Meeting Report: American Heart Association Scientific Sessions 2014

American Heart Association Scientific Sessions 2014

Chicago, Illinois

November 15-19, 2014

Each year, the American Heart Association’s (AHA’s) Scientific Sessions is the organization’s largest yearly gathering of healthcare professionals and researchers in the field of cardiovascular disease and stroke. Providing 5 days of comprehensive education with more than 4000 presentations by world leaders in cardiovascular disease, the AHA 2014 Scientific Sessions featured the results of landmark and long-awaited clinical trials.

Cardiology Review covers the DAPT Trial, IMPROVE-IT, FACTOR-64, ODYSSEY ALTERNATIVE, BASKET-PROVE II, the EVOLVE II Clinical Trial, and the Japanese Primary Prevention Project with Aspirin.

Longer Dual-Antiplatelet Therapy Better After DES Implantation

In one of the most anticipated presentations at the AHA sessions, Laura Mauri, MD, MSC, and colleagues from Brigham & Women’s Hospital in Boston, who conducted the Dual Antiplatelet Therapy (DAPT) trial, reported that DAPT (clopidogrel or prasugrel) beyond 1 year after placement of a drug-eluting stent (DES) significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events versus continuing with aspirin alone. The use of DAPT beyond 1 year did, however, increase the risk of bleeding.

Dr Mauri and colleagues randomly assigned 9961 patients to continue clopidogrel or prasugrel treatment, or to receive placebo; all patients continued to receive aspirin, as well. For an additional 18 months after the first 12 months, treatment with DAPT, compared with placebo, reduced stent thrombosis rates by a relative 71% compared with aspirin alone (.4% vs 1.4% from months 12 to 30; P <.001), and reduced major adverse cardiovascular and cerebrovascular events by a relative 20% (4.3% vs 5.9% over the same time interval; P <.001). Dr Mauri said that although the positives of extending thienopyridine were counterbalanced by a higher risk of bleeding (2.5% vs 1.6%; P = .001), the benefits of prolonged DAPT were larger than anticipated.

The patients who were assigned to thienopyridine treatment had lower rates of myocardial infarction than the placebo group (2.1% vs 4.1%; P <.001). The rate of death from any cause in the group that continued on clopidogrel or prasugrel treatment was 2% versus 1.5% in the placebo group (P = .05).

The trial’s findings were in opposition to the trend of shorter DAPT. Results of the study were simultaneously published online in the New England Journal of Medicine.

The FDA posted an online drug safety recommendation during the AHA session recommending that physicians continue prescribing at they have been while the agency continues to analyze the new trial data. Consult published study for disclosures.

Statin Plus Nonstatin Reduces LDL More Than Statin Alone

A new study of 18,000 stabilized acute coronary syndrome (ACS) patients suggests that there are more therapeutic options to consider for high-risk ACS patients than statins alone. The IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) trial found that compared with statins alone, adding ezetimibe to statin therapy in high-risk patients lowered low-density lipoprotein (LDL) cholesterol by an average of 17 mg/dL and reduced cardiovascular events. Forty-two percent of patients stopped the study drug before the end of the trial.

Christopher Cannon, MD, of Brigham and Women’s Hospital, principal investigator for the trial, said the finding was the first time that adding a nonstatin lipid-lowering therapy to a statin showed clinical benefit. He and his colleagues presented their data as an abstract prior to its publication in a journal.

Prior to this finding, adding niacin, fibrates, and cholesterylester transfer protein inhibitors to statins did not show a benefit. In IMPROVE-IT, however, ezetimibe plus simvastatin reduced the rate of cardiovascular death, myocardial infarction, or stroke by 2 percentage points (34.7% for simvastatin alone vs 32.7% for ezetimibe plus simvastatin). At 1 year, average LDL in the simvastatin arm was 69.9 mg/dL versus 53.2 mg/dL in the ezetimibe/simvastatin group. There were no differences in levels of high-density lipoprotein (HDL) cholesterol or in C-reactive protein.

The data suggested that there were 270 fewer events over 7 years of follow up, with no significant difference in cancer, muscle, or gallbladder-related events, pointing to the safety of ezetimibe, said Dr Cannon. “Treating 100 patients would prevent 2 events.”

The IMPROVE-IT trial was funded by Merck Sharp and Dohme.

