings of Swedish researchers who studied the effects of five modifiable health measures in 20,721 men from 1997 to 2009. No, lipoprotein(a) levels were not among them. Instead, this group measured the benefits of eating a healthy diet, drinking two (or fewer) alcoholic drinks daily, exercising regularly, having a small belt size, and not smoking. Each factor incrementally lowered the risk for first myocardial infarction, and those men who achieved all five measures were 79% less likely to have a heart attack than those who accomplished none.

Perhaps the strongest support that simple lifestyle factors are potent elixirs for health came from data on AF ablation results. In the ARREST-AF trial, [a team of scientists from Australia showed that patients enrolled in an aggressive risk-factor modification clinic increased their chance of ablation success fivefold.

Akesson A, Larsson SC, Discacciati A, Wolk A. Low-risk diet and lifestyle habits in the primary prevention of myocardial infarction in men: a population-based prospective cohort study. J Am Coll Cardiol. 2014;64:1299-1306. Abstract

Pathak RK, Middeldorp ME, Lau DH, et al. Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: The ARREST-AF cohort study. J Am Coll Cardiol. 2014;64:2222-2231. Abstract