American College of Cardiology

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1 Meeting Highlights American College of Cardiology Walter Alexander The American College of Cardiology (ACC) 67th Annual Scientific Session drew more than 12,000 cardiology professionals to Orlando from March 9 to 12. Key sessions reviewed below report on findings in noncardiac surgery, pharmacological agents in the setting of heart attacks and acute coronary syndromes, and cardiotoxicity of cancer therapy. ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab Philippe Gabriel Steg, MD, Hôpital Bichat, Paris, France In the ODYSSEY Outcomes trial in patients with acute coronary syndromes (ACS), alirocumab (Praluent, Sanofi/ Regeneron) 75 or 150 mg once every two weeks reduced major adverse cardiac events (MACE), myocardial infarction (MI), and ischemic stroke. Investigators targeted low-density lipoproteincholesterol (LDL-C) levels of mg/dl and allowed levels as low as 15 mg/dl, Dr. Steg stated in an ACC press briefing. Dr. Steg noted that despite substantial progress, cardiovascular event rates are high in the first year after MI and remain high in the following 3.5 years despite evidence-based preventive therapies. Those high rates, he continued, are related in part to levels of LDL-C. Alirocumab is a fully human monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9. It has been shown to produce substantial and sustained reductions in LDL-C and other atherogenic lipoproteins, and has been safe and well tolerated in studies to date. The ODYSSEY Outcomes hypothesis was that alirocumab (versus placebo) would reduce cardiovascular morbidity and mortality after recent ACS (acute MI or unstable angina one to 12 months prior to randomization) in patients with elevated levels of atherogenic lipoproteins despite intensive maximumtolerated statin therapy (atorvastatin mg daily or rosuvastatin mg daily or the maximum tolerated dose of either for two weeks or longer). Included patients had an LDL-C of 70 mg/dl or higher, non-high-density lipoprotein-cholesterol of 100 mg/dl or higher, or apolipoprotein B of 80 mg/dl or higher. Investigators attempted to maximize the number of patients in the target range and minimize the number below target. The trial s primary efficacy outcome was time to first occurrence of coronary heart disease (CHD), death, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. The trial included 18,924 patients randomized 1:1 to alirocumab or placebo via injection at 1,315 sites in 57 countries. Mean patient age was 58 years, and 75% were men. About 49% had non-st-segment MI, and approximately 17% had unstable angina. Roughly 73% of the patients had been revascularized after their index The author is a freelance writer living in New York City. ACS. Most patients (92.5%) qualified based on having LDL-C of 70 mg/dl or higher. Most (about 89%) were receiving highdose atorvastatin or rosuvastatin and guideline-recommended post-acs medications (aspirin, 96%; P2Y 12 antagonists, 88%; angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, 78%; beta blockers, 85%). After a follow-up of at least two years (44% were followed for three years or more), the primary MACE endpoint was reported at rates of 9.5% for alirocumab and 11.1% for placebo (hazard ratio [HR], 0.85; 95% confidence interval [CI], ; P = ). Rates for CHD death were similar (2.2% alirocumab versus 2.3% placebo; P = not significant), but nonfatal MI (6.6% versus 7.6%), ischemic stroke (1.2% versus 1.6%) and unstable angina (0.4% versus 0.6%) all favored alirocumab significantly. The rate for ischemia-driven coronary revascularization was also reduced significantly in the alirocumab group (7.7% versus 8.8%; P = 0.009). The alirocumab benefits were driven by those patients with baseline LDL-C of 100 mg/dl or higher, among whom the MACE rate was 11.5% for alirocumab versus 14.9% for placebo (HR, 0.76; 95% CI, ). Because the treatment effect was so much more marked in the patients with the highest LDL cholesterol, we believe that these patients are the optimal candidates for therapy, he said. Given that the annual retail cost of alirocumab is in the tens of thousands of dollars and is often not covered by insurers, results of a planned cost-effectiveness analysis of ODYSSEY Outcomes are eagerly awaited. The Effect of Dabigatran in Patients Suffering Myocardial Injury After Noncardiac Surgery P.J. Devereaux, MD, PhD, McMaster University, Hamilton, Canada Among patients who were at elevated risk of death, myocardial infarction (MI), stroke, or other cardiac or vascular complications because of heart damage subsequent to major noncardiac surgery, dabigatran (Pradaxa, Boehringer Ingelheim) significantly reduced events. Dr. Devereaux, lead author of the Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial, noted