Cannon CP et al. IMPROVE-IT Trial: a comparison of ezetimibe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes after acute coronary syndromes. AHA 2014. Consult abstract for disclosures.

Daily Low-Dose Aspirin Not Helpful for Primary Prevention in Elderly

A Japanese trial suggests that daily low-dose aspirin did not lower the higher stroke and cardiovascular risk in older adults with diabetes, hypertension, or dyslipidemia. The Japanese Primary Prevention Project was a 5-year open-label trial that included 14,464 people aged 60 to 85 years at 1007 clinics in Japan as candidates for primary prevention because of hypertension, diabetes, and dyslipidemia. The patients were randomized to open-label treatment with once-daily enteric-coated aspirin (100 mg) or to no aspirin. Adherence to aspirin was at 76% at 5 years.

The 5-year cumulative rate of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (MI) was 2.77% with aspirin (100 mg enteric-coated) compared with 2.96% without it (P = .54).

According to Yasuo Ikeda, MD, of Waseda University in Tokyo, and colleagues, aspirin significantly reduced nonfatal MI by a relative 47% and transient ischemic attack by a relative 43%. However, extracranial hemorrhage requiring transfusions or hospitalization increased significantly, by a relative 85%, compared with no aspirin.

The study was terminated early by the data monitoring committee after a median follow-up of 5.02 years based on likely futility. In both the aspirin and no-aspirin groups there were 56 fatal events.

The study was published online in JAMA on November 17, 2014. Consult published study for disclosures.

Investigational PSK9 Inhibitor May Help Statin-Intolerant Patients

Alirocumab, an investigational proprotein convertase subtilisin/kexin type 9 (PSK9) monoclonal antibody, produced significantly greater reductions in low-density lipoprotein cholesterol (LDL-C) in 314 statin-intolerant patients with very high baseline LDL-C levels (mean baseline, 190 mg/dL) compared with ezetimibe, according to results of the ODYSSEY ALTERNATIVE Study.

In the study, patients were randomized to alirocumab 75 mg or 150 mg subcutaneously every 2 weeks (n = 126), ezetimibe 10 mg once daily (n = 125), or atorvastatin 20 mg once daily (n = 63). Then, all patients continued on open-label alirocumab. Patrick Moriarity, MD, of the University of Kansas Medical Center, Kansas City, reported that alirocumab was better tolerated than atorvastatin, yielded greater LDL reductions, and was associated with fewer muscle-related adverse events than both atorvastatin and ezetimibe. Mean LDL 24 weeks after the initiation of the study was 154 mg/dL with ezetimibe versus 96 mg/dL in the alirocumab group. The majority of patients reported some adverse events with each of the 3 treatments, but skeletal muscle events were fewer in the alirocumab group.

In addition, Dr Moriarity noted that 75% of patients labeled as statin-intolerant were actually able to tolerate the 20-mg dose of atorvastatin. He said that the study showed many patients who believe they are statin-intolerant may be able to be treated with statins, and those who really are intolerant may find PSK9 agents a suitable alternative. However, long-term safety and efficacy of PSK9 agents must be further studied.

During the blinded-treatment phase of the study, 23% of alirocumab patients stopped treatment versus 33% in the other arms. Asked if compliance would be a problem given that the alirocumab is administered by injection, Dr Moriarity said it was not because patients with very high LDL know they are at high risk and are willing to sacrifice convenience to see their LDL drop. He commented that patients put on alirocumab told him it was the first time their LDL went below 100. “They are ecstatic,” he said.

Moriarity PM, Thompson PD, Cannon CP, et al. ODYSSEY ALTERNATIVE: efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody, alirocumab, versus ezetimibe, in patients with statin intolerance as defined by a placebo run-in and statin rechallenge arm. AHA 2014 Scientific Sessions: November 17, 2014.

Consult abstract for disclosures.

CTA Screening in Asymptomatic Diabetics Has Little Effect on Outcome

Coronary computed tomographic angiography (CTA) screening of asymptomatic people with diabetes can improve their cardiovascular (CV) risk profile by guiding them toward more aggressive therapeutic interventions, but screening has little effect on mortality or nonfatal CV events over 4 years, according to results of the 900-patient FACTOR-64 trial.

