3. Deferred Stent Implantation in STEMI Patients

Results of the open-label, randomised controlled DANAMI 3-DEFER trial in patients with symptoms of acute myocardial infarction and ST-segment elevation of 0·1 mV (STEMI) or more were presented at ACC2016. All patients underwent immediate percutaneous coronary intervention (PCI) and were randomly assigned to either immediate stent implementation (n=612) versus postponed or deferred stent implantation after 48 hours (n=603).

At a median follow-up of 42 months, 109 (18%) patients in the standard PCI arm and 105 (17%) patients in the deferred stent implantation arm experienced a primary composite endpoint event, which was all-cause mortality, hospital admission for heart failure, recurrent infarction, and any unplanned revascularisation of the target vessel (HR 0·99; 95% CI, 0·76–1·29; p=0·92).

4. IV Beta blockers in STEMI patients before primary PCI

Early-BAMI trial randomised 683 patients with ST-levation Myocardial Infarction (STEMI) patients presenting

342 patients (54.8% of total) were evaluated by magnetic resonance imaging (MRI) for the primary endpoint myocardial infarct size by MRI at 30 days. Infarct size (% of LV) by MRI was similar in the 336 patient who received metoprolol (15.3 ± 11.0%) and the 346 patients receiving placebo (14.9 ± 11.5% p=0.616).  LVEF was 51.0 ± 10.9%  and  51.6 ± 10.8% (P =0.68) respectively. There was a small but significant difference for the secondary endpoint ventricular arrhythmias. Malignant arrhythmias occurred in 3.6% of the metoprolol-treated patients vs 6.9% in placebo group (P = 0.050). The incidence of adverse events was not different between groups. No significant difference in toxicities was observed.

5. Intermediate Risk Patients without CVD: Cholesterol and Blood Pressure

Results of the HOPE-3 Trial (ClinicalTrials.gov: NCT00468923), a study with a 2-by-2 factorial design, at a median follow-up of 5.6 years were reported at ACC2016. The study randomised 12,705 subjects with intermediate cardiovascular risk and without history of cardiovascular disease to receive:

1. Cholesterol lowering with rosuvastatin (10 mg/day) versus placebo, and
2. Blood pressure (BP) lowering with candesartan (16 mg/day) plus hydrochlorothiazide (12.5 mg/day) vs.placebo

The two co-primary composite endpoints of the study were:

1. Death from cardiovascular causes, nonfatal myocardial infarction and nonfatal stroke.
2. Resuscitated cardiac arrest, heart failure, and revascularization.

The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization.

5.1 Blood Pressure

Baseline mean BP was 138.1/81.9 mm Hg. When comparing candesartan plus hydrochlorothiazide vs placebo first co-primary endpoint occurred in 260 (4.1%) vs. 279 (4.4%) respectively (HR=0.93; 95% CI, 0.79 to 1.10; P =0.40) and second co-primary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%) respectively (HR=0.95; 95% CI, 0.81 to 1.11; P =0.51). Decrease in BP was 6.0/3.0 mm Hg greater in candesartan plus hydrochlorothiazide vs placebo [5].

5.2 Cholesterol

When comparing rosuvastatin vs placebo first co-primary endpoint occurred in 235 (3.7%) vs. 304 (4.8%) respectively (HR=0.76; 95% CI, 0.64 to 0.002; P=0.002) and second co-primary outcome occurred in 277 participants (4.4%) and 363 participants (5.7%) respectively (HR=0.75; 95% CI, 0.64 to 0.88; P <0.001). In the rosuvastatin group overall mean LDL-C level was 26.5% lower when compared to placebo. Adverse events were similar but 3.8% of rosuvastatin-treated patients vs. 3.1% placebo-receiving patients had cataract surgery (P=0.02). Muscle symptoms were higher with 5.8% of participants vs. 4.7% respectively (P =0.005) [6].

6. Genetic component of hypercholesterolaemia

This study investigated the genetic component in 26,025 patients with severe (LDL-C ≥ 190 ml/dl) hypercholesterolaemia by gene sequencing. Three known genes that are currently known to cause familial hypercholesteraemia (FH) LDLR, APOB, PCSK9 and their genetic variants were sequenced. Coronary Arterial Disease (CAD) risk correlation with mutations was assessed in these patients as well.

In the population with LDL-C ≥190 mg/dl (N=1386), 24 patients (1.7%) carried one of the FH mutations. The risk of CAD was found to be highest in subjects with LDL-C ≥190 mg/dl with FH mutations when compared to the reference group of LDL cholesterol

7. PARTNER2: Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients

The non-inferiority trial PARTNER 2 (ClinicalTrials.gov: NCT01314313) investigated transcatheter aortic-valve replacement (TAVR) with surgical replacement in 2032 intermediate-risk patients with severe aortic stenosis.

Before randomization, patients were stratified based on clinical and imaging findings to either the transfemoral-access cohort ( 76.3%) or the transthoracic-access cohort (23.7%). The primary endpoint of death from any cause or disabling stroke at 2 years was equally met in TAVR group and the surgery group (P=0.001 for noninferiority). Event rates were 19.3% and 21.1%  for the TAVR group and surgery group respectively (HR TAVR: 0.89; 95% CI, 0.73 to 1.09; P = 0.25). TAVR resulted in less primary endpoints in the transfemoral-access cohort when compared to surgery (HR: 0.79; 95% CI, 0.62 to 1.00; P = 0.05) but was similar for TAVR vs surgery in the transthoracic-access cohort [8].

8. CoreValve: Three-Year Outcomes in High-Risk Patients Who Underwent Surgical or Transcatheter Aortic Valve Replacement

Another study, the CoreValve, reported the sustained benefit over time at 3 years time-point for self-expanding transcatheter aortic valve replacement (TAVR) versus open surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis at increased risk for surgery at the ACC2016.

750 eligible subjects were randomised 1:1 to either TAVR or SAVR and underwent an attempted procedure. Three-year all-cause mortality or stroke was significantly lower in TAVR (37.3%) versus SAVR (46.7%) (P = 0.006). Furthermore, when comparing TAVR with SAVR at three-years time-point, all stroke (12.6% versus 19.0%; respectively P = 0.034), and major adverse cardiovascular or cerebrovascular events (40.2% versus 47.9%; respectively P=0.025) were both lower. There was a trend towards lower all-cause mortality (32.9% versus 39.1%, respectively; P=0.068) but this was not statistically significant. At 3 years mean aortic valve gradient was better in TAVR patients when compared to SAVR (7.62 ± 3.57 mm Hg vs. 11.40 ± 6.81 mm Hg in SAVR, P < 0.001). Moderate and severe residual aortic regurgitation proved higher in TAVR patients compared to SAVR (6.8% versus 0.0% in SAVR; P < 0.001) [9].

References

1. Velazquez EJ et al. N Engl J Med. 2016
2. Nissen SE et al. JAMA. 2016
3. Kelbæk H et al. Lancet. 2016
4. Roolvink V et al. J Am Coll Cardiol. 2016
5. Lonn EM et al. N Engl J Med. 2016
6. Yusuf S et al. N Engl J Med. 2016
7. Khera AV et al. J Am Coll Cardiol. 2016;
8. Leon MB et al. N Engl J Med. 2016
9. Deeb MG et al. J Am Coll Cardiol. 2016