that about eight million people develop myocardial injury after noncardiac surgery (MINS) annually, especially after hip or knee replacement, bowel resection, or abdominal aortic aneurysm repair. MINS, he said, includes MI and isolated ischemic troponin elevation within the first 30 days of surgery, but excludes nonischemic myocardial injury, such as sepsis, rapid atrial fibrillation, pulmonary embolism (PE), or chronically elevated troponin. It is independently associated with an increased risk of cardiovascular events and death within the first two years after surgery. The rationale for MANAGE, he explained, comes from the elevated thrombotic complication risk of patients with MINS and the high-quality evidence demonstrating the benefits of Vol. 43 No. 5 May 2018 P&T 301

2 anticoagulation therapy in nonoperative patients at risk for thrombotic events. Dabigatran, an oral direct thrombin inhibitor, has been shown to prevent venous thromboembolism in the perioperative setting and has potential to prevent a broader range of vascular complications in MINS patients. MANAGE investigators included patients 45 years of age or older from centers in North and South America, Europe, India, Australia, and Africa. All had undergone noncardiac surgery and were within 35 days of being positive for MINS diagnostic criteria (universal definition of MI or ischemic elevated troponin after surgery). On the day of randomization, patients started taking dabigatran 110 mg twice daily or matching placebo. Based on slow recruitment, curtailed funding, and COMPASS trial results, the sample size was reduced to 1,750 patients (3,200 were originally intended), and the primary composite outcome of vascular mortality, nonfatal MI, stroke, peripheral arterial thrombosis, and symptomatic PE was expanded to include amputation and symptomatic proximal deep vein thrombosis. The primary safety outcome was the composite of life-threatening major and critical organ bleeding. An additional group of 556 patients was randomized to omeprazole or placebo. Mean patient age was 70 years, and 51.5% were men. Twenty percent of patients met MI criteria, and 80% met isolated ischemic troponin elevation criteria. Most MINS patients (91%) did not experience an ischemic symptom. After a mean follow-up of 16 months, the primary outcome was reported in 11% of patients receiving dabigatran and in 15% of patients receiving placebo (hazard ratio [HR], 0.72; 95% confidence interval [CI], ; P = 0.012). Omeprazole dosing had no effect on the primary efficacy outcome. Safety was similar between groups with composite bleeding at 3% and 4% for dabigatran and placebo, respectively. Significant lower gastrointestinal (GI) bleeds were more common in the dabigatran group (HR, 2.50; 95% CI, ), as were nonsignificant lower GI bleeds (HR, 4.77; 95% CI, ). Dr. Devereaux concluded that patients who have MINS are at substantial risk of major vascular complications. Among patients in MANAGE who had MINS, dabigatran 110 mg twice a day resulted in lower risk of major vascular complications compared to placebo. Without routine postoperative troponin measurement, clinicians will not recognize most MINS, he said. SECURE-PCI: Statin Evaluation in Coronary Procedures and Revascularization Otávio Berwanger, MD, PhD, Brazilian Clinical Research Institute, São Paulo, Brazil While a periprocedural loading dose of atorvastatin did not reduce major adverse coronary events (MACE) at 30 days among acute coronary syndrome (ACS) patients with planned invasive management, an atorvastatin loading dose did improve outcomes for those undergoing percutaneous coronary interventions (PCIs). Dr. Berwanger noted at an ACC press briefing that the effect of a statin loading dose in ACS patients is uncertain because existing studies have had low numbers of events and varying statin doses and regimens. The SECURE-PCI study s objective was to determine if periprocedural loading doses of atorvastatin decrease 30-day MACE in patients with ACS and planned invasive management. Investigators enrolled 4,291 patients (mean age, approximately 62 years; approximately 75% male) at 58 Brazilian hospitals, randomizing them to atorvastatin 80 mg preprocedure and 80 mg 24 hours after PCI, or to conventional management with placebo before and after PCI. The primary outcome was MACE at 30 days (all-cause mortality, nonfatal acute myocardial infarction [MI], stroke, or recurrent ischemia leading to urgent revascularization). About 60% of patients had non-st-segment MI, approximately 25% had ST-segment MI, and about 14% had unstable angina. PCI was performed in approximately 65% of patients. The primary outcome incidence of cumulative MACE was similar for both groups (6.2% atorvastatin versus 7.1% placebo; P = 0.27), with a nonsignificant 