Patients enrolled in FACTOR-64 had type 1 or type 2 diabetes of at least 3 years’ duration (mean, 12 years). Patients were randomized to coronary CTA screening using the same 64-slice scanner at 1 location (452 patients) or to standard management (448 patients). Standard management was medical therapy consistent with standard national guidelines—based optimal diabetes care, with A1C targets to <7.0%, <100 mg/dL for low-density lipoprotein cholesterol (LDL-C) and <130 Hg for systolic blood pressure.

Joseph B. Muhlestein, MD, of the Intermountain Medical Center Heart Institute in Murray, Utah, said the findings did not support CTA screening in this population. At a mean follow-up of 4 years, the primary outcome event rates were not significantly different between the screening arm of the study and the control group.

Patients with severe disease were referred for diagnostic angiography, and those with moderate disease were referred to stress perfusion imaging and, if appropriate, diagnostic angiography. Treating physicians decided whether to revascularize. Medical therapy in the coronary-CTA group consisted of standard management for patients with normal coronary arteries and aggressive management in those with mild to severe proximal disease or distal coronary artery disease.

After 4 years, the primary end point of all-cause mortality, nonfatal myocardial infarction, or unstable angina requiring hospitalization was met by 6.2% of screened patients and 7.6% of patients receiving standard care by intention to treat (hazard ratio, 0.80; CI, 0.60-2.19; P = .38). There were no significant differences for any components of the primary end point, for the secondary end point of ischemic major adverse CV events, or for stroke or heart failure hospitalization. Patients who were screened showed significant improvements in mean levels of diastolic blood pressure, LDL-C, and high-density lipoprotein cholesterol. Neither group showed improved A1C.

The study was published in JAMA on December 1, 2014. FACTOR-64 was supported by Toshiba and Bracco Diagnostics.

Trials Test Biodegradeable-Polymer DES

Two new studies testing first-generation and second-generation drug-eluting stents (DES) with a bioabsorbable polymer found that the 2 stents are noninferior compared with a durable-polymer DES.

Christoph Kaiser, MD, of University Hospital, Basel, Switzerland, presented the results of the BASKET-PROVE II study, which compared the biodegradable polymer with a biolimus-eluting stent (Nobori; Terumo) against a second-generation everolimus-eluting stent (Xience Prime; Abbott Vascular) and a bare-metal stent (BMS) with thin struts (ProKinetik; Biotronik) in 2291 patients with acute or stable coronary disease requiring coronary stenting in large vessels (≥3.0 mm diameter). Patients received dual-antiplatelet therapy (DAPT) with prasugrel for 12 months following DES implantation and for 4 weeks with BMS implantation.

The primary end point (composite of cardiac death, myocardial infarction [MI], and clinically indicated target vessel revascularization [TVR]) at 2 years occurred in 7.6% of patients treated with the Nobori stent, in 6.8% with the Xience Prime, and in 12.7% with the BMS stent. The Nobori stent was noninferior to the Xience Prime stent in the composite end point of cardiac death, MI, and TVR. The Nobori stent was superior in efficacy compared with the BMS, which researchers said was because of reduced rates of TVR.

With respect to safety at 24 months, there was no significant differences in rates of death, MI, and TVR, as well as no difference in rates of stent thrombosis between the 3 stents. The biodegradable-polymer DES failed to meet the statistical definition of noninferiority compared with Xience Prime in the per protocol analysis. Most patients were excluded from this analysis because of DAPT protocol violations. Dr Kaiser noted that there is no late advantage in using the biodegradable-polymer Nobori stent over the everolimus stent with durable polymer, and said the additional cost of the Nobori stent is not justified.

The second study, EVOLVE II, compared a second-generation bioabsorbable-polymer everolimus-eluting stent (Synergy; Boston Scientific) with a durable-polymer everolimus-eluting stent (Promus Element Plus; Boston Scientific) in 1684 patients. Dean Kereiakes, MD, of Christ Hospital Heart and Vascular Center, Cincinnati, Ohio, said the researchers found that at 1 year, the primary target lesion failure end point, a composite of cardiac death, MI, or ischemia-driven revascularization, occurred in 6.5% of Promus-treated patients and 6.7% of Synergy patients. Because the difference was not significant, noninferiority between the 2 stents was proved. There was no difference in revascularization or stent thrombosis rates at 12 months. There were 2 definite and 3 probable cases of stent thrombosis with Promus, and 2 definite and 1 probabl case of stent thrombosis with Synergy.

Dr. Kereiakes said he will present these data to the FDA on behalf of Boston Scientific. Consult abstract for disclosures.