Four Days in Orlando
Editor’s Corner | Alfred A. Bove, MD, MACC, PhD Editor-in-Chief, CardioSource WorldNews
My travels to Orlando, FL, in the past have been motivated by entertaining children at Disney World, activity related to the Navy, or attending a major cardiology meeting at the Orange County Convention Center. In November, the reason to be in Orlando was to attend the annual scientific sessions of the American Heart Association. In the past few years, we have seen the major national meetings often dominated by one important clinical trial. At AHA.15, most attention was directed toward the report from the SPRINT trial on targets for hypertension therapy.
This trial compared clinical outcomes (ACS, stroke, heart failure [HF] or cardiovascular [CV] death) related to a systolic blood pressure (BP) target of 120 mm Hg versus 140 mm Hg. Several clinical trials published over the past 10 years have indicated that aiming for a lower target had an adverse effect on cardiovascular mortality. ACCORD, INVEST, and HYVET all demonstrated an increased CV event rate with lower systolic BP targets. In these trials, stroke rate was reduced with the lower BP target, but the increase in CV mortality and morbidity was not offset by the lower stroke rate. These findings have been incorporated into new guidelines on treatment of hypertension.
The SPRINT data will challenge these guidelines and provoke a long discussion on how to manage hypertension. SPRINT showed a 25% reduction in the combined endpoint (2.19%/year to 1.65%/year), but a significant increase in renal failure or acute kidney injury, and an increase in syncope and orthostasis. However, they did not report an increase in injury due to falls. Hypertension therapy needs to be individualized and a target systolic BP of 120 mm Hg will not work for everyone.
Heart failure therapy is being rejuvenated by the development of new therapies now available in clinical practice. The addition of the neprilysin inhibitor LCZ696 and ivabradine to our armamentarium of HF drugs provides two new therapies to be assimilated into practice.
One of two BEAT-HF trials presented at AHA.15 likely will add yet another new mechanism for managing late-stage HF. The study examined the use of a beta-3 agonist (yes, there is a beta-3 receptor) for therapy of systolic heart failure. The data were neutral in the effect on myocardial function, measured by ejection fraction (EF), but in the subjects with severe LV dysfunction and EF < 20%, there was an improvement. The finding fits the mechanism of action of the drug, which improves the sodium-potassium exchange in these failing myocytes. The beta-3 agonist is already approved for relaxing bladder spasticity and we will see future trials testing the drug in patients with severe LV dysfunction.
Two neutral studies from the Heart Failure Clinical Research Network are also helpful in tailoring HF therapy. The FIGHT study examined the use of liraglutide, a glucagon-like peptide to improve glucose metabolism in the failing heart. The study showed no difference in post-hospitalization clinical stability in patients with class II or class III HF. There was a trend for a detrimental effect on the composite endpoint of death, HF hospitalization, and renal function. The NEAT trial examined the use of isosorbide mononitrate in patients with heart failure with preserved EF. Here again the study showed no beneficial effect of the nitrate therapy on physical activity quantitated with an accelerometer. While there was a small improvement compared to baseline for active treatment versus placebo, there was a reduction in physical activity.
The other BEAT-HF trial, examining the effect of a telemedicine surveillance system for post-hospital management of patients with HF, also failed to show a benefit. The study contributes to the mixed message of the value of telemedicine in home surveillance of patients with HF. In BEAT-HF, patients who were adherent to the use of the telemedicine system trended toward a better outcome.
In other HF studies, the degree of participation in self-monitoring and the support system for managing the data were important components of success. The future of chronic HF care is likely to involve not just remote monitoring but the development of care teams that can provide the needed surveillance and feedback to avoid deterioration in clinical status. Other HF trials include SOCRATES-REDUCED, which demonstrated failure of vericiguat to improve B-type natriuretic peptide in heart failure patients, and COSMIC-HF, wich demonstrated improvement in left ventricular function with use of the myosin activator omecamtiv mecarbil, but no difference in hospital admissions or HF exacerbations.
Modifying platelet function continues to generate interest in the world of interventional cardiology. Data from the DAPT trial were analyzed to develop a risk score that would allow selection of patients post-PCI who would benefit from long-term dual antiplatelet therapy. The risk balances thrombosis and bleeding risk, and is based on a number of clinical characteristics. The calculator can be found at daptstudy.org/for-clinicians/score_calculator.htm and can be used to assess the value of long-term DAPT in a patient after percutaneous intervention. The role of platelets in migraines was examined in the CANOA trial wherein patients post-closure of an atrial septal defect using an Amplatzer percutaneous device who developed migraine symptoms were treated with aspirin or aspirin plus clopidogrel. The group taking clopidogrel had a significant reduction in migraine symptoms post-procedure. With the data suggesting that activated platelets contribute to migraine events, inhibition of platelet function with clopidogrel blocks the platelet activity and reduces migraine headache events.
Four days in Orlando left me with some important messages. First, the continuing attempts at developing new HF therapies are often unsuccessful, but never give up on new ideas. Second, we may yet find a way to sort out who should be taking long-term DAPT using a clinical score. Third, platelets likely have a role in migraine, and fourth, the SPRINT results are not a surprise. Therapy of hypertension in the elderly will likely continue to require higher systolic blood pressure compared to a middle-age population to avoid syncope and renal decompensation, and blood pressure targets for heart failure patients should be low enough to stabilize HF and often will go below usual standards for hypertension management. My travels this time were fruitful indeed.
Alfred A. Bove, MD, PhD, is professor emeritus of medicine at Temple University School of Medicine in Philadelphia, and former president of the ACC.
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