12% risk reduction for the atorvastatin group (hazard ratio [HR], 0.88; 95% confidence interval [CI], ). Among patients undergoing PCI, however, MACE was reduced by 28% (HR, 0.72; 95% CI, ; P = 0.02), occurring at a rate of 6.0% and 8.2% in the atorvastatin and placebo groups, respectively. Three cases of rhabdomyolysis were reported in the placebo group (0.1%), but none occurred in the atorvastatin group. Dr. Berwanger pointed out that subgroup analysis showed the greatest atorvastatin benefit in patients with ST-segment MI and those undergoing PCI. These findings do not support the routine use of loading doses of atorvastatin among unselected patients undergoing PCI. Among patients undergoing PCI, however, loading doses of atorvastatin seem to improve clinical periprocedural outcomes and might be an attractive treatment strategy for patients with acute coronary syndromes, he concluded. The SECURE-PCI trial results were published simultaneously in the Journal of the American Medical Association. 1 In an accompanying editorial, Stephen J. Nicholls, MBBS, PhD, and Peter J. Psaltis, MBBS, PhD, both of the South Australian Health and Medical Research Institute at the University of Adelaide in Australia, wrote, SECURE-PCI certainly provides reassurance that such early administration [of atorvastatin] is not associated with harm. The subgroup findings suggest potential benefit among patients who are deemed more likely to undergo PCI at the time of angiography. To what degree such findings may be exclusive to intensive statin therapy, or whether similar results would be observed with early initiation of additional lipid-lowering agents, some of which do not appear to have pleiotropic effects in humans, is unknown. The editorial authors urged further large-scale study. 2 Carvedilol for Prevention of Chemotherapy- Induced Cardiotoxicity: Results of the CECCY Trial Monica Samuel Avila, MD, Heart Institute, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, Brazil Although the beta blocker carvedilol failed to prevent cardiac complications in breast cancer patients receiving chemotherapy compared with placebo, it did reduce markers of cardiac injury, according to results of the CECCY trial. Dr. Avila noted that treatment-related cardiovascular complications, particularly heart failure in women with breast cancer 302 P&T May 2018 Vol. 43 No. 5

3 receiving anthracyclines, limit prognosis. Cumulative doses of anthracyclines are known to damage and weaken heart muscle. Findings from clinical trials testing primary prevention of cardiotoxicity with beta blockers are controversial, Dr. Avila said in an ACC press briefing, because they have been observational with design limitations (e.g., open-label, single-blind, combined interventions, small sample size). The CECCY trial objective was to evaluate the effectiveness of carvedilol for prevention of early-onset chemotherapy-induced cardiomyopathy in patients with breast cancer. Investigators enrolled 200 women with breast cancer and normal left ventricular ejection fraction (LVEF) receiving doxorubicin (240 mg/m 2 ) in the randomized, double-blind, placebo-controlled trial. They were assigned 1:1 to receive carvedilol (median daily dose of 18.4 mg/day) or placebo while also on chemotherapy. The primary endpoint was reduction in LVEF of 10% or greater. Changes in troponin I, brain natriuretic peptide, and diastolic dysfunction were secondary measures. Patient mean age was approximately 52 years, and about half of the women were premenopausal. Fourteen percent of patients in the placebo group had changes in LVEF of 10% or greater compared with 15% in the carvedilol group (P = not significant). Mean change in LVEF was 1.3% in the placebo group and 0.9% in the carvedilol group (P = 0.84). For the secondary endpoint of troponin I levels, elevations were more common in the placebo group at 24 weeks (P = 0.003). In addition, more patients in the placebo group had troponin I values greater than 0.04% (41.6% versus 26.0%; P = 0.03). At 24 weeks, diastolic dysfunction was more common in the placebo group (P = 0.039) and left ventricular end-diastolic diameter was larger (P = 0.057). Adverse events were similar between the groups. Dr. Avila noted that the incidence of early-onset cardiotoxicity in the CECCY trial was lower than expected. She concluded that while carvedilol did not impact left ventricular function after up to six months, it did attenuate the elevation of troponin I levels and reduce the percentage of patients with diastolic dysfunction. In addition, there was a trend toward a less pronounced increase in left ventricular diastolic diameter. Carvedilol might reduce myocardial injury, influence the cardiotoxicity-dependent left ventricular remodeling process, and reduce the appearance of diastolic dysfunction, she said. Dr. Avila commented that the discordance between the increase in troponin without a concomitant change in LVEF needs explanation, although differences could appear with longer follow-up. Lisinopril or Carvedilol for Prevention of Trastuzumab-Induced Cardiotoxicity Maya Guglin, MD, PhD, University of Kentucky, Lexington, Kentucky While anthracycline-based regimens are more effective for high-risk breast cancer patients, their use has been limited because of cardiotoxicity. A trial of the angiotensin-converting enzyme (ACE) inhibitor lisinopril or the beta blocker carvedilol compared with placebo found that neither drug prevented cadiotoxicity in breast cancer patients being treated with trastuzumab (Herceptin, Genentech) with or without anthracyclines, Dr. Guglin said in an ACC press conference. However, both drugs were effective in preserving left ventricular ejection fraction (LVEF) in the women with prior exposure to anthracyclines. She noted that, while trastuzumab has been hailed as a breakthrough treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, an especially aggressive form of the disease, some studies have shown that up to one-quarter of women receiving trastuzumab experience cardiac effects, including symptomatic heart failure. Strict clinical guidelines, as a consequence, now require that physicians establish that women have ejection fractions greater than 50%, the lower limit of normal, before initiating treatment with trastuzumab. But while trastuzumab has been associated with milder and often temporary declines in heart function, anthracycline chemotherapy can cause long-lasting, potentially irreversible heart muscle damage. Dr. Guglin and colleagues hypothesized that an ACE inhibitor or a beta blocker during trastuzumab therapy would prevent a decrease in LVEF. The primary endpoint of the trial was change in LVEF. The secondary objectives were to determine if adding lisinopril or carvedilol led to fewer interruptions in trastuzumab therapy and if treatment effects were consistent in the anthracycline and nonanthracycline cohorts. Cardiotoxicity was defined as an LVEF decrease from baseline of 10% or greater or an absolute decrease of 5% or more in LVEF when LVEF was less than 50% at follow-up. Investigators enrolled 468 HER2-positive breast cancer patients at 127 participating sites (mean age, 51 years; baseline LVEF, approximately 63%), all for whom trastuzumab was clinically indicated. In addition, all patients had LVEF in the normal range. Patients were randomized to daily lisinopril (10 mg), carvedilol (10 mg), or placebo and were followed through one year of trastuzumab treatment and one subsequent year. Analysis showed neither lisinopril nor carvedilol prevented cardiotoxicity or prevented related disruptions in therapy compared with placebo. In women receiving anthracyclines, however, both drugs reduced declines in heart function by 50% (odds ratio, 0.49 and 0.53 for carvedilol and lisinopril, respectively, versus placebo). Adverse cardiac effects, typically hypotension and dizziness, were reported in 32% of patients receiving placebo and in 29% and 30% of those receiving carvedilol and lisinopril, respectively. Carvedilol, Dr. Gugline noted, was generally better tolerated than lisinopril. The senior study author, oncologist Pamela Munster, MD, commented, This study is of great importance as it provides the oncologist the option to use an anthracycline in HER2- positive, early-stage breast cancer patients. Dr. Guglin added, This trial is one of the first and the largest to date to test whether these drugs can prevent trastuzumabrelated heart damage and prevent the need to discontinue a potentially life-saving treatment In high risk patients who may benefit from an anthracycline-containing regimen, the use of lisinopril or carvedilol is justified and should be considered to offset cardiotoxic events by the use of anthracyclines in combination with trastuzumab. Vol. 43 No. 5 May 2018 P&T 303

4 Pragmatic Trial of a Low-Dose Triple- Combination Blood Pressure Lowering Pill for Initial Treatment of Hypertension Ruth Webster, PhD, MBBS, MPH, BMedSc, University of New South Wales, Sydney, Australia In the TRIUMPH trial, more patients reached their blood pressure targets taking a pill combining an angiotensin receptor blocker, a calcium antagonist, and a thiazide diuretic than patients treated with usual care. In addition, adverse effects were not increased with the Triple Pill, according to Dr. Webster. She noted that despite the availability of effective antihypertensive medications, hypertension remains a worldwide problem, with only about one-third of those in treatment achieving recommended reductions. Control rates range widely from 75% in Australia, to 53% in the United States, to 33.5% in South America, and just 20.7% in Africa. The frequent need to take multiple medications often leads to patient nonadherence to therapy, Dr. Webster observed. Low-dose combinations potentially offer additive benefits (blood pressure lowering at lower doses), minimized adverse effects, better patient adherence, and reduced physician inertia to uptitration. TRIUMPH, Dr. Webster said, is the first large trial testing the theory that initiating treatment with low doses of three drugs would achieve better blood pressure control than usual care. It was conducted in Sri Lanka with 700 patients (average age, 56 years; 58% female), most of whom (59%) were receiving their first treatment for hypertension. Mean blood pressure was 154/90 mm Hg. Thirty-two percent had diabetes or chronic kidney disease. Investigators randomized patients to the Triple Pill consisting of telmisartan (20 mg), amlodipine (2.5 mg), and chlorthalidone (12.5 mg) or to usual care consisting of the physician s choice of antihypertensive drug. The primary endpoint was the proportion of patients at six months who achieved a blood pressure of 140/90 mm Hg or lower (130/80 or lower in those with diabetes or chronic kidney disease). Included patients had persistent hypertension (systolic pressure greater than 140 mm Hg and/or diastolic pressure greater than 90 mm Hg; or systolic pressure greater than 130 mm Hg and/or diastolic pressure greater than 80 mm Hg in patients with diabetes mellitus or chronic kidney disease) requiring pharmacological treatment. TRIUMPH investigators enrolled 350 patients in each group, adjusting doses at six and 12 weeks as required. Among 647 patients with data at six months, the Triple Pill strategy was associated with greater achievement of target blood pressure levels compared with usual care (70% versus 55%, respectively) (relative risk [RR] 1.23; 95% confidence interval [CI], ; P = ), with the maximum difference observed at six weeks (68% versus 44%) (RR, 1.53; 95% CI, ). In addition, at six months, the mean change in blood pressure was 29.1/ 13.9 mm Hg for the Triple Pill compared with 20.3/ 9.3 mm Hg for usual care (P < 0.001). Adherence was high for both groups (about 95%), and adverse event rates low (serious events 7.7% for the Triple Pill; 6.0% for usual care; P = not significant). Withdrawal from the study for adverse events was 6.6% and 6.8%, respectively, for the Triple Pill and usual care groups. Dr. Webster concluded, Early use of a low-dose three-in-one combination blood pressure lowering pill is safe and provides faster, better control of blood pressure compared to usual care. The POISE Trial: One-Year Outcomes of Perioperative Beta-Blockade in Patients Undergoing Noncardiac Surgery P.J. Devereaux, MD, PhD, McMaster University, Hamilton, Canada While patients undergoing noncardiac surgery receiving the beta blocker metoprolol are less likely to have myocardial infarctions (MIs) and undergo cardiac revascularization, their mortality and stroke risk goes up, Dr. Devereaux said at an ACC press briefing. Among the 200 million adults who undergo noncardiac surgery annually, more than three million will suffer MIs. The POISE trial hypothesis was that because beta blockers attenuate the effects of perioperative increases in catecholamine levels, they would reduce the risk of perioperative MI and its sequela. POISE investigators randomized 8,351 patients from 191 sites in 23 countries to placebo or extended-release metoprolol (100 mg) given two to four hours preoperatively and six hours after surgery, followed the next day by 200 mg daily for 30 days. In the presence of hypotension or bradycardia, the dose was reduced to 100 mg daily. In 30-day results presented previously, extended-release metoprolol reduced MI risk (hazard ratio [HR], 0.73; 95% confidence interval [CI], ), but increased risk of stroke (HR, 2.17; 95% CI, ) and mortality (HR, 1.33; 95% CI, ) due to sepsis/infection (36 versus 18 deaths; P = 0.016). Mean patient age was 69 years (63.5% male). Forty-three percent of patients had a history of coronary artery disease, while about 41% had a history of peripheral arterial disease. Fifteen percent had prior stroke. Most were undergoing vascular surgery (41.5%), with 21.5% and 21% undergoing intraperitoneal and orthopedic surgery, respectively. Dr. Devereaux reported that after one year, morality rates were lower in the metoprolol group (10% metoprolol versus 9% placebo; P = 0.036), with cardiovascular mortality similar between groups (4% for both; P = 0.37), but noncardiovascular mortality was higher with metoprolol (6% versus 5%; P = 0.043). MI rates were lower for metoprolol (5% versus 6%; P = 0.008), as were cardiac revascularization rates (HR, 0.47; P = 0.004). Stroke rates doubled with metoprolol (2% versus 1%; HR, 1.52; P = 0.014). Cardiac arrest rates were 1% (P = 0.79) and pulmonary embolism rates were less than 1% (P = 0.43) in both groups. Dr. Devereaux noted that independent predictors of one-year mortality were MI (odds ratio [OR], 3.07), stroke (OR, 5.94), cardiac arrest (OR, 11.80), and pulmonary embolism (OR, 11.6). The findings show that for every 1,000 patients having noncardiac surgery, extended-release metoprolol would prevent MI in 12 patients and cardiac revascularization in six at the cost of 13 deaths and six strokes. 304 P&T May 2018 Vol. 43 No. 5

5 While there is little doubt that some patients benefit from receiving beta blockers during the period immediately before and after noncardiac surgery, Dr. Devereaux commented, these data show that at least as many patients are seriously harmed. These data tell us that we need to exercise caution when using beta blockers in this setting until we figure out how to mitigate the substantial risks and enable all patients to obtain the potential benefits of this intervention. The main contributor to adverse events in this setting, he added, is that following major noncardiac surgery (e.g., hip or knee replacement, bowel resection, abdominal aneurysm repair), patients usually receive opioid medications for analgesia that can mask dangerously low heart rates or blood pressure levels. SMART-DATE: Safety of Six-Month Dual Antiplatelet Therapy After Percutaneous Coronary Intervention In Patients With Acute Coronary Syndrome Hyeon Cheol Gwon, MD, Samsung Medical Center, Seoul, South Korea Despite meeting the SMART-DATE trial noninferiority criteria, six-month versus 12-month dual antiplatelet therapy (DAPT) cannot be considered safe because of heightened myocardial infarction (MI) risk, Dr. Gwon said at an ACC press briefing. Patients with acute coronary syndromes (ACS) have a higher risk of recurrent ischemic events than those with stable ischemic heart disease. While current ACC/American Heart Association guidelines recommend 12 months or more of DAPT for ACS patients without excessive bleeding risk after implantation of a drug-eluting stent (DES), some recent studies have suggested that six months of DAPT may offer similar benefits with respect to reducing risk of death, MI, stroke, bleeding, or other adverse events. However, Dr. Gwon said, those studies were too small to provide a foundation for firm conclusions. The primary objective of the SMART-DATE trial was to investigate whether six months of DAPT would be noninferior to the conventional 12-month or longer duration of DAPT after implantation of DES in ACS patients for prevention of major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of all-cause mortality, MI, and cerebrovascular events at 18 months after the index procedure. Patients included in SMART-DATE (N = 2,700) had ACS with target lesions in native coronary arteries amenable to percutaneous coronary interventions with DES implantation. They were randomized open-label at 31 South Korean centers to DAPT with aspirin plus a P2Y 12 inhibitor for either six or 12 or more months. The primary outcome was 18-month MACCE. Patient mean age was 62.5 years (approximately 75% male). Adherence to antiplatelet therapy protocol was 73.7% in the six-month group and 95.7% in the 12-month group. MACCE was reported at a rate of 4.7% in the six-month group and at 4.2% in the 12-month group (hazard ratio [HR], 1.13; 95% confidence interval [CI], ; P = 0.51). Analysis confirmed noninferiority (P = 0.027). Rates for MI, however, were higher in the six-month group at 1.8% compared with 0.8% in the 12-month group (HR, 2.41; 95% CI ; P = 0.02). Between six and 18 months after stent insertion when patients in the six-month group were being treated with aspirin only, there was a 5.1-fold risk of having a heart attack in six-month patients compared with 12-month patients. In addition, the risk of dying from any cause or having an MI or stroke was increased by 69% in the six-month DAPT group. This is the largest trial to address the optimal duration of DAPT in patients with ACS, Dr. Gwon said. Based on our findings, we can t say that short-term DAPT is safe in patients with ACS who have received drug-eluting stents. Prolonged DAPT in ACS patients without excessive risk of bleeding should remain the standard of care, Dr. Gwon concluded. Current guidelines should continue to be followed. REFERENCES 1. Berwanger O, Santucci EV, de Barros E Silva PGM, et al. Effect of loading dose of atorvastatin prior to planned percutaneous coronary intervention on major adverse cardiovascular events in acute coronary syndrome: The SECURE-PCI randomized clinical trial. JAMA 2018 Mar 11. doi: /jama Nicholls SJ, Psaltis PJ. Lipid lowering in acute coronary syndrome: is treatment early enough? JAMA 2018 Mar 11. doi: / jama n Vol. 43 No. 5 May 2018 P